The regulation of IL-10 expression

Interleukin (IL)-10 is an important immunoregulatory cytokine and an understanding of how IL-10 expression is controlled is critical in the design of immune intervention strategies. IL-10 is produced by almost all cell types within the innate (including macrophages, monocytes, dendritic cells (DCs), mast cells, neutrophils, eosinophils and natural killer cells) and adaptive (including CD4(+) T cells, CD8(+) T cells and B cells) immune systems. The mechanisms of IL-10 regulation operate at several stages including chromatin remodelling at the Il10 locus, transcriptional regulation of Il10 expression and post-transcriptional regulation of Il10 mRNA. In addition, whereas some aspects of Il10 gene regulation are conserved between different immune cell types, several are cell type- or stimulus-specific. Here, we outline the complexity of IL-10 production by discussing what is known about its regulation in macrophages, monocytes, DCs and CD4(+) T helper cells

Metapopulation structure for perpetuation of Francisella tularensis tularensis

<p>Abstract</p> <p>Background</p> <p>Outbreaks of Type A tularemia due to <it>Francisella tularensis tularensis </it>are typically sporadic and unstable, greatly hindering identification of the determinants of perpetuation and human risk. Martha's Vineyard, Massachusetts has experienced an outbreak of Type A tularemia which has persisted for 9 years. This unique situation has allowed us to conduct long-term eco-epidemiologic studies there. Our hypothesis is that the agent of Type A tularemia is perpetuated as a metapopulation, with many small isolated natural foci of transmission. During times of increased transmission, the foci would merge and a larger scale epizootic would occur, with greater likelihood that humans become exposed.</p> <p>Methods</p> <p>We sampled questing dog ticks from two natural foci on the island and tested them for tularemia DNA. We determined whether the force of transmission differed between the two foci. In addition, we examined the population structure of <it>F. tularensis </it>from ticks by variable number tandem repeat (VNTR) analysis, which allowed estimates of diversity, linkage disequilibrium, and eBURST analysis.</p> <p>Results</p> <p>The prevalence of tularemia DNA in ticks from our two field sites was markedly different: one site was stable over the course of the study yielding as many as 5.6% positive ticks. In contrast, infected ticks from the comparison site markedly increased in prevalence, from 0.4% in 2003 to 3.9% in 2006. Using 4 VNTR loci, we documented 75 different haplotypes (diversity = 0.91). eBURST analysis indicates that the stable site was essentially clonal, but the comparison site contained multiple unrelated lineages. The general bacterial population is evolving clonally (multilocus disequilibrium) and the bacteria in the two sites are reproductively isolated.</p> <p>Conclusion</p> <p>Even within an isolated island, tularemia natural foci that are no more than 15 km apart are uniquely segregated. One of our sites has stable transmission and the other is emergent. The population structure at the stable site is that of a clonal complex of circulating bacteria, whereas the emerging focus is likely to be derived from multiple founders. We conclude that the agent of tularemia may perpetuate in small stable natural foci and that new foci emerge as a result of spillover from such stable sites.</p

Improving accuracy of genomic prediction by genetic architecture based priors in a Bayesian model

BACKGROUND: In recent years, with the development of high-throughput sequencing technology and the commercial availability of genotyping bead chips, more attention is being directed towards the utilization of abundant genetic markers in animal and plant breeding programs, human disease risk prediction and personal medicine. Several useful approaches to accomplish genomic prediction have been developed and used widely, but still have room for improvement to gain more accuracy. In this study, an improved Bayesian approach, termed BayesBπ, which differs from the original BayesB in priors assigning, is proposed. An effective method for calculating the locus-specific π by converting p-values from association between SNPs and traits’ phenotypes is given and systemically validated using a German Holstein dairy cattle population. Furthermore, the new method is applied to a loblolly pine (Pinus taeda) dataset. RESULTS: Compared with the original BayesB, BayesBπ can improve the accuracy of genomic prediction up to 7.62 % for milk fat percentage, a trait which shows a large effect of quantitative trait loci (QTL). For milk yield, which is controlled by small to moderate effect genes, the accuracy of genomic prediction can be improved up to 4.94 %. For somatic cell score, of which no large effect QTL has been reported, GBLUP performs better than Bayesian methods. BayesBπ outperforms BayesCπ in 10 out of 12 scenarios in the dairy cattle population, especially in small to moderate population sizes where accuracy of BayesCπ are dramatically low. Results of the loblolly pine dataset show that BayesBπ outperforms BayesB in 14 out of 17 traits and BayesCπ in 8 out of 17 traits, respectively. CONCLUSIONS: For traits controlled by large effect genes, BayesBπ can improve the accuracy of genomic prediction and unbiasedness of BayesB in moderate size populations. Knowledge of traits’ genetic architectures can be integrated into practices of genomic prediction by assigning locus-specific priors to markers, which will help Bayesian approaches perform better in variable selection and marker effects shrinkage. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12863-015-0278-9) contains supplementary material, which is available to authorized users

Spatial variability in oceanic redox structure 1.8 billion years ago

The evolution of ocean chemistry during the Proterozoic eon (2.5-0.542 billion years ago) is thought to have played a central role in both the timing and rate of eukaryote evolution(1,2). The timing of the deposition of iron formations implies that, early in the Earth's history, oceans were predominantly anoxic and rich in dissolved iron(3). However, global deposition of iron formations ceased about 1.84 billion years ago. This termination indicates a major upheaval in ocean chemistry(4), but the precise nature of this change remains debated(5-8). Here we use iron and sulphur systematics to reconstruct oceanic redox conditions from the 1.88- to 1.83-billion-year-old Animikie group from the Superior region, North America. We find that surface waters were oxygenated, whereas at mid-depths, anoxic and sulphidic (euxinic) conditions extended over 100 km from the palaeoshoreline. The spatial extent of euxinia varied through time, but deep ocean waters remained rich in dissolved iron. Widespread euxinia along continental margins would have removed dissolved iron from the water column through the precipitation of pyrite, which would have reduced the supply of dissolved iron and resulted in the global cessation of the deposition of 'Superior-type' iron formations. We suggest that incursions of sulphide from the mid-depths into overlying oxygenated surface waters may have placed severe constraints on eukaryotic evolution.The evolution of ocean chemistry during the Proterozoic eon (2.5–0.542 billion years ago) is thought to have played a central role in both the timing and rate of eukaryote evolution1,2. The timing of the deposition of iron formations implies that, early in the Earth’s history, oceans were predominantly anoxic and rich in dissolved iron3. However, global deposition of iron formations ceased about 1.84 billion years ago. This termination indicates a major upheaval in ocean chemistry4, but the precise nature of this change remains debated5,6,7,8. Here we use iron and sulphur systematics to reconstruct oceanic redox conditions from the 1.88- to 1.83-billion-year-old Animikie group from the Superior region, North America. We find that surface waters were oxygenated, whereas at mid-depths, anoxic and sulphidic (euxinic) conditions extended over 100 km from the palaeoshoreline. The spatial extent of euxinia varied through time, but deep ocean waters remained rich in dissolved iron. Widespread euxinia along continental margins would have removed dissolved iron from the water column through the precipitation of pyrite, which would have reduced the supply of dissolved iron and resulted in the global cessation of the deposition of ‘Superior-type’ iron formations. We suggest that incursions of sulphide from the mid-depths into overlying oxygenated surface waters may have placed severe constraints on eukaryotic evolution