Social entrepreneurship: problems and ways of their solution

For modern constantly developing societies, it is normal to create categories in the process of the activity of the participants of socio-economic processes themselves. Practice is theoretical, and theory is pragmatic, because it creates those concepts in which «practice» exists and develops. Such a category is "social entrepreneurship", which is "umbrella" for a number of socio-economic phenomena. The general term for social entrepreneurship includes those types of entrepreneurial activity that contradict the traditional notion of entrepreneurship as an activity of independent economic entities aimed at maximizing their profits. The development of social entrepreneurship is an indicator of the quality of the business climate in the region and requires a set of measures to ensure the mechanism and access of non-governmental organizations to the provision of services in the social sphere, the provision of state support to socially-oriented non-profit organizations, and the promotion of the development of PPP practices in the social sphere

Molecular Basis of Circadian Desynchrony in Cardiometabolic Disease

The circadian system is a key integrator of behavior and metabolism that synchronizes physiological process to anticipate and respond to recurrent daily changes in the environment. Studies from our laboratory have shown that, in addition to disruption in circadian activity rhythm and sleep-related pathologies, perturbation of normal circadian gene function leads to diet-induced obesity and cardiometabolic syndrome. Conversely, high fat diet (HFD) disrupts sleep, feeding, and locomotor activity rhythms. These observations raise interest in uncovering signaling mechanisms intersecting nutrient fl ux and dietary lipid composition to circadian homeostasis, at both the behavioral and gene regulatory levels. Here, we show that mice fed a diet high in saturated fat display increased activity during the normal rest (light) period in contrast to mice provided control diet (i.e. regular chow). In addition, saturated and unsaturated fat diets show opposite eff ects on circadian activity rhythm: HFD containing mainly saturated fatty acid (SFD) lengthened circadian period whereas an isocaloric diet containing unsaturated fatty acids (UFD) shortened the period. The eff ects of each diet were examined at the level of isolated live cultures of suprachiasmatic nuclei (SCN) in genetic reporter mouse, mPer2Luc, to compare the eff ects of saturated versus unsaturated fat master pacemaker neurons. Remarkably, the overt behavioral eff ects of HFD on locomotor activity were recapitulated in live-cell cultures of SCN from mPer2Luc mice. These observations delineate a relationship between dietary fatty acid composition per se on behavioral and molecular circadian rhythms in mice. Genetic and nutritional manipulations provide a new entry point to probe the reciprocal relationship between obesogenic diet and circadian disruptio

Studies on the Roles of Quinone Reductase and the Reductones in an Enzymatic Browning Reaction

Quinone reductase was prepared from white potato. In the presence of NADH, this enzyme reduced two active substituted quinones, quinone-N-acetylcysteine and menadione-N-acetylcysteine, which were produced as the model substances in an enzymatic browning reaction. Furthermore, this enzymatic reduction rate was accelerated by pretreatment of the substituted quinones with reductones, such as triose reductone, ascorbic acid, 5-methy-3, 4_dihydroxytetrone, dopa and epinephrine, but not accelerated by pretreatment of the quione reductase with the reductone

Requirement for NF-κB in maintenance of molecular and behavioral circadian rhythms in mice.

The mammalian circadian clock is encoded by an autoregulatory transcription feedback loop that drives rhythmic behavior and gene expression in the brain and peripheral tissues. Transcriptomic analyses indicate cell type-specific effects of circadian cycles on rhythmic physiology, although how clock cycles respond to environmental stimuli remains incompletely understood. Here, we show that activation of the inducible transcription factor NF-κB in response to inflammatory stimuli leads to marked inhibition of clock repressors, including the , , and genes, within the negative limb. Furthermore, activation of NF-κB relocalizes the clock components CLOCK/BMAL1 genome-wide to sites convergent with those bound by NF-κB, marked by acetylated H3K27, and enriched in RNA polymerase II. Abrogation of NF-κB during adulthood alters the expression of clock repressors, disrupts clock-controlled gene cycles, and impairs rhythmic activity behavior, revealing a role for NF-κB in both unstimulated and activated conditions. Together, these data highlight NF-κB-mediated transcriptional repression of the clock feedback limb as a cause of circadian disruption in response to inflammation

Generation, characterization, and molecular cloning of the Noerg-1 mutation of rhodopsin in the mouse

We performed genome-wide mutagenesis of C57BL/6J mice using the mutagen N-ethyl-N-nitrosourea (ENU) and screened the third generation (G3) offspring for visual system alterations using electroretinography and fundus photography. Several mice in one pedigree showed characteristics of retinal degeneration when tested at 12–14 weeks of age: no recordable electroretinogram (ERG), attenuation of retinal vessels, and speckled pigmentation of the fundus. Histological studies showed that the retinas undergo a photoreceptor degeneration with apoptotic loss of outer nuclear layer nuclei but visual acuity measured using the optomotor response under photopic conditions persists in spite of considerable photoreceptor loss. The Noerg-1 mutation showed an autosomal dominant pattern of inheritance in progeny. Studies in early postnatal mice showed degeneration to occur after formation of partially functional rods. The Noerg-1 mutation was mapped genetically to chromosome 6 by crossing C57BL/6J mutants with DBA/2J or BALB/cJ mice to produce an N2 generation and then determining the ERG phenotypes and the genotypes of the N2 offspring at multiple loci using SSLP and SNP markers. Fine mapping was accomplished with a set of closely spaced markers. A nonrecombinant region from 112.8 Mb to 115.1 Mb was identified, encompassing the rhodopsin (Rho) coding region. A single nucleotide transition from G to A was found in the Rho gene that is predicted to result in a substitution of Tyr for Cys at position 110, in an intradiscal loop. This mutation has been found in patients with autosomal dominant retinitis pigmentosa (RP) and results in misfolding of rhodopsin expressed in vitro. Thus, ENU mutagenesis is capable of replicating mutations that occur in human patients and is useful for generating de novo models of human inherited eye disease. Furthermore, the availability of the mouse genomic sequence and extensive DNA polymorphisms made the rapid identification of this gene possible, demonstrating that the use of ENU-induced mutations for functional gene identification is now practical for individual laboratories