RESUMEN
Periodontal health is dependent on a symbiotic relationship of the host immune response with the oral microbiota. Pathologic shifts of the microbial plaque elicit an immune response that eventually leads to the recruitment and activation of osteoclasts and matrix metalloproteinases and the eventual tissue destruction that is evident in periodontal disease. Once the microbial stimulus is removed, an active process of inflammatory resolution begins. The goal of this work was to use scRNAseq to demonstrate the unique cellular immune response across three distinct conditions of periodontal health, disease, and resolution using mouse models. Periodontal disease was induced using a ligature model. Resolution was modeled by removing the ligature and allowing the mouse to recover. Immune cells (Cd45+) were isolated from the periodontium and analyzed via scRNAseq. Gene signature shifts across the three conditions were characterized and shown to be largely driven by macrophage and neutrophils during the periodontal disease and resolution conditions. Resolution of periodontal disease was characterized by the differential regulation of unique gene subsets. Clustering analysis characterized multiple cellular subpopulations within B Cells, macrophages, and neutrophils that demonstrated differential expansion and contraction across conditions of periodontal health, disease, and resolution. Interestingly, we identified a transcriptionally distinct macrophage subpopulation that expanded during the resolution condition and demonstrated an immunoregulatory gene signature. We identified a cell surface marker for this resolution-associated macrophage subgroup (Cd74) and validated the expansion of this subgroup during resolution via flow cytometry. This work presents a robust immune cell atlas for study of the immunological changes in the oral mucosa during three distinct conditions of periodontal health, disease, and resolution and it improves our understanding of the cellular and molecular markers that characterize health from disease for the development of future diagnostics and therapies.
RESUMEN
We investigate the two-dimensional packing of extremely prolate (aspect ratio alpha=L/D>10) granular materials, comparing experiments with Monte Carlo simulations. The average packing fraction of particles with aspect ratio alpha=12 is 0.68+/-0.03. We quantify the orientational correlation of particles and find a correlation length of two particle lengths. The functional form of the orientational correlation is the same in both experiments and simulations which three orders of magnitude in aspect ratio, all decaying over a distance of two particle lengths. It is possible to identify voids in the pile with sizes ranging over two orders of magnitude. The experimental void distribution function is a power law with exponent -beta=-2.43+/-0.08. Void distributions in simulated piles do not decay as a power law, but do show a broad tail. We extend the simulation to investigate the scaling at very large aspect ratios. A geometric argument predicts the pile number density to scale as alpha(-2). Simulations do indeed scale this way, but particle alignment complicates the picture, and the actual number densities are quite a bit larger than predicted.