66 research outputs found

    Whole-blood transcriptomic signatures induced during immunization by chloroquine prophylaxis and Plasmodium falciparum sporozoites

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    A highly effective vaccine that confers sterile protection to malaria is urgently needed. Immunization under chemoprophylaxis with sporozoites (CPS) consistently confers high levels of protection in the Controlled Human Malaria infection (CHMI) model. To provide a broad, unbiased assessment of the composition and kinetics of direct ex vivo human immune responses to CPS, we profiled whole-blood transcriptomes by RNA-seq before and during CPS immunization and following CHMI challenge. Differential expression of genes enriched in modules related to T cells, NK cells, protein synthesis, and mitochondrial processes were detected in fully protected individuals four weeks after the first immunization. Non-protected individuals demonstrated transcriptomic changes after the third immunization and the day of treatment, with upregulation of interferon and innate inflammatory genes and downregulation of B-cell signatures. Protected individuals demonstrated more significant interactions between blood transcription modules compared to non-protected individuals several weeks after the second and third immunizations. These data provide insight into the molecular and cellular basis of CPS-induced immune protection from P. falciparum infection

    A new model for non-typeable Haemophilus influenzae middle ear infection in the Junbo mutant mouse

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    Acute otitis media, inflammation of the middle ear, is the most common bacterial infection in children and, as a consequence, is the most common reason for antimicrobial prescription to this age group. There is currently no effective vaccine for the principal pathogen involved, non-typeable Haemophilus influenzae (NTHi). The most frequently used and widely accepted experimental animal model of middle ear infection is in chinchillas, but mice and gerbils have also been used. We have established a robust model of middle ear infection by NTHi in the Junbo mouse, a mutant mouse line that spontaneously develops chronic middle ear inflammation in specific pathogen-free conditions. The heterozygote Junbo mouse (Jbo/+) bears a mutation in a gene (Evi1, also known as Mecom) that plays a role in host innate immune regulation; pre-existing middle ear inflammation promotes NTHi middle ear infection. A single intranasal inoculation with NTHi produces high rates (up to 90%) of middle ear infection and bacterial titres (104-105 colony-forming units/µl) in bulla fluids. Bacteria are cleared from the majority of middle ears between day 21 and 35 post-inoculation but remain in approximately 20% of middle ears at least up to day 56 post-infection. The expression of Toll-like receptor-dependent response cytokine genes is elevated in the middle ear of the Jbo/+ mouse following NTHi infection. The translational potential of the Junbo model for studying antimicrobial intervention regimens was shown using a 3 day course of azithromycin to clear NTHi infection, and its potential use in vaccine development studies was shown by demonstrating protection in mice immunized with killed homologous, but not heterologous, NTHi bacteria

    Strangers in a strange land: relations between perceptions of others' values and both civic engagement and cultural estrangement

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    Healthy democracies require civic engagement (e.g., voting) from their citizens. Past research has suggested that civic engagement is positively associated with self-transcendence values of care and concern for the welfare of others, and negatively associated with self-enhancement values of self-interest, dominance, and personal success. However, research has yet to address whether people's perceptions of others' values are related to civic engagement. Across three studies with nationally representative samples in the UK and US (Ns ≥ 1,000), we explored how civic engagement relates to (a) perceptions of national values, (b) perceptions of the values of one's typical compatriot, and (c) perceptions of the values encouraged by social and cultural institutions. Study 1 showed that the tendency for British citizens to perceive British culture as valuing self-transcendence was associated with an increased likelihood of voting in the 2015 general election. These findings were replicated for “a typical British person” (Study 2) and “a typical American person” (Study 3); Studies 2 and 3 also found that perceived self-enhancement values of typical compatriots were negatively correlated with reported voting. We also examined how perceptions of others' values relate to cultural estrangement—the feeling of not fitting in one's culture or of being atypical. Like civic engagement, those who perceived less self-transcendence and more self-enhancement in their culture felt more culturally estranged. Mediation analyses in Studies 2 and 3 revealed that estrangement helped to explain the relationship between perceptions of others' values and voting. In sum, the extent to which Brits and Americans perceive that self-transcendence values are strongly held by other citizens is associated with feeling less estranged and with reports of being more civically engaged. In contrast, the perception that these targets hold or promote self-enhancement values is positively associated with feelings of estrangement, to the detriment of civic engagement. Implications for future research and democratic processes are discussed

    The impact of using novel equations to predict nitrogen excretion and associated emissions from pasture-based beef production systems

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    Excretion of nitrogen (N) in faeces and urine from beef cattle contributes to atmospheric pollution through greenhouse gas and ammonia emissions and eutrophication of land and aquatic habitats through excessive N deposition and nitrate leaching to groundwater. As N excretion by beef cattle is rarely measured directly, it is important to accurately predict losses utilising a combined knowledge of diet and production parameters so that the effect of dietary changes on the potential environmental impact of beef production systems can be estimated. This study aimed to identify differences between IPCC and more detailed country-specific models in the prediction of N excretion and N losses at a system level and determine how the choice of model influences the interpretation of differences in diet at the system scale. The data used in this study were derived from a farm-scale experimental system consisting of three individual grazing farms, each with a different sward type: permanent pasture, a high sugar ryegrass monoculture, and a high sugar ryegrass with white clover (~30% groundcover). Data were analysed using a mixed linear model (residual maximum likelihood analysis). The IPCC methods demonstrated significantly lower estimates of N excretion than country-specific models for the first housing period and significantly greater losses for the grazing and second housing periods. The country-specific models enabled prediction of N partitioning to urine and faeces, important for estimation of subsequent N losses through the production system, although the models differed in their estimates. Overall, predicted N losses were greater using the IPCC approaches compared to using more detailed country-specific approaches. The outcomes of the present study have highlighted that different models can have a substantial impact on the predicted N outputs and subsequent losses to the environment for pasture-based beef finishing systems, and the importance, therefore, of using appropriate models and parameters

    The impact of using novel equations to predict nitrogen excretion and associated emissions from pasture-based beef production systems.

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    Publication history: Accepted - 6 June 2022; Published online - 14 June 2022The excretion of nitrogen (N) in faeces and urine from beef cattle contributes to atmospheric pollution through greenhouse gas and ammonia emissions and eutrophication of land and aquatic habitats through excessive N deposition and nitrate leaching to groundwater. As N excretion by beef cattle is rarely measured directly, it is important to accurately predict losses by utilising a combined knowledge of diet and production parameters so that the effect of dietary changes on the potential environmental impact of beef production systems can be estimated. This study aimed to identify differences between IPCC and more detailed country-specific models in the prediction of N excretion and N losses at a system level and determine how the choice of model influences the interpretation of differences in diet at the system scale. The data used in this study were derived from a farm-scale experimental system consisting of three individual grazing farms, each with a different sward type: a permanent pasture, a high sugar ryegrass monoculture, and a high sugar ryegrass with white clover (~30% groundcover). Data were analysed using a mixed linear model (residual maximum likelihood analysis). The IPCC methods demonstrated significantly lower estimates of N excretion than country-specific models for the first housing period and significantly greater losses for the grazing and second housing periods. The country-specific models enabled prediction of N partitioning to urine and faeces, which is important for estimation of subsequent N losses through the production system, although the models differed in their estimates. Overall, predicted N losses were greater using the IPCC approaches compared to using more detailed country-specific approaches. The outcomes of the present study have highlighted that different models can have a substantial impact on the predicted N outputs and subsequent losses to the environment for pasture-based beef finishing systems, and the importance, therefore, of using appropriate models and parametersThe authors would like to acknowledge funding support from the University of Reading, Rothamsted Research, and UK Biotechnology and Biological Sciences Research Council (BBS/E/C/000I0320). The NWFP is a UK National Capability, also supported by the Biotechnology and Biological Sciences Research Council (BBS/E/C/000J0100)

    Transcriptomic evidence for modulation of host inflammatory responses during febrile Plasmodium falciparum malaria

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    Identifying molecular predictors and mechanisms of malaria disease is important for understanding how Plasmodium falciparum malaria is controlled. Transcriptomic studies in humans have so far been limited to retrospective analysis of blood samples from clinical cases. In this prospective, proof-of-principle study, we compared whole-blood RNA-seq profiles at pre-and post-infection time points from Malian adults who were either asymptomatic (n = 5) or febrile (n = 3) during their first seasonal PCR-positive P. falciparum infection with those from malaria-naïve Dutch adults after a single controlled human malaria infection (n = 5). Our data show a graded activation of pathways downstream of pro-inflammatory cytokines, with the highest activation in malaria-naïve Dutch individuals and significantly reduced activation in malaria-experienced Malians. Newly febrile and asymptomatic infections in Malians were statistically indistinguishable except for genes activated by pro-inflammatory cytokines. The combined data provide a molecular basis for the development of a pyrogenic threshold as individuals acquire immunity to clinical malaria

    The Perception of Family, City, and Country Values Is Often Biased

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    People often make inferences about the values of other people in their families, cities, and countries, but there are reasons to expect systematic biases in these inferences. Across four studies ( N = 1,763), we examined people’s perceptions of the values of their families, fellow citizens of the cities in which they live, and compatriots across three nations (Brazil, Germany, the United Kingdom). Our results show that people systematically misperceive comparison groups’ values. People underestimate the importance that their compatriots ascribe to more important values and overestimate the importance of less important values. This occurs in comparison with their own values, the actual values of the people living in the same city and the actual values of their compatriots. The effect sizes were medium to large. Furthermore, the results occurred independently of participants’ culture, time spent in the culture, and the underlying value model used. These results consistently show that people’s speculations about values in their community and society are biased in a self- and family favoring direction. In addition, we found that the structure of values (e.g., as proposed by Schwartz) holds for perceived family, fellow citizens of the cities in which they live, and compatriots’ values. Overall, our findings suggest that the values of other people are more selfless than is often believed
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