The susceptibility to and the severity of Bordetella pertussis infections in infants and children varies widely, suggesting that genetic differences between individuals influence the course of infection. We have previously identified three novel loci that influence the severity of whooping cough by using recombinant congenic strains of mice: Bordetella pertussis susceptibility loci 1, 2, and 3 (Bps1, -2, and -3). Because these loci could not account for all genetic differences between mice, we extended our search for additional susceptibility loci. We therefore screened 11 inbred strains of mice for susceptibility to a pertussis infection after intranasal infection. Susceptibility was defined by the number of bacteria in the lungs, being indicative of the effect between the clearance and replication of bacteria. The most resistant (A/J) and the most susceptible (C3H/HeJ) strains were selected for further genetic and phenotypic characterization. The link between bacterial clearance and chromosomal location was investigated with 300 F 2 mice, generated by crossing A/J and C3H/HeJ mice. We found a link between the delayed clearance of bacteria from the lung and a large part of chromosome 4 in F 2 mice with a maximum log of the odds score of 33.6 at 65.4 Mb, which is the location of Tlr4. C3H/HeJ mice carry a functional mutation in the intracellular domain of Tlr4. This locus accounted for all detectable genetic differences between these strains. Compared to A/J mice, C3H/HeJ mice showed a delayed clearance of bacteria from the lung, a higher relative lung weight, and increased body weight loss. Splenocytes from infected C3H/HeJ mice produced almost no interleukin-1␤ (IL-1␤) and tumor necrosis factor alpha (TNF-␣) upon ex vivo restimulation with B. pertussis compared to A/J mice and also showed a delayed gamma interferon (IFN-␥) production. TNF-␣ expression in the lungs 3 days after infection was increased fivefold compared to uninfected controls in A/J mice and was not affected in C3H/HeJ mice. In conclusion, Tlr4 is a major host factor explaining the differences in the course of infection between these inbred strains of mice. Functional Tlr4 is essential for an efficient IL-1-␤, TNF-␣, and IFN-␥ response; efficient clearance of bacteria from the lung; and reduced lung pathology.The clinical course of Bordetella pertussis infection varies widely. Knowledge about host genetic and immunological factors that influence susceptibility and severity of infection may lead to the identification of new approaches for prevention or treatment of this disease (13). Knowledge of human genetic factors that influence B. pertussis infection is still very limited. A number of studies have provided clues for the role of host genes in the susceptibility of mice to B. pertussis infection (4,11,19,23). We have recently shown that host genes of mice affect the clearance of bacteria from the lung and that B. pertussis infection is under multigenic control. This study resulted in the identification of three novel loci (Bps1 to -3) that inf...

The use of low-cost sensors for air quality measurements is expanding rapidly, with an associated rise in the number of citizens measuring air quality themselves. This has major implications for traditional air quality monitoring as performed by Environmental Protection Agencies. Here we reflect on the experiences of the Dutch Institute for Public Health and the Environment (RIVM) with the use of low-cost sensors, particularly NO2 and PM10/PM2.5-sensors, and related citizen science, over the last few years. Specifically, we discuss the Dutch Innovation Program for Environmental Monitoring, which comprises the development of a knowledge portal and sensor data portal, new calibration approaches for sensors, and modelling and assimilation techniques for incorporating these uncertain sensor data into air pollution models. Finally, we highlight some of the challenges that come with the use of low-cost sensors for air quality monitoring, and give some specific use-case examples. Our results show that low-cost sensors can be a valuable addition to traditional air quality monitoring, but so far, their use in official monitoring has been limited. More research is needed to establish robust calibration methods while ongoing work is also aimed at a better understanding of the public’s needs for air quality information to optimize the use of low-cost sensors.

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Producing sufficient, healthy food for a growing world population amid a changing climate is a major challenge for the twenty-first century. Agricultural trade could help alleviate this challenge by using comparative productivity advantages between countries. However, agricultural trade has implications for national food security and could displace environmental impacts from developed to developing countries. This study illustrates the global effects resulting from the agricultural trade of a single country, by analysing the global cropland and greenhouse gas impacts of the UK's food and feed supply. The global cropland footprint associated with the UK food and feed supply increased by 2022 kha (þ23%) from 1986 to 2009. Greenhouse gas emissions (GHGE) associated with fertilizer and manure application, and rice cultivation remained relatively constant at 7.9 Mt CO 2 e between 1987 and 2008. Including GHGE from land-use change, however, leads to an increase from 19.1 in 1987 to 21.9 Mt CO 2 e in 2008. The UK is currently importing over 50% of its food and feed, whereas 70% and 64% of the associated cropland and GHGE impacts, respectively, are located abroad. These results imply that the UK is increasingly reliant on external resources and that the environmental impact of its food supply is increasingly displaced overseas.