26 research outputs found

    Different Vocal Parameters Predict Perceptions of Dominance and Attractiveness

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    Low mean fundamental frequency (F0) in men’s voices has been found to positively influence perceptions of dominance by men and attractiveness by women using standardized speech. Using natural speech obtained during an ecologically valid social interaction, we examined relationships between multiple vocal parameters and dominance and attractiveness judgments. Male voices from an unscripted dating game were judged by men for physical and social dominance and by women in fertile and non-fertile menstrual cycle phases for desirability in short-term and long-term relationships. Five vocal parameters were analyzed: mean F0 (an acoustic correlate of vocal fold size), F0 variation, intensity (loudness), utterance duration, and formant dispersion (Df, an acoustic correlate of vocal tract length). Parallel but separate ratings of speech transcripts served as controls for content. Multiple regression analyses were used to examine the independent contributions of each of the predictors. Physical dominance was predicted by low F0 variation and physically dominant word content. Social dominance was predicted only by socially dominant word content. Ratings of attractiveness by women were predicted by low mean F0, low Df, high intensity, and attractive word content across cycle phase and mating context. Low Df was perceived as attractive by fertile-phase women only. We hypothesize that competitors and potential mates may attend more strongly to different components of men’s voices because of the different types of information these vocal parameters provide

    Quality indicators for multiple sclerosis

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    Determining whether persons with multiple sclerosis (MS) receive appropriate, comprehensive healthcare requires tools for measuring quality. The objective of this study was to develop quality indicators for the care of persons with MS. We used a modified version of the RAND/UCLA Appropriateness Method in a two-stage process to identify relevant MS care domains and to assess the validity of indicators within high-ranking care domains. Based on a literature review, interviews with persons with MS, and discussions with MS providers, 25 MS symptom domains and 14 general health domains of MS care were identified. A multidisciplinary panel of 15 stakeholders of MS care, including 4 persons with MS, rated these 39 domains in a two-round modified Delphi process. The research team performed an expanded literature review for 26 highly ranked domains to draft 86 MS care indicators. Through another two-round modified Delphi process, a second panel of 18 stakeholders rated these indicators using a nine-point response scale. Indicators with a median rating in the highest tertile were considered valid. Among the most highly rated MS care domains were appropriateness and timeliness of the diagnostic work-up, bladder dysfunction, cognition dysfunction, depression, disease-modifying agent usage, fatigue, integration of care, and spasticity. Of the 86 preliminary indicators, 76 were rated highly enough to meet predetermined thresholds for validity. Following a widely accepted methodology, we developed a comprehensive set of quality indicators for MS care that can be used to assess quality of care and guide the design of interventions to improve care among persons with MS

    Gene Expression Profiles of Colonic Mucosa in Healthy Young Adult and Senior Dogs

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    Background: We have previously reported the effects of age and diet on nutrient digestibility, intestinal morphology, and large intestinal fermentation patterns in healthy young adult and senior dogs. However, a genome-wide molecular analysis of colonic mucosa as a function of age and diet has not yet been performed in dogs. Methodology/Principal Findings: Colonic mucosa samples were collected from six senior (12-year old) and six young adult (1-year old) female beagles fed one of two diets (animal protein-based vs. plant protein-based) for 12 months. Total RNA in colonic mucosa was extracted and hybridized to Affymetrix GeneChipH Canine Genome Arrays. Results indicated that the majority of gene expression changes were due to age (212 genes) rather than diet (66 genes). In particular, the colonic mucosa of senior dogs had increased expression of genes associated with cell proliferation, inflammation, stress response, and cellular metabolism, whereas the expression of genes associated with apoptosis and defensive mechanisms were decreased in senior vs. young adult dogs. No consistent diet-induced alterations in gene expression existed in both age groups, with the effects of diet being more pronounced in senior dogs than in young adult dogs. Conclusion: Our results provide molecular insight pertaining to the aged canine colon and its predisposition to dysfunction and disease. Therefore, our data may aid in future research pertaining to age-associated gastrointestinal physiologica

    Distance dependence and salt sensitivity of pairwise, coulombic interactions in a protein, Protein Sci

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    Abstract Histidine pK a values were measured in charge-reversal (K78E, K97E, K127E, and K97E/K127E) and charge-neutralization (E10A, E101A, and R35A) mutants of staphylococcal nuclease (SNase) by 1 H-NMR spectroscopy. Energies of interaction between pairs of charges (⌬G ij ) were obtained from the shifts in pK a values relative to wild-type values. The data describe the distance dependence and salt sensitivity of pairwise coulombic interactions. Calculations with a continuum electrostatics method captured the experimental ⌬G ij when static structures were used and when the protein interior was treated empirically with a dielectric constant of 20. The ⌬G ij when r ij Յ 10 Å were exaggerated slightly in the calculations. Coulomb's law with a dielectric constant near 80 and a Debye-Hückel term to account for screening by the ionic strength reproduced the salt sensitivity and distance dependence of ⌬G ij as well as the structure-based method. In their interactions with each other, surface charges behave as if immersed in water; the Debye length describes realistically the distance where interactions become negligible at a given ionic strength. On average, charges separated by distances (r ij ) ≈5 Å interacted with ⌬G ij ≈ 0.6 kcal/mole in 0.01 M KCl, but ⌬G ij decayed to Յ0.10 kcal/mole when r ij ‫ס‬ 20 Å. In 0.10 M KCl, ⌬G ij ≈ 0.10 kcal/mole when r ij ‫ס‬ 10 Å. In 1.5 M KCl, only short-range interactions with r ij Յ 5 Å persisted. Although at physiological ionic strengths the interactions between charges separated by more than 10 Å are extremely weak, in situations where charge imbalance exists many weak interactions can cumulatively produce substantial effects. Keywords: Electrostatics; Poisson-Boltzmann; determinants of pK a values; salt effects; ionic strength; coulombic interactions; staphylococcal nuclease The structure, stability, and function of many proteins are governed by electrostatics. Therefore, knowledge of the pK a values of ionizable residues and of their molecular determinants is often required to understand the physical basis of stability and function. pK a values can be measured experimentally in small, soluble proteins, but in larger proteins and in membrane proteins they are experimentally inaccessible. In such cases, structure-based pK a calculations are useful for analysis of the relationship between protein structure and function. This approach is only productive if the reliability of the computational methods is established by comparison with experimental data. Here we present an experimental study of the magnitude, distance dependence, and salt sensitivity of the energy of coulombic interaction between pairs of surface charges in staphylococcal nuclease (SNase). The data are used to assess coulombic contributions to pK a values and to test the ability of a continuum method for structure-based pK a calculations to reproduce the experimental data. The validity of physical models for calculation of electrostatic energies in proteins is usually established by comparison of measured and calculated pK a values. In calculations, the contributions from coulombic interactions between charged groups, and contributions related to the selfenergies of the charged groups, are usually treated separatel

    Electrostatic Contributions to the Stability of the GCN4 Leucine Zipper Structure

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    Ion pairs are ubiquitous in X-ray structures of coiled coils, and mutagenesis of charged residues can result in large stability losses. By contrast, pK(a) values determined by NMR in solution often predict only small contributions to stability from charge interactions. To help reconcile these results we used triple-resonance NMR to determine pK(a) values for all groups that ionize between pH 1 and 13 in the 33-residue leucine zipper fragment, GCN4p. In addition to the native state we also determined comprehensive pK(a) values for two models of the GCN4p denatured state: the protein in 6 M urea, and unfolded peptide fragments of the protein in water. Only residues that form ion pairs in multiple X-ray structures of GCN4p gave large pK(a) differences between the native and denatured states. Moreover, electrostatic contributions to stability were not equivalent for oppositely charged partners in ion pairs, suggesting that the interactions between a charge and its environment are as important as those within the ion pair. The pH dependence of protein stability calculated from NMR-derived pK(a) values agreed with the stability profile measured from equilibrium urea-unfolding experiments as a function of pH. The stability profile was also reproduced with structure-based continuum electrostatic calculations, although contributions to stability were overestimated at the extremes of pH. We consider potential sources of errors in the calculations, and how pK(a) predictions could be improved. Our results show that although hydrophobic packing and hydrogen bonding have dominant roles, electrostatic interactions also make significant contributions to the stability of the coiled coil
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