Biology subjects

Bailey, C. A.

Publications and source records attributed to Bailey, C. A..

6 recordsLinked to original sources

bioRxiv2025

Phosphite Production by Streptomyces viridochromogenes

The industrial production of phosphochemicals is highly energy-intensive, involving the reduction of the phosphate mineral apatite to white phosphorus, a toxic and reactive intermediate with significant environmental risk. Phosphite, an activated form of phosphorus, is a potential alternative substrate for phosphochemical synthesis, yet direct reduction of phosphate to phosphite remains challenging. While environmental and microbial studies have suggested biochemical pathways for reducing phosphate to phosphite, these pathways have not been conclusively demonstrated in axenic culture. In this study, we characterize phosphite production by Streptomyces viridochromogenes and demonstrate that phosphite is an abiological product of phosphonoformyl-CMP decomposition, an intermediate in the biosynthesis of the herbicide phosphinothricin. The phosphonoformyl-CMP intermediate yields an "activated" phosphonoformate for decarboxylation, producing phosphite at biological temperatures and pH following phosphoanhydride hydrolysis. Using S. viridochromogenes spent media, we demonstrate a hybrid biotic-abiotic synthesis of the metal chelator aminotris(methylenephosphonate), illustrating a potential synthetic route to phosphochemicals from biogenic phosphite.

biochemistry↗

bioRxiv2024

Ablation of hematopoietic stem cell derived adipocytes reduces tumor burden in syngeneic mouse models of high-grade serous carcinoma

Hematopoietic stem cell-derived adipocytes (HSCDAs) are an adipose subtype derived from myeloid precursors that are distinct from conventional mesenchymal adipocytes (CMAs). We hypothesized that HSCDAs promote high grade serous carcinoma (HGSC), the most common form of ovarian cancer. Despite similar rates of differentiation, primary human HSCDAs from female donors showed marked transcriptional differences from CMAs, including downregulation of cell cycle and upregulation of lipid metabolic pathways. HSCDAs secreted greater amounts of inflammatory cytokines than CMAs. We also conducted two independent tumor studies using ID8 and SO syngeneic HGSC murine models in immunocompetent mice that were either HSCDA Proficient (HSCDA-Pro; can make both adipocyte subtypes) or Deficient (HSCDA-Def; can only make CMAs). Tumor burden trended lower in HSCDA-Def mice in both models. Relative to HSCDA-Pro mice, omental ID8 tumors from HSCDA-Def mice downregulated transcription of multiple metabolic pathways that were enriched in human HSCDA cells in vitro, suggesting that ablation of HSCDAs altered the tumor metabolic environment. Compared to HSCDA-Pro mice, tumors from HSCDA-Def mice had lower densities of dendritic cells (DC) and natural killer (NK) cells, as well as fewer DCs, NKs, and B-cells in proximity to tumor cells. Our data suggest that HSCDAs alter the peritoneal immune and metabolic environment to support HGSC progression. ONE SENTENCE SUMMARYHematopoietic stem cell derived adipocytes may alter the peritoneal metabolic and immune environment to establish a metastatic niche and support ovarian cancer progression.

cancer biology↗

bioRxiv2023

Combinatory EHMT and PARP inhibition induces an interferon response and a CD8 T cell-dependent tumor regression in PARP inhibitor-resistant models

Euchromatic histone lysine methyltransferases 1 and 2 (EHMT1/2), which catalyze demethylation of histone H3 lysine 9 (H3K9me2), contribute to tumorigenesis and therapy resistance through unknown mechanisms of action. In ovarian cancer, EHMT1/2 and H3K9me2 are directly linked to acquired resistance to poly-ADP-ribose polymerase (PARP) inhibitors and are correlated with poor clinical outcomes. Using a combination of experimental and bioinformatic analyses in several PARP inhibitor resistant ovarian cancer models, we demonstrate that combinatory inhibition of EHMT and PARP is effective in treating PARP inhibitor resistant ovarian cancers. Our in vitro studies show that combinatory therapy reactivates transposable elements, increases immunostimulatory dsRNA formation, and elicits several immune signaling pathways. Our in vivo studies show that both single inhibition of EHMT and combinatory inhibition of EHMT and PARP reduces tumor burden, and that this reduction is dependent on CD8 T cells. Together, our results uncover a direct mechanism by which EHMT inhibition helps to overcome PARP inhibitor resistance and shows how an epigenetic therapy can be used to enhance anti-tumor immunity and address therapy resistance.

cancer biology↗

bioRxiv2023

Smartwatch-based prediction of single-stride and stride-to-stride gait outcomes using regression-based machine learning

2.Abstract and key termsSpatiotemporal variability during gait is linked to fall risk and could be monitored using wearable sensors. Although many users prefer wrist-worn sensors, most applications position at other sites. We developed and evaluated an application using a consumer-grade smartwatch inertial measurement unit (IMU). Young adults (N = 41) completed seven-minute conditions of treadmill gait at three different speeds. Single-stride outcomes (stride time, length, width, and speed) and spatiotemporal variability (coefficient of variation of each single-stride outcome) were recorded using an optoelectronic system, while 232 single- and multi-stride IMU metrics were recorded using an Apple Watch Series 5. These metrics were input to train linear, ridge, support vector machine (SVM), random forest, and extreme gradient boosting (xGB) models of each spatiotemporal outcome. We conducted Model x Condition ANOVAs to explore model sensitivity to speed-related responses. xGB models were best for single-stride outcomes (relative mean absolute error [% error]: 7-11%; intraclass correlation coefficient [ICC2,1]: 0.60-0.86) and SVM models were best for spatiotemporal variability (% error: 18-22%; ICC2,1 = 0.47-0.64). Spatiotemporal changes with speed were captured by these models (Condition: p < 0.00625). Results support the feasibility of monitoring multi-stride spatiotemporal parameters using a smartwatch IMU and machine learning.

bioengineering↗

bioRxiv2022

Multi-omic analysis of the cardiac cellulome defines a vascular contribution to cardiac diastolic dysfunction in obese female mice

Coronary microvascular dysfunction (CMD) is associated with cardiac dysfunction and predictive of cardiac mortality in obesity, especially in females. Emerging evidence suggests development of heart failure with preserved ejection fraction in females with CMD and that mineralocorticoid receptor (MR) antagonism may be more efficacious in obese female, versus male, HFpEF patients. Accordingly, we examined the hypothesis that smooth muscle cell (SMC)-specific MR deletion prevents obesity-associated coronary and cardiac diastolic dysfunction in females. Obesity was induced in female mice via western diet (WD) feeding alongside littermates fed standard diet. Initial studies revealed that global MR blockade with spironolactone prevented impaired coronary vasodilation and diastolic dysfunction in obese females. Importantly, specific deletion of SMC-MR similarly prevented obesity-associated coronary and cardiac dysfunction. Cardiac gene expression profiling suggested reduced cardiac inflammation in WD-fed mice with SMC-MR deletion independent of blood pressure, aortic stiffening, and cardiac hypertrophy. Further mechanistic studies utilizing single-cell RNA sequencing of non-cardiomyocyte cell populations revealed novel impacts of SMC-MR deletion on the cardiac cellulome in obese mice. Specifically, WD feeding induced inflammatory gene signatures in multiple non-myocyte populations (B/T cells, macrophages, and endothelium), independent of cardiac fibrosis, that was prevented by SMC-MR deletion. Further, SMC-MR deletion induced a basal reduction in cardiac mast cells and prevented WD-induced cardiac pro-inflammatory chemokine expression and leukocyte recruitment. These data reveal a central role for SMC-MR signaling in obesity-associated coronary and cardiac dysfunction thus supporting the emerging paradigm of a vascular origin of cardiac dysfunction in obesity.

physiology↗

bioRxiv2021

Effects of arm swing amplitude and lower limb asymmetry on motor variability patterns during treadmill gait

Motor variability is a fundamental feature of gait. Altered arm swing and lower limb asymmetry (LLA) may be contributing factors having been shown to affect the magnitude and dynamics of variability in spatiotemporal and trunk motion. However, the effects on lower limb joints remain unclear. Full-body kinematics of 15 healthy young adults were recorded during treadmill walking using the Computer-Assisted Rehabilitation Environment system. Participants completed six trials, combining three arm swing (AS) amplitude (normal, active, held) and two LLA (symmetrical, asymmetrical) conditions. The mean standard deviation (meanSD), maximum Lyapunov exponent ({lambda}max), detrended fluctuation analysis scaling exponent of range of motion (DFA), and sample entropy (SaEn) were computed for tridimensional trunk, pelvis, and lower limb joint angles, and compared using repeated-measures ANOVAs. Relative to normal AS, active AS increased meanSD of all joint angles, {lambda}max of frontal plane hip and ankle angles, and SaEn of sagittal plane ankle angles. Active AS, however, did not affect {lambda}max or SaEn of trunk or pelvis angles. LLA increased meanSD of sagittal plane joint angles, {lambda}max of Euclidean norm trunk angle and of lower limb joint angles, and SaEn of ankle dorsiflexion/ plantarflexion, but decreased SaEn of tridimensional trunk angles and hip rotation in the slower moving leg. Alterations in lower limb variability with active AS and LLA suggest that young adults actively exploit their lower limb redundancies to maintain gait. This appears to preserve trunk stability and regularity during active AS but not during LLA.

bioengineering↗