Project description:Nitric oxide (NO) is implicated in the pathogenesis of various neuropathologies characterised by oxidative stress. NO has been reported to be involved in the exacerbation of oxidative stress by various mechanisms, including protein modification, genotoxic damage and elevated production of reactive oxygen species resulting in deregulation and disruption of cellular homeostasis. Although multiple roles for NO has been reported in neuronal death signaling, existent data fail to provide a holistic description of how nitrergic pathobiology elicits neuronal injury. Here we provide a comprehensive description of mechanisms contributing to NO-induced neuronal injury by global transcriptomic profiling.
Project description:Nitric oxide (NO) is implicated in the pathogenesis of various neuropathologies characterised by oxidative stress. NO has been reported to be involved in the exacerbation of oxidative stress by various mechanisms, including protein modification, genotoxic damage and elevated production of reactive oxygen species resulting in deregulation and disruption of cellular homeostasis. Although multiple roles for NO has been reported in neuronal death signaling, existent data fail to provide a holistic description of how nitrergic pathobiology elicits neuronal injury. Here we provide a comprehensive description of mechanisms contributing to NO-induced neuronal injury by global transcriptomic profiling. Microarray analysis was carried out using 14 GeneChip Mouse Genome 430 2.0 array (Affymetrix, Santa Clara, CA). The assignment of the arrays (GeneChip) was as follows: vehicle-treated control (n=5); NOC-18-treatment for 8, 15 and 24 hour (n=3 for each time-point).
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.