Pals1 functions as a tumor suppressor regulating cell polarity, Hippo signaling and cancer progression

Epithelial cell polarity is of vital importance for the organization and function of epithelial tissues and is primarily maintained by three protein complexes, the Crumbs complex, the Par complex and the Scribble complex. Most of the polarity proteins within these complexes are highly conserved and play pivotal roles in embryonic development, cell-cell adhesion and cell migration. Recent studies have demonstrated that deregulation of epithelial polarity is a hallmark of tumor progression, in particular during the metastatic process. This study was conducted to examine the role of the tight junction protein Pals1 in the maintenance of cell polarity, and cancer. RNA interference and CRISPR/Cas9 gene deletion approaches were used to downregulate or deplete Pals1 in MDCKII, HCT116 and DLD1 cell lines. Reduction in Pals1 resulted in atypical expression levels of polarity proteins and defects in Hippo pathway regulation. Moreover, Pals1 loss caused E-cadherin reduction and enhanced cell migration. Pals1 deficient cells exhibited typical markers, inferring epithelial-to-mesenchymal transition. Further in vivo xenograft experiments revealed a function of Pals1 in cancer progression, as tumors derived from Pals1-deficient cells showed increased growth and more extensive liver and lung metastases. Taken together, these findings support a close link between epithelial cell polarity and tumorigenesis, and suggest the existence of a novel Pals1-mediated mechanism of tumor suppression. Thus, the pathophysiological consequences of Pals1 alteration must be investigated further, and used to develop new therapeutic strategies against this devastating disease

Creation of Clusters of Small Enterprises of the Region

Under the conditions of continuous economic progress, modernization of production, development of the world market there is the need for increasing competitiveness of small enterprises of the country and regions. This dynamics of changes demands new approaches to socio-economic development of the Russian industries. Each region of the country can be competitive not only in the domestic market, but also and in the world if it uses the reserve which has necessary economic, intellectual and financial potential. Thus, one of the ways of the effective realization of economic potential and stimulation of economic growth is the creation of competitive regional clusters, both large-scale organizations and small enterprises. Now the given problem is one of essential for the decision in the sphere of economic regional government as the analysis of world practice shows rather high efficiency of development of economies of many countries on the basis of use of cluster approach as opposed to branch that is acceptable for our country. The government of Russia also defined cluster approach as the main instrument of management of regional development. However, this approach demands detailed studying, first of all, from the point of view of adaptation of the international experience to the Russian conditions. Keywords: cluster, small enterprises, development, region, economic progress JEL Classifications: A10, C38, O1

THE STUDY OF DOMESTIC AND INTERNATIONAL PRACTICE OF DETERMINING STANDARD COSTS ON RENDERING OF STATE SERVICES IN THE SPHERE OF EDUCATION AND SCIENCE

The article presents a review of existing domestic and foreign practice of the tools of budgetary financing of educational organizations, in particular, the definition of standard costs on rendering of state services, reconsideration which, according to the authors, may contribute to the development of common technical requirements for their determination. It is shown that, depending on applied methodology of standard costs, adaptation of domestic government budget institutions to the new mechanism of financial security was carried out in three variants, as well as suggestions for improved planning of activity of educational organizations and their financial support during the transition period

TRANSFORMATION OF THE ECONOMIC BEHAVIOR OF UNIVERSITIES UNDER CONDITIONS OF DEMOGRAPHIC DECLINE

The article discusses the economic behavior of the national educational institutions of higher school at the current demographic trends, that universities are trying to stabilize their financial condition, to overcome the crisis and meet the needs of the organization in performing its core functions; the specificity of the economic behavior of universities associated with the educational status of the organization, its specialization, the degree of resource dependence on major institutional actors; statistical data confirming the relevance of the research topic; basic models of economic behavior of Russian universities in the conditions of demographic crisis

Lead ions abrogate lipopolysaccharide-induced nitric monoxide toxicity by reducing the expression of STAT1 and iNOS

Lead is a widespread environmental pollutant and the highly poisonous metal compromises multiple organs in the body. Among other tissues and cells, lead ions (Pb2+) can affect macrophages and microglia cells. The present study observed a concentration-dependent protection of BV-2 microglia and RAW 264.7 macrophages by Pb2+ against lipopolysaccharide (LPS)-induced toxicity. Both cell lines are potent producers of two substances that have previously been shown to mediate cytotoxic effects of LPS. These are the pro-inflammatory cytokine tumor necrosis factor (TNF)-alpha and nitric monoxide (NO), which creates nitrosative stress, hampering the distribution of invading pathogens and tumor cells. While the expression of TNF-alpha. was unaffected by Pb2+, the production of NO was significantly inhibited. Moreover, blocking NO synthesis by low molecular weight inhibitors prevented LPS-mediated toxicity, confirming the role of NO in these events. Pb2+ exposure led to a downregulation of LPS-induced expression of the transcription factor STAT1, which is involved in iNOS transcription. Moreover, iNOS mRNA and protein levels were reduced in the presence of Pb2+, explaining the reduced formation of NO and a subsequent increase of cellular viability in vitro. In vivo, the effect might limit collateral damage caused by excessive NO production, but also impair the efficiency of NO as a central mediator of the defense against various pathogens. (C) 2016 Elsevier GmbH. All rights reserved

Mechanical properties of microwave sintered Si3N4-based ceramics

The mechanical properties and microstructure formation processes in Si3N4+3% AI2O3+5% Y2O3(Yb2O3) ceramic compacts sintered under microwave heating (MWH) and under traditional heating (TH) were investigated. The initial ceramic materials were powder blends of silicon nitride with oxides. The mean powder particle sizes were 0.5-1.0 mim. The content of alfa-phase in the Si3N4 powder was more than 95 %. The samples were sintered at 1800BC in nitrogen at normal pressure, the heating rate in all experiments was 60BC/min. The Vickers hardness (HV), fracture toughness (K1C) and bending strength (on) were determined. The microstructures of fracture surfaces of samples were studied by SEM. Quantitative microstructure analysis was carried out. It was shown that the values of HV and Kic of ceramic samples sintered under MWH at 1800BC rose steadily with the sintering time. This caused an increase in density, which reached maximum as fast as after 30 min of the MWH sintering; the mass loss at that time amounted to 3-4 %. The porosity of sintered samples with an addition of yttria was less than 1 %, that of ytterbia was greater, 2.4 %. For similar values of relative density, the hardness and fracture toughness of ceramic samples produced under MWH were higher as compared with those of samples sintered under TH. The microstructure of samples had the form of elongated grains in a matrix of polyhedral grains of the beta-Si3N4 phase. Measurements showed the mean size of grains in samples produced by MWH to be greater that in samples produced by TH. A larger number of elongated grains were formed. It was concluded that for sintering under MWH of Si3N4-based ceramics the growth of elongated beta-Si3N4 grains and formation of a "reinforced" microstructure were promoted and thereby improved the mechanical properties of such ceramics