Molecular dynamics of ion transport through the open conformation of a bacterial voltage-gated sodium channel

The crystal structure of the open conformation of a bacterial voltage-gated sodium channel pore from Magnetococcus sp. (NaVMs) has provided the basis for a molecular dynamics study defining the channel’s full ion translocation pathway and conductance process, selectivity, electrophysiological characteristics, and ion-binding sites. Microsecond molecular dynamics simulations permitted a complete time-course characterization of the protein in a membrane system, capturing the plethora of conductance events and revealing a complex mixture of single and multi-ion phenomena with decoupled rapid bidirectional water transport. The simulations suggest specific localization sites for the sodium ions, which correspond with experimentally determined electron density found in the selectivity filter of the crystal structure. These studies have also allowed us to identify the ion conductance mechanism and its relation to water movement for the NavMs channel pore and to make realistic predictions of its conductance properties. The calculated single-channel conductance and selectivity ratio correspond closely with the electrophysiology measurements of the NavMs channel expressed in HEK 293 cells. The ion translocation process seen in this voltage-gated sodium channel is clearly different from that exhibited by members of the closely related family of voltage-gated potassium channels and also differs considerably from existing proposals for the conductance process in sodium channels. These studies simulate sodium channel conductance based on an experimentally determined structure of a sodium channel pore that has a completely open transmembrane pathway and activation gate

Physical activity and subjective well-being among people with spinal cord injury: a meta-analysis

Study design: Meta-analysis of cross-sectional, quasi-experimental and experimental studies. Objective: To determine if there is an association between physical activity (PA) and subjective well-being (SWB) among people living with spinal cord injury (SCI). Methods: Literature searches were conducted using multiple databases (Embase, CINAHL, Medline, PsychINFO and SPORTDiscus) to identify studies involving people with SCI that included a measure of PA and at least one measure of SWB (for example, symptoms of depression, life satisfaction, mood). Relevant data were extracted from the studies and subjected to meta-analysis. Results: A total of 21 studies were retrieved yielding 78 effect sizes and a total sample size of 2354. Overall, there were statistically significant, small- to medium-sized effects for the relationships between PA and SWB (broadly defined), PA and depressive symptoms, and PA and life satisfaction. Studies using experimental and quasi-experimental designs yielded larger effects for SWB (broadly defined) and life satisfaction, than studies using nonexperimental study designs. Conclusions: There is a small- to medium-sized positive relationship between PA and SWB among people with SCI that holds across a wide range of measures and operational definitions of these constructs

Canine Aortofemoral Bypass: a New Technique for the Evaluation of Prosthetic Implants

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/67957/2/10.1177_000331977402500901.pd

Collective Quartics and Dangerous Singlets in Little Higgs

Any extension of the standard model that aims to describe TeV-scale physics without fine-tuning must have a radiatively-stable Higgs potential. In little Higgs theories, radiative stability is achieved through so-called collective symmetry breaking. In this letter, we focus on the necessary conditions for a little Higgs to have a collective Higgs quartic coupling. In one-Higgs doublet models, a collective quartic requires an electroweak triplet scalar. In two-Higgs doublet models, a collective quartic requires a triplet or singlet scalar. As a corollary of this study, we show that some little Higgs theories have dangerous singlets, a pathology where collective symmetry breaking does not suppress quadratically-divergent corrections to the Higgs mass.Comment: 4 pages; v2: clarified the existing literature; v3: version to appear in JHE

The Simplest Little Higgs

We show that the SU(3) little Higgs model has a region of parameter space in which electroweak symmetry breaking is natural and in which corrections to precision electroweak observables are sufficiently small. The model is anomaly free, generates a Higgs mass near 150 GeV, and predicts new gauge bosons and fermions at 1 TeV.Comment: 13 pages + appendix, typos corrected, version to appear in JHE

The Superpartner Spectrum of Gaugino Mediation

We compute the superpartner masses in a class of models with gaugino mediation (or no-scale) boundary conditions at a scale between the GUT and Planck scales. These models are compelling because they are simple, solve the supersymmetric flavor and CP problems, satisfy all constraints from colliders and cosmology, and predict the superpartner masses in terms of very few parameters. Our analysis includes the renormalization group evolution of the soft-breaking terms above the GUT scale. We show that the running above the GUT scale is largely model independent and find that a phenomenologically viable spectrum is obtained.Comment: 15 page

Critical Hysteresis from Random Anisotropy

Critical hysteresis in ferromagnets is investigated through a $N$-component spin model with random anisotropies, more prevalent experimentally than the random fields used in most theoretical studies. Metastability, and the tensorial nature of anisotropy, dictate its physics. Generically, random field Ising criticality occurs, but other universality classes exist. In particular, proximity to $\mathcal{O}(N)$ criticality may explain the discrepancy between experiment and earlier theories. The uniaxial anisotropy constant, which can be controlled in magnetostrictive materials by an applied stress, emerges as a natural tuning parameter.Comment: four pages, revtex4; minor corrections in the text and typos corrected (published version

Structural Connectivity of the Developing Human Amygdala

<div><p>A large corpus of research suggests that there are changes in the manner and degree to which the amygdala supports cognitive and emotional function across development. One possible basis for these developmental differences could be the maturation of amygdalar connections with the rest of the brain. Recent functional connectivity studies support this conclusion, but the structural connectivity of the developing amygdala and its different nuclei remains largely unstudied. We examined age related changes in the DWI connectivity fingerprints of the amygdala to the rest of the brain in 166 individuals of ages 5-30. We also developed a model to predict age based on individual-subject amygdala connectivity, and identified the connections that were most predictive of age. Finally, we segmented the amygdala into its four main nucleus groups, and examined the developmental changes in connectivity for each nucleus. We observed that with age, amygdalar connectivity becomes increasingly sparse and localized. Age related changes were largely localized to the subregions of the amygdala that are implicated in social inference and contextual memory (the basal and lateral nuclei). The central nucleus’ connectivity also showed differences with age but these differences affected fewer target regions than the basal and lateral nuclei. The medial nucleus did not exhibit any age related changes. These findings demonstrate increasing specificity in the connectivity patterns of amygdalar nuclei across age.</p></div

Epigenetic predictors of all-cause mortality are associated with objective measures of neighborhood disadvantage in an urban population

BACKGROUND: Neighborhood characteristics are robust predictors of overall health and mortality risk for residents. Though there has been some investigation of the role that molecular indicators may play in mediating neighborhood exposures, there has been little effort to incorporate newly developed epigenetic biomarkers into our understanding of neighborhood characteristics and health outcomes. METHODS: Using 157 participants of the Detroit Neighborhood Health Study with detailed assessments of neighborhood characteristics and genome-wide DNA methylation profiling via the Illumina 450K methylation array, we assessed the relationship between objective neighborhood characteristics and a validated DNA methylation-based epigenetic mortality risk score (eMRS). Associations were adjusted for age, race, sex, ever smoking, ever alcohol usage, education, years spent in neighborhood, and employment. A secondary model additionally adjusted for personal neighborhood perception. We summarized 19 neighborhood quality indicators assessed for participants into 9 principal components which explained over 90% of the variance in the data and served as metrics of objective neighborhood quality exposures. RESULTS: Of the nine principal components utilized for this study, one was strongly associated with the eMRS (β = 0.15; 95% confidence interval = 0.06-0.24; P = 0.002). This principal component (PC7) was most strongly driven by the presence of abandoned cars, poor streets, and non-art graffiti. Models including both PC7 and individual indicators of neighborhood perception indicated that only PC7 and not neighborhood perception impacted the eMRS. When stratified on neighborhood indicators of greenspace, we observed a potentially protective effect of large mature trees as this feature substantially attenuated the observed association. CONCLUSION: Objective measures of neighborhood disadvantage are significantly associated with an epigenetic predictor of mortality risk, presenting a potential novel avenue by which neighborhood-level exposures may impact health. Associations were independent of an individual's perception of their neighborhood and attenuated by neighborhood greenspace features. More work should be done to determine molecular risk factors associated with neighborhoods, and potentially protective neighborhood features against adverse molecular effects