TP53 mutations in myelodysplastic syndrome and acute myeloid leukemia differ significantly in distribution and functional consequences. These differences suggest distinct biological roles for mutated p53 in initiation of myeloid dysplasia and progression to acute leukemia.
Identified the production rate of interferon as the major driver of strain-specific immune responses observed in mice infected with low-pathogenic H1N1 or high-pathogenic H5N1 influenza viruses using mathematical modeling. Uncovering the relationship between the viral load and lung epithelial interferon production as the main source of variance between infection outcomes can be used to guide treatment development and improve clinical outcomes of infections with high-pathogenic viral strains.
Over the past several years, micromobility devices—small-scale, networked vehicles used to travel short distances—have begun to pervade cities, bringing promises of sustainable transportation and decreased congestion. Drawing on interviews with disabled activists, government officials, and commercial representatives, we chart how devices and policies co-evolve to fulfill municipal sustainability goals, while creating obstacles for people with disabilities whose activism has long resisted inaccessible infrastructure. We reflect on efforts to redistribute space, institute tech governance, and offer accountability to those who involuntarily encounter interventions on the ground.
8 proteins are prioritized as possible drug repositioning targets for SARS-CoV-2 where two, PVR and SCARB1, are previously unexplored. Known compounds targeting these genes are suggested for viral inhibition study. Prioritized proteins in agreement with previous analysis and viral inhibition studies verify the ability of network controllability to predict biologically relevant candidates using small amounts of virus-specific data.
Identified 24 proteins as holding regulatory roles specific to the infected cell by measures of topology, controllability, and functional role. This research aims to increase the efficiency of antiviral drug target discovery using existing protein-protein interaction data and network analysis methods.
Developed a mechanism-based mathematical model to compare the immune dynamics invoked by deadly H5N1 and moderately pathogenic H1N1 influenza viruses to aid in clinical understanding of infection severity. Results suggest that the kinetics of the immune response, specifically those related to the virus as well as those involved in interferon production, differ between H1N1 and H5N1 infections.
Host factors of influenza infection are identified using a novel virus-host protein network. Interaction cascades between host proteins that directly interact with viral proteins and host factors that are important to influenza replication are enriched for signaling and immune processes. Novel host factors are validated with an siRNA screen, demonstrating that integrated virus-host networks are useful in the identification of antiviral drug target candidates.
A review of the current state of mathematical models of influenza-induced host responses. Analysis shows that the structure of current models does not allow for significant responses to increased interferon concentrations, suggesting that the current library of available published models of influenza infection does not adequately represent the complex interactions of the virus, interferon, and other aspects of the immune response.