Project description:We found that co-culturing BNL CL.2 liver cells with RAW 264.7 macrophages increased IRP binding in the first. To further investigate this modulation we investigated the gene expression profile in BNL CL.2 cells cultured alone, with iron, with RAW 264.7 macrophages or in the presence of both iron and macrophages. This novel reconstituted liver cell-macrophage communication pathway with the present gene expression data provides a platform for addressing how macrophages participate in the iron homeostasis of liver cells and, ultimately, in systemic iron homeostasis.
Project description:We found that co-culturing BNL CL.2 liver cells with RAW 264.7 macrophages increased IRP binding in the first. To further investigate this modulation we investigated the gene expression profile in BNL CL.2 cells cultured alone, with iron, with RAW 264.7 macrophages or in the presence of both iron and macrophages. This novel reconstituted liver cell-macrophage communication pathway with the present gene expression data provides a platform for addressing how macrophages participate in the iron homeostasis of liver cells and, ultimately, in systemic iron homeostasis. We used microarrays to determine the gene expression modulation in BNL CL.2 cells in response to 24h culture with 100 micromolar ferric ammonium citrate (FAC), co-culture with RAW 264.7 macrophages or both
Project description:We collected whole genome testis expression data from hybrid zone mice. We integrated GWAS mapping of testis expression traits and low testis weight to gain insight into the genetic basis of hybrid male sterility.
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:Acute kidney disease caused by ischemia-reperfusion (IRI-AKI) is characterized by ectopic inflammation and tubular injury, in which macrophage infiltration and inflammatory activation play a critical pathogenic role. Calycosin is an active flavone from the root of Astragalus membranaceus and shows anti-inflammatory effects in various diseases. In this study, we investigated the renoprotective role of calycosin against IRI-AKI and the underlying mechanism. Our results showed that calycosin treatment reduced the levels of serum creatinine and urea nitrogen along with attenuated tubular necrosis and cast formation in IRI-AKI mice. Calycosin significantly suppressed the activation of NF-κB signaling and the expression of inflammatory mediators IL-1β and TNF-α in IRI-AKI kidneys. In vitro, calycosin inhibited LPS-induced inflammatory activation in RAW 264.7 cells. Interestingly, RNA-seq revealed that calycosin remarkably down-regulated chemotaxis-related pathways in RAW 264.7 cells. Among the differentially expressed genes, Ccl2/MCP-1, a critical chemokine mediating macrophage inflammatory chemotaxis, was down-regulated in both LPS-stimulated RAW 264.7 cells and IRI-AKI kidneys. Consistently, calycosin treatment attenuated macrophage infiltration in the IRI-AKI kidneys. Importantly, in combination with target prediction, molecular docking, and surface plasmon resonance, we showed that calycosin can directly bind to macrophage migration inhibitory factor (MIF). Functionally, calycosin abrogated MIF-stimulated NF-κB signaling activation and Ccl2 expression and MIF-mediated chemotaxis in RAW 264.7 cells without influencing its expression. Collectively, calycosin protects from IRI-AKI by suppressing MIF-mediated macrophage inflammatory chemotaxis. Calycosin could be a promising candidate medicine for clinical treatment of IRI-AKI.