Biology subjects

Sellers, R. S.

Publications and source records attributed to Sellers, R. S..

3 recordsLinked to original sources

bioRxiv2026

Ultrasonic Detection of Venous Gas Emboli and Tissue Gas in Rodents: Toward Imaging Biomarkers for Decompression Stress

Introduction In humans, decompression sickness (DCS) risk assessment often relies on surrogate ultrasound detection of venous gas emboli (VGE). Rodents are widely used to study DCS and mortality, yet no established relationship exists between imaging and decompression outcomes. We exposed rats to dives with differing DCS risk and investigated whether ultrasound measurements reflected modeled DCS risk and revealed tissue-level manifestations of decompression stress. Methods Rats underwent dry saturation exposures to 700 KPA in a hyperbaric chamber while breathing either heliox (low-risk; pDCS = 0.1%) or air (high-risk; pDCS = 13%), where pDCS was estimated using an existing rodent DCS risk model. Following decompression, animals were anesthetized for serial cardiac and renal ultrasound imaging. Echocardiograms were evaluated for VGE using an ordinal scale. The mean grayscale intensity (arbitrary units, a.u.) was also quantified in renal region of interest (ROI). In a separate set of animals, histopathology was conducted to evaluate renal manifestations. Results Observed peak VGE grades increased with estimated DCS risk, from grade 1 at pDCS 0.1% to grade 2 at pDCS 13%. Multi-organ analysis found lower renal ROI echogenicity during periods of high VGE, with mean grayscale intensities of 67.0 a.u. and 60.7 a.u. for VGE grades 0-1 and 2-4, respectively. Renal histopathology identified round voids consistent with pre-mortem gas emboli. Conclusions VGE burden tracked with pDCS risk. The decrease in renal image intensity during high VGE may indicate ultrasound attenuation from acoustic shadowing caused by excess tissue gas bubbles. These findings advance the development of physiologically relevant imaging biomarkers of decompression stress.

bioengineering↗

bioRxiv2025

Sex-Dependent Responses in Mice to Indomethacin-Induced Injury and Gut Microbiome-Targeted Alleviation

Nonsteroidal anti-inflammatory drugs (NSAIDs) are used widely but produce gastrointestinal (GI) toxicities in both short- and long-term users. Previous studies have shown that the intestinal microbiota play an important role in gut damage and that gut microbial {beta}-glucuronidase (GUS) inhibitors can alleviate NSAID-induced injury in male mice by blocking the GI reactivation of NSAID-glucuronides. Here, in both male and female C57BL/6 mice, we examine the effects of indomethacin alone and with the GUS inhibitor UNC10201652. Oral delivery of 5 mg/kg body weight indomethacin over five days decreased body weight, induced colonic and hepatic inflammatory cytokine gene expression, and enlarged the spleens of both male and female mice. However, sex-specific inflammatory responses to indomethacin were observed, with males demonstrating more colonic injury while females presented greater splenic and hepatic toxic responses. Females also showed a unique indomethacin-induced bloom of fecal Verrucomicrobia as measured by 16S rRNA metagenomic sequencing. UNC10201652 alleviated aspects of these indomethacin-induced toxicities, including features of the male-specific colonic damage and the female-specific compositional changes and spleen and liver toxicities. Thus, GI and non-GI tissues in male and female mice respond distinctly to indomethacin-induced damage. These findings advance our understanding of how sex impacts systemic responses to xenobiotic exposure and may lead to improved therapeutic outcomes with these widely used drugs.

biochemistry↗

bioRxiv2020

BNT162b vaccines are immunogenic and protect non-human primates against SARS-CoV-2

A safe and effective vaccine against COVID-19 is urgently needed in quantities sufficient to immunise large populations. We report the preclinical development of two BNT162b vaccine candidates, which contain lipid-nanoparticle (LNP) formulated nucleoside-modified mRNA encoding SARS-CoV-2 spike glycoprotein-derived immunogens. BNT162b1 encodes a soluble, secreted, trimerised receptor-binding domain (RBD-foldon). BNT162b2 encodes the full-length transmembrane spike glycoprotein, locked in its prefusion conformation (P2 S). The flexibly tethered RBDs of the RBD-foldon bind ACE2 with high avidity. Approximately 20% of the P 2S trimers are in the two-RBD down, one-RBD up state. In mice, one intramuscular dose of either candidate elicits a dose-dependent antibody response with high virus-entry inhibition titres and strong TH1 CD4+ and IFN{gamma}+ CD8+ T-cell responses. Prime/boost vaccination of rhesus macaques with BNT162b candidates elicits SARS-CoV-2 neutralising geometric mean titres 8.2 to 18.2 times that of a SARS-CoV-2 convalescent human serum panel. The vaccine candidates protect macaques from SARS-CoV-2 challenge, with BNT162b2 protecting the lower respiratory tract from the presence of viral RNA and with no evidence of disease enhancement. Both candidates are being evaluated in phase 1 trials in Germany and the United States. BNT162b2 is being evaluated in an ongoing global, pivotal Phase 2/3 trial (NCT04380701, NCT04368728).

immunology↗