In agreement with the results of

In agreement with the results of the previous studies conducted in our laboratory, it was found that the regulation of the STIM2→nSOCE signaling pathway was impaired in 5×FAD mice. It was established that downregulated STIM2 expression was observed as early as at the age of 4 months. At this age, downregulated STIM2 expression precedes downregulated expression of the PSD95 synaptic marker protein (see Fig. 1). At the age of 6 months, both STIM2 and PSD95 expression was significantly downregulated (see Fig. 1). The results obtained suggest that an earlier stage of the disease, when calcium (see Fig. 1) and amyloid (see Fig. 2) signaling are already impaired but that does not yet lead to significant cognitive impairment, must be the most effective (from a therapeutic standpoint) for activating the STIM2→nSOCE pathway. Thus, the age of 4 months was selected as an early stage of AD in 5×FAD mice. The estimate of the amount of amyloid plaques in the GS-7340 fumarate of the test mice was chosen as a marker for AD pathology progression (sees Figs. 2 and 3). As a result of the study, we have discovered that activation of the STIM2→nSOCE pathway by STIM2 overexpression in the hippocampus of 5×FAD mice can delay the progression of AD pathology, manifesting as a decrease in the number of amyloid plaques in the cerebral cortex (see Fig. 3b). To summarize, the results of this study confirm the hypothesis we have previously advanced about the STIM2→nSOCE pathway impairment in AD [7–9]. Accordingly, the activators/modulators of the STIM2→nSOCE signaling pathway can be used as potential targets for developing AD medication. This study has also established that activation of the STIM2→nSOCE pathway at an early stage can delay AD pathogenesis progression, which also agrees with the assumption that the use of medication is more effective in the early stages of the disease.
Acknowledgement The study was supported by a Russian Science Foundation grant no. 14-25-0024 (the part of the study corresponding to Figs. 1 and 2) and by a grant of the Dynasty private fund no. ДП-Б-49/15 (the part of the study corresponding to Fig. 3)
Introduction The only alternative to the acoustoelastic method is strain measurement, but what it essentially registers are the deformations of the surface to which the strain gauge is attached. The acoustic anisotropy method actually measures the mechanical stresses average over the cross-section of a component. However, this advantage is canceled out by the fact that plastic strain, internal defects, and other ‘imperfections’ all contribute to the measured signal. For this reason the 2007 GOST [1] explicitly states that measurements must be performed only in the elastic range in the absence of plastic strain. This restriction is crucial. As a rule, structural elements are destroyed upon plastic strain, so technical diagnostics in deformation values is of fundamental interest to the industry. A special technology needs to be developed for dividing acoustic anisotropy into parts related to different factors, such as initial anisotropy of the material,mechanical stresses,plastic strain,defects within the material. The existing generalized approaches to solving this problem [2] are based on the Murnaghan model of nonlinear elastic material. Our experimental studies of standard rolled samples [3] proved that these approaches did not fully meet the necessary requirements. The experimental dependences we obtained for acoustic anisotropy versus strain are, even in the simple case of uniaxial loading, fundamentally different, for example, from those described in [4]. Using a more complex viscoelastic material model yields only qualitative agreement with the experiment [3]. Significant advances in this field [5,6] were made through simplifying assumptions. As a matter of fact, only the hydrostatic stress component of the stress tensor is used in simulations of acoustic waves.
Underlying assumptions for constructing the model