Amyotrophic lateral sclerosis (ALS) is characterized by motoneuron (MN) degeneration, generalized weakness, and muscle atrophy. The premature death of MNs is thought to be a determinant in the onset of this disease. In a transgenic mouse model of ALS expressing the G86R mutant superoxide dismutase 1 (mSOD1), we demonstrated previously that CREB (cAMP response element-binding protein)-binding protein (CBP) and histone acetylation levels were specifically decreased in nuclei of degenerating MNs. We show here that oxidative stress and mSOD1 overexpression can both impinge on CBP levels by transcriptional repression, in an MN-derived cell line. Histone deacetylase inhibitor (HDACi) treatment was able to reset proper acetylation levels and displayed an efficient neuroprotective capacity against oxidative stress in vitro. Interestingly, HDACi also upregulated CBP transcriptional expression in MNs. Moreover, when injected to G86R mice in vivo, the HDACi sodium valproate (VPA) maintained normal acetylation levels in the spinal cord, efficiently restored CBP levels in MNs, and significantly prevented MN death in these animals. However, despite neuroprotection, mean survival of treated animals was not significantly improved (Ͻ5%), and they died presenting the classical ALS symptoms. VPA was not able to prevent disruption of neuromuscular junctions, although it slightly delayed the onset of motor decline and retarded muscular atrophy to some extent. Together, these data show that neuroprotection can improve disease onset, but clearly provide evidence that one can uncouple MN survival from whole-animal survival and point to the neuromuscular junction perturbation as a primary event of ALS onset.

The objective of the study is to develop a method for the evaluation of efficiency of the regional infrastructure facilities for the support of scientific, research, technical and innovation activities. This paper presents an analysis of the methods currently used in Russia and abroad, identifying their advantages and disadvantages. Based on the analysis, the author suggests a list of parameters characterizing the given domain, and develops a system for the integrated parameter calculation; a list of the regions is provided with the potential for the most objective efficiency evaluation and testing of the developed method; conclusions are made based on the demonstrated calculations. As a result, the developed method is considered effective and promising. Regardless of the composite index currently being in the stability zone, some of its components may lie in the catastrophic risk zone, posing potential threats to the further innovative development of the subject. At the same time, it is found out that an important role in the efficient functioning of the infrastructure supporting the scientific, research, technical and innovation activities belongs to the legislative environment and the closed innovative cycle (synergy effect).

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The article is devoted to understanding the features of the implementation of the cultural and educational function in the programs of the television channel «Russia-C». As a rule, coverage of culture and science topics on television channels occurs through programs that capture the difference between trained, «qualified» viewers and a wide audience, and either focus on the former, choosing formats and genres that are not interesting to the majority, or shift the focus to entertainment. In this regard, the resolution of this contradiction and the choice of a format for the TV channel about culture to meet the demand of broad layers of Russian television viewers for high-quality intellectual leisure seems to be significant. The authors of the article analyzed all the Russia-C TV channel programs that are regularly broadcast. The authors identified the features of the programs and concluded that the format of the TV channel is focused on the implementation, first of all, of the cultural and educational function, and also that the programs on TV channels are designed to overcome this contradiction. Competent interlocutors and presenters, who have a flexible strategy and tactics, take part in these programs. The variety of genres and the specifics of camera work are noted, patterns in the design of studios are revealed.