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Kingsbury, D.

Publications and source records attributed to Kingsbury, D..

2 recordsLinked to original sources

A Functional Basis for the Developmental Sequence of the Macrostructure of the Venus Flower Basket (Euplectella aspergillum)

Despite receiving significant interest from the biological and engineering communities, several questions about the underlying reasons for the form of the deep-sea sponge Venus Flower Basket (Euplectela aspergillum) remain unanswered. In particular, the basis for the sequence of emergence of three distinct macroscopic geometric features, while speculated upon, has not been validated. These features are (i) an interwoven cross-grid in the juvenile stage, (ii) a diagonal weave atop this initial grid, and (iii) a helical ridge that emerges in the mature phase of the sponge. This work uses computational design and additive manufacturing to fabricate models of each of these phases in sequence and subjects the models to mechanical tests in compression, bending and torsion. The results show that each feature has a singular advantage, even after accounting for the increase in mass associated with their addition: increased compliance for interwoven cross-grid, increased bending stiffness for diagonal weaves, and improved torsional rigidity for the helical ridge. The work postulates that the prioritization of compliance in the juvenile phase and a transition to a stiffer structure in the mature phase is a strategy that enables the sponge to avoid high internal stresses to avoid failure in its inherently brittle, silica-derived architecture. Highlights1. The benefits of three macrostructural design elements of the Venus Flower Basket (E. aspergillum) that emerge sequentially in its development are examined: (i) the interweaving cross-grid, (ii) the diagonal weave that overlays this cross-grid, and (iii) the helical ridge reinforcement that forms over this diagonal weave. 2. For the first time, this work models each of these design features sequentially and studies their mechanical benefits through an experimental exploration of the behavior of idealized geometries in three test domains: compression, bending, and torsion. 3. Results show that each of these three structural elements has a unique functional advantage depending on the organisms growth stage, even after accounting for differences in mass: interweaving enables higher compliance under compression, the diagonal weave improves bending stiffness, and the helical ridge improves torsional stiffness.

developmental biology↗

Adult Canine Intestinal Derived Organoids: A Novel In Vitro System for Translational Research in Comparative Gastroenterology

BackgroundLarge animal models, such as the dog, are increasingly being used over rodent models for studying naturally occurring diseases including gastrointestinal (GI) disorders. Dogs share similar environmental, genomic, anatomical, and intestinal physiologic features with humans. To bridge the gap between currently used animal models (e.g. mouse) and humans, and expand the translational potential of the dog model, we developed a three dimensional (3D) canine GI organoid (enteroid and colonoid) system. Organoids have recently gained interest in translational research as this model system better recapitulates the physiological and molecular features of the tissue environment in comparison with two-dimensional cultures.\n\nResultsOrganoids were propagated from isolation of adult intestinal stem cells (ISC) from whole jejunal tissue as well as endoscopically obtained duodenal, ileal and colonic biopsy samples of healthy dogs and GI cases, including inflammatory bowel disease (IBD) and intestinal carcinomas. Intestinal organoids were comprehensively characterized using histology, immunohistochemistry, RNA in situ hybridization and transmission electron microscopy, and organoids mimicked the in vivo tissue environment. Physiological relevance of the enteroid system was defined using functional assays such as Optical Metabolic Imaging (OMI), the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) function assay, and Exosome-Like Vesicles (EV) uptake assay, as a basis for wider applications of this technology in basic, preclinical and translational GI research.\n\nConclusionsIn summary, our findings establish the canine GI organoid systems as a novel model to study naturally occurring intestinal diseases in dogs and humans. Furthermore, canine organoid systems will help to elucidate host-pathogen interactions contributing to GI disease pathogenesis.

cell biology↗