Biology subjects

Thomas, K. A.

Publications and source records attributed to Thomas, K. A..

5 recordsLinked to original sources

bioRxiv2026

HS3ST1 regulates pulmonary inflammation and is a determinant of clinical outcomes after trauma and hemorrhagic shock

Mechanisms that promote organ injury after trauma and hemorrhagic shock (T/HS) remain poorly defined. Endothelial heparan sulfates with a 3-O-sulfate (3-OS) modification, controlled by the HS3ST1 gene, have anticoagulant and anti-inflammatory properties through their interaction with antithrombin. Our objective was to determine whether HS3ST1 deficiency drives organ injury and poor outcomes after T/HS. Hs3st1-/- and wild-type (WT) mice were subjected to T/HS followed by resuscitation with lactated ringers (LR) or fresh frozen plasma (FFP). While no differences were observed between WT and Hs3st1-/- LR resuscitated mice, lung injury and leukocyte infiltrates were significantly increased in FFP resuscitated Hs3st1-/-compared to WT mice. In vitro, leukocyte slow rolling and adherence was increased in HS3ST1 KO compared to WT cells. Among 472 T/HS patients, of which 31 (7%) were homozygous for the rs16881446 variant allele (GG), the number of ventilator free days was lower, and mortality was significantly higher in AG and GG patients. The rs16881446 genotype was independently associated with mortality. In conclusion, HS3ST1 deficiency mitigates organ protection from FFP resuscitation, partly through mediating EC:leukocyte engagement, and predicts mortality after T/HS. These findings identify a novel therapeutic target and prognostic tool that can be leveraged towards improved risk stratification after trauma.

cell biology↗

bioRxiv2026

Platelet Molecular Maturation Links Platelet Aging and the Platelet Storage Lesion

Human platelets change over their 7-10 day lifespan, yet the molecular mechanisms underlying platelet aging remain poorly defined. Using two independent RNA sequencing datasets of fluorescence-activated cell sorted young and old human platelets, we developed a unified transcriptomic model to characterize RNA metabolism across the platelet lifespan, which we termed platelet molecular maturation. This was applied to RNA sequencing data from room-temperature stored platelets (up to 7 days) and cold-stored platelets (7, 14, or 21 days). We identified highly concordant aging signatures, including 6,015 shared expressed genes and 2,008 shared differentially expressed genes (DEGs) with strongly correlated fold changes, demonstrating a conserved platelet aging program. Nucleotide-level analyses revealed preferential 3'-directed degradation among downregulated transcripts during endogenous platelet aging and room-temperature storage, supporting an organized RNA decay process that was correlated with platelet function changes. Room-temperature storage recapitulated platelet molecular maturation, showing concordance with aging-related gene expression changes and enrichment of downregulated gene sets. In contrast, cold-storage significantly attenuated platelet molecular maturation and 3'-directed degradation. A total of 669 genes were consistently differentially expressed between room-temperature and cold-stored platelets, while no DEGs were detected during cold-storage, indicating transcriptional stability. Platelet transcript stability in cold-storage correlated with preserved platelet hemostatic function. These findings establish platelet molecular maturation as a conserved, functionally relevant model linking endogenous platelet aging to platelet storage lesions and providing mechanistic insight into preserved platelet hemostatic function in cold-storage. This atlas of platelet RNA metabolism supports biomarker discovery and strategies to improve storage. KEY POINTSO_LIBy integrating multiple high-quality RNA sequencing datasets with novel analytic approaches tailored to the biology of anucleate platelets, we show that platelet aging is not a passive process of transcript decay, but follows a structured and reproducible molecular trajectory both endogenously and in storage, which we term platelet molecular maturation. C_LIO_LIStorage temperature emerged as a dominant modifier of this trajectory, with cold-storage markedly slowing RNA metabolic kinetics and preserving transcripts associated with younger, more hemostatically competent platelets. C_LIO_LITogether, these findings provide mechanistic insight into the platelet storage lesion and identify transcriptomic features that may serve as biomarkers or therapeutic targets to extend platelet shelf life. C_LI

genomics↗

bioRxiv2026

A snapshot of Joshua tree (Yucca brevifolia and Y. jaegeriana) stand structure in the eastern Mojave Desert of California

The long-term viability of the iconic Joshua tree of the Mojave Desert is being evaluated. In 2022, we measured the abundance and heights of Joshua tree stems on 62 1000 m2 plots in the eastern Mojave Desert of California. The 2022 plots were represented by 33 plots in a population of western Joshua trees (Yucca brevifolia) and 29 plots in a population of eastern Joshua trees (Y. jaegeriana). Five plots had no Joshua trees; two of which in the western Joshua tree population were destroyed by fire. The 57 plots with Joshua trees supported 627 stems ranging from stems less than 25 cm to mature trees. The plots were examined by abundance and four size classes of the stems, as indicated by their height and indicative of their reproductive status. The western Joshua tree population had more stems (407) than the eastern population (220 stems) although the median difference was not significant. The western population had significantly more stems in pre-reproductive size classes, juvenile (> 25 cm to one-meter, p = 0.001) and sub_adult (> one- to two-meters, p = 0.001), than the eastern population but significantly fewer adult (> two-meters, p < 0.001) stems. The eastern population had significantly greater mean height of adult trees (302 cm +/- 75.3 cm) than the western population (263 cm +/- 52.9 cm) and a larger proportion of stems taller than two-meters (56%) than the western population (39%). In contrast, the western population has 77% of its population in younger size classes (> 25 cm to < 2 meters). These abundance and size class measures alone do not predict whether either population has sufficient natural stand regeneration for long term persistence, but the younger size class structure of the western population suggests greater long-term resilience than for the eastern population.

ecology↗

bioRxiv2022

Can static optimization detect changes in peak medial knee contact forces induced by gait modifications?

Medial knee contact force (MCF) is related to the pathomechanics of medial knee osteoarthritis. However, MCF cannot be directly measured in the native knee, making it difficult for therapeutic gait modifications to target this metric. Static optimization, a musculoskeletal simulation technique, can estimate MCF, but there has been little work validating its ability to detect changes in MCF induced by gait modifications. In this study, we quantified the error in MCF estimates from static optimization compared to measurements from instrumented knee replacements during normal walking and seven different gait modifications. We then identified minimum magnitudes of simulated MCF changes for which static optimization correctly identified the direction of change at least 70% of the time. A full-body musculoskeletal model with a multi-compartment knee and a custom static optimization implementation was used to estimate MCF. Simulations were evaluated using experimental data from three subjects for a total of 115 steps. Static optimization underpredicted the first peak (mean absolute error = 0.16 bodyweights) and overpredicted the second peak (mean absolute error = 0.31 bodyweights) of MCF. Average root mean square error in MCF over stance phase was 0.32 bodyweights. Static optimization detected the direction of change with at least 70% accuracy for early-stance reductions, late-stance reductions, and early-stance increases in peak MCF of 0.10 bodyweights and greater. These results suggest that a simple static optimization approach accurately detects directional effects on early-stance medial knee loading, potentially making it a valuable tool for evaluating the biomechanical efficacy of gait modifications for knee osteoarthritis.

bioengineering↗

bioRxiv2018

How does cilium length affect beating?

The effects of cilium length on the dynamics of cilia motion were investigated by high-speed video microscopy of uniciliate mutants of the swimming alga, Chlamydomonas reinhardtii. Cells with short cilia were obtained by deciliating cells via pH shock and allowing cilia to reassemble for limited times. The frequency of cilia beating was estimated from motion of the cell body and of the cilium. Key features of the ciliary waveform were quantified from polynomial curves fitted to the cilium in each image frame. Most notably, periodic beating did not emerge until the cilium reached a critical length between 2-4 {micro}m. Surprisingly, in cells that exhibited periodic beating, the frequency of beating was similar for all lengths with only a slight decrease in frequency as length increased from 4 {micro}m to the normal length of 10-12 {micro}m. The waveform average curvature (rad/{micro}m) was also conserved as the cilium grew. The mechanical metrics of ciliary propulsion: force, torque, and power all increased in proportion to length. Mechanical efficiency of beating appeared to be maximal at the normal wild-type length of 10-12 m. These quantitative features of ciliary behavior illuminate the biophysics of cilia motion and, in future studies, may help distinguish competing hypotheses of the underlying mechanism of oscillation.

biophysics↗