Heterotrimeric G proteins are immediate transducers of G protein-coupled receptors—the biggest receptor family in metazoans—and play innumerate functions in health and disease. A set of de novo point mutations in GNAO1 and GNAI1, the genes encoding the α-subunits (Gαo and Gαi1, respectively) of the heterotrimeric G proteins, have been described to cause pediatric encephalopathies represented by epileptic seizures, movement disorders, developmental delay, intellectual disability, and signs of neurodegeneration. Among such mutations, the Gln52Pro substitutions have been previously identified in GNAO1 and GNAI1. Here, we describe the case of an infant with another mutation in the same site, Gln52Arg. The patient manifested epileptic and movement disorders and a developmental delay, at the onset of 1.5 weeks after birth. We have analyzed biochemical and cellular properties of the three types of dominant pathogenic mutants in the Gln52 position described so far: Gαo[Gln52Pro], Gαi1[Gln52Pro], and the novel Gαo[Gln52Arg]. At the biochemical level, the three mutant proteins are deficient in binding and hydrolyzing GTP, which is the fundamental function of the healthy G proteins. At the cellular level, the mutants are defective in the interaction with partner proteins recognizing either the GDP-loaded or the GTP-loaded forms of Gαo. Further, of the two intracellular sites of Gαo localization, plasma membrane and Golgi, the former is strongly reduced for the mutant proteins. We conclude that the point mutations at Gln52 inactivate the Gαo and Gαi1 proteins leading to aberrant intracellular localization and partner protein interactions. These features likely lie at the core of the molecular etiology of pediatric encephalopathies associated with the codon 52 mutations in GNAO1/GNAI1.

Problem of empty cavity dynamics in a two-phase medium is considered. The initial equilibrium state of “cavity-medium” system is disturbed when pressure inside cavity falls abruptly up to 0. Rarefaction wave arising on an interface initiates a cavitation development. Two-phase mathematical model is applied to investigate the medium state dynamics. The medium parameters correspond to a distilled water state: microbubbles, 1.5 μm, their density 106 cm-3, and gas concentration, about 10-5. The numerical analysis has shown that interface “cavity-medium” becomes a cavitating spherical layer. The concluding process of cavity collapse can be characterized by two stages. First, the interface as a spherical layer in a result of its cumulation is transformed into a spherical bubbly cluster with 1 mm radius. Cluster contains 2.5·105 см-3 microbubbles with 40 μm radii. Gas concentration is distributed from 20%,cluster center, up to 1% on its surface. Second, the cumulation of flow on the spherical bubbly cluster will determine a level of internal energy of compressed bubbly cluster and its further dynamics. The similar phenomenon was found in the experiments on the development, structure, and collapse of a rupture forming in cavitating layer of distilled water at its shock-wave loading. The analysis of experimental data has shown that a rupture in the cavitating layer is the cavity with interface as thin layer of cavitating liquid and its collapse tends to the bubbly cluster formation. [Support RFBR, grant 15-05-03336.]

Introduction Following approval in 2009 of vagus nerve stimulation (VNS Therapy) for drug‐resistant epilepsy (DRE) in the Russian Federation, this is the first multicenter study across Russia to evaluate the safety and efficacy of adjunctive VNS Therapy. Methods The retrospective, observational registry included 58 pediatric patients with DRE (5–17 years old at implantation) who had ≥2 years of VNS. To ensure a robust evaluation process, changes in seizure frequency were evaluated for all seizure types as well as “most disabling” seizures (defined as seizures accompanied by falls, physical trauma, and/or incontinence in the absence of preventative measures). Results With 2 years of VNS Therapy, 37 of 49 patients (76%) experiencing the most disabling epileptic seizures had a >50% decrease in frequency of such seizures, and 16 (33%) reported no longer experiencing the “most disabling” seizure type. In addition, based on the McHugh Outcome scale, VNS Therapy had a positive outcome on both frequency and severity of all epileptic seizure types, with a >50% decrease in frequency of all epileptic seizure types noted in 37 of 58 patients (64%), and 31% of patients had a Class I outcome, including 11 patients (19%) who achieved seizure freedom. VNS Therapy also had a positive effect on the frequency of status epilepticus: 13 patients (22%) had status epilepticus prior to implantation with a mean rate of 9.4 ± 17.7 events per year (range, 0–52), and after VNS Therapy, only one patient continued to experience status epilepticus (at 1 event per 4–6 months). VNS Therapy had an acceptable safety profile and no adverse events leading to VNS discontinuation were reported. Conclusions The results demonstrate that VNS Therapy is being safely and effectively applied to pediatric patients in the Russian healthcare system.

The effect of an ambient liquid state on a spherical cavity dynamics under atmospheric hydrostatic pressure p and extremely low initial gas pressure p(0) inside was investigated. The equilibrium bubbly (cavitating) medium with sound velocity C as the function of gas phase concentration k was considered as the ambient liquid model. The cavity dynamics is analyzed within the framework of Herring-equation for the following diapasons of main parameters : k = 0—5%, р(0) = 0.02—10(−6) atm. Numerical analysis has shown that the deceleration C by two order does not have an influence neither on an asymptotic value of collapsed cavity radius nor on the acoustical losses under its collapse. It means than in the whole the integral acoustical losses remain invariable. However the collapse cavity dynamics and the radiation structure are essentially changed: from numerous pulsations with a decreasing amplitudes up to a single collapse and from a wave packet up to a single wave, correspondingly. It has turned out that the acoustic corrections in the Herring-equation don’t influence practically on the cavity dynamics if the term of equation with dH/dt is absent. Naturally, the deceleration C exerts essential influence on an empty cavity dynamics. The graphs of dR/Cdt values as a function of R/Ro for different C values are located higher the data of classical models of Herring, Gilmore and Hunter. So the value M = 1 is reached at R/Ro = 0.023 for k = 0, and at the value 0.23 when k = 5 %. [Support RFBR, grant 12-01-00314.]

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