Project description:The gene expression levels in murine bone marrow-derived dendritic cells treated with γ-PGA NPs were examined by oligonucleitide microarray and compared with those in the cells treated with other adjuvants. The gene expression of proinflammatory chemokines, cytokines, and costimulatory molecules was upregulated considerably in DCs treated with γ-PGA NPs. The upregulation pattern was similar to that in DCs treated with LPS but not in DCs treated with unparticulate γ-PGA. The activation of DCs by γ-PGA NPs was confirmed by real-time RT-PCR analysis for the genes related to TLR signaling. The effect of γ-PGA NPs on DCs was not annihilated by treating with polymixin B, an inhibitor of LPS. Furthermore, the immunization of mice with γ-PGA NPs carrying OVA significantly induced Ag-specific CD8+ T cells and Ag-specific production of IL-2, TNF-α, and IFN-γ from the cells. Such activities of γ-PGA NPs were more prominent, when compared to the immunization with OVA plus aluminum hydroxide or OVA plus CFA. These results suggest that γ-PGA NPs induce a CD8+ T cell response through activating innate immunity in a fashion different from that of LPS. Thus, γ-PGA NPs may be an attractive adjuvant to be further developed for vaccine therapy.
Project description:Introgressed variants from other species can be an important source of genetic variation because they may arise rapidly, can include multiple mutations on a single haplotype, and have often been pretested by selection in the species of origin. Although introgressed alleles are generally deleterious, several studies have reported introgression as the source of adaptive alleles-including the rodenticide-resistant variant of Vkorc1 that introgressed from Mus spretus into European populations of Mus musculus domesticus. Here, we conducted bidirectional genome scans to characterize introgressed regions into one wild population of M. spretus from Spain and three wild populations of M. m. domesticus from France, Germany, and Iran. Despite the fact that these species show considerable intrinsic postzygotic reproductive isolation, introgression was observed in all individuals, including in the M. musculus reference genome (GRCm38). Mus spretus individuals had a greater proportion of introgression compared with M. m. domesticus, and within M. m. domesticus, the proportion of introgression decreased with geographic distance from the area of sympatry. Introgression was observed on all autosomes for both species, but not on the X-chromosome in M. m. domesticus, consistent with known X-linked hybrid sterility and inviability genes that have been mapped to the M. spretus X-chromosome. Tract lengths were generally short with a few outliers of up to 2.7 Mb. Interestingly, the longest introgressed tracts were in olfactory receptor regions, and introgressed tracts were significantly enriched for olfactory receptor genes in both species, suggesting that introgression may be a source of functional novelty even between species with high barriers to gene flow.
Project description:The gene expression levels in murine bone marrow-derived dendritic cells treated with γ-PGA NPs were examined by oligonucleitide microarray at 6, 12 and 24 hours. The gene expression of proinflammatory chemokines, cytokines, and costimulatory molecules was upregulated considerably in DCs treated with γ-PGA NPs at 6 hours.