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The purpose of the article is to evaluate the effectiveness of managing the educational markets in the countries of the world that have the highest global competitiveness in the sphere of education, to determine and compare the factors of development of universities in the conditions of Industry 4.0 in these countries, and to develop recommendations for increasing the effectiveness of managing the educational market. For evaluating the effectiveness of managing the educational market, the authors' method is used, which is based on the classical formula of measuring effectiveness as a ratio of results and costs. For evaluating the susceptibility of the indicators of development of universities in the conditions of Industry 4.0 to the influence of various factors, the authors use the method of correlation analysis and the method of calculation of direct average. The information and analytical basis of the research includes the analytical and rating materials of CWUR, Legatum Institute, Online learning consortium, QS, Times Higher Education (THE) and World Bank for 2019. It is substantiated that quality is the basis of effective management of the educational market and is a goal of development of universities in the conditions of Industry 4.0. Growth of the volume of state financing of education and improvement of the macro-economic environment will allow achieveing internationalization of education, but they have small influence on its results. Quality of education determines the effectiveness of the national market of education, but is hardly managed at the level of macro-economy.

The article deals with the issues of sustainable development of the world market of cultivated mushrooms. The authors of the article have studied the time series of the world gross value, world volumes of imports and exports, the world price index for cultivated mushrooms and truffles in order to analyze their growth and dynamics. The results of calculations carried out using the statistical database of the Food and Agriculture Organization of the United Nations from 1961 to 2022 showed that the indicated time series are non-stationary. The gross value of mushroom production increased 70 times during the study period, the volume of imports increased 98 times, the volume of exports increased 93 times, and the producer price index doubled. The price index for cultivated mushrooms and truffles is stable without sharp fluctuations. The authors reveled shifts in a series of world gross value of mushroom production in 2000, 2009, 2011. Additive emissions, level shifts and temporary changes were found in the dynamics of world imports and exports.

The article raises the problem of improving the quality of vocational education which largely depends on the joint efforts of all stakeholders of the labor market of territorial education. Therefore, the creation and successful functioning of social partnership will allow in the long term to prepare qualified and in-demand specialists for regional enterprises. According to the authors, the process of formation and development of social partnership in the field of vocational education takes place on the background of reconsidering the role of the State in organizing and governing vocational education under conditions of rapid labor market development.

The study justifies the methodological approach to managing the ecological-and-economic development of the region, based on the principle of strategical safe ecological-and-economic development. The analysis of the effectiveness of the strategic decision-making system for the social-and-economic development of the region was carried out. The principal scheme of the decision-making mechanism for the environmental-and-economic development management was developed, including the strategic environmental assessment, which takes into account the ecological and economic state of the region. The proposed methodological approach to the assessment of the ecological-and-economic situation in the region will allow to reveal some influencing factors, to form the system of assessment indicators, which can be used to control the ecological-and-economic situation and to develop strategical management decisions for the economic development of the region. The scheme of interaction of the strategical managerial decision-making systems as well as the system of regulation of the investment climate in the region can become the basis for the selection of the type of investment policy, corresponding to the ecological-and-economic development of the region. The conceptual framework of decision-making for the ecological-and-economic development of the region as a management tool will make it possible to choose the environmentally acceptable option for the development and functioning of the balanced environmental-and-economic sector.

This paper assesses trends in the development of agricultural enterprises in the XXI century and marks the reasons for the low efficiency of partnerships. The features of integration stages of agricultural producers and processing enterprises are reviewed. Signs which may classify the integration are proposed. A conclusion about the need for a new conception of the organizational structure of the cultivated mushrooms market is made. The basic idea behind the concept could be the creation in the cultivated mushrooms market of a variety of organizational integrated structures, which would maintain competitive environment. The development of integration processes in the direction of economic recovery in agriculture will reduce the investment risks in the mushroom growing, the functions of cultivated mushrooms market will be accumulated in a single integrated structure. In conclusion, a number of conceptual provisions that must be considered in the strategy of diversification for mushroom growing companies of intersectoral agroeconomic integration are highlighted.

Secretagogin is a recently cloned human [beta]-cell-expressed EF-hand [Ca.sup.2+]-binding protein. Converging evidence indicates that it exerts [Ca.sup.2+] sensor activity and is involved in regulation of insulin synthesis and secretion. To obtain a potent tool for the extension of its functional analysis in rat in vitro systems, we cloned the rat homolog of human secretagogin. Using comparative sequence analysis, immunostaining, and immunoblotting, we demonstrated a high degree of sequence homology and similar tissue expression patterns of human and rat secretagogin. Highest rat secretagogin expression levels were found in pancreatic [beta]-cells. On the basis of newly generated anti-rat secretagogin antibodies, we established a rat secretagogin-specific sandwich capture ELISA and demonstrated release of secretagogin from viable Rin-5F cells. Dexamethasone treatment of Rin-5F cells resulted in an increased secretagogin release rate, which was inversely correlated with insulin secretion. In contrast, the secretagogin transcription rate was markedly reduced. This resulted in a decreased intracellular secretagogin content under the influence of dexamethasone. Sucrose gradient cell fractionation analysis of Rin-5F cells confirmed the predominant cytosolic localization of secretagogin, with only limited association of secretagogin with insulin granules. The loss of intracellular secretagogin alter dexamethasone treatment affected predominantly the insulin granule-associated secretagogin fractions. The sequence homology and the comparable tissue expression patterns of human and rat secretagogin indicate conserved intracellular functions. The effects of dexamethasone on the total secretagogin content in Rin-5F cells and on its intracellular distribution might result in an impaired [Ca.sup.2+] sensitivity of dexamethasone-treated insulin-secreting cells. EF-hand protein; insulin granules; dexamethasone; calcium sensor doi:10.1152/ajpendo.00055.2007

The purpose of the article is to evaluate the effectiveness of managing the educational markets in the countries of the world that have the highest global competitiveness in the sphere of education, to determine and compare the factors of development of universities in the conditions of Industry 4.0 in these countries, and to develop recommendations for increasing the effectiveness of managing the educational market. For evaluating the effectiveness of managing the educational market, the authors’ method is used, which is based on the classical formula of measuring effectiveness as a ratio of results and costs. For evaluating the susceptibility of the indicators of development of universities in the conditions of Industry 4.0 to the influence of various factors, the authors use the method of correlation analysis and the method of calculation of direct average. The information and analytical basis of the research includes the analytical and rating materials of CWUR, Legatum Institute, Online learning consortium, QS, Times Higher Education (THE) and World Bank for 2019. It is substantiated that quality is the basis of effective management of the educational market and is a goal of development of universities in the conditions of Industry 4.0. Growth of the volume of state financing of education and improvement of the macro-economic environment will allow achieveing internationalization of education, but they have small influence on its results. Quality of education determines the effectiveness of the national market of education, but is hardly managed at the level of macro-economy. [ABSTRACT FROM AUTHOR]

Abstract: This study was performed on the basis of previously obtained investigative gene array data concerning the over-expression of CXCL12/SDF-1 in human insulinomas versus human pancreatic islet preparations. The presence of CXCL12/SDF-1 was studied by RT-qPCR in human insulinomas (n =8) versus pancreatic islets (n =3), and was found to be significantly up-regulated in the former (p <0.012). The mRNA data were confirmed by immunostaining and confocal microscopy of human normal pancreatic islets, which showed the absence of CXCL12 protein and high expression in insulinoma tissue. Individual human insulinoma cells at cytospins stained positive for CXCL12 in the paranuclear region. These morphological data were extended by consecutive immunoblotting for cell-compartment-specific marker proteins of fractions obtained by sucrose gradient fractionation using Rin-5F insulinoma cells. CXCL12-containing fractions were positive for the membrane marker NSF but negative for SNAP-25 and appeared at a lighter density in the gradient than heavy insulin granules, suggesting packaging in specific granules different from insulin. In order to determine the biological relevance of the protein in insulinomas, we investigated the colony-forming potential of human CXCL12 stable-transfected rat Rin-5F insulinoma cells. These clones secreted human CXCL12 and contained 50–1000-fold higher copy numbers compared to its endogenous rat homologue. In colony-forming assays, these transfectant clones developed greater colony numbers, which were larger than wild-type and sham transfectants. To elucidate the mechanism of action, we identified a CXCL12 transfectant-specific increase in the pro-survival factor Mn-SOD, which is considered important for the inactivation of reactive oxygen species, thereby prolonging cell survival. These data demonstrate the importance of CXCL12 in the tumor biology of insulinoma. [Copyright &y& Elsevier]

In the present study, we characterized the gene product of open reading frame 3 encoded at human chromosome 20 (C20orf3), which represents a member of the lactonohydrolase super family. Multiple-tissue Northern blot analysis showed ubiquitous expression of the 2.4 kb transcript coding for 416 amino acids, with highest levels in human liver, placenta and kidney. After recombinant production of protein variants in Escherichia coli and insect cells, antibodies directed against different epitopes within the C20orf3 gene product were generated. Using these immunoreagents, protein expression was demonstrated in the liver, and glomerular and tubular structures of the kidney, as well as in endothelial cells and arterial wall. Positive staining was also observed at the pancreatic islets of Langerhans. Using immunoblotting, we identified three size variants. In line with the results of in silico analysis demonstrating a single transmembrane sequence (amino acids 40–61) at the N-terminus of the full-length protein, FACS cell-surface staining confirmed a mainly extracellular localization of the full-length protein. Sucrose density gradient cell fractionation revealed membrane association of the dominant 50 kDa variant in HepG2 and Rin-5F cells. The finding of a strong arylesterase activity with β-naphthyl acetate and phenyl acetate of the C20orf3 protein-containing fractions suggests potential involvement of this protein in enzymatic processes. C20orf3 promoter-driven reporter assays, which were verified by gene-specific RT-qPCR (real-time quantitative PCR) showed a strong inhibitory effect of human serum on transcription using the HEK-293 human embryonic kidney cell line. In conclusion, we characterized the structure and expression pattern of the C20orf3 gene product. According to a series of analogies with PON (paraoxonase) family members, we speculate that the C20orf3 gene product represents a new member of this important protein family present at the cellular level. [ABSTRACT FROM AUTHOR]

Aiming to identify signalling pathways relevant for ?-cell growth we performed an explorative micro-array analysis comparing the gene expression profiles of three human insulinomas and one normal pancreatic islet preparation. This revealed an insulinoma-associated down-regulation of the transforming growth factor beta 1 (TGF-?1) and its target genes. Comparative quantitative real-time PCR (qRT-PCR) including an expanded sample number of both insulinomas (n=9) and pancreatic islet preparations (n=4) confirmed the decreased TGF-?1 expression and its target molecules (TGFBI, NNMT, RPN2) in insulinomas. Similarly, TGF-?1 immunofluorescense analysis revealed reduced expression in insulinomas when compared to pancreatic islets. In contrast, TGFBR2 (transforming growth factor beta receptor II) was found up-regulated. However, the consistent down-regulation of the TGF-?1 targets TGFBI (transforming growth factor, beta-induced), NNMT (nicotinamide N-methyltransferase), RPN2 (ribophorin II) indicates that the parallel up-regulation of TGFBR2 does not compensate for the only marginal TGF-?1 expression levels in insulinomas. TGFBR2 expression was confirmed at the protein level in insulinomas. SMAD2/3 protein expression was found at higher levels in human pancreatic islets when compared with insulinomas by dual colour confocal microscopy. TGF-?1 signalling is known to be involved in cell replication and is abrogated in ductal pancreatic tumours. The down-regulation of TGF-?1 expression and its target molecules in insulinomas is a new aspect of this cytokine. Our data underline parallels in endocrine and exocrine pancreatic tumour development, which may implicate common progenitor cells. [ABSTRACT FROM AUTHOR]

Objective: Long-term in vitro maintenance of human insulin-secreting insulinoma cells. Methods: (1) Cell culture of ex vivo-derived insulinoma cell suspensions from 8 individual human donors, using various cell culture medium supplementations; (2) determination of insulin synthesis and secretion using immunocytochemistry and insulin and pro-insulin radioimmunoassays; (3) nestin-immunostaining of long-term in vitro grown insulinoma cell suspensions, and (4) phase-contrast light microscopy for analyzing the in vitro growth characteristics of the insulinoma cells. Results: (1) Parallel persistence of in vitro insulinoma cell proliferation as well as insulin-synthesizing and -secreting capacity depended on both the co-culture of insulinoma cells with human fibroblasts and the supplementation of the cell culture medium with tissue culture supernatant derived from the rodent pituitary adenoma cell line GH-3; (2) immunostaining for insulin and secretagogin confirmed the neuroendocrine origin of the insulinoma cells grown in vitro; (3) insulin secretion capability persisted up to an observation period of 25 weeks; (4) insulin secretion rates after 6 weeks of in vitro growth ranged from 3.5 to 83.3 μU/ml/h/60,000 cells plated, and (5) after long-term in vitro growth of insulinoma-derived cell suspensions with persistent insulin-secreting capacity, nestin staining was observed predominantly in co-cultured fibroblasts. Conclusion: Our data describe for the first time the long-term in vitro culture of insulin-secreting human insulinomas and highlight the importance of β-cell trophic factors for insulinoma cell growth. Copyright © 2006 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

In the present study, we characterized the gene product of open reading frame 3 encoded at human chromosome 20 (C20orf3), which represents a member of the lactonohydrolase super family. Multiple-tissue Northern blot analysis showed ubiquitous expression of the 2.4 kb transcript coding for 416 amino acids, with highest levels in human liver, placenta and kidney. After recombinant production of protein variants in Escherichia coli and insect cells, antibodies directed against different epitopes within the C20orf3 gene product were generated. Using these immunoreagents, protein expression was demonstrated in the liver, and glomerular and tubular structures of the kidney, as well as in endothelial cells and arterial wall. Positive staining was also observed at the pancreatic islets of Langerhans. Using immunoblotting, we identified three size variants. In line with the results of in silico analysis demonstrating a single transmembrane sequence (amino acids 40-61) at the N-terminus of the full-length protein, FACS cell-surface staining confirmed a mainly extracellular localization of the full-length protein. Sucrose density gradient cell fractionation revealed membrane association of the dominant 50 kDa variant in HepG2 and Rin-5F cells. The finding of a strong arylesterase activity with beta-naphthyl acetate and phenyl acetate of the C20orf3 protein-containing fractions suggests potential involvement of this protein in enzymatic processes. C20orf3 promoter-driven reporter assays, which were verified by gene-specific RT-qPCR (real-time quantitative PCR) showed a strong inhibitory effect of human serum on transcription using the HEK-293 human embryonic kidney cell line. In conclusion, we characterized the structure and expression pattern of the C20orf3 gene product. According to a series of analogies with PON (paraoxonase) family members, we speculate that the C20orf3 gene product represents a new member of this important protein family present at the cellular level.

Aiming to identify signalling pathways relevant for ss-cell growth we performed an explorative micro-array analysis comparing the gene expression profiles of three human insulinomas and one normal pancreatic islet preparation. This revealed an insulinoma-associated down-regulation of the transforming growth factor beta 1 (TGF-beta1) and its target genes. Comparative quantitative real-time PCR (qRT-PCR) including an expanded sample number of both insulinomas (n=9) and pancreatic islet preparations (n=4) confirmed the decreased TGF-beta1 expression and its target molecules (TGFBI, NNMT, RPN2) in insulinomas. Similarly, TGF-beta1 immunofluorescence analysis revealed reduced expression in insulinomas when compared to pancreatic islets. In contrast, TGFBR2 (transforming growth factor beta receptor II) was found up-regulated. However, the consistent down-regulation of the TGF-beta1 targets TGFBI (transforming growth factor, beta-induced), NNMT (nicotinamide N-methyltransferase), RPN2 (ribophorin II) indicates that the parallel up-regulation of TGFBR2 does not compensate for the only marginal TGF-beta1 expression levels in insulinomas. TGFBR2 expression was confirmed at the protein level in insulinomas. SMAD2/3 protein expression was found at higher levels in human pancreatic islets when compared with insulinomas by dual colour confocal microscopy. TGF-beta1 signalling is known to be involved in cell replication and is abrogated in ductal pancreatic tumours. The down-regulation of TGF-beta1 expression and its target molecules in insulinomas is a new aspect of this cytokine. Our data underline parallels in endocrine and exocrine pancreatic tumour development, which may implicate common progenitor cells.