Milk production is modulated by the paracellular barrier function of tight junction (TJ) proteins located in the mammary epithelium. The aim of our study was the molecular analysis of TJs in native lactating murine mammary gland epithelium as this process may strongly challenge epithelial barrier properties and regulation. Mammary gland tissue specimens from lactating control mice and animals after a 20-h interruption of suckling were prepared; histological analyses were performed by light and electron microscopy; and expression of TJ proteins was detected by PCR, Western blotting, immunofluorescent staining, and confocal laser scanning microscopy. Discontinuation of suckling resulted in a substantial accumulation of milk in mammary glands, an increase of alveolar size, and a flattening of epithelial cells without effects on inflammatory indicators. In control tissues, PCR and Western blots showed signals for occludin, and claudin-1, -2, -3, -4, -5, -7, -8, -15, and -16. After a 20-h accumulation of milk, expression of two sealing TJ proteins, claudin-1 and -3, was markedly increased, whereas two TJ proteins involved in cation transport, claudin-2 and -16, were reduced. Real-time PCR validated increased transcripts of claudin-1 and claudin-3. During extension of mammary glands in the process of lactation, claudin-1 and -3 are markedly induced and claudin-2 and -16 are decreased. Volume and composition of milk might be strongly dependent on this counter-regulation of sealing claudins with permeability-mediating claudins, indicating a physiological process of a tightening of TJs against a back-leak of solutes and ions from the alveolar lumen.
Large companies implement their business activities in the form of projects. The problem of implementing business projects based on the concept of sustainable development is becoming more urgent. The concept assumes management of business projects in such a way that allows a balance to be struck between the economic, social and environmental interests of groups of stakeholders on an institutional basis at the current time and over the long term. However, there are currently no universal and generally accepted developments in sustainability management. This study aims to develop and test a methodology for assessing and managing the sustainability of business projects that includes values, motives, and the level of maturity of sustainability. The novelty and originality of the methodology lies in the fact that it takes into account four sustainability criteria at once – economic, social, environmental and institutional. It allows the user to identify the level of sustainability, both on the basis of individual criteria and an integral indicator. It also corresponds to the current trend of studying the motives and values of implementing the concept of sustainability in projects. The proposed methodology and the test results from 36 large companies in Russia will help business project managers cope with the growing complexity of the social, environmental and economic environments.
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