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Purpose The purpose of this paper is to determine the perspectives and to adapt the analysis of “underdevelopment whirlpools” to the current needs of state management of digital modernization of the regional market of educational services in the aspect of determination and assessment of its disproportions as a tool of managing the regional market of education and managing the process of reorganization of regional universities in the conditions of transition to Industry 4.0. Design/methodology/approach Analysis of “underdevelopment whirlpools”, adapted by the authors to the specifics of the regional market of educational services, is used. The statistical basis for this paper includes the information and analytical materials as a result of monitoring the effectiveness of activities of educational organizations of higher education and the materials of the Federal State Statistics Service of the Russian Federation. Findings “Underdevelopment whirlpools” of the Kirov branch of St. Petersburg University of the Humanities and Social Sciences are analyzed, and reorganization of this university is recommended. “Underdevelopment whirlpools” in Kirov Oblast are analyzed, and an increase of regulation of this market is recommended. Originality/value It is substantiated that the method of analysis of “underdevelopment whirlpools” could be a tool of managing the regional educational market and managing the process of reorganization of regional universities in the conditions of transition to Industry 4.0. The advantage of analysis of “underdevelopment whirlpools”, as compared to the existing similar methods of assessment of disproportions in the development of the regional market of educational services (e.g. comparative analysis and plan-fact analysis), is the possibility not only to evaluate the static underrun from the model/plan but also to study its dynamics (depth and speed of sucking into “underdevelopment whirlpool”), which allows achieving high precision of the results of assessment.

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.

The article describes some general methods of diagnostics of the sensors of microprocessor control systems controlling a hybrid transmission of a vehicle. The task to research the processes of sensors diagnosing is stated.

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.

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.

Secretagogin is a recently cloned human β-cell-expressed EF-hand Ca2+-binding protein. Converging evidence indicates that it exerts Ca2+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 β-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 after 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 Ca2+sensitivity of dexamethasone-treated insulin-secreting cells.

Disturbed calcium homeostasis plays a crucial role in the aetiology of Alzheimer's disease (AD) and the aging process. We evaluated immunoreactivity of secretagogin, a recently cloned calcium binding protein, in hippocampus and adjacent entorhinal cortex of 30 neuropathologically examined post mortem brains (m:f=12:18; mean age, 79.8+/-15.1 years). The study group consisted of 15 cases fulfilling the criteria for high probability of AD according to the NIA-Reagan Institute Criteria and 15 cases with no to medium probability. Sections were incubated with secretagogin-specific antibodies and the number of immunoreactive neurons as well as staining intensities in both neurons and neuropil were assessed. Both cellular and neuropil immunoreactivity were restricted to subiculum and Ammons horn. Cellular immunoreactivity was further restricted to pyramidal neurons and showed a hierarchical distribution: the mean percentage of immunoreactive neurons was highest in sector CA3 (64.41%), followed by CA2 (44.09%), CA4 (34.38%), CA1 (10.9%), and the subiculum (2.92%; P0.001, except CA2-CA4, P0.05), while it did not differ significantly between groups with different degrees of AD pathology. The pattern of secretagogin immunoreactivity resembles that of calcium sensor proteins as it is restricted to a subset of neurons and therefore secretagogin could serve highly specialized tasks in neuronal calcium signalling.

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.

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.