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Intercellular Stress Generation During 1D Collective Migration of Cancer Cells
Get PDFPhysical forces drive many cellular processes such as migration and proliferation. A metastatic tumor will have invasive strands/chains that extend from the main tumor. These chains of cells collectively migrate away from the main tumor to establish new colonies elsewhere in the body. However, how physical forces drive this collective invasion and the required energy for this process is not well understood. Invasion of a metastatic tumor to surrounding tissues leads to a majority of cancer-associated death and is often a collective effort among cells, it is therefore important to fully understand the process behind collective cancer invasion.
The goal of this project is to determine the forces that drive collective cell migration in a one-dimensional system of cells. Analyzing a single strand of migrating cells allows for an in vitro analysis of metastatic chains developed by a tumor.
To confine migrating cells to a one-dimensional chain we engineered the extracellular environment via micropatterning such that cells only migrated along a thin line of extracellular matrix proteins patterned onto an elastic substrate. Once contained on a patterned elastic substrate with known physical properties, cell-matrix, and cell-cell forces were quantified via Traction Force Microscopy (TFM) by tracking substrate deformations. To connect these forces with cellular bioenergetics, we quantify the energy level of these migrating cell chains by measuring the cellular NADH:NAD+ ratio with a genetically encoded molecular probe.
Current results suggest that cells leading the collective migration experience greater forces, implying that these cells have greater bioenergetic needs. We have not found a statistically significant correlation between cellular energy and force generation, more replicates are needed to establish a relationship between the two.https://scholarworks.uark.edu/hnrcsturpc25/1047/thumbnail.jp
Identifying Novel Molecular Targets to Induce Ferroptosis in Drug-Tolerant Cancer Cells Through Computational Modeling
No full textFerroptosis is an iron-dependent, reactive oxygen species (ROS)-driven form of regulated cell death in which the cell membrane is degraded by lipid peroxidation. It is regulated by multiple enzymes, such as glutathione peroxidase 4 (GPX4), which prevents membrane degradation by reducing lipid peroxides and protecting cells from oxidative damage. When inhibitors like RSL3 target GPX4, lipid peroxides build up, and toxic ROS compromises membrane integrity. Traditional anticancer treatments, such as most chemotherapies, aim to eliminate tumor cells by damaging DNA and triggering apoptosis. However, resistance to apoptosis is a “hallmark of cancer,” often resulting in treatment failure. As a distinct form of programmed cell death, ferroptosis offers an alternative to traditional genotoxic treatment strategies. In this project, a mechanistic model of the ferroptosis pathway is developed to gain insights into molecular drivers and identify novel targets for enhancing ferroptosis activation. The model is constructed in PySB, a Python-based modeling and simulation platform for complex biological systems. Using PyDREAM, a Bayesian parameter estimation tool, the model is calibrated to experimental dose-response data from two cancer cell lines exposed to the ferroptosis inducer erastin. Parameter distributions generated by PyDREAM are compared against each other and reveal that differences associated with System Xc⁻, the cystine-glutamate antiporter, explain disparate drug responses between the two cell lines, i.e., System Xc⁻ is a potential target for modifying sensitivity to ferroptosis in these cells. Future research will focus on performing similar analyses for additional cell lines and utilizing time-course data with absolute (rather than relative) molecular concentrations. The model will also be expanded to include additional molecular components and models of related processes, like mitochondrial metabolism, enhancing its predictive power
An Assessment of Transformations in American and Canadian Women Homesteaders in the Mid-Nineteenth to Early Twentieth Century Wests
No full textEvery woman’s western experience was not the same, regardless of whether they were from the United States or Canada. Therefore, the various physical, social and psychological transformations of each woman who made the journey west cannot be grouped into one generalization. Yet a great deal can be said for the amount of women who did and did not experience such significant changes during the rough journey westward, changes that are determined by the differences in each woman’s attitude and behavior prior to and after their arrival in the western regions of North America
Encountering the Sublime: Early Hermit Lifeways, Visual-Spatial Worlds, and the Global Recluse
No full textThis paper will assess the degree to which reclusion in the early period can be labeled a global phenomenon and will examine three key areas, the institutional ambits of reclusion, the visual-spatial world of the eremite, and the enduring cultural canon associated with eremitisms across both geographical and temporal distances. In addition, the author will perform an epistemological and phenomenological exercise in deriving humanistic insight from the experiences of recluses, as gleaned through deep consideration of their environments and cultural products
Release of Growth Factors at Wound Healing Stages
No full textThe present invention provides collagen-binding agents that can be used to treat wounds, ischemic heart disease, and other conditions. The collagen-binding agents comprise a therapeutic agent, a protease cleavage site, and a collagen-binding domain. The present invention further provides pharmaceutical compositions and biomedical devices comprising the disclosed collagen-binding agents, as well as methods for treating a condition using the collagen-binding agents
Rice Cultivar \u27ARoma 22\u27
No full textA rice cultivar designated ARoma 22 is disclosed herein. The present invention provides seeds, plants, and plant parts derived from rice cultivar ARoma 22. Further, it provides methods for producing a rice plant by crossing ARoma 22 with itself or another rice variety. The invention also encompasses any rice seeds, plants, and plant parts produced by the methods disclosed herein, including those in which additional traits have been transferred into ARoma 22 through the introduction of a transgene or by breeding ARoma 22 with another rice cultivar
Fires and Protests of Peace: The Catholic Anti-War Movement in Sixties America
No full textThis study reviews the history of the Catholic Peace Movement and the impact of the publication, Catholic Worker, and individuals such as Thomas Merton, Phillip and Daniel Berrigan, and Dorothy Day on the anti-war movement against the Vietnam War
Kinetics of Protein and Amino Acids
No full textProtein and amino acid nutrition is key to poultry growth and sustainability, with synchrony between glucose and amino acid availability being critical for efficient feed conversion. While non-bound amino acids (NBAA) are rapidly absorbed and increasingly used to reduce crude protein levels, their fast uptake may disrupt amino acid balance and reduce nutrient utilization compared to protein-bound amino acids. Future research should redefine amino acid requirements in low-CP diets, explore the metabolic fate of NBAA, and investigate how protein sources affect gut microbiota and host metabolism