DMT1 Protects Macrophages from Salmonella Infection by Controlling Cellular Iron Turnover and Lipocalin 2 Expression

Macrophages are at the center of innate pathogen control and iron recycling. Divalent metal transporter 1 (DMT1) is essential for the uptake of non-transferrin-bound iron (NTBI) into macrophages and for the transfer of transferrin-bound iron from the endosome to the cytoplasm. As the control of cellular iron trafficking is central for the control of infection with siderophilic pathogens such as Salmonella Typhimurium, a Gram-negative bacterium residing within the phagosome of macrophages, we examined the potential role of DMT1 for infection control. Bone marrow derived macrophages lacking DMT1 (DMT1fl/fl^LysMCre(+)) present with reduced NTBI uptake and reduced levels of the iron storage protein ferritin, the iron exporter ferroportin and, surprisingly, of the iron uptake protein transferrin receptor. Further, DMT1-deficient macrophages have an impaired control of Salmonella Typhimurium infection, paralleled by reduced levels of the peptide lipocalin-2 (LCN2). LCN2 exerts anti-bacterial activity upon binding of microbial siderophores but also facilitates systemic and cellular hypoferremia. Remarkably, nifedipine, a pharmacological DMT1 activator, stimulates LCN2 expression in RAW264.7 macrophages, confirming its DMT1-dependent regulation. In addition, the absence of DMT1 increases the availability of iron for Salmonella upon infection and leads to increased bacterial proliferation and persistence within macrophages. Accordingly, mice harboring a macrophage-selective DMT1 disruption demonstrate reduced survival following Salmonella infection. This study highlights the importance of DMT1 in nutritional immunity and the significance of iron delivery for the control of infection with siderophilic bacteria.     

Simulation reality and stereotype strength: A problem for equipment designers

In designing human–machine interfaces, it may be necessary for designers to simulate the interface in order to find an acceptable arrangement of controls and displays which have a high expectancy of the relationship between these. We report experiments aimed at determining the level of simulation required to obtain valid measures of stereotype strength relating control movement to display movement. Two experiments are reported, using devices of apparently low and high complexity. Low complexity devices were similar to electronic devices that might be used in the home; the chosen high complexity device was a crane control cabin. For two-dimensional control/display arrangements a low level of simulation generally gave valid results for stereotype strength; a high level of simulation is required for three-dimensional arrangements. With the more complex crane control system, there was a strong effect of the control layout, but little effect of the level of simulation: paper/pencil tests performed as well as computer simulation in giving stereotype strengths. Implications for designers are discussed.     

Regulations and research on RC&S for hydrogen storage relevant to transport and vehicle issues with special focus on composite containments

Developers interested in high pressure storage of hydrogen for mobile use increasingly rely on composite cylinders for onboard storage or transport of dangerous goods. Thus, composite materials and systems deserve special consideration. History gives interesting background information important to the understanding of the current situation as to regulations, codes and standards.     

Water Penetration—Its Effect on the Strength and Toughness of Silica Glass

When a crack forms in silica glass, the surrounding environment flows into the crack opening, and water from the environment reacts with the glass to promote crack growth. A chemical reaction between water and the strained crack-tip bonds is commonly regarded as the cause of subcritical crack growth in glass. In silica glass, water can also have a secondary effect on crack growth. By penetrating into the glass, water generates a zone of swelling and, hence, creates a compression zone around the crack tip and on the newly formed fracture surfaces. This zone of compression acts as a fracture mechanics shield to the stresses at the crack tip, modifying both the strength and subcritical crack growth resistance of the glass. Water penetration is especially apparent in silica glass because of its low density and the fact that it contains no modifier ions. Using diffusion data from the literature, we show that the diffusion of water into silica glass can explain several significant experimental observations that have been reported on silica glass, including (1) the strengthening of silica glass by soaking the glass in water at elevated temperatures, (2) the observation of permanent crack face displacements near the crack tip of a silica specimen that had been soaked in water under load, and (3) the observation of high concentrations of water close to the fracture surfaces that had been formed in water. These effects are consistent with a model suggesting that crack growth in silica glass is modified by a physical swelling of the glass around the crack tip. An implication of water-induced swelling during fracture is that silica glass is more resistant to crack growth than it would be if swelling did not occur.     

Development and Performance of Crystallization with Additives Applied on Different Milk Samples

Crystallization with additives is developed on milk samples from different processing treatments. Performance tests are carried out based on structure analysis of the crystallization patterns. Crystallization with milk as additive is applied following changes in milk after different processing treatments. When an aqueous cupric chloride dihydrate solution crystallizes in the presence of milk as additive, specific patterns emerge, which can be evaluated by image analysis. Milk samples were heated and homogenized in a pilot plant and characterized by various parameters. Furthermore, milk samples from the market were tested. Patterns from milk after heat treatment and homogenization are significantly different from those derived from untreated milk. The experiments could be reproduced for other milk samples, on different days and in another laboratory.     

Residual tumor after laser ablation of human non-small-cell lung cancer demonstrated by ex vivo staining: correlation with invasive temperature measurements

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Histology is the gold standard for confirming thermally induced necrosis. Generally, however, no specimen is obtained from thermal ablation therapy for pathological examination. The aim of this study was to provide evidence for the relationship between temperatures reached and resulting tissue coagulation during laser ablation in a near-physiological ex vivo lung tumor model by combining viability staining and direct temperature measurement.