Modeling The Spatiotemporal Dynamics Of Cells In The Lung

Multiple research problems related to the lung involve a need to take into account the spatiotemporal dynamics of the underlying component cells. Two such problems involve better understanding the nature of the allergic inflammatory response to explore what might cause chronic inflammatory diseases such as asthma, and determining the rules underlying stem cells used to engraft decellularized lung scaffolds in the hopes of growing new lungs for transplantation. For both problems, we model the systems computationally using agent-based modeling, a tool that enables us to capture these spatiotemporal dynamics by modeling any biological system as a collection of agents (cells) interacting with each other and within their environment. This allows to test the most important pieces of biological systems together rather than in isolation, and thus rapidly derive biological insights from resulting complex behavior that could not have been predicted beforehand, which we can then use to guide wet lab experimentation. For the allergic response, we hypothesized that stimulation of the allergic response with antigen results in a response with formal similarity to a muscle twitch or an action potential, with an inflammatory phase followed by a resolution phase that returns the system to baseline. We prepared an agent-based model (ABM) of the allergic inflammatory response and determined that antigen stimulation indeed results in a twitch-like response. To determine what might cause chronic inflammatory diseases where the twitch presumably cannot resolve back to baseline, we then tested multiple potential defects to the model. We observed that while most of these potential changes lessen the magnitude of the response but do not affect its overall behavior, extending the lifespan of activated pro-inflammatory cells such as neutrophils and eosinophil results in a prolonged inflammatory response that does not resolve to baseline. Finally, we performed a series of experiments involving continual antigen stimulation in mice, determining that there is evidence in the cytokine, cellular and physiologic (mechanical) response consistent with our hypothesis of a finite twitch and an associated refractory period. For stem cells, we made a 3-D ABM of a decellularized scaffold section seeded with a generic stem cell type. We then programmed in different sets of rules that could conceivably underlie the cell\u27s behavior, and observed the change in engraftment patterns in the scaffold over selected timepoints. We compared the change in those patterns against the change in experimental scaffold images seeded with C10 epithelial cells and mesenchymal stem cells, two cell types whose behaviors are not well understood, in order to determine which rulesets more closely match each cell type. Our model indicates that C10s are more likely to survive on regions of higher substrate while MSCs are more likely to proliferate on regions of higher substrate

Improving Community Health with Affordable Internet Access

Internet access is associated with increases in health information seeking and benefits in health statuses. However, many individuals of low socioeconomic status (SES) lack Internet access, thereby creating significant disadvantages from a health perspective. In this project, we describe a potential project for providing affordable Internet access to a neighborhood of Newport, VT containing many SES individuals. This network includes a splash page that provides regular health event promotion and health information dissemination to everyone connecting the network. We then discuss how to determine the impacts of the Internet on multiple aspects of health within the community.https://scholarworks.uvm.edu/fmclerk/1189/thumbnail.jp

Assessing Barriers to Healthy Living in Economically Challenged Communities of the Greater Winooski Area

Introduction: NeighborKeepers (Winooski, VT) is a non-profit, anti-poverty organization that focuses on building supportive friend networks that direct families and individuals toward the resources they need to improve their health, get training and education, find jobs, and discover a sense of purpose and belonging. Keeping with the NeighborKeepers philosophy of giving those in need the tools to help improve their own circumstances, our project goals were to: •Engage community members •Connect individuals with community resources geared toward healthy living and improved healthcare access •Identify health needs and potential areas for intervention or further inquiryhttps://scholarworks.uvm.edu/comphp_gallery/1058/thumbnail.jp

Generative modeling of the enteric nervous system employing point pattern analysis and graph construction

We describe a generative network model of the architecture of the enteric nervous system (ENS) in the colon employing data from images of human and mouse tissue samples obtained through confocal microscopy. Our models combine spatial point pattern analysis with graph generation to characterize the spatial and topological properties of the ganglia (clusters of neurons and glial cells), the inter-ganglionic connections, and the neuronal organization within the ganglia. We employ a hybrid hardcore-Strauss process for spatial patterns and a planar random graph generation for constructing the spatially embedded network. We show that our generative model may be helpful in both basic and translational studies, and it is sufficiently expressive to model the ENS architecture of individuals who vary in age and health status. Increased understanding of the ENS connectome will enable the use of neuromodulation strategies in treatment and clarify anatomic diagnostic criteria for people with bowel motility disorders.Comment: 17 pages, 5 figure

Interactions of Cu(I) with Selenium-Containing Amino Acids Determined by NMR, XAS, and DFT Studies

Cu(I) coordination by organoselenium compounds was recently reported as a mechanism for their prevention of copper-mediated DNA damage. To establish whether direct Se–Cu coordination may be involved in selenium antioxidant activity, Cu(I) coordination of the selenoamino acids methyl-<i>Se</i>-cysteine (MeSeCys) and selenomethionine (SeMet) was investigated. NMR results in D₂O indicate that Cu(I) binds to the Se atom of both MeSeCys and SeMet as well as the carboxylic acid oxygen atom(s) or amine nitrogen atoms. X-ray absorption spectroscopy (XAS) and density functional theory (DFT) results confirm Se–Cu coordination, with the identification of a 2.4 Å Se–Cu vector in both the Se- and Cu-EXAFS data. XAS studies also show Cu(I) in an unusual three-coordinate environment with the additional two ligands arising from O/N (2.0 Å). DFT models of 1:1 Cu-selenoamino acid complexes suggest that both selenoamino acids coordinate Cu(I) through the selenium and amino groups, with the third ligand assumed to be water. These compounds represent the first structurally characterized copper(I) complexes with sulfur- or selenium-containing amino acids