Biology subjects

Frank, D. W.

Publications and source records attributed to Frank, D. W..

3 recordsLinked to original sources

bioRxiv2021

Phospholipid peroxidation fuels ExoU phospholipase-dependent cell necrosis and supports Pseudomonas aeruginosa-driven pathology

Regulated cell necrosis supports immune and anti-infectious strategies of the body; however, dysregulation of these processes drives pathological organ damage. Pseudomonas aeruginosa expresses a phospholipase, ExoU that triggers pathological host cell necrosis through a poorly characterized pathway. Here, we investigated the molecular and cellular mechanisms of ExoU-mediated necrosis. We show that cellular peroxidised phospholipids enhance ExoU phospholipase activity, which drives necrosis of immune and non-immune cells. Conversely, both the endogenous lipid peroxidation regulator GPX4 and the pharmacological inhibition of lipid peroxidation delay ExoU-dependent cell necrosis and improve bacterial elimination in vitro and in vivo. Our findings also pertain to the ExoU-related phospholipase from the bacterial pathogen Burkholderia thailandensis, suggesting that exploitation of peroxidised phospholipids might be a conserved virulence mechanism among various microbial phospholipases. Overall, our results identify an original lipid peroxidation-based virulence mechanism as a strong contributor of microbial phospholipase-driven pathology.

immunology↗

bioRxiv2018

A Neurophysiological Measure of Reward Sensitivity and its Limited Association with Anhedonia in Adolescents and Young Adults

Anhedonia (i.e., the attenuated ability to enjoy pleasurable stimuli) characterizes multiple mood disorders, but its neurophysiological underpinnings are not yet clear. Here, we measured event-related potentials in 116 adolescents and young adults engaged in a signal detection task designed to objectively characterize the anhedonic phenotype. In line with previous studies, the behavioral results showed that approximately 35% of the sample did not develop a response bias towards the more frequently rewarded stimuli (a sign of low hedonic capacity). The event-related potentials (ERPs) evoked by the reward feedback stimuli delivered during the task showed that individuals that did not develop a response bias had significantly less cortical positivity at Fz from 224 ms to 316 ms post feedback onset compared to those that developed a response bias during the task. However, further analyses showed that this between groups difference was relatively weak, as it disappeared when we controlled for response-locked ERPs. Furthermore, the response bias observed in the signal detection task was not strongly associated with self-reported ratings of hedonic capacity. We conclude that even though the signal detection task may be used as a reward sensitivity measure in neurotypical adolescents and young adults, this task may only be able to detect clinically significant levels of anhedonia in this particular population.

neuroscience↗

bioRxiv2017

The reality of "food porn": Larger brain responses to food-related cues than to erotic images predict cue-induced eating.

While some individuals can defy the lure of temptation, many others find appetizing food irresistible. Using event-related potentials, we showed that individuals who find food-related images more motivationally relevant than erotic ones (\"sign-trackers\") are more susceptible to cue-induced eating and, in the presence of a palatable food option, eat twice as much as individuals with the opposite brain reactivity profile (\"goal-trackers\"). These findings contribute to the understanding of the neurobiological basis of vulnerability to cue-induced behaviors.

neuroscience↗