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NEUTRON STARS. “Recent theoretical models propose some alternatives, such as inner cores containing a mix of neutrons, protons, and exotic matter made of quarks or new combinations of quarks.” The old impossible is the new probable. https://lnkd.in/dZCjeAB View in LinkedIn

FURTHER VALIDATION. “Next, we carried out microsecond MD simulations of the TMD embedded in a phospatidylcholine (POPC) bilayer in either H2O or D2O (for details including our model of D2O effectively including nuclear quantum effects, (see SI, Tables S2–S4). Note that water molecules enter the TMD domain and cluster at positions that partially overlap with the modeled water positions, see Fig. 7a.” https://lnkd.in/dzPDm5w View in LinkedIn

MOLECULAR VALIDATION. “Fig. 7: Differences between the behavior of the transmembrane part of the human sweet taste receptor in H2O vs D2O base on analysis of three independent microsecond trajectories.” https://lnkd.in/dzPDm5w View in LinkedIn

“FUTURE STUDIES should be able to elucidate the precise sites and mechanisms of action, as well as the reason why D2O activates TAS1R2/TAS1R3 in particular, resulting in sweet (but not other) taste. To this end, site-directed mutagenesis as well as determination of the precise structure of the TAS1R2/TAS1R3 receptor will be of key importance.” https://lnkd.in/dzPDm5w View in LinkedIn

MOLECULAR DOSE RESPONSE. “Next, TAS1R2/TAS1R3 receptor along with the chimeric Gα16gust44 subunit were transiently expressed, and the functionality was illustrated by dose-dependent response to D-glucose (Fig. 6c). Finally, and in agreement with calcium imaging, we found that 10% D2O activated these cells. Activation by 100% D2O was even more pronounced (Fig. 6d).” https://lnkd.in/dzPDm5w View in LinkedIn

NUCLEAR QUANTUM EFFECT. “At a molecular level, this general behavior may be traced back to the slightly stronger hydrogen bonding in D2O vs H2O, which is due to a nuclear quantum effect, namely difference in zero-point energy. Biologically relevant situations where one may expect strong nuclear quantum effects as implications of H/D substitution directly involve proton or deuteron transfer. Unless a yet unknown indirect mechanism is involved, this is not the case for the TAS1R2/TAS1R3 sweet taste receptor, thus the nuclear quantum effect is probably weak in the present case.” https://lnkd.in/dzPDm5w View in LinkedIn

CELLULAR DOSE RESPONSE. “We further used an IP1 assay on non-transfected HEK 293T cells, where we observed that dose-dependent curves of carbachol—an agonist of the endogenous muscarinic receptor 3 (M3)47—did not show any difference between H2O and D2O-based media (Fig. 6a) and that cell medium that had either 10% or 100% D2O, did not activate basal IP1 accumulation (Fig. 6b).” https://lnkd.in/dzPDm5w View in LinkedIn

MOLECULAR MECHANISM. “Our findings point to the human sweet taste receptor TAS1R2/TAS1R3 as being essential for sweetness of D2O. Molecular dynamics simulations show, in agreement with experiment, that proteins in general are slightly more rigid and compact in D2O than in H2O.” https://lnkd.in/dzPDm5w View in LinkedIn

TITRATION. “The inhibitory effect of lactisole on D2O-activation of the human sweet taste receptor was confirmed using an IP1 assay, while lactisole exposure had no effect on cells treated with pure H2O water, as expected (Fig. 5c). As a control, 960 mM D-glucose elicited increase in IP1 levels in TAS1R2/TAS1R3 expressing cell, which was inhibited in the presence of lactisole.” https://lnkd.in/dzPDm5w View in LinkedIn

DATA SUMMARY. “In support of these observations we have demonstrated that HEK 293T cells transfected with TAS1R2/TAS1R3 and Gα16gust chimera, but not the non-transfected cells, are activated by D2O, as measured by IP1 accumulation compared to control values. Finally, taste experiments on mice show that these animals do not prefer D2O over H2O.” https://lnkd.in/dzPDm5w View in LinkedIn