BackgroundAcid-sensing ion channels (ASICs) have a significant role in the sensation of pain and constitute an important target for the search of new antinociceptive drugs. In this work we studied the antinociceptive properties of the BM-21 extract, obtained from the sea grass Thalassia testudinum, in chemical and thermal models of nociception in mice. The action of the BM-21 extract and the major phenolic component isolated from this extract, a sulphated flavone glycoside named thalassiolin B, was studied in the chemical nociception test and in the ASIC currents of the dorsal root ganglion (DRG) neurons obtained from Wistar rats.ResultsBehavioral antinociceptive experiments were made on male OF-1 mice. Single oral administration of BM-21 produced a significant inhibition of chemical nociception caused by acetic acid and formalin (specifically during its second phase), and increased the reaction time in the hot plate test. Thalassiolin B reduced the licking behavior during both the phasic and tonic phases in the formalin test. It was also found that BM-21 and thalassiolin B selectively inhibited the fast desensitizing (τ < 400 ms) ASIC currents in DRG neurons obtained from Wistar rats, with a nonsignificant action on ASIC currents with a slow desensitizing time-course. The action of thalassiolin B shows no pH or voltage dependence nor is it modified by steady-state ASIC desensitization or voltage. The high concentration of thalassiolin B in the extract may account for the antinociceptive action of BM-21.ConclusionsTo our knowledge, this is the first report of an ASIC-current inhibitor derived of a marine-plant extract, and in a phenolic compound. The antinociceptive effects of BM-21 and thalassiolin B may be partially because of this action on the ASICs. That the active components of the extract are able to cross the blood-brain barrier gives them an additional advantage for future uses as tools to study pain mechanisms with a potential therapeutic application.
CgNa (Condylactis gigantea neurotoxin) is a 47-amino-acid- residue toxin from the giant Caribbean sea anemone Condylactis gigantea. The structure of CgNa, which was solved by 1H-NMR spectroscopy, is somewhat atypical and displays significant homology with both type I and II anemone toxins. CgNa also displays a considerable number of exceptions to the canonical structural elements that are thought to be essential for the activity of this group of toxins. Furthermore, unique residues in CgNa define a characteristic structure with strong negatively charged surface patches. These patches disrupt a surface-exposed cluster of hydrophobic residues present in all anemone-derived toxins described to date. A thorough characterization by patch-clamp analysis using rat DRG (dorsal root ganglion) neurons indicated that CgNa preferentially binds to TTX-S (tetrodotoxin-sensitive) voltage-gated sodium channels in the resting state. This association increased the inactivation time constant and the rate of recovery from inactivation, inducing a significant shift in the steady state of inactivation curve to the left. The specific structural features of CgNa may explain its weaker inhibitory capacity when compared with the other type I and II anemone toxins.
This paper presents the simulation of a two-rotor aircraft in different geometric configurations during hover flight. The analysis was performed using an implementation of the unsteady vortex-lattice method (UVLM). A description of the UVLM is presented as well as the techniques used to enhance the stability of results for rotors in hover flight. The model is validated for an isolated rotor in hover, comparing numerical results to experimental data (high-Reynolds, low-Mach conditions). Results show that an exclusion of the root vortex generates a more stable wake, without affecting results. Results for the two-rotor aircraft show an important influence of the number of blades on the vertical thrust. Furthermore, the geometric configuration has a considerable influence on the pitching moment.
The research's objective is to evaluate the differential effect that a metacognitive scaffolding for information web searches has on learning achievement of high school students with different cognitive style in the field dependence and independence dimension and on learning style in the dimension proposed by Honey and Alonso known as CHAEA. One hundred and four students from a school in the city of Bogotá, Colombia participated in the study. The research was quasi-experimental and was conducted with three 10th-grade groups, which worked with three scaffolding versions: fixed, optional, and without scaffolding. A multivariate analysis of covariance established that the fixed scaffolding favored learning achievement. Regarding cognitive style in the field dependence and independence dimension, the findings allow to conclude that the field independent students exhibited better
This study deals with the three-dimensional unsteady numerical simulation of the flow around a cross-flow vertical-axis water turbine (CFWT) of the Darrieus type. The influence of turbine design on its hydrodynamic characteristics and performance is investigated by means of a time-accurate Reynolds Averaged Navier Stokes (RANS) commercial solver. The flow unsteadiness is described using a transient rotor-stator model in connection with a sliding interface. A classical Darrieus straight blade turbine, based on the NACA0025 airfoil, has been modified adding winglets (symmetric and asymmetric designs) to the blades' tips with the objective of reducing the strength of the detached trailing vortices. The turbulent features of the flow have been modelled by using different turbulence models (k-ε Renormalization Group, standard Shear Stress Transport, transition Shear Stress Transport and Reynolds Stress Model). As a result, the predicted hydrodynamic performance of the turbine including winglets increases, independently of the employed turbulence model, being the improvement higher when a symmetric winglet design is considered. Moreover, visualization of skin friction lines pattern and their connection with vorticity isosurfaces, illustrating the flow detachment in the three blade configurations, has been carried out. Finally, a short discussion about the intermittency behavior along a turbine revolution is presented.
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