Biology subjects

Bagley, E.

Publications and source records attributed to Bagley, E..

3 recordsLinked to original sources

bioRxiv2026

Differences in T-cell counts and neighborhood patterns in human colorectal adenomas and sessile serrated lesions

BackgroundT-cell responses influence recurrence and survival in colorectal cancer. T-cell subset distributions vary by molecular phenotype and location, shaping cytotoxic or immune-cold tumor immune microenvironments (TiMEs). However, the T-cell contexture and their spatial proximities within preinvasive lesions are not well characterized. MethodsWe analyzed sessile serrated lesions (SSLs), tubulovillous/villous adenomas (TVs), and tubular adenomas (TAs) from three completed studies (N=120). Whole-slide multiplex immunofluorescence was used to quantify eight T-cell subsets (CD4, CD8, Th1, Th17, Treg, Tc1, Tc17, TcTreg). Counts were compared by histology using a generalized linear mixed model with a negative binomial distribution, including an offset for total cell counts and adjusting for age, sex, anatomic location, and lesion size. Nearest-neighbor (NN) analyses assessed proximities of T-cell pairs across lesion types. ResultsTAs and SSLs had higher CD4 and CD8 T-cell counts compared with TVs (q<0.05). SSLs had lower Th17 counts than TAs (q<0.05) and compared with TVs leaned toward fewer Tregs (q=0.07). NN analysis showed that TVs, compared with SSLs and TAs, had increased Treg clustering. In contrast, TA versus SSL comparisons revealed predominant CD4 clustering with Th17, Th1, and CD8 subsets. ConclusionTVs are characterized by lower T-cell infiltration and a greater tendency for regulatory T-cell clustering, consistent with an immune-cold TiME relative to TAs. SSLs and TAs were both more immune-infiltrated than TVs, but SSLs appeared less inflamed and less dominated by regulatory subsets. In contrast, CD4dominant clustering in TAs suggested stronger helper coordination. Preinvasive lesions therefore demonstrate immune and spatial heterogeneity by lesion types.

pathology↗

bioRxiv2025

Orthorexia is associated with a paradoxical appetitive gastric response to unhealthy foods

Orthorexia involves an obsessive tendency towards "healthy" foods. It is a risk factor for eating disorders (anorexia nervosa and the proposed "orthorexia nervosa") and psychological distress, but its biological mechanism remains unknown. We hypothesised that this mechanism operates through the stomach: increased gastric power differentiates appetising from unappetising foods, vagal stimulation reduces food liking, and gastric proto-nausea can be evoked by disgust; all contributors to disordered eating. We used electrogastrography alongside high-density facial landmark tracking to gauge responses to minimally processed ("healthy"), highly processed ("unhealthy"), and culturally unaccepted ("disgusting") foods in a non-clinical sample (N=77). Trait orthorexia was associated with increased self-reported desire to eat healthy foods. Moreover, we found that higher orthorexia was associated with increasing disgust-related facial responses to unhealthy and disgusting foods. We then identified a relationship between food-healthiness ratings and gastric power: those who generally assigned lower healthiness ratings to foods showed higher gastric power for unhealthy than healthy foods, whereas those who expressed higher healthiness ratings showed higher gastric power for healthy over unhealthy foods. This suggests that the stomach tracks individual differences in eating preferences. Crucially, and contrary to our expectations, higher trait orthorexia was associated with a paradoxical increase in gastric power to unhealthy foods. One explanation is that higher gastric power for unhealthy foods reflects increased appetite for self-denied foods. Alternatively, orthorexia itself could be an adaptive response to exert stronger cognitive control over a pre-existing gastric appetite for unhealthy foods.

physiology↗

bioRxiv2017

Brief optogenetic inhibition of rat lateral or ventrolateral periaqueductal gray augments the acquisition of Pavlovian fear conditioning.

The midbrain periaqueductal gray (PAG) coordinates the expression and topography of defensive behaviors to threat and also plays an important role in Pavlovian fear learning itself. Whereas the role of PAG in expression of defensive behavior is well understood, the relationship between activity of PAG neurons and fear learning, the exact timing of PAG contributions to learning during the conditioning trial, and the contributions of different PAG columns to fear learning are poorly understood. We assessed the effects of optogenetic inhibition of lateral (LPAG) and ventrolateral (VLPAG) PAG neurons on fear learning. Using adenoassociated viral vectors expressing halorhodopsin (eNpHR3.0), we show that brief optogenetic inhibition of LPAG or VLPAG during delivery of the shock unconditioned stimulus (US) augments acquisition of contextual or cued fear conditioning and we also show that this inhibition augments post-encounter defensive responses to a non-noxious threat. Taken together, these results show that LPAG and VLPAG serve a key role in regulation of Pavlovian fear learning at the time of US delivery. These findings provide strong support for existing models which state that LPAG and VLPAG contribute to a fear prediction error signal determining variations in the effectiveness of the aversive US in supporting learning.

neuroscience↗