Solute Effects on the Helix-Coil Transition

We discuss the effects of the solvent composition on the helix-coil transition of a polypeptide chain. We use a simple model to demonstrate that improving the hydrogen-bonding ability of the solvent can make the transition less cooperative, without affecting the transition temperature. This effect is very different from other solvent effects which primarily influence the melting transition rather than the cooperativity.Comment: 9 pages, 1 figur

Equilibrium Bundle Size of Rodlike Polyelectrolytes with Counterion-Induced Attractive Interactions

Multivalent counterions can induce an effective attraction between like-charged rodlike polyelectrolytes, leading to the formation of polelectrolyte bundles. In this paper, we calculate the equilibrium bundle size using a simple model in which the attraction between polyelectrolytes (assumed to be pairwise additive) is treated phenomenologically. If the counterions are point-like, they almost completely neutralize the charge of the bundle, and the equilibrium bundle size diverges. When the counterions are large, however, steric and short-range electrostatic interactions prevent charge neutralization of the bundle, thus forcing the equilibrium bundle size to be finite. We also consider the possibility that increasing the number of nearest neighbors for each rod in the bundle frustrates the attractive interaction between the rods. Such a frustration leads to the formation of finite size bundles as well, even when the counterions are small.Comment: 4 pages, 2 figures; v2: typos corrected, references added, minor changes made to conten

Scaling Perspectives of Underscreening in Concentrated Electrolyte Solutions

We present a scaling view of underscreening observed in salt solutions in the range of concentrations greater than about 1M, in which the screening length increases with concentration. The system consists of hydrated clusters of positive and negative ions with a single unpaired ion as suggested by recent simulations. The environment of this ion is more hydrated than average which leads to a self-similar situation in which the size of this environment scales with the screening length. The prefactor involves the local dielectric constant and the cluster density. The scaling arguments as well as the cluster model lead to scaling of the screening length with the ion concentration, in agreement with observations

Charge Fluctuations on Membrane Surfaces in Water

We generalize the predictions for attractions between over-all neutral surfaces induced by charge fluctuations/correlations to non-uniform systems that include dielectric discontinuities, as is the case for mixed charged lipid membranes in an aqueous solution. We show that the induced interactions depend in a non-trivial way on the dielectric constants of membrane and water and show different scaling with distance depending on these properties. The generality of the calculations also allows us to predict under which dielectric conditions the interaction will change sign and become repulsive

Predictors of long-term pain and disability in patients with low back pain investigated by magnetic resonance imaging: A longitudinal study

<p>Abstract</p> <p>Background</p> <p>It is possible that clinical outcome of low back pain (LBP) differs according to the presence or absence of spinal abnormalities on magnetic resonance imaging (MRI), in which case there could be value in using MRI findings to refine case definition of LBP in epidemiological research. We therefore conducted a longitudinal study to explore whether spinal abnormalities on MRI for LBP predict prognosis after 18 months.</p> <p>Methods</p> <p>A consecutive series of patients aged 20-64 years, who were investigated by MRI because of mechanical LBP (median duration of current episode 16.2 months), were identified from three radiology departments, and those who agreed completed self-administered questionnaires at baseline and after a mean follow-up period of 18.5 months (a mean of 22.2 months from MRI investigation). MRI scans were assessed blind to other clinical information, according to a standardised protocol. Associations of baseline MRI findings with pain and disability at follow-up, adjusted for treatment and for other potentially confounding variables, were assessed by Poisson regression and summarised by prevalence ratios (PRs) with their 95% confidence intervals (CIs).</p> <p>Results</p> <p>Questionnaires were completed by 240 (74%) of the patients who had agreed to be followed up. Among these 111 men and 129 women, 175 (73%) reported LBP in the past four weeks, 89 (37%) frequent LBP, and 72 (30%) disabling LBP. In patients with initial disc degeneration there was an increased risk of frequent (PR 1.3, 95%CI 1.0-1.9) and disabling LBP (PR 1.7, 95%CI 1.1-2.5) at follow-up. No other associations were found between MRI abnormalities and subsequent outcome.</p> <p>Conclusions</p> <p>Our findings suggest that the MRI abnormalities examined are not major predictors of outcome in patients with LBP. They give no support to the use of MRI findings as a way of refining case definition for LBP in epidemiological research.</p

Three-Dimensional Stochastic Off-Lattice Model of Binding Chemistry in Crowded Environments

Molecular crowding is one of the characteristic features of the intracellular environment, defined by a dense mixture of varying kinds of proteins and other molecules. Interaction with these molecules significantly alters the rates and equilibria of chemical reactions in the crowded environment. Numerous fundamental activities of a living cell are strongly influenced by the crowding effect, such as protein folding, protein assembly and disassembly, enzyme activity, and signal transduction. Quantitatively predicting how crowding will affect any particular process is, however, a very challenging problem because many physical and chemical parameters act synergistically in ways that defy easy analysis. To build a more realistic model for this problem, we extend a prior stochastic off-lattice model from two-dimensional (2D) to three-dimensional (3D) space and examine how the 3D results compare to those found in 2D. We show that both models exhibit qualitatively similar crowding effects and similar parameter dependence, particularly with respect to a set of parameters previously shown to act linearly on total reaction equilibrium. There are quantitative differences between 2D and 3D models, although with a generally gradual nonlinear interpolation as a system is extended from 2D to 3D. However, the additional freedom of movement allowed to particles as thickness of the simulation box increases can produce significant quantitative change as a system moves from 2D to 3D. Simulation results over broader parameter ranges further show that the impact of molecular crowding is highly dependent on the specific reaction system examined

Neural progenitor cells from an adult patient with fragile X syndrome

BACKGROUND: Currently, there is no adequate animal model to study the detailed molecular biochemistry of fragile X syndrome, the leading heritable form of mental impairment. In this study, we sought to establish the use of immature neural cells derived from adult tissues as a novel model of fragile X syndrome that could be used to more fully understand the pathology of this neurogenetic disease. METHODS: By modifying published methods for the harvest of neural progenitor cells from the post-mortem human brain, neural cells were successfully harvested and grown from post-mortem brain tissue of a 25-year-old adult male with fragile X syndrome, and from brain tissue of a patient with no neurological disease. RESULTS: The cultured fragile X cells displayed many of the characteristics of neural progenitor cells, including nestin and CD133 expression, as well as the biochemical hallmarks of fragile X syndrome, including CGG repeat expansion and a lack of FMRP expression. CONCLUSION: The successful production of neural cells from an individual with fragile X syndrome opens a new avenue for the scientific study of the molecular basis of this disorder, as well as an approach for studying the efficacy of new therapeutic agents