Growth factors regulate cellular proliferation and differentiation by activating plasma membrane tyrosine kinase receptors and triggering a cascade of events mediated by intracellular signaling proteins. The mechanism underlying growth factor modification of cellular functions, such as gap-junctional communication (gjc), has not been established clearly. Addition of epidermal growth factor (EGF) to T51B rat liver epithelial cells resulted in the rapid activation of EGF receptor tyrosine kinase activity followed by a transient dose-dependent disruption of gjc. This change did not result from the gross disturbance of membrane gap junction plaques as measured by immunofluorescence microscopy, but instead correlated with markedly elevated phosphorylation of the connexin43 (cx43) gap junction protein, a profound shift to predominantly phosphorylated forms of cx43, and the appearance of a novel phosphorylated cx43 protein. These changes in cx43 phosphorylation involved only serine residues. On restoration of gjc, these alterations in cx43 phosphorylation reverted to the pre-EGF treatment state. Both events were inhibited by the serine/threonine protein phosphatase inhibitor, okadaic acid. Therefore, unlike the case for pp60v-src, EGF-induced disruption of gjc is not associated with tyrosine phosphorylation of cx43, but instead may result from phosphorylation of cx43 by activated intracellular signaling serine protein kinase(s).

No abstract

No abstract

One of the major challenges in big cities is planning and implementation of an optimized, integrated solid waste management system. This optimization is crucial if environmental problems are to be prevented and the expenses to be reduced. A solid waste management system consists of many stages including collection, transfer and disposal. In this research, an integrated model was proposed and used to optimize two functional elements of municipal solid waste management (storage and collection systems) in the Ahmadabad neighbourhood located in the City of Mashhad - Iran. The integrated model was performed by modelling and solving the location allocation problem and capacitated vehicle routing problem (CVRP) through Geographic Information Systems (GIS). The results showed that the current collection system is not efficient owing to its incompatibility with the existing urban structure and population distribution. Application of the proposed model could significantly improve the storage and collection system. Based on the results of minimizing facilities analyses, scenarios with 100, 150 and 180 m walking distance were considered to find optimal bin locations for Alamdasht, C-metri and Koohsangi. The total number of daily collection tours was reduced to seven as compared to the eight tours carried out in the current system (12.50% reduction). In addition, the total number of required crews was minimized and reduced by 41.70% (24 crews in the current collection system vs 14 in the system provided by the model). The total collection vehicle routing was also optimized such that the total travelled distances during night and day working shifts was cut back by 53%.