Ca2+ Influx and Tyrosine Kinases Trigger Bordetella Adenylate Cyclase Toxin (ACT) Endocytosis. Cell Physiology and Expression of the CD11b/CD18 Integrin Major Determinants of the Entry Route

Humans infected with Bordetella pertussis, the whooping cough bacterium, show evidences of impaired host defenses. This pathogenic bacterium produces a unique adenylate cyclase toxin (ACT) which enters human phagocytes and catalyzes the unregulated formation of cAMP, hampering important bactericidal functions of these immune cells that eventually cause cell death by apoptosis and/or necrosis. Additionally, ACT permeabilizes cells through pore formation in the target cell membrane. Recently, we demonstrated that ACT is internalised into macrophages together with other membrane components, such as the integrin CD11b/CD18 (CR3), its receptor in these immune cells, and GM1. The goal of this study was to determine whether ACT uptake is restricted to receptor-bearing macrophages or on the contrary may also take place into cells devoid of receptor and gain more insights on the signalling involved. Here, we show that ACT is rapidly eliminated from the cell membrane of either CR3-positive as negative cells, though through different entry routes, which depends in part, on the target cell physiology and characteristics. ACT-induced Ca2+ influx and activation of non-receptor Tyr kinases into the target cell appear to be common master denominators in the different endocytic strategies activated by this toxin. Very importantly, we show that, upon incubation with ACT, target cells are capable of repairing the cell membrane, which suggests the mounting of an anti-toxin cell repair-response, very likely involving the toxin elimination from the cell surface.

Agent based modeling of energy networks

Attempts to model any present or future power grid face a huge challenge because a power grid is a complex system, with feedback and multi-agent behaviors, integrated by generation, distribution, storage and consumption systems, using various control and automation computing systems to manage electricity flows. Our approach to modeling is to build upon an established model of the low voltage electricity network which is tested and proven, by extending it to a generalized energy model. But, in order to address the crucial issues of energy efficiency, additional processes like energy conversion and storage, and further energy carriers, such as gas, heat, etc., besides the traditional electrical one, must be considered. Therefore a more powerful model, provided with enhanced nodes or conversion points, able to deal with multidimensional flows, is being required. This article addresses the issue of modeling a local multi-carrier energy network. This problem can be considered as an extension of modeling a low voltage distribution network located at some urban or rural geographic area. But instead of using an external power flow analysis package to do the power flow calculations, as used in electric networks, in this work we integrate a multiagent algorithm to perform the task, in a concurrent way to the other simulation tasks, and not only for the electric fluid but also for a number of additional energy carriers. As the model is mainly focused in system operation, generation and load models are not developed.