Biology subjects

Morrow, M.

Publications and source records attributed to Morrow, M..

6 recordsLinked to original sources

bioRxiv2026

Determining critical water potentials for creeping bentgrass seedling root elongation when exposed to PEG induced dehydration

Creeping bentgrass (Agrostis stolonifera) is a turfgrass species established on golf course surfaces but is criticized for high irrigation requirements. While genetic variation for water deficit stress tolerance exists between cultivars, the lack of defined critical soil water potential thresholds (Soil {Psi}crit) for this species complicates precise irrigation strategies and benchmarks for plant breeding. This study utilized a polyethylene glycol (PEG) infused agar-based system to simulate water potential reductions and determine the water potential threshold ({Psi}crit) for seedling root elongation. Creeping bentgrass cv Pure distinction seedlings were subjected to six water potentials ({Psi}) ranging from -0.36 MPa (no PEG applied) to -1.72 MPa. Daily digital imaging was used to measure root elongation over 5 days. Results across two experiments demonstrated that creeping bentgrass seedlings are highly sensitive to mild reductions in {Psi}. A reduction to -0.61 MPa significantly decreased root length and growth rates by over 50% compared to the control. Regression models predicted that a {Psi}crit of approximately -0.45 MPa reduced daily root growth by 25%, while upwards {Psi} of -1.0 MPa resulted in a 75% reduction of seedlings root growth. Furthermore, seedlings exposed to the lowest water potentials were predicted to require an additional 30 to 46 days to achieve the same root length as control plants. These findings establish specific {Psi}crit benchmarks for water deficit stress tolerance using a PEG-based system to induce dehydration. These methods can be used in breeding programs, and will help develop more accurate experiments examining the mechanisms of water deficit stress tolerance.

plant biology↗

bioRxiv2023

Colonic spermidine promotes the proliferation and migration of intestinal epithelial cells.

The gut microbiome, comprising trillions of diverse microorganisms, profoundly influences the efficient development and maintenance of the intestinal barrier. While shifts in microbial composition are observed in Inflammatory Bowel Disease (IBD) and Colorectal Cancer (CRC), the causal relationship between these changes and resolution of inflammation remains elusive. Notably, IBD is not only marked by shifts in microbial composition but also by changes in microbial metabolites. Polyamines, produced by both gut bacteria and human cells, have emerged as potential regulators of gut pathology, cancer and mucosal repair. Investigating how elevated polyamine levels influence intestinal epithelial cells (IEC) can provide insights into their role in the regeneration of mucosal epithelia and restoration of gut barrier functions. To dissect the complex interplay between the gut microbiome, polyamines, and IEC, we focused on the overrepresented bacterium B. uniformis and its primary metabolite, spermidine. Here, we show that B. uniformis, a dominant member of gut microbiota, expands during the repair & resolution phase of the chemically induced chronic murine colitis. Furthermore, we found that the abundance of colonic polyamines was also altered, with spermidine being the abundant polyamine. Our RNA sequencing and transcriptomic analysis of cultured colonic epithelial cells demonstrate that spermidine regulates the expression of genes and pathways involved in different cellular functions, including proliferation, differentiation, adhesion, lipid metabolism, migration, chemotaxis, and receptor expression. We also found that spermidine stimulates the proliferation of cultured colonic epithelial cells in vitro. Additionally, our findings indicate that spermidine enhances the migrations of enterocytes. Our study emphasizes the crucial functions of the gut microbiome and polyamines in governing the functions of intestinal epithelial cells. Thus, these microorganisms and their metabolic byproducts hold promise as prospective therapeutic agents.

microbiology↗

bioRxiv2022

Obesity promotes breast epithelium DNA damage in BRCA mutation carriers

Obesity is an established risk factor for breast cancer among women in the general population after menopause. Whether elevated bodyweight is a risk factor for women with a germline mutation in BRCA1 or BRCA2 is less clear due to inconsistent findings from epidemiological studies and lack of mechanistic studies in this population. Here, we show that DNA damage in normal breast epithelium of BRCA mutation carriers is positively correlated with body mass index and with biomarkers of metabolic dysfunction. Additionally, RNA-sequencing reveals significant obesity-associated alterations to the breast adipose microenvironment of BRCA mutation carriers, including activation of estrogen biosynthesis, which impacts neighboring breast epithelial cells. We found that blockade of estrogen biosynthesis or estrogen receptor activity decreases DNA damage, whereas treatment with leptin or insulin increases DNA damage in BRCA heterozygous epithelial cells. Furthermore, we show that increased adiposity is associated with mammary gland DNA damage and increased penetrance of mammary tumors in Brca1+/- mice. Overall, our results provide mechanistic evidence in support of a link between bodyweight and breast cancer development in BRCA mutation carriers and suggests that maintaining a healthy bodyweight or pharmacologically targeting estrogen or metabolic dysfunction may reduce the risk of breast cancer in this population. One Sentence SummaryElevated bodyweight is positively associated with DNA damage in breast epithelium of BRCA mutation carriers

cancer biology↗

bioRxiv2021

FGFR inhibitor mediated dismissal of SWI/SNF complexes from YAP-dependent enhancers induces adaptive therapeutic resistance

How cancer cells adapt to evade the therapeutic effects of drugs targeting oncogenic drivers is poorly understood. Here we report an epigenetic mechanism leading to the adaptive resistance of triple-negative breast cancer (TNBC) to fibroblast growth factor receptor (FGFR) inhibitors. Prolonged FGFR inhibition suppresses the function of BRG1-dependent chromatin remodeling leading to an epigenetic state that derepresses YAP-associated enhancers. These chromatin changes induce the expression of several amino acid transporters resulting in increased intracellular levels of specific amino acids that reactivate mTORC1. Collectively, these findings reveal a novel feedback loop involving an epigenetic state transition and metabolic reprogramming that leads to adaptive therapeutic resistance.

cancer biology↗

bioRxiv2020

Calibration and Evaluation of a Force Measurement Glove for Field-Based Monitoring of Manual Wheelchair Users

Manual wheelchair users exhibit pain related to repetitive and demanding shoulder activities of daily living. Wearable sensing systems like force measurement gloves can provide insights about upper extremity loading in the community and home environments. We calibrated and evaluated the accuracy of a novel force measurement glove with a body-worn data logger. The device was calibrated with loads of 0-800 N applied to the palmar surface of the glove. Calibration conditions were tested that varied the stiffness of the material in the glove, the temperature, and the curvature of the force applicator. Calibration equations from each condition were evaluated by comparing the gloves force prediction with the output of an instrumented wheelchair rim during propulsion and weight relief exercises. The force measurement glove detected 72.7% of 355 propulsion peaks and had a strong linear correlation with the instrumented rim force measurements (r=0.80). The most accurate calibration equation was constructed using data from all conditions, with an RMS force measurement error of 64.7 N and 31.7 N for weight relief exercise and propulsion, respectively. The force measurement glove design described here may serve as a useful tool for detection of loading events and relative magnitude changes.

bioengineering↗

bioRxiv2017

Active site alanine substitutions can convert deubiquitinating enzymes into avid ubiquitin-binding domains

A common strategy for studying the biological role of deubiquitinating enzymes (DUBs) in different pathways is to study the effects of replacing the wild type DUB with a catalytically inactive mutant in cells. We report here that a commonly studied DUB mutation, in which the catalytic cysteine is replaced with alanine, can dramatically increase the affinity of some DUBs for ubiquitin. Overexpression of these tight-binding mutants thus has the potential to sequester cellular pools of monoubiquitin and ubiquitin chains. As a result, cells expressing these mutants may display unpredictable dominant negative physiological effects that are not related to loss of DUB activity. The structure of the SAGA DUB module bound to free ubiquitin reveals the structural basis for the 30-fold higher affinity of Ubp8C146A for ubiquitin. We show that an alternative option, substituting the active site cysteine with arginine, can inactivate DUBs while also decreasing the affinity for ubiquitin.

biochemistry↗