Biology subjects

Martin, E. L.

Publications and source records attributed to Martin, E. L..

3 recordsLinked to original sources

bioRxiv2025

Investigating Rat-Brain Normal Tissue and Tumor FLASH Effects with a Novel Very High Energy Electron Beam

PurposeUltra-high dose rate (FLASH) irradiation is reported to reduce normal tissue toxicity while maintaining tumor control, however mechanism(s) remain obscure. To study FLASH mechanisms in brain tissue, we developed a novel experimental platform featuring a unique high-energy electron linear accelerator (High Intensity Gamma Source, HIGS) paired with an organotypic ex vivo brain metastasis model. MethodsWe varied inter-pulse spacing to modulate the mean dose rate (MDR) of our unique 35 MeV electron beam, while maintaining extremely high instantaneous dose rate (IDR), and used film dosimetry to characterize dosimetry and targeting accuracy. We combined this HIGS-FLASH beam with an organotypic rat brain slice/breast carcinoma co-culture model of brain metastasis to assess effects on normal and neoplastic tissues. Live cell and bioluminescence imaging demonstrated cancer cell growth effects, while normal tissue responses and immune activation were assessed with live cell imaging, cytokine profiles, and confocal microscopy. We performed comparison experiments with 20 MeV electrons from a Varian clinical linear accelerator (VCLA) operating at conventional dose rate. ResultsThe highest IDR of the HIGS-FLASH beam to-date was 20.7 {+/-} 0.6 MGy/s, with maximum MDR of 20.7 MGy/s (1 s pulse of 20.7 Gy). Beam targeting was accurate to < 1 mm and reproducible. HIGS-FLASH and VCLA dose rates equivalently decreased cancer cell growth. HIGS-FLASH irradiation significantly increased TNF and fractalkine levels and confocal microscopy revealed distinct changes in microglial morphology in normal brain slices, suggesting microglia activation following HIGS-FLASH irradiation. ConclusionsOur novel experimental platform produces extremely high dose rates and rapid normal/neoplastic tissue readouts for mechanistic research into the effects of FLASH radiation on the brain. HIGS-FLASH irradiation induces comparable cancer cell growth inhibition but differential effects on cytokines and microglial morphology, suggesting that acute innate immune responses may be involved in FLASH normal tissue effects in the brain.

cancer biology↗

bioRxiv2025

Larger larval sea lamprey (Petromyzon marinus) have longer survival times when exposed to the lampricide 3-trifluoromethyl-4-nitrophenol

Invasive sea lamprey (Petromyzon marinus) in the Laurentian Great Lakes have negatively impacted ecological and economically important fishes for nearly a century. To mitigate these effects, the lampricide 3-trifluoromethyl-4-nitrophenol (TFM) is applied annually on a rotating basis to selected Great Lakes tributaries to kill larval lamprey before they become juveniles, out-migrate to the lakes, and parasitize other fishes. It has been hypothesized that larval size (e.g., mass, length) may affect survival time in response to TFM. To test this hypothesis, we conducted an experiment with 8,611 larvae across four temporal replicates, in which TFM concentrations equivalent to those used in present-day stream treatments were applied for up to 18 hours. When examining the survival times of larval lamprey exposed to TFM, we found a significant, positive relationship between length, mass, toxicity, and their interactions. For every one mm increase in total length, a corresponding increase by one gram of mass reduced survival time by 0.4315 minutes [95% CI: 0.5283 - 0.2992] and vice versa (i.e., the significant interaction between length and mass revealed that as larvae increase in mass, the survival benefit to being longer decreases, and vice versa). The changes in total length and mass of larval sea lamprey stored in ethanol for four months was also quantified. The observation that five larvae survived well past the 12-hour time window of a typical TFM field treatment highlights the need for continuous monitoring and the development of new control strategies to ensure the continued effective management of this invasive species.

evolutionary biology↗

bioRxiv2022

The BNT162b2 mRNA SARS-CoV-2 vaccine induces transient afucosylatedIgG1 in naive but not antigen-experienced vaccinees

The onset of severe SARS-CoV-2 infection is characterized by the presence of afucosylated IgG1 responses against the viral spike (S) protein, which can trigger exacerbated inflammatory responses. Here, we studied IgG glycosylation after BNT162b2 SARS-CoV-2 mRNA vaccination to explore whether vaccine-induced S protein expression on host cells also generates afucosylated IgG1 responses. SARS-CoV-2 naive individuals initially showed a transient afucosylated anti-S IgG1 response after the first dose, albeit to a lower extent than severely ill COVID-19 patients. In contrast, previously infected, antigen-experienced individuals had low afucosylation levels, which slightly increased after immunization. Afucosylation levels after the first dose correlated with low fucosyltransferase 8 (FUT8) expression levels in a defined plasma cell subset. Remarkably, IgG afucosylation levels after primary vaccination correlated significantly with IgG levels after the second dose. Further studies are needed to assess efficacy, inflammatory potential, and protective capacity of afucosylated IgG responses. One sentence summaryA transient afucosylated IgG response to the BNT162b2 mRNA vaccine was observed in naive but not in antigen-experienced individuals, which predicted antibody titers upon the second dose.

immunology↗