BackgroundThere are over 200 million reported cases of malaria each year, and most children living in endemic areas will experience multiple episodes of clinical disease before puberty. We set out to understand how frequent clinical malaria, which elicits a strong inflammatory response, affects the immune system and whether these modifications are observable in the absence of detectable parasitaemia.MethodsWe used a multi-dimensional approach comprising whole blood transcriptomic, cellular and plasma cytokine analyses on a cohort of children living with endemic malaria, but uninfected at sampling, who had been under active surveillance for malaria for 8 years. Children were categorised into two groups depending on the cumulative number of episodes experienced: high (≥ 8) or low (< 5).ResultsWe observe that multiple episodes of malaria are associated with modification of the immune system. Children who had experienced a large number of episodes demonstrated upregulation of interferon-inducible genes, a clear increase in circulating levels of the immunoregulatory cytokine IL-10 and enhanced activation of neutrophils, B cells and CD8+ T cells.ConclusionTranscriptomic analysis together with cytokine and immune cell profiling of peripheral blood can robustly detect immune differences between children with different numbers of prior malaria episodes. Multiple episodes of malaria are associated with modification of the immune system in children. Such immune modifications may have implications for the initiation of subsequent immune responses and the induction of vaccine-mediated protection.Electronic supplementary materialThe online version of this article (10.1186/s12916-019-1292-y) contains supplementary material, which is available to authorized users.

Weeds represent a significant threat to crop yields and global food security. We analysed data on weed competition from the world's longest running agricultural experiment to ask whether potential yield losses from weeds have increased in response to management and environmental change since the advent of the Green Revolution in the 1960s. On plots where inorganic nitrogen fertiliser has been applied, potential yield losses from weeds have consistently increased since 1969. This was explained by a warming climate, measured as air temperature averaged over the growing season for the weeds, and a shift towards shorter crop cultivars. Weeds also reduced yield proportionally more on plots with higher rates of nitrogen which had higher yields when weeds were controlled; the relative benefit of herbicides was, therefore, proportional to potential crop yield. Reducing yield losses from weed competition is increasingly challenging because of the evolution of herbicide resistance. Our results demonstrate that weeds now represent a greater inherent threat to crop production than before the advent of herbicides and integrated, sustainable solutions to weed management are urgently needed to protect the high yield potential of modern crop genotypes.

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Background Plasmodium interspersed repeat (pir) is the largest multigene family in the genomes of most Plasmodium species. A variety of functions for the PIR proteins which they encode have been proposed, including antigenic variation, immune evasion, sequestration and rosetting. However, direct evidence for these is lacking. The repetitive nature of the family has made it difficult to determine function experimentally. However, there has been some success in using gene expression studies to suggest roles for some members in virulence and chronic infection. Methods Here pir gene expression was examined across the life cycle of Plasmodium berghei using publicly available RNAseq data-sets, and at high resolution in the intraerythrocytic development cycle using new data from Plasmodium chabaudi. Results Expression of pir genes is greatest in stages of the parasite which invade and reside in red blood cells. The marked exception is that liver merozoites and male gametocytes produce a very large number of pir gene transcripts, notably compared to female gametocytes, which produce relatively few. Within the asexual blood stages different subfamilies peak at different times, suggesting further functional distinctions. Representing a subfamily of its own, the highly conserved ancestral pir gene warrants further investigation due to its potential tractability for functional investigation. It is highly transcribed in multiple life cycle stages and across most studied Plasmodium species and thus is likely to play an important role in parasite biology. Conclusions The identification of distinct expression patterns for different pir genes and subfamilies is likely to provide a basis for the design of future experiments to uncover their function.