Stimulation of inositol 1,4,5-trisphosphate (IP₃) receptor subtypes by Adenophostin A and its analogues

Inositol 1,4,5-trisphosphate receptors (IP3R) are intracellular Ca(2+) channels. Most animal cells express mixtures of the three IP3R subtypes encoded by vertebrate genomes. Adenophostin A (AdA) is the most potent naturally occurring agonist of IP3R and it shares with IP3 the essential features of all IP3R agonists, namely structures equivalent to the 4,5-bisphosphate and 6-hydroxyl of IP3. The two essential phosphate groups contribute to closure of the clam-like IP3-binding core (IBC), and thereby IP3R activation, by binding to each of its sides (the α- and β-domains). Regulation of the three subtypes of IP3R by AdA and its analogues has not been examined in cells expressing defined homogenous populations of IP3R. We measured Ca(2+) release evoked by synthetic adenophostin A (AdA) and its analogues in permeabilized DT40 cells devoid of native IP3R and stably expressing single subtypes of mammalian IP3R. The determinants of high-affinity binding of AdA and its analogues were indistinguishable for each IP3R subtype. The results are consistent with a cation-π interaction between the adenine of AdA and a conserved arginine within the IBC α-domain contributing to closure of the IBC. The two complementary contacts between AdA and the α-domain (cation-π interaction and 3″-phosphate) allow activation of IP3R by an analogue of AdA (3″-dephospho-AdA) that lacks a phosphate group equivalent to the essential 5-phosphate of IP3. These data provide the first structure-activity analyses of key AdA analogues using homogenous populations of all mammalian IP3R subtypes. They demonstrate that differences in the Ca(2+) signals evoked by AdA analogues are unlikely to be due to selective regulation of IP3R subtypes

Large eddy simulation of a turbulent non-premixed propane-air reacting flame in a cylindrical combustor

Large Eddy Simulation (LES) is applied to investigate the turbulent non-premixed combustion flow, including species concentrations and temperature, in a cylindrical combustor. Gaseous propane (C3H8) is injected through a circular nozzle which is attached at the centre of the combustor inlet. Preheated air with a temperature of 773 K is supplied through the annulus surrounding of this fuel nozzle. In LES a spatial filtering is applied to the governing equations to separate the flow field into large-scale and small-scale eddies. The large-scale eddies which carry most of the turbulent energy are resolved explicitly, while the unresolved small-scale eddies are modelled using the Smagorinsky model with Cs = 0.1 as well as dynamically calibrated Cs. The filtered values of the species mass fraction, temperature and density, which are the functions of the mixture fraction (conserved scalar), are determined by integration over a beta probability density function (β-PDF). The computational results are compared with those of the experimental investigation conducted by Nishida and Mukohara. According to this experiment, the overall equivalence ratio of 0.6, which is calculated from the ratio of the air flow rate supplied to the combustion chamber to that of the stoichiometric reaction, is kept constant so that the turbulent combustion at the fuel nozzle exit starts under the fuel-rich conditions

The interfascicular matrix enables fascicle sliding and recovery in tendon, and behaves more elastically in energy storing tendons

While the predominant function of all tendons is to transfer force from muscle to bone and position the limbs, some tendons additionally function as energy stores, reducing the cost of locomotion. Energy storing tendons experience extremely high strains and need to be able to recoil efficiently for maximum energy storage and return. In the equine forelimb, the energy storing superficial digital flexor tendon (SDFT) has much higher failure strains than the positional common digital extensor tendon (CDET). However, we have previously shown that this is not due to differences in the properties of the SDFT and CDET fascicles (the largest tendon subunits). Instead, there is a greater capacity for interfascicular sliding in the SDFT which facilitates the greater extensions in this particular tendon (Thorpe et al., 2012). In the current study, we exposed fascicles and interfascicular matrix (IFM) from the SDFT and CDET to cyclic loading followed by a test to failure. The results show that IFM mechanical behaviour is not a result of irreversible deformation, but the IFM is able to withstand cyclic loading, and is more elastic in the SDFT than in the CDET. We also assessed the effect of ageing on IFM properties, demonstrating that the IFM is less able to resist repetitive loading as it ages, becoming stiffer with increasing age in the SDFT. These results provide further indications that the IFM is important for efficient function in energy storing tendons, and age-related alterations to the IFM may compromise function and predispose older tendons to injury

A CsI(Tl) Scintillating Crystal Detector for the Studies of Low Energy Neutrino Interactions

Scintillating crystal detector may offer some potential advantages in the low-energy, low-background experiments. A 500 kg CsI(Tl) detector to be placed near the core of Nuclear Power Station II in Taiwan is being constructed for the studies of electron-neutrino scatterings and other keV-MeV range neutrino interactions. The motivations of this detector approach, the physics to be addressed, the basic experimental design, and the characteristic performance of prototype modules are described. The expected background channels and their experimental handles are discussed.Comment: 34 pages, 11 figures, submitted to Nucl. Instrum. Method

A multi-scale comparison of modeled and observed seasonal methane emissions in northern wetlands

Wetlands are the largest global natural methane (CH4/ source, and emissions between 50 and 70° N latitude contribute 10-30% to this source. Predictive capability of land models for northern wetland CH4 emissions is still low due to limited site measurements, strong spatial and temporal variability in emissions, and complex hydrological and biogeochemical dynamics. To explore this issue, we compare wetland CH4 emission predictions from the Community Land Model 4.5 (CLM4.5-BGC) with siteto regional-scale observations. A comparison of the CH4 fluxes with eddy flux data highlighted needed changes to the model's estimate of aerenchyma area, which we implemented and tested. The model modification substantially reduced biases in CH4 emissions when compared with CarbonTracker CH4 predictions. CLM4.5 CH4 emission predictions agree well with growing season (May-September) CarbonTracker Alaskan regional-level CH4 predictions and sitelevel observations. However, CLM4.5 underestimated CH4 emissions in the cold season (October-April). The monthly atmospheric CH4 mole fraction enhancements due to wetland emissions are also assessed using the Weather Research and Forecasting-Stochastic Time-Inverted Lagrangian Transport (WRF-STILT) model coupled with daily emissions from CLM4.5 and compared with aircraft CH4 mole fraction measurements from the Carbon in Arctic Reservoirs Vulnerability Experiment (CARVE) campaign. Both the tower and aircraft analyses confirm the underestimate of cold-season CH4 emissions by CLM4.5. The greatest uncertainties in predicting the seasonal CH4 cycle are from the wetland extent, coldseason CH4 production and CH4 transport processes. We recommend more cold-season experimental studies in highlatitude systems, which could improve the understanding and parameterization of ecosystem structure and function during this period. Predicted CH4 emissions remain uncertain, but we show here that benchmarking against observations across spatial scales can inform model structural and parameter improvements

Origins of the Ambient Solar Wind: Implications for Space Weather

The Sun's outer atmosphere is heated to temperatures of millions of degrees, and solar plasma flows out into interplanetary space at supersonic speeds. This paper reviews our current understanding of these interrelated problems: coronal heating and the acceleration of the ambient solar wind. We also discuss where the community stands in its ability to forecast how variations in the solar wind (i.e., fast and slow wind streams) impact the Earth. Although the last few decades have seen significant progress in observations and modeling, we still do not have a complete understanding of the relevant physical processes, nor do we have a quantitatively precise census of which coronal structures contribute to specific types of solar wind. Fast streams are known to be connected to the central regions of large coronal holes. Slow streams, however, appear to come from a wide range of sources, including streamers, pseudostreamers, coronal loops, active regions, and coronal hole boundaries. Complicating our understanding even more is the fact that processes such as turbulence, stream-stream interactions, and Coulomb collisions can make it difficult to unambiguously map a parcel measured at 1 AU back down to its coronal source. We also review recent progress -- in theoretical modeling, observational data analysis, and forecasting techniques that sit at the interface between data and theory -- that gives us hope that the above problems are indeed solvable.Comment: Accepted for publication in Space Science Reviews. Special issue connected with a 2016 ISSI workshop on "The Scientific Foundations of Space Weather." 44 pages, 9 figure

Transitions of cardio-metabolic risk factors in the Americas between 1980 and 2014

Describing the prevalence and trends of cardiometabolic risk factors that are associated with non-communicable diseases (NCDs) is crucial for monitoring progress, planning prevention, and providing evidence to support policy efforts. We aimed to analyse the transition in body-mass index (BMI), obesity, blood pressure, raised blood pressure, and diabetes in the Americas, between 1980 and 2014