682 research outputs found
Modelling and simulation of biased agonism dynamics at a G protein-coupled receptor.
Theoretical models of G protein-coupled receptor (GPCR) concentration-response relationships often assume an agonist producing a single functional response via a single active state of the receptor. These models have largely been analysed assuming steady-state conditions. There is now much experimental evidence to suggest that many GPCRs can exist in multiple receptor conformations and elicit numerous functional responses, with ligands having the potential to activate different signalling pathways to varying extents-a concept referred to as biased agonism, functional selectivity or pluri-dimensional efficacy. Moreover, recent experimental results indicate a clear possibility for time-dependent bias, whereby an agonist's bias with respect to different pathways may vary dynamically. Efforts towards understanding the implications of temporal bias by characterising and quantifying ligand effects on multiple pathways will clearly be aided by extending current equilibrium binding and biased activation models to include G protein activation dynamics. Here, we present a new model of time-dependent biased agonism, based on ordinary differential equations for multiple cubic ternary complex activation models with G protein cycle dynamics. This model allows simulation and analysis of multi-pathway activation bias dynamics at a single receptor for the first time, at the level of active G protein (αGTP), towards the analysis of dynamic functional responses. The model is generally applicable to systems with NG G proteins and N* active receptor states. Numerical simulations for NG=N*=2 reveal new insights into the effects of system parameters (including cooperativities, and ligand and receptor concentrations) on bias dynamics, highlighting new phenomena including the dynamic inter-conversion of bias direction. Further, we fit this model to 'wet' experimental data for two competing G proteins (Gi and Gs) that become activated upon stimulation of the adenosine A1 receptor with adenosine derivative compounds. Finally, we show that our model can qualitatively describe the temporal dynamics of this competing G protein activation
Quantitative analysis of the importance of wind-induced circulation for the spatial structuring of planktonic populations
1. Several studies have shown that wind-induced water movements have an important effect on the spatial distribution of crustacean zooplankton. However, few attempts have been made to quantify the effect of physical processes on these broad-scale patterns. Much of our understanding of this spatial structure has been based on the results of isolated surveys, which do not capture the dynamic nature of the pelagic environment.
2. In this study, we have used a combination of high-speed sampling (at a spatial resolution of 240 m) and spatial data analysis to quantify the factors influencing the horizontal spatial structure of the Daphnia galeata population in Windermere.
3. The results show that lake-wide circulation patterns, as indicated by water temperature, account for 29–47% of the basin-scale spatial variance in D. galeata abundance. However, these patterns are highly dynamic and change in response to the prevailing weather. This lack of temporal persistence means that the results of single-survey sampling campaigns must be interpreted with caution
The application of inelastic neutron scattering to investigate the interaction of methyl propanoate with silica
A modern industrial route for the manufacture of methyl methacrylate involves the reaction of methyl propanoate and formaldehyde over a silica-supported Cs catalyst. Although the process has been successfully commercialised, little is known about the surface interactions responsible for the forward chemistry. This work concentrates upon the interaction of methyl propanoate over a representative silica. A combination of infrared spectroscopy, inelastic neutron scattering, DFT calculations, X-ray diffraction and temperature-programmed desorption is used to deduce how the ester interacts with the silica surface
Response of ceramic microbial fuel cells to direct anodic airflow and novel hydrogel cathodes
© 2019 The Authors The presence of air in the anode chamber of microbial fuel cells (MFCs)might be unavoidable in some applications. This study purposely exposed the anodic biofilm to air for sustained cycles using ceramic cylindrical MFCs. A method for improving oxygen uptake at the cathode by utilising hydrogel was also trialled. MFCs only dropped by 2 mV in response to the influx of air. At higher air-flow rates (up to 1.1 L/h)after 43–45 h, power did eventually decrease because chemical oxygen demand (COD)was being consumed (up to 96% reduction), but recovered immediately with fresh feedstock, highlighting no permanent damage to the biofilm. Two months after the application of hydrogel to the cathode chamber, MFC power increased 182%, due to better contact between cathode and ceramic surface. The results suggest a novel way of improving MFC performance using hydrogels, and demonstrates the robustness of the electro-active biofilm both during and following exposure to air
An Energetically-Autonomous Robotic Tadpole with Single Membrane Stomach and Tail
We present an energetically autonomous robotic tadpole that uses a single membrane component for both electrical energy generation and propulsive actuation. The coupling of this small bio-inspired power source to a bio-inspired actuator demonstrates the first generation design for an energetically autonomous swimming robot consisting of a single membrane. An ionic polymer metal composite (IPMC) with a Nafion polymer layer is demonstrated in a novel application as the ion exchange membrane and anode and cathode electrode of a microbial fuel cell (MFC), whilst being used concurrently as an artificial muscle tail. In contrast to previous work using stacked units for increased voltage, a single MFC with novel, 0.88ml anode chamber architecture is used to generate suitable voltages for driving artificial muscle actuation, with minimal step up. This shows the potential of the small forces generated by IPMCs for propulsion of a bio-energy source. The work demonstrates great potential for reducing the mass and complexity of bio-inspired autonomous robots. The performance of the IPMC as an ion exchange membrane is compared to two conventional ion exchange membranes, Nafion and cation exchange membrane (CEM). The MFC anode and cathode show increased resistance following inclusion within the MFC environment
Effects of size‐ and sex‐selective harvesting: an integral projection model approach
Harvesting is often size‐selective, and in species with sexual size dimorphism, it may also be sex‐selective. A powerful approach to investigate potential consequences of size‐ and/or sex‐selective harvesting is to simulate it in a demographic population model. We developed a population‐based integral projection model for a size‐ and sex‐structured species, the commonly exploited pike (Esox lucius). The model allows reproductive success to be proportional to body size and potentially limited by both sexes. We ran all harvest simulations with both lower size limits and slot limits, and to quantify the effects of selective harvesting, we calculated sex ratios and the long‐term population growth rate (λ). In addition, we quantified to what degree purely size‐selective harvesting was sex‐selective, and determined when λ shifted from being female to male limited under size‐ and sex‐selective harvesting. We found that purely size‐selective harvest can be sex‐selective, and that it depends on the harvest limits and the size distributions of the sexes. For the size‐ and sex‐selective harvest simulations, λ increased with harvest intensity up to a threshold as females limited reproduction. Beyond this threshold, males became the limiting sex, and λ decreased as more males were harvested. The peak in λ, and the corresponding sex ratio in harvest, varied with both the selectivity and the intensity of the harvest simulation. Our model represents a useful extension of size‐structured population models as it includes both sexes, relaxes the assumption of female dominance, and accounts for size‐dependent fecundity. The consequences of selective harvesting presented here are especially relevant for size‐ and sex‐structured exploited species, such as commercial fisheries. Thus, our model provides a useful contribution toward the development of more sustainable harvesting regimes
Microbial fuel cell – A novel self-powered wastewater electrolyser for electrocoagulation of heavy metals
© 2016 The Authors This paper describes the suitability of the Microbial Fuel Cell (MFC) for generation of electrical power with a simultaneous synthesis of active catholyte in the form of caustic solution. The active solution formed inside a terracotta based MFC reactor was a product of self-powered wastewater electrolysis utilizing i) wastewater with added sodium acetate as a carbon source and ii) neat urine. The catholyte solution that has been actively synthesized was harvested and used for precipitation of heavy metals such as: iron, copper and zinc showing its suitability for use in electro-coagulation (electro-flocculation). This proposed alternative approach to self-powered electrocoagulation is based on electrochemically formed caustic catholyte within the inner cathode chamber of the MFC and then used ex situ to form metal hydroxides that precipitate out from heavy metal solutions
Spectroscopy of excited states of unbound nuclei 30 Ar and 29 Cl
Several states of proton-unbound isotopes
30
Ar
and
29
Cl
were investigated by measuring their in-flight decay products,
28
S
+ proton + proton and
28
S
+ proton, respectively. A refined analysis of
28
S
-proton angular correlations indicates that the ground state of
30
Ar
is located at
2
.
45
+
0.05
−
0.10
MeV above the two-proton emission threshold. The investigation of the decay mechanism of the
30
Ar
ground state demonstrates that it has the transition dynamics. In the “transitional” region, the correlation patterns of the decay products present a surprisingly strong sensitivity to the two-proton decay energy of the
30
Ar
ground state and the one-proton decay energy as well as the one-proton decay width of the
29
Cl
ground state. The comparison of the experimental
28
S
-proton angular correlations with those resulting from Monte Carlo simulations of the detector response illustrates that other observed
30
Ar
excited states decay by sequential emission of protons via intermediate resonances in
29
Cl
. Based on the findings, the decay schemes of the observed states in
30
Ar
and
29
Cl
were constructed. For calibration purposes and for checking the performance of the experimental setup, decays of the previously known states of a two-proton emitter
19
Mg
were remeasured. Evidences for one new excited state in
19
Mg
and two unknown states in
18
Na
were found.Helmholtz International Center for FAIR de Alemania (HIC for FAIR) IK-RU-002Russian Ministry of Education and Science. NSh-932.2014.2Russian Science Foundation. 17-12-01367Polish National Science Center. UMO-2011/01/B/ST2/01943Polish Ministry of Science and Higher Education. 0079/DIA/2014/43HelmholtzCAS Joint Research Group de Alemania. HCJRG-108Ministerio de Ciencia, Innovación y Universidades de España (MICINN). FPA2009-0884
- …