Calibrated Langevin dynamics simulations of intrinsically disordered proteins

We perform extensive coarse-grained (CG) Langevin dynamics simulations of intrinsically disordered proteins (IDPs), which possess fluctuating conformational statistics between that for excluded volume random walks and collapsed globules. Our CG model includes repulsive steric, attractive hydrophobic, and electrostatic interactions between residues and is calibrated to a large collection of single-molecule fluorescence resonance energy transfer data on the inter-residue separations for 36 pairs of residues in five IDPs: $\alpha$-, $\beta$-, and $\gamma$-synuclein, the microtubule-associated protein $\tau$, and prothymosin $\alpha$. We find that our CG model is able to recapitulate the average inter-residue separations regardless of the choice of the hydrophobicity scale, which shows that our calibrated model can robustly capture the conformational dynamics of IDPs. We then employ our model to study the scaling of the radius of gyration with chemical distance in 11 known IDPs. We identify a strong correlation between the distance to the dividing line between folded proteins and IDPs in the mean charge and hydrophobicity space and the scaling exponent of the radius of gyration with chemical distance along the protein.Comment: 16 pages, 10 figure

The effects of color contrast on performance of the WAIS-R digit symbol subtest

Color contrast has been shown to aid in visual search tasks using electronic displays, while the research regarding the usefulness of color contrast in aiding visual search using a paper medium is mixed. The present study questions whether subjects’ performance will improve on a paper task where the search target is in high color contrast when compared with a task where the target color does not differ from the rest of the search field. Thirty-nine adults with normal vision were administered two forms of the WAIS-R digit symbol subtest, one with low chromatic contrast and one with high chromatic contrast, in a within-subjects design. No significant difference was found in performance on the two tasks. Explanations offered for these results include the effects of surround luminance, contrast of saturation, and short-term visual memory

Book Reviews

Reviews of the following books: Tidewater Ice of the Kennebec River by Jennie G. Everson; The Indians of Maine: A Bibliographical Guide by Roger B. Ra

The Epiregolith

The physical properties of the lunar regolith were originally inferred from remotely sensed data, first from the Earth and later from orbiting spacecraft. The Surveyor landings and the Apollo surface explorations produced a more concrete characterization of the macroscopic properties. In general, the upper regolith consists of a loosely consolidated layer centimeters thick underlain by a particulate but extremely compacted layer to depths of meters or tens of meters. The median particle size as determined by mechanical sieving in terrestrial laboratories is several tens of micrometers. However, the comminuting processes that form the layer produce particles in all sizes down to manometers. The smallest particles, having a high surface to volume ratio, tend to be electrostatically bound to larger particles and are quite difficult to separate mechanically in the laboratory. Particle size distributions determined from lunar soil samples often group particles smaller than 10 micrometers

A Coupled Experimental and Computational Approach to Quantify Deleterious Hemodynamics, Vascular Alterations, and Mechanisms of Long-Term Morbidity in Response to Aortic Coarctati

Introduction Coarctation of the aorta (CoA) is associated with morbidity despite treatment. Although mechanisms remain elusive, abnormal hemodynamics and vascular biomechanics are implicated. We present a novel approach that facilitates quantification of coarctation-induced mechanical alterations and their impact on vascular structure and function, without genetic or confounding factors. Methods Rabbits underwent thoracic CoA at 10 weeks of age (~ 9 human years) to induce a 20 mm Hg blood pressure (BP) gradient using permanent or dissolvable suture thereby replicating untreated and corrected CoA. Computational fluid dynamics (CFD) was performed using imaging and BP data at 32 weeks to quantify velocity, strain and wall shear stress (WSS) for comparison to vascular structure and function as revealed by histology and myograph results. Results Systolic and mean BP was elevated in CoA compared to corrected and control rabbits leading to vascular thickening, disorganization and endothelial dysfunction proximally and distally. Corrected rabbits had less severe medial thickening, endothelial dysfunction, and stiffening limited to the proximal region despite 12 weeks of normal BP (~ 4 human years) after the suture dissolved. WSS was elevated distally for CoA rabbits, but reduced for corrected rabbits. Discussion These findings are consistent with alterations in humans. We are now poised to investigate mechanical contributions to mechanisms of morbidity in CoA using these methods