One outcome of interspecific hybridization and subsequent effects of evolutionary forces is introgression, which is the integration of genetic material from one species into the genome of an individual in another species. The evolution of several groups of eukaryotic species has involved hybridization, and cases of adaptation through introgression have been already established. In this work, we report on PhyloNet-HMM—a new comparative genomic framework for detecting introgression in genomes. PhyloNet-HMM combines phylogenetic networks with hidden Markov models (HMMs) to simultaneously capture the (potentially reticulate) evolutionary history of the genomes and dependencies within genomes. A novel aspect of our work is that it also accounts for incomplete lineage sorting and dependence across loci. Application of our model to variation data from chromosome 7 in the mouse (Mus musculus domesticus) genome detected a recently reported adaptive introgression event involving the rodent poison resistance gene Vkorc1, in addition to other newly detected introgressed genomic regions. Based on our analysis, it is estimated that about 9% of all sites within chromosome 7 are of introgressive origin (these cover about 13 Mbp of chromosome 7, and over 300 genes). Further, our model detected no introgression in a negative control data set. We also found that our model accurately detected introgression and other evolutionary processes from synthetic data sets simulated under the coalescent model with recombination, isolation, and migration. Our work provides a powerful framework for systematic analysis of introgression while simultaneously accounting for dependence across sites, point mutations, recombination, and ancestral polymorphism.
Peripheral arterial disease (PAD) is a progressive atherosclerotic disorder characterized by narrowing and occlusion of arteries supplying the lower extremities. Approximately 200 million people worldwide are affected by PAD. The current standard of operative care is open or endovascular revascularization in which blood flow restoration is the goal. However, many patients are not appropriate candidates for these treatments and are subject to continuous ischemia of their lower limbs. Current research in the therapy of PAD involves developing modalities that induce angiogenesis, but the results of simple cell transplantation or growth factor delivery have been found to be relatively poor mainly due to difficulties in stem cell retention and survival and rapid diffusion and enzymolysis of growth factors following injection of these agents in the affected tissues. Biomaterials, including hydrogels, have the capability to protect stem cells during injection and to support cell survival. Hydrogels can also provide a sustained release of growth factors at the injection site. This review will focus on biomaterial systems currently being investigated as carriers for cell and growth factor delivery, and will also discuss biomaterials as a potential stand-alone method for the treatment of PAD. Finally, the challenges of development and use of biomaterials systems for PAD treatment will be reviewed.
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