Biology subjects

Bushell, C.

Publications and source records attributed to Bushell, C..

4 recordsLinked to original sources

bioRxiv2023

Genetic control of cell layer interactions in plants via tissue mechanics

Plant development depends on coordination of growth between different cell layers. Coordination may be mediated by molecular signalling or mechanical connectivity between cells, but evidence for genetic control via direct mechanics has been lacking. We show that a brassinosteroid-deficient dwarf mutant of the aquatic plant Utricularia gibba has twisted internal tissue, likely caused by a mechanical constraint from a slow-growing epidermis creating tissue stresses. This conclusion is supported by showing that inhibition of brassinosteroid action in an Arabidopsis mutant compromised for cell adhesion, enhances epidermal crack formation, an indicator of increased tissue tension. Thus, genes driving brassinosteroid synthesis can promote growth of internal tissue by reducing mechanical epidermal constraint, showing that tissue mechanics plays a key role in coordinating growth between cell layers. One-Sentence SummaryInternal twists in a mutant carnivorous plant reveal how genes control growth via tissue mechanics.

plant biology↗

bioRxiv2021

Acyloxyacyl Hydrolase Modulates the Gut Microbiome Through Transcriptional Regulators of Corticotropin-Releasing Factor

Gut microbiome-host interactions play a crucial role in health and disease. Altered gut microbiome composition has been observed in patients with interstitial cystitis/bladder pain syndrome (IC/BPS), a disorder characterized by pelvic pain, voiding dysfunction, and often co-morbid with anxiety/depression. We recently showed that mice deficient for acyloxyacyl hydrolase (AOAH) mimic pelvic pain symptoms and comorbidities of IC/BPS and also exhibit gut dysbiosis. In addition, we previously identified that the conditional knockout (cKO) of two transcriptional regulators of the gene encoding corticotropin-releasing factor, Crf, that are downstream of AOAH, aryl hydrocarbon receptor (AhR) and peroxisome proliferator-activated receptor-{gamma} (PPAR{gamma}), alleviate anxiety/depressive and voiding phenotypes of AOAH-deficient mice. Here, we examined the effects of AhR and PPAR{gamma} in CRF-expressing cells on the dysbiosis of AOAH-deficiency. AOAH-deficient mice with cKO of PPAR{gamma} and AhR/PPAR{gamma} exhibited reduced pelvic allodynia compared to AOAH-deficient mice, suggesting a role for PPAR{gamma} in regulating pelvic pain. 16S rRNA sequencing of fecal stool from female AOAH-deficient mice with a cKO of AhR and/or PPAR{gamma} in CRF-expressing cells identified altered gut microbiota distinct from AOAH-deficient stool. The cKO of AhR and PPAR{gamma} showed improved cecum barrier function in females compared to AOAH-deficient mice, whereas males were primarily affected by PPAR{gamma}, suggesting sex differences in gut responses. Pair-wise comparison of microbiota also suggested sex differences in response to AOAH-deficiency and conditional knockout of AhR and PPAR{gamma}. Our findings suggest that the dysbiosis and leaky gut of AOAH deficiency is mediated by AhR and PPAR{gamma} in CRF-expressing cells and reveal a novel mechanism and therapeutic targets for pelvic pain.

systems biology↗

bioRxiv2021

Acyloxyacyl Hydrolase is a Host Determinant of Gut Microbiome-Mediated Pelvic Pain

Dysbiosis of gut microbiota is associated with many pathologies, yet host factors modulating microbiota remain unclear. Interstitial cystitis/bladder pain syndrome (IC/BPS or "IC") is a debilitating condition of chronic pelvic pain often with co-morbid urinary dysfunction and anxiety/depression, and recent studies find fecal dysbiosis in IC/BPS patients. We previously identified the locus encoding acyloxyacyl hydrolase, Aoah, as a modulator of pelvic pain severity in a murine IC/BPS model. AOAH-deficient mice spontaneously develop rodent correlates of pelvic pain, increased responses to induced pelvic pain models, voiding dysfunction, and anxious/depressive behaviors. Here, we report that AOAH-deficient mice exhibit dysbiosis of GI microbiota. AOAH-deficient mice exhibit an enlarged cecum, a phenotype long associated with germ-free rodents, and reduced trans-epithelial electrical resistance consistent with a "leaky gut" phenotype. AOAH-deficient ceca showed altered gene expression consistent with inflammation, Wnt signaling, and urologic disease. 16S rRNA sequencing of stool revealed altered microbiota in AOAH-deficient mice, and GC-MS identified altered metabolomes. Co-housing AOAH-deficient mice with wild type mice resulted in converged microbiota and altered predicted metagenomes. Co-housing also abrogated the pelvic pain phenotype of AOAH-deficient mice, which was corroborated by oral gavage of AOAH-deficient mice with stool slurry of wild type mice. Converged microbiota also alleviated comorbid anxiety-like behavior in AOAH-deficient mice. Oral gavage of AOAH-deficient mice with anaerobes cultured from IC/BPS stool resulted in exacerbation of pelvic allodynia. Together, these data indicate that AOAH is a host determinant of normal gut microbiota, and the dysbiosis associated with AOAH deficiency contributes to pelvic pain. These findings suggest that the gut microbiome is a potential therapeutic target for IC/BPS.

systems biology↗

bioRxiv2017

ClusterEnG: An interactive educational web resource for clustering big data

SummaryClustering is one of the most common techniques used in data analysis to discover hidden structures by grouping together data points that are similar in some measure into clusters. Although there are many programs available for performing clustering, a single web resource that provides both state-of-the-art clustering methods and interactive visualizations is lacking. ClusterEnG (acronym for Clustering Engine for Genomics) provides an interface for clustering big data and interactive visualizations including 3D views, cluster selection and zoom features. ClusterEnG also aims at educating the user about the similarities and differences between various clustering algorithms and provides clustering tutorials that demonstrate potential pitfalls of each algorithm. The web resource will be particularly useful to scientists who are not conversant with computing but want to understand the structure of their data in an intuitive manner.\n\nAvailabilityClusterEnG is part of a bigger project called KnowEnG (Knowledge Engine for Genomics) and is available at http://education.knoweng.org/clustereng.\n\nContactsongi@illinois.edu

bioinformatics↗