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- Genre: Academic theses
- Creators: Kusumi, Kenro
- Member of: Theses and Dissertations
Structural Equation Modeling (SEM) is a multivariate analysis methodology that could potentially be utilized to examine the barrier effect that river systems have on genetic differentiation. In this project, river systems are split into the variables of Daily Average Discharge, Average River Width, and Seasonality measurements and regressed onto the genetic differentiation, measured as Fst. This data was collected from the USGS database (U.S. Geological Survey, 2020), sequencing files from differing literature, or Google Earth measurements. Different Structural Equation Modeling models are used to model different system structures as well as compare it to more traditional methodologies like Generalized Linear Modeling and Generalized Linear Mixed Modeling. Ultimately results were limited by the small sample size, however, interesting patterns still emerged from the models. The SE models indicate that Discharge plays a primary role in the genetic differentiation of adjacent river populations. In addition to this, the results demonstrate how quantification of indirect effects, particularly those relating to discharge, give more informative interpretations than traditional multivariate statistics alone. These findings prompt further investigations into this potential methodology.
Monkeypox virus is a reemerging human pathogen. Despite a partial amino-terminal deletion in its E3 homolog, it does not activate PKR. In chapter 2, I show that MPXV produces less dsRNA than VACV, which could explain how the virus avoids activating PKR.
The amino-terminus of vaccinia is associated with ZNA binding, inhibition of PKR, and inhibition of necroptosis. To determine the roles of PKR inhibition and ZNA binding in necroptosis inhibition, I characterized the VACV mutants Za(ADAR1)-E3, which binds ZNA but does not inhibit PKR, and E3:Y48A, which cannot bind ZNA. I found that while Za(ADAR1)-E3 fails to induce necroptosis, E3:Y48A does not activate PKR but does induce necroptosis. This suggests that Z-form nucleic acid binding is not necessary for vaccinia E3-mediated inhibition of PKR, nor is the inhibition of PKR sufficient for the inhibition of necroptosis.
Finally, all known ZNA-binding proteins have immune functions and home to stress granules. I asked if stress granule formation alone could lead to necroptosis. I found that in L929 cells sodium arsenite, a known inducer of stress granules, could trigger DAI-dependent necroptosis. This suggests that DAI/ZBP1 is not necessarily a sensor of viral ligands but perhaps is a sensor of stress signals brought about by infection.