One of the potential risk factors of recombinant adeno-associated virus (rAAV)-based gene therapy is insertional mutagenesis, which has been associated with the development of hepatocellular carcinoma (HCC) in rAAV-treated neonatal mice. The objective of this study was to investigate if well-established in vitro cell transformation assays (CTA) in mouse cell lines can detect AAV2 or AAVdj-mediated cell transformation. Since AAV integration at the Rian locus in neonatal mice has been implicated in AAV-mediated HCC, an rAAV vector specifically targeting the mouse Rian locus and an additional rAAV vector previously shown to cause HCC in neonatal mice were both tested for the induction of cell transformation in NIH3T3 cells.
View Article and Find Full Text PDFPlant genebanks contain large numbers of germplasm accessions that likely harbor useful alleles or genes absent in commercial plant breeding programs. Broadening the genetic base of commercial alfalfa germplasm with these valuable genetic variations can be achieved by screening the extensive genetic diversity in germplasm collections and enabling maximal recombination among selected genotypes. In this study, we assessed the genetic diversity and differentiation of germplasm pools selected in northern U.
View Article and Find Full Text PDFContingency (or "luck") in early life plays an important role in shaping individuals' development. By comparing the developmental trajectories of functionally genetically identical free-living mice who either experienced high levels of resource competition (males) or did not (females), we show that competition magnifies early contingency. Male resource competition results in a feedback loop that magnifies the importance of early contingency and pushes individuals onto divergent, self-reinforcing life trajectories, while the same process appears absent in females.
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