Asymmetric Berry-Phase Interference Patterns in a Single-Molecule Magnet

A Mn4 single-molecule magnet displays asymmetric Berry-phase interference patterns in the transverse-field (HT) dependence of the magnetization tunneling probability when a longitudinal field (HL) is present, contrary to symmetric patterns observed for HL=0. Reversal of HL results in a reflection of the transverse-field asymmetry about HT=0, as expected on the basis of the time-reversal invariance of the spin-orbit Hamiltonian which is responsible for the tunneling oscillations. A fascinating motion of Berry-phase minima within the transverse-field magnitude-direction phase space results from a competition between noncollinear magnetoanisotropy tensors at the two distinct Mn sites.Comment: 4 double-column page

The Ubiquitin Binding Domain ZnF UBP Recognizes the C-Terminal Diglycine Motif of Unanchored Ubiquitin

SummaryUbiquitin binding proteins regulate the stability, function, and/or localization of ubiquitinated proteins. Here we report the crystal structures of the zinc-finger ubiquitin binding domain (ZnF UBP) from the deubiquitinating enzyme isopeptidase T (IsoT, or USP5) alone and in complex with ubiquitin. Unlike other ubiquitin binding domains, this domain contains a deep binding pocket where the C-terminal diglycine motif of ubiquitin is inserted, thus explaining the specificity of IsoT for an unmodified C terminus on the proximal subunit of polyubiquitin. Mutations in the domain demonstrate that it is required for optimal catalytic activation of IsoT. This domain is present in several other protein families, and the ZnF UBP domain from an E3 ligase also requires the C terminus of ubiquitin for binding. These data suggest that binding the ubiquitin C terminus may be necessary for the function of other proteins

Small amounts of involuntary muscle activity reduce passive joint range of motion

When assessing passive joint range of motion in neurological conditions, concomitant involuntary muscle activity is generally regarded small enough to ignore. This assumption is untested. If false, many clinical and laboratory studies that rely on these assessments may be in error. We determined to what extent small amounts of involuntary muscle activity limit passive range of motion in 30 able-bodied adults. Subjects were seated with the knee flexed 90° and the ankle in neutral, and predicted maximal plantarflexion torque was determined using twitch interpolation. Next, with the knee flexed 90° or fully extended, the soleus muscle was continuously electrically stimulated to generate 1, 2.5, 5, 7.5, and 10% of predicted maximal torque, in random order, while the ankle was passively dorsiflexed to a torque of 9 N·m by a blinded investigator. A trial without stimulation was also performed. Ankle dorsiflexion torque-angle curves were obtained at each percent of predicted maximal torque. On average (mean, 95% confidence interval), each 1% increase in plantarflexion torque decreases ankle range of motion by 2.4° (2.0 to 2.7°; knee flexed 90°) and 2.3° (2.0 to 2.5°; knee fully extended). Thus 5% of involuntary plantarflexion torque, the amount usually considered small enough to ignore, decreases dorsiflexion range of motion by ~12°. Our results indicate that even small amounts of involuntary muscle activity will bias measures of passive range and hinder the differential diagnosis and treatment of neural and nonneural mechanisms of contracture

Structure of the Shroom-Rho Kinase Complex Reveals a Binding Interface with Monomeric Shroom That Regulates Cell Morphology and Stimulates Kinase Activity

Shroom-mediated remodeling of the actomyosin cytoskeleton is a critical driver of cellular shape and tissue morphology that underlies the development of many tissues including the neural tube, eye, intestines, and vasculature. Shroom uses a conserved SD2 domain to direct the subcellular localization of Rho-associated kinase (Rock), which in turn drives changes in the cytoskeleton and cellular morphology through its ability to phosphorylate and activate non-muscle myosin II. Here, we present the structure of the human Shroom-Rock binding module, revealing an unexpected stoichiometry for Shroom in which two Shroom SD2 domains bind independent surfaces on Rock. Mutation of interfacial residues impaired Shroom-Rock binding in vitro and resulted in altered remodeling of the cytoskeleton and loss of Shroom-mediated changes in cellular morphology. Additionally, we provide the first direct evidence that Shroom can function as a Rock activator. These data provide molecular insight into the Shroom-Rock interface and demonstrate that Shroom directly participates in regulating cytoskeletal dynamics, adding to its known role in Rock localization

A qualitative study of independent fast food vendors near secondary schools in disadvantaged Scottish neighbourhoods

Background: Preventing and reducing childhood and adolescent obesity is a growing priority in many countries. Recent UK data suggest that children in more deprived areas have higher rates of obesity and poorer diet quality than those in less deprived areas. As adolescents spend a large proportion of time in school, interventions to improve the food environment in and around schools are being considered. Nutrient standards for school meals are mandatory in the UK, but many secondary pupils purchase foods outside schools at break or lunchtime that may not meet these standards. Methods: Qualitative interviews were conducted with fast food shop managers to explore barriers to offering healthier menu options. Recruitment targeted independently-owned shops near secondary schools (pupils aged c.12-17) in low-income areas of three Scottish cities. Ten interviews were completed, recorded, and transcribed for analysis. An inductive qualitative approach was used to analyse the data in NVivo 10. Results: Five themes emerged from the data: pride in what is sold; individual autonomy and responsibility; customer demand; profit margin; and neighbourhood context. Interviewees consistently expressed pride in the foods they sold, most of which were homemade. They felt that healthy eating and general wellbeing are the responsibility of the individual and that offering what customers want to eat, not necessarily what they should eat, was the only way to stay in business. Most vendors felt they were struggling to maintain a profit, and that many aspects of the low-income neighbourhood context would make change difficult or impossible. Conclusions: Independent food shops in low-income areas face barriers to offering healthy food choices, and interventions and policies that target the food environment around schools should take the neighbourhood context into consideration

Verified lifting of stencil computations

This paper demonstrates a novel combination of program synthesis and verification to lift stencil computations from low-level Fortran code to a high-level summary expressed using a predicate language. The technique is sound and mostly automated, and leverages counter-example guided inductive synthesis (CEGIS) to find provably correct translations. Lifting existing code to a high-performance description language has a number of benefits, including maintainability and performance portability. For example, our experiments show that the lifted summaries can enable domain specific compilers to do a better job of parallelization as compared to an off-the-shelf compiler working on the original code, and can even support fully automatic migration to hardware accelerators such as GPUs. We have implemented verified lifting in a system called STNG and have evaluated it using microbenchmarks, mini-apps, and real-world applications. We demonstrate the benefits of verified lifting by first automatically summarizing Fortran source code into a high-level predicate language, and subsequently translating the lifted summaries into Halide, with the translated code achieving median performance speedups of 4.1X and up to 24X for non-trivial stencils as compared to the original implementation.United States. Department of Energy. Office of Science (Award DE-SC0008923)United States. Department of Energy. Office of Science (Award DE-SC0005288

Relationship between Cardiorespiratory Fitness and Anthropometric Variables among school-going adolescents in Nigeria

The increase in physical activity (PA) levels has been known to be associated with improved cardiorespiratory fitness status which helps in reducing the risk factors of non-communicable disease. However, the interaction between cardiorespiratory fitness and anthropometric variables remains unclear and needs further investigation. This study assessed the relationship between cardiorespiratory fitness and anthropometric variables among school-going adolescents in Nigeria. Two hundred and fifty apparently healthy participants ranging from 12 to 20 years of age, who were randomly selected, participated in this study. Height, body weight, and body mass index (BMI) were measured. Cooper’s 12 minutes run/walk test was conducted to assess cardiorespiratory fitness (estimated by maximal oxygen uptake: VO2max). There was a significant correlation betweenVO2max and BMI. In the regression model, weight, height, gender, and BMI accounted for ninety-five percent of the total variance in the participants’ cardiorespiratory fitness. Body weight, height, gender, and BMI were significant predictors of cardiorespiratory fitness in the school-going Nigerian adolescents.IS

Nonlinear Krylov Acceleration Applied to a Discrete Ordinates Formulation of the k-Eigenvalue Problem

We compare variants of Anderson Mixing with the Jacobian-Free Newton-Krylov and Broyden methods applied to an instance of the k-eigenvalue formulation of the linear Boltzmann transport equation. We present evidence that one variant of Anderson Mixing finds solutions in the fewest number of iterations. We examine and strengthen theoretical results of Anderson Mixing applied to linear problems.Comment: This final revision includes results of the C5G7-MOX problem; Nonlinear Krylov Acceleration Applied to a Discrete Ordinates Formulation of the k-Eigenvalue Problem, Accepted by the Journal of Computational Physics December 201

Molecular basis of association of receptor activity-modifying protein 3 with the family B G protein-coupled secretin receptor

The three receptor activity-modifying proteins (RAMPs) have been recognized as being important for the trafficking and function of a subset of family B G protein-coupled receptors, although the structural basis for this has not been well established. In the current work, we use morphological fluorescence techniques, bioluminescence resonance energy transfer, and bimolecular fluorescence complementation to demonstrate that the secretin receptor associates specifically with RAMP3, but not with RAMP1 or RAMP2. We use truncation constructs, peptide competition experiments, and chimeric secretin-GLP1 receptor constructs to establish that this association is structurally specific, dependent on the intramembranous region of the RAMP and TM6 and TM7 of this receptor. There were no observed changes in secretin-stimulated cAMP, intracellular calcium, ERK1/2 phosphorylation, or receptor internalization in receptor-bearing COS or CHO-K1 cells in the presence or absence of exogenous RAMP transfection, although the secretin receptor trafficks normally to the cell surface in these cells in a RAMP-independent manner, resulting in both free and RAMP-associated receptor on the cell surface. RAMP3 association with this receptor was shown to be capable of rescuing a receptor mutant (G241C) that is normally trapped intracellularly in the biosynthetic machinery. Similarly, secretin receptor expression had functional effects on adrenomedullin activity, with increasing secretin receptor expression competing for RAMP3 association with the calcitonin receptor-like receptor to yield a functional adrenomedullin receptor. These data provide important new insights into the structural basis for RAMP3 interaction with a family B G protein-coupled receptor, potentially providing a highly selective target for drug action. This may be representative of similar interactions between other members of this receptor family and RAMP proteins