Biology subjects

Gill, B. J.

Publications and source records attributed to Gill, B. J..

2 recordsLinked to original sources

bioRxiv2025

Convection-enhanced delivery of dexamethasone in glioma suppresses myeloid inflammation while avoiding systemic toxicities

Dexamethasone is widely used to control cerebral edema and inflammation in glioblastoma, but its benefits are limited by systemic toxicities and adverse prognostic associations. We evaluated local administration of dexamethasone via convection-enhanced delivery (CED) to maximize intratumoral anti-inflammatory effects by increasing local corticosteroid exposure while minimizing systemic exposure. In two glioma mouse models, continuous intraparenchymal infusion of dexamethasone was well tolerated with no adverse effects. Pharmacokinetic analyses supported preferential intratumoral distribution and reduced systemic exposure with CED compared with systemic dosing. Single-nucleus RNA sequencing (snRNA-seq) and immunohistochemistry showed attenuation of glioma-associated inflammation with downregulation of reactive microglial/macrophage programs and reduced tumor-infiltrating myeloid cells with a morphology consistent with a less activated state. Experiments in human induced pluripotent stem cell (iPSC)-derived microglia confirmed that dexamethasone directly suppresses inflammatory gene expression, indicating a conserved mechanism across species. This inflammatory suppression was recapitulated in both immortalized microglial (HMC3) and macrophage (THP1) cell lines. These findings suggest that localized dexamethasone delivered by CED reprograms the glioma immune microenvironment and achieves control of inflammation without the systemic adverse effects associated with standard systemic dexamethasone therapy. This clinically translatable strategy may improve symptom management and provide a platform for integrating local immunomodulation with future glioblastoma therapies.

cancer biology↗

bioRxiv2020

Loss of graded enemy recognition in a Whitehead population allopatric with brood parasitic Long-tailed Cuckoos

Many avian hosts of brood parasitic birds discriminate between different types of threats and may respond with categorically different, specifically anti-predatory or anti-parasitic behaviors. Alternatively, hosts may adjust their responses to threat level in a graded manner, responding more aggressively to brood parasites during the laying and incubation stages of nesting, when nests are most susceptible to parasitism, and more aggressively to nest predators during the nestling and fledgling stages when predation would be more costly than parasitism. In New Zealand, endemic host Whiteheads act inconspicuously around their nests in the presence of sympatric Long-tailed Cuckoos, their obligate brood parasite, perhaps to avoid disclosing nest location. We tested behavioral responses of a Whitehead population on Tiritiri Matangi Island that has been breeding allopatrically from cuckoos for 17 years. We presented models of the allopatric parasite, a sympatric predator (Morepork Owl), and a sympatric non-threatening heterospecific (Song Thrush) during the egg and chick stages, and to groups of cooperatively breeding Whiteheads. We compared responses across nest stage and stimulus type. We found that, unlike sympatric Whiteheads elsewhere in New Zealand, Whiteheads on Tiritiri Matangi produced alarm calls in response to the cuckoo model. Furthermore, the rate of alarm calling was similar towards the cuckoo and the owl and across egg and chick stage and higher than to the control stimulus. These results are consistent with allopatric Whiteheads having lost their specific anti-parasitic defense tactics in response to brood parasitic cuckoos.

animal behavior and cognition↗