Biology subjects

Mathur, T.

Publications and source records attributed to Mathur, T..

6 recordsLinked to original sources

bioRxiv2026

Polystyrene Nanoplastics Disrupt Mouse Placenta Development in a Sex-Dependent Manner

Plastic production has been increasing exponentially. Throughout their lifespan, plastics degrade into smaller particles that accumulate in our bodies and the environment. Recent studies found these plastic particles can cross the placental barrier and reach the fetus. However, the impact of plastic particles on placental function is still unknown. We hypothesized that nanoplastics would disrupt placental growth and function, specifically focusing on transforming growth factor beta (TGF{beta}) signaling. To understand the impact of plastic particles on the placenta, we orally exposed pregnant CD-1 mice to 50 nm or 200 nm polystyrene plastic particles from gestation day 8 to day 15 at a human-relevant concentration of 5 mg/kg/day. After euthanization on day 15, placenta and fetus weights were recorded, and tissues were prepared for histomorphology and gene expression analysis. We observed a statistically significant decrease in the area of the decidua in the placentas for the 200 nm treatment group and a borderline significant decrease in decidua area for the 50 nm treatment group compared to control. However, when we separated by sex, only the male decidua were significantly decreased in the 200 nm group. Gene expression analysis of key signaling factors in the TGF{beta} pathway identified increased expression of Smad2 and Smad3, which may be suppressing prolactin and estrogen receptor signaling. Overall, both particle sizes disrupted placenta structure and signaling in a sex-dependent manner and may be acting as endocrine disruptors.

pharmacology and toxicology↗

bioRxiv2026

Ubiquitin recognition integrates plant immune signaling by cell-surface and intracellular receptors

Plant immunity is activated by cell-surface and intracellular receptors that detect pathogen-derived molecules. Mutual potentiation between these two receptor types is essential for robust disease resistance, but the mechanisms underpinning integrated dual receptor immunity remain unknown. Here, we found that activation of the intracellular receptor, ZAR1, induces its site-specific modification by non-proteolytic ubiquitin chains. ZAR1-anchored ubiquitin chains promote oligomerization of ZAR1 into a calcium-permeable resistosome pore and are recognized by RH3, a ubiquitin-binding DEAD-box RNA helicase. Remarkably, RH3 recruits both ZAR1 resistosomes and cell-surface receptor components into a dual receptor complex, thereby enhancing calcium-dependent mRNA translation of core defense proteins and establishing robust immunity. These findings identify ubiquitin recognition as the missing link in mutual potentiation of plant immunity by cell-surface and intracellular receptors.

plant biology↗

bioRxiv2023

Evaluation of the morphological and biological functions of vascularized microphysiological systems with supervised machine learning

Vascularized microphysiological systems and organoids are contemporary preclinical experimental platforms representing human tissue or organ function in health and disease. While vascularization is emerging as a necessary physiological organ-level feature required in most such systems, there is no standard tool or morphological metric to measure the performance or biological function of vascularized networks within these models. Further, the commonly reported morphological metrics may not correlate to the networks biological function - oxygen transport. Here, a large library of vascular network images was analyzed by the measure of each samples morphology and oxygen transport potential. The oxygen transport quantification is computationally expensive and user-dependent, so machine learning techniques were examined to generate regression models relating morphology to function. Principal component and factor analyses were applied to reduce dimensionality of the multivariate dataset, followed by multiple linear regression and tree-based regression analyses. These examinations reveal that while several morphological data relate poorly to the biological function, some machine learning models possess a relatively improved, but still moderate predictive potential. Overall, random forest regression model correlates to the biological function of vascular networks with relatively higher accuracy than other regression models.

bioengineering↗

bioRxiv2023

AngioMT: An in silico platform for digital sensing of oxygen transport through heterogenous microvascular networks

Measuring the capacity of microvascular networks in delivering soluble oxygen and nutrients to its organs is essential in health, disease, and surgical interventions. Here, a finite element methodbased oxygen transport program, AngioMT, is designed and validated to predict spatial oxygen distribution and other physiologically relevant transport metrics within both the vascular network and the surrounding tissue. The software processes acquired images of microvascular networks and produces a digital mesh which is used to predict vessel and tissue oxygenation. The image-to-physics translation by AngioMT correlated with results from commercial software, however only AngioMT could provide predictions within the solid tissue in addition to vessel oxygenation. AngioMT predictions were sensitive and positively correlated to spatial heterogeneity and extent of vascularization of 500 different vascular networks formed with variable vasculogenic conditions. The predictions of AngioMT cross-correlate with experimentally-measured oxygen distributions in vivo. The computational power of the software is increased by including calculations of higher order reaction mechanisms, and the program includes defining additional organ and tissue structures for a more physiologically relevant analysis of tissue oxygenation in complex co-cultured systems, or in vivo. AngioMT may serve as a digital performance measuring tool of vascular networks in microcirculation, experimental models of vascularized tissues and organs, and in clinical applications, such as organ transplants.

bioengineering↗

bioRxiv2022

A novel fluorobenzothiazole RBx 10080758 as a dual inhibitor against bacterial GyraseB (GyrB) and Topoisomerase IV (parE) of Gram-positive pathogens causing skin and respiratory infections

Development of a novel inhibitor targeting Gyrase B and Topoisomerase IV offers a potential opportunity to combat the drug resistance. In the present study, we extensively investigated the efficacy of RBx 10080758, a novel fluorobenzothiazole, against skin and respiratory infections caused by Staphylococci and Streptococci in in vitro and in vivo models. RBx 10080758 showed a potent IC50 of 0.06 M against Gyrase and Topoisomerase IV and also exhibited a strong whole cell in vitro activity with MIC ranges of 0.015-0.06, 0.015-0.03, 0.008-0.03, 0.008-0.03, 0.008-0.0.06, 0.015-0.06 g/ml against Staphylococcus. aureus, Streptococcus pneumoniae, Coagulase negative Staphylococci, Streptococcus viridans, Streptococcus pyogenes and Enterococcus, respectively. As expected from the novel class of molecule, it retains potent even against linezolid and vancomycin resistant strains. Interesting, in mouse systemic infection 10 mg/kg, IV dose protected 100% mice from lethal infections. In rat thigh infection model with MRSA WCUH29 at 45 mg/kg exhibited >3-log10 cfu reduction in thigh muscles. RBx 10080758 displayed potent in vitro and in vivo activity against a panel of MDR Gram-positive bacteria. As a novel chemical class, the fluorobenzothiazoles have the potential to become clinically viable antibiotics, to address the drug resistance problem by its unique dual targeting mechanism of action.

microbiology↗

bioRxiv2020

A Novel Class of Azoles with potent Anti-Leishmanial activity

ObjectivesTo investigate the anti-leishmanial activity of novel azole compounds against Leishmania donovani, which causes deadly visceral leishmaniasis disease. MethodsA focused azole-based library was screened both against promastigotes and amastigotes forms of L. donovani strains in flat-bottomed 96-well tissue-culture plates and J774A.1 macrophages infected with L. donovani. The comprehensive screening azole-based library against L. donovani strains provided novel hits, which can serve as a good starting point to initiate hit to lead optimization campaign. ResultsHits identified from azole-based library exhibited potent in vitro activity against promastigotes and amastigotes of L. donovani. ConclusionsThese potent novel azole hits could be a good starting point to carry out for further medicinal chemistry exploration for anti-leishmania program.

microbiology↗