Study protocol: a randomised controlled trial investigating the effect of exercise training on peripheral blood gene expression in patients with stable angina

Background: Exercise training has been shown to reduce angina and promote collateral vessel development in patients with coronary artery disease. However, the mechanism whereby exercise exerts these beneficial effects is unclear. There has been increasing interest in the use of whole genome peripheral blood gene expression in a wide range of conditions to attempt to identify both novel mechanisms of disease and transcriptional biomarkers. This protocol describes a study in which we will assess the effect of a structured exercise programme on peripheral blood gene expression in patients with stable angina, and correlate this with changes in angina level, anxiety, depression, and exercise capacity. Methods/Design: Sixty patients with stable angina will be recruited and randomised 1: 1 to exercise training or conventional care. Patients randomised to exercise training will attend an exercise physiology laboratory up to three times weekly for supervised aerobic interval training sessions of one hour in total duration. Patients will undergo assessments of angina, anxiety, depression, and peripheral blood gene expression at baseline, after six and twelve weeks of training, and twelve weeks after formal exercise training ceases. Discussion: This study will provide comprehensive data on the effect of exercise training on peripheral blood gene expression in patients with angina. By correlating this with improvement in angina status we will identify candidate peripheral blood transcriptional markers predictive of improvements in angina level in response to exercise training

Wanted dead or alive : high diversity of macroinvertebrates associated with living and ’dead’ Posidonia oceanica matte

The Mediterranean endemic seagrass Posidonia oceanica forms beds characterised by a dense leaf canopy and a thick root-rhizome ‘matte’. Death of P. oceanica shoots leads to exposure of the underlying matte, which can persist for many years, and is termed ‘dead’ matte. Traditionally, dead matte has been regarded as a degraded habitat. To test whether this assumption was true, the motile macroinvertebrates of adjacent living (with shoots) and dead (without shoots) matte of P. oceanica were sampled in four different plots located at the same depth (5–6 m) in Mellieha Bay, Malta (central Mediterranean). The total number of species and abundance were significantly higher (ANOVA; P<0.05 and P<0.01, respectively) in the dead matte than in living P. oceanica matte, despite the presence of the foliar canopy in the latter. Multivariate analysis (MDS) clearly showed two main groups of assemblages, corresponding to the two matte types. The amphipods Leptocheirus guttatus and Maera grossimana, and the polychaete Nereis rava contributed most to the dissimilarity between the two different matte types. Several unique properties of the dead matte contributing to the unexpected higher number of species and abundance of motile macroinvertebrates associated with this habitat are discussed. The findings have important implications for the conservation of bare P. oceanica matte, which has been generally viewed as a habitat of low ecological value.peer-reviewe

Hidden in plain sight: species richness and habitat characterisation of sublittoral pebble beds

Sublittoral pebble beds are generally considered to be impoverished, but the physical and biological characteristics of these habitats are poorly known. We characterised nineteen pebble bed sites in the Maltese Islands, providing detailed habitat data for Mediterranean sublittoral pebble beds for the first time. Nearly 40,000 individuals belonging to 332 taxa were recorded in all, with total richness estimated to reach 440 taxa; molluscs, crustaceans and polychaetes were the most diverse faunal groups. This high diversity is likely due to the structural complexity of the pebble beds, which had a vertically stratified arrangement of sediment particles that is likely maintained through periodic physical disturbance. Variation in the biotic assemblage from site to site was correlated with changes in the quantity of sand and silt, with the area of the pebble bed, with water depth, and with the thickness of the pebble layer. This indicates that pebble-bed macrofaunal assemblages are sensitive to changes in hydrodynamic conditions and sediment loading, to alterations to the stratification of the pebble beds, and to fragmentation of the habitat patches. These results contradict assertions that sublittoral pebble beds are impoverished, instead showing that they can be highly diverse habitats supporting biotic assemblages that respond to a complex set of environmental variables. The present findings enable better understanding of the ecological importance of pebble beds and of the potential impacts of anthropogenic disturbance, enabling more informed decisions for habitat conservation and management

Appetite, gut hormone and energy intake responses to low volume sprint interval and traditional endurance exercise.

Sprint interval exercise improves several health markers but the appetite and energy balance response is unknown. This study compared the effects of sprint interval and endurance exercise on appetite, energy intake and gut hormone responses. Twelve healthy males [mean (SD): age 23 (3) years, body mass index 24.2 (2.9) kg m(-2), maximum oxygen uptake 46.3 (10.2) mL kg(-1) min(-1)] completed three 8 h trials [control (CON), endurance exercise (END), sprint interval exercise (SIE)] separated by 1 week. Trials commenced upon completion of a standardised breakfast. Sixty minutes of cycling at 68.1 (4.3) % of maximum oxygen uptake was performed from 1.75-2.75 h in END. Six 30-s Wingate tests were performed from 2.25-2.75 h in SIE. Appetite ratings, acylated ghrelin and peptide YY (PYY) concentrations were measured throughout each trial. Food intake was monitored from buffet meals at 3.5 and 7 h and an overnight food bag. Appetite (P 0.05). Therefore, relative energy intake (energy intake minus the net energy expenditure of exercise) was lower in END than that in CON (15.7 %; P = 0.006) and SIE (11.5 %; P = 0.082). An acute bout of endurance exercise resulted in lower appetite perceptions in the hours after exercise than sprint interval exercise and induced a greater 24 h energy deficit due to higher energy expenditure during exercise

A Regularized Graph Layout Framework for Dynamic Network Visualization

Many real-world networks, including social and information networks, are dynamic structures that evolve over time. Such dynamic networks are typically visualized using a sequence of static graph layouts. In addition to providing a visual representation of the network structure at each time step, the sequence should preserve the mental map between layouts of consecutive time steps to allow a human to interpret the temporal evolution of the network. In this paper, we propose a framework for dynamic network visualization in the on-line setting where only present and past graph snapshots are available to create the present layout. The proposed framework creates regularized graph layouts by augmenting the cost function of a static graph layout algorithm with a grouping penalty, which discourages nodes from deviating too far from other nodes belonging to the same group, and a temporal penalty, which discourages large node movements between consecutive time steps. The penalties increase the stability of the layout sequence, thus preserving the mental map. We introduce two dynamic layout algorithms within the proposed framework, namely dynamic multidimensional scaling (DMDS) and dynamic graph Laplacian layout (DGLL). We apply these algorithms on several data sets to illustrate the importance of both grouping and temporal regularization for producing interpretable visualizations of dynamic networks.Comment: To appear in Data Mining and Knowledge Discovery, supporting material (animations and MATLAB toolbox) available at http://tbayes.eecs.umich.edu/xukevin/visualization_dmkd_201

Mechanical properties of pristine and nanoporous graphene

We present molecular dynamics simulations of monolayer graphene under uniaxial tensile loading. The Morse, bending angle, torsion and Lennard-Jones potential functions are adopted within the mdFOAM library in the OpenFOAM software, to describe the molecular interactions in graphene. A well-validated graphene model using these set of potentials is not yet available. In this work, we investigate the accuracy of the mechanical properties of graphene when derived using these simpler potentials, compared to the more commonly used complex potentials such as the Tersoff-Brenner and AIREBO potentials. The computational speed-up of our approach, which scales O(1.5N), where N is the number of carbon atoms, enabled us to vary a larger number of system parameters, including graphene sheet orientation, size, temperature and concentration of nanopores. The resultant effect on the elastic modulus, fracture stress and fracture strain is investigated. Our simulations show that graphene is anisotropic, and its mechanical properties are dependant on the sheet size. An increase in system temperature results in a significant reduction in the fracture stress and strain. Simulations of nanoporous graphene were created by distributing vacancy defects, both randomly and uniformly, across the lattice. We find that the frac- ture stress decreases substantially with increasing defect density. The elastic modulus was found to be constant up to around 5% vacancy defects, and decreases for higher defect densities

Effect of Galactose Ingestion Before and During Exercise on Substrate Oxidation, Postexercise Satiety, and Subsequent Energy Intake in Females.

OBJECTIVE: To examine the effects of consuming a galactose carbohydrate (CHO) drink on substrate oxidation, postexercise satiety, and subsequent energy intake. METHODS: Nine recreationally active eumenorrheic females undertook 3 trials, each consisting of running for 60 minutes at 65% VO2peak followed immediately by a 90-minute rest period. Prior to (300 ml) and at 15-minute intervals during exercise (150 ml), participants consumed either a glucose (GLU: GI 89) or galactose (GAL: GI 20) drink, each of which contained 45 g of CHO, or an artificially sweetened placebo (PLA). Following the rest period, participants were provided with an ad libitum test lunch and asked to record food intake for the remainder of the day. RESULTS: Plasma glucose was significantly greater throughout exercise and rest following the GLU trial compared with the GAL and PLA trials (P < 0.05); however there were no differences in CHO oxidation. Hunger was significantly lower (P < 0.05) throughout the GAL compared to the GLU and PLA trials. There were no significant differences between trials for energy intake during the postexercise meal. Overall net energy balance for the 24 hours was negative in both the GAL (-162 ± 115 kcal; P < 0.05 vs GLU) and PLA trials (-49 ± 160 kcal). CONCLUSIONS: Results demonstrate that ingesting a solution containing GAL before and during exercise can positively impact postexercise satiety and energy balance throughout the day, compared to a more readily available and widely consumed form of CHO. Despite this, there appears to be no apparent benefit in consuming a CHO beverage on fuel utilization for this moderate exercise intensity and duration

Smoothing a rugged protein folding landscape by sequence-based redesign

The rugged folding landscapes of functional proteins puts them at risk of misfolding and aggregation. Serine protease inhibitors, or serpins, are paradigms for this delicate balance between function and misfolding. Serpins exist in a metastable state that undergoes a major conformational change in order to inhibit proteases. However, conformational labiality of the native serpin fold renders them susceptible to misfolding, which underlies misfolding diseases such as $\alpha_1$-antitrypsin deficiency. To investigate how serpins balance function and folding, we used consensus design to create $\textit{conserpin}$, a synthetic serpin that folds reversibly, is functional, thermostable, and polymerization resistant. Characterization of its structure, folding and dynamics suggest that consensus design has remodeled the folding landscape to reconcile competing requirements for stability and function. This approach may offer general benefits for engineering functional proteins that have risky folding landscapes, including the removal of aggregation-prone intermediates, and modifying scaffolds for use as protein therapeutics.BTP is a Medical Research Council Career Development Fellow. AAN and JJH are supported by the Wellcome Trust (grant number WT 095195). SM acknowledges fellowship support from the Australian Research Council (FT100100960). NAB is an Australian Research Council Future Fellow (110100223). GIW is an Australian Research Council Discovery Outstanding Researcher Award Fellow (DP140100087). AMB is a National Health and Medical Research Senior Research Fellow (1022688). JCW is an NHMRC Senior Principal Research fellow and also acknowledges the support of an ARC Federation Fellowship. We thank the Australian Synchrotron for beam-time and technical assistance. This work was supported by the Multi-modal Australian ScienceS Imaging and Visualisation Environment (MASSIVE) (www.massive.org.au). We acknowledge the Monash Protein Production Unit and Monash Macromolecular Crystallization Facilit

Hybrid molecular-continuum simulations of water flow through carbon nanotube membranes of realistic thickness

We present new hybrid molecular-continuum simulations of water flow through filtration membranes. The membranes consist of aligned carbon nanotubes (CNTs) of high aspect ratio, where the tube diameters are ~1–2 nm and the tube lengths (i.e. the membrane thicknesses) are 2–6 orders of magnitude larger than this. The flow in the CNTs is subcontinuum, meaning standard continuum fluid equations cannot adequately model the flow; also, full molecular dynamics (MD) simulations are too computationally expensive for modelling these membrane thicknesses. However, various degrees of scale separation in both time and space in this problem can be exploited by a multiscale method: we use the serial-network internal-flow multiscale method (SeN-IMM). Our results from this hybrid method compare very well with full MD simulations of flow cases up to a membrane thickness of 150 nm, beyond which any full MD simulation is computationally intractable. We proceed to use the SeN-IMM to predict the flow in membranes of thicknesses 150 nm–2 μm, and compare these results with both a modified Hagen–Poiseuille flow equation and experimental results for the same membrane configuration. We also find good agreement between experimental and our numerical results for a 1-mm-thick membrane made of CNTs with diameters around 1.1 nm. In this case, the hybrid simulation is orders of magnitude quicker than a full MD simulation would be

Smoothing a rugged protein folding landscape by sequence-based redesign

The rugged folding landscapes of functional proteins puts them at risk of misfolding and aggregation. Serine protease inhibitors, or serpins, are paradigms for this delicate balance between function and misfolding. Serpins exist in a metastable state that undergoes a major conformational change in order to inhibit proteases. However, conformational labiality of the native serpin fold renders them susceptible to misfolding, which underlies misfolding diseases such as α1-antitrypsin deficiency. To investigate how serpins balance function and folding, we used consensus design to create conserpin, a synthetic serpin that folds reversibly, is functional, thermostable, and polymerization resistant. Characterization of its structure, folding and dynamics suggest that consensus design has remodeled the folding landscape to reconcile competing requirements for stability and function. This approach may offer general benefits for engineering functional proteins that have risky folding landscapes, including the removal of aggregation-prone intermediates, and modifying scaffolds for use as protein therapeutics