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The overall characteristics of the solar and atmospheric neutrino oscillations are approximately consistent with a tribimaximal form of the mixing matrix U of the lepton sector. Exact tribimaximal mixing leads to θ 13 = 0 . However, the results from the Daya Bay and RENO experiments have established, such that in comparison to the other neutrino mixing angles, θ 13 is small. Moreover, the atmospheric and solar mass splitting differ by two orders of magnitude. These significant differences constitutes the great enthusiasm and main motivation for our research herein reported. Keeping the behavior of U as tribimaximal, we would make a response to the following questions: at some level, whether or not the small parameters such as the solar neutrino mass splitting and U e 3 , which vanish in a new framework, can be interpreted as a modified FL neutrino mass model? Subsequently, a minimal single perturbation leads to nonzero values for both of them? Our minimal perturbation matrix is constructed solely from computing the third mass eigenstate, using the rules of perturbation theory. Let us point out that, unlike other investigations, this matrix is not adopted on an ad hoc basis, but is created following a series of steps that we will describe. Also in compared to the original FL neutrino mass model which generalize it by inserting phase factors, our work is more accurate. Subsequently, we produce the following results that add new contributions to the literature: (a) we obtain a realistic neutrino mixing matrix with δ ≠ 0 and θ 23 = 45 ∘ ; (b) the solar mass splitting term is dominated by an imaginary term, which could induce the existence of Majorana neutrinos, along with explaining a large CP violation in nature; (c) the ordering of the neutrino masses is normal; however, at the end of the allowed range, it becomes more degenerate ( 97 % ); (d) we also obtain the allowed range of the mass parameters, which not only are in accordance with the experimental data but also allow falsifiable predictions for the masses of the neutrinos and the CP violating phases which none of these results has been achieved in the original FL neutrino mass model. Finally, let us emphasize that the results obtained by our framework here are much more efficient compared to those obtained in previous works in terms of currently available experimental data (namely, the best fit column). [ABSTRACT FROM AUTHOR]

Mutations in the photoreceptor protein rhodopsin are known as one of the leading causes of retinal degeneration in humans. Two rhodopsin mutations, Y102H and I307N, obtained in chemically mutagenized mice, are currently the subject of increased interest as relevant models for studying the process of retinal degeneration in humans. Here, we report on the biochemical and functional characterization of the structural and functional alterations of these two rhodopsin mutants and we compare them with the G90V mutant previously analyzed, as a basis for a better understanding of in vivo studies. This mechanistic knowledge is fundamental to use it for developing novel therapeutic approaches for the treatment of inherited retinal degeneration in retinitis pigmentosa. We find that Y102H and I307N mutations affect the inactive–active equilibrium of the receptor. In this regard, the mutations reduce the stability of the inactive conformation but increase the stability of the active conformation. Furthermore, the initial rate of the functional activation of transducin, by the I307N mutant is reduced, but its kinetic profile shows an unusual increase with time suggesting a profound effect on the signal transduction process. This latter effect can be associated with a change in the flexibility of helix 7 and an indirect effect of the mutation on helix 8 and the C-terminal tail of rhodopsin, whose potential role in the functional activation of the receptor has been usually underestimated. In the case of the Y102H mutant, the observed changes can be associated with conformational alterations affecting the folding of the rhodopsin intradiscal domain, and its presumed involvement in the retinal binding process by the receptor. [ABSTRACT FROM AUTHOR]

Rhodopsin is the G protein-coupled receptor of rod photoreceptor cells that mediates vertebrate vision at low light intensities. Mutations in rhodopsin cause inherited retinal degenerative diseases such as retinitis pigmentosa. Several therapeutic strategies have attempted to address and counteract the deleterious effect of rhodopsin mutations on the conformation and function of this photoreceptor protein, but none has been successful in efficiently preventing retinal degeneration in humans. These approaches include, among others, the use of small molecules, known as pharmacological chaperones, that bind to the receptor stabilizing its proper folded conformation. Valproic acid, in its sodium valproate form, has been used as an anticonvulsant in epileptic patients and in the treatment of several psychiatric disorders. More recently, this compound has been tested as a potential therapeutic agent for the treatment of retinal degeneration associated with retinitis pigmentosa caused by rhodopsin mutations. We now report on the effect of sodium valproate on the conformational stability of heterologously expressed wild-type rhodopsin and a rhodopsin mutant, I307N, which has been shown to be an appropriate model for studying retinal degeneration in mice. We found no sign of enhanced stability for the dark inactive conformation of the I307N mutant. Furthermore, the photoactivated conformation of the mutant appears to be destabilized by sodium valproate as indicated by a faster decay of its active conformation. Therefore, our results support a destabilizing effect of sodium valproate on rhodopsin I307N mutant associated with retinal degeneration. These findings, at the molecular level, agree with recent clinical studies reporting negative effects of sodium valproate on the visual function of retinitis pigmentosa patients. [ABSTRACT FROM AUTHOR]