Biology subjects

Chevalier, A.

Publications and source records attributed to Chevalier, A..

4 recordsLinked to original sources

bioRxiv2025

Stuck on you! Social brain stimulation increases the cognitive effort required to return to the egocentric perspective

Flexible switching between self and other perspectives is critical for adaptive social cognition and is thought to rely on the dynamic regulation of self-other representations. Although neuroimaging implicates the dorsomedial prefrontal cortex (dmPFC) and right temporoparietal junction (rTPJ) in perspective-taking, causal evidence for their specific contributions to perspective switching is lacking. Here, we applied focal transcranial direct current stimulation (f-tDCS) to the dmPFC and rTPJ while participants completed a visual perspective-taking task requiring switches between egocentric and altercentric viewpoints. Anodal stimulation to either site selectively increased the cognitive cost of switching back to the egocentric-perspective, without affecting switches into the altercentric-perspective. Rather than facilitating re-engagement with self-referential processing, stimulation enhanced altercentric persistence or impaired disengagement from the altercentric perspective. These findings provide novel causal evidence that both the dmPFC and rTPJ are involved in regulating the inhibition and updating of self-other representations during perspective switching. Results suggest that stimulation of these hubs may disrupt efficient realignment to the self, highlighting their role in maintaining an altercentric cognitive state. Future studies are required to uncover the precise neural computations that account for the comparable behavioural outcomes observed across distinct social brain hubs.

neuroscience↗

bioRxiv2023

HNF4a regulates acyl chain remodeling and ether lipid accumulation in hepatic steatosis

Hepatocyte nuclear factor 4 (HNF4) is an established transcriptional master regulator of differentiation, maintenance, and metabolism. Polymorphisms in HNF4 are linked to several diseases in humans including diabetes and nonalcoholic fatty liver disease (NAFLD). Identifying novel regulation of lipid metabolism by HNF4 would inform on NAFLD development and progression. We directly assessed HNF4 activity through chromatin immunoprecipitation (ChIP)-sequencing and integration of untargeted lipidomics. Direct regulation by HNF4 can be difficult to assess due to the role of HNF4 in liver homeostasis; to rapidly disrupt activity, mice were exposed to cold stress which induces hepatic steatosis in several hours. Cold exposure shifted HNF4 activity with differential genome occupancy of more than 50% of HNF4 binding sites. Focusing on HNF4 binding to promoter with active transcription determined that HNF4 directly regulates fatty acid desaturation, ether lipid synthesis, and peroxisomal biogenesis in response to cold exposure. Integration of lipidomics found that cold exposure increases the very long chain polyunsaturated fatty acid composition of the hepatic lipid pool, including ether lipids, in an HNF4 dependent manner. Because portions of ether lipid synthesis are in the peroxisome and peroxisomal biogenesis is directly HNF4 regulated, we analyzed peroxisomal abundance and found increases with cold exposure that are ablated with loss of HNF4. This peroxisomal regulation was independent of PPAR-- a known regulator of peroxisomes and lipid metabolism--since loss of HNF4 was not rescued by PPAR overexpression. These data determined that regulation of hepatic steatosis by HNF4 is more complex than triglyceride accumulation and includes acyl chain modifications, ether lipid synthesis, and peroxisomal oxidation.

molecular biology↗

bioRxiv2020

The Mutational Signature Comprehensive Analysis Toolkit (musicatk) for the discovery, prediction, and exploration of mutational signatures

Mutational signatures are patterns of somatic alterations in the genome caused by carcinogenic exposures or aberrant cellular processes. To provide a comprehensive workflow for preprocessing, analysis, and visualization of mutational signatures we created the Mutational Signature Comprehensive Analysis Toolkit (musicatk) package. musicatk enables users to select different schemas for counting mutation types and easily combine count tables from different schemas. Multiple distinct methods are available to deconvolute signatures and exposures or to predict exposures in individual samples given a pre-existing set of signatures. Additional exploratory features include the ability to compare signatures to the COSMIC database, embed tumors in two dimensions with UMAP, cluster tumors into subgroups based on exposure frequencies, identify differentially active exposures between tumor subgroups and plot exposure distributions across user-defined annotations such as tumor type. Overall, musicatk will enable users to gain novel insights into the patterns of mutational signature observed in cancer cohorts.

bioinformatics↗

bioRxiv2018

Chlamydia muridarum infection differentially changes smooth muscle contractility and responses to prostaglandins in uterus and cervix

Chlamydia trachomatis infection is a primary cause of reproductive tract diseases including chronic pelvic pain and infertility. Previous studies showed that this infection alters physiological activities in mouse oviducts. Whether this occurs in the uterus and cervix has never been investigated. This study characterized the physiological activity of the uterus and the cervix in a Chlamydia muridarum (Cmu) mouse model of reproductive tract infection. Uterine or cervix smooth muscle contractility, responses to oxytocin or prostaglandins (PGF2 and PGE2) and mRNA expression of oxytocin and PG receptors were assessed 14 days post infection. Cmu infection did not affect the contractions of the uterine horn but significantly decreased the contraction amplitude of the cervix. Cmu infection did not alter the responses of uterine horn or cervix to oxytocin, however PGF2 induced contractions of the uterine horn, but not the cervix, were significantly increased following Cmu infection. PGE2 contraction amplitude in both the uterine horn and cervix was unaffected by Cmu infection. An upregulation of Ptgfr and a down-regulation of Ptegr4 mRNA expression was observed in the uterine horn following Cmu infection. These results indicate that Cmu infection alters contractility and prostaglandin signalling in the female reproductive tract but the effects are localised to specific regions.

physiology↗