Aims/hypothesis Increased exposure to enteric microbes as a result of intestinal barrier disruption is thought to contribute to the development of several intestinal inflammatory diseases; however, it less clear whether such exposure modulates the development of extra-intestinal inflammatory and autoimmune diseases. The goal of this study was to examine the potential role of pathogenic enteric microbes and intestinal barrier dysfunction in the pathogenesis of type 1 diabetes. Methods Using NOD mice, we assessed: (1) intrinsic barrier function in mice at different ages by measuring serum levels of FITC-labelled dextran; and (2) the impact on insulitis development of infection by strains of an enteric bacterial pathogen (Citrobacter rodentium) either capable (wild-type) or incapable (lacking Escherichia coli secreted protein F virulence factor owing to deletion of the gene [ΔespF]) of causing intestinal epithelial barrier disruption. Results Here we demonstrate that prediabetic (12-weekold) NOD mice display increased intestinal permeability compared with non-obese diabetes-resistant and C57BL/6 mice. We also found that young (4-week-old) NOD mice infected with wild-type C. rodentium exhibited accelerated development of insulitis in concert with infection-induced barrier disruption. In contrast, insulitis development was not altered in NOD mice infected with the non-barrier-disrupting ΔespF strain. Moreover, C. rodentium-infected NOD mice demonstrated increased activation and proliferation of pancreatic-draining lymph node T cells, including diabetogenic CD8 + T cells, compared with uninfected NOD mice. Conclusions/interpretation This is the first demonstration that a loss of intestinal barrier integrity caused by an enteric bacterial pathogen results in the activation of diabetogenic CD8 + T cells and modulates insulitis.

This study compared parr from three strains of rainbow trout Oncorhynchus mykiss to examine intraspecific variation in metabolic traits, hypoxia tolerance and upper thermal tolerance in this species. At the strain level, variation in absolute aerobic scope (AAS), critical oxygen level (O ), incipient lethal oxygen saturation (ILOS) and critical thermal maximum (CT ) generally exhibited consistent differences among the strains, suggesting the possibility of functional associations among these traits. This possibility was further supported at the individual level by a positive correlation between ILOS and O and a negative correlation between O and AAS. These results indicate that intraspecific differences in hypoxia tolerance among strains of O. mykiss may be primarily determined by differences in the ability to maintain oxygen uptake in hypoxia and that variation in aerobic scope in normoxia probably plays a role in determining the ability of these fish to sustain metabolism aerobically as water oxygen saturation is reduced.

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A design approach of extending the anode zone for miniaturization of the fuel cells was investigated in an air-breathing micro-direct methanol fuel cell (mDMFC) with an extended anode catalyst region on the walls of the fuel flow channel. This non-conventional design is demonstrated to be a feasible approach to enhance the volumetric power density of a micro-direct methanol fuel cell by increasing the total anode catalyst amount without affecting the cell dimensions. The fuel cell with extra anode catalyst on the fuel channel walls improves the maximum power density of a micro-fuel cell by at least 20% compared to the conventional design with only a catalyst coated membrane (CCM). The effects of key operating conditions on the overall cell and individual electrode performances are examined. The mass transport of methanol to the catalyst active sites is more efficient in the fuel cell with anode catalyst on both the membrane and channel walls than the conventional fuel cell design with anode catalyst only on the membrane.