Biology subjects

Dupuis, M.

Publications and source records attributed to Dupuis, M..

3 recordsLinked to original sources

bioRxiv2023

Effects of sex and gonadal hormones on manually segmented hypothalamic and pituitary gland volumes in young healthy adults

The hypothalamus and pituitary regulate, amongst other functions, third order endocrine systems, and their volumes have been associated with normal and pathological outcomes. Yet, there are very few studies that examine their combined structural variations in vivo. This is due, in part, to their small size and a lack of comprehensive image segmentation protocols. In the current project we acquired high-resolution T1- (1mm isotropic) and T2-weighted (0.4mm in plane resolution) 3T magnetic resonance images (MRI) of the hypothalamus and pituitary gland, as well as salivary estradiol and testosterone from 31 (17M, 14F) young healthy adults. Women reported oral contraceptive use. Image preprocessing included non-uniformity correction, signal intensity normalization and standard stereotaxic space registration. We applied a comprehensive manual segmentation protocol of the whole hypothalamus, with detailed segmentation of the pituitary stalk, the anterior and posterior pituitary gland, and the posterior bright spot. We also propose a novel medial-lateral hypothalamic parcellation into medial preoptic, periventricular (PVN), and lateral hypothalamic regions. The protocol yielded good inter- (range: 0.78-0.92) and intra-rater (range: 0.79-0.94) Dice kappa overlap coefficients. We detected sex differences of the whole hypothalamus and each hemisphere, and a trend for the right preoptic region to be larger in males than in females, with a moderate effect size. Sex differences were maintained or enhanced when covarying for estradiol, but not when covarying for testosterone. In addition, testosterone was associated with the volume of the PVN, but only in women. In summary, these results suggest that there are morphometric differences at the level of the pituitary and hypothalamus that are likely driven by central regulation of gonadal hormones. The here described protocol allows the structural investigation of neuroendocrine effects in the central nervous system.

neuroscience↗

bioRxiv2019

Transketolase is involved in the control of Sigma B during chronic infection by Staphylococcus aureus

Staphylococcus aureus is a leading cause of both acute and chronic infections in humans. The importance of the pentose phosphate pathway (PPP) during S. aureus infection is currently largely unexplored. Here, we focused on one key PPP enzyme, transketolase. We showed that inactivation of the unique gene encoding transketolase activity in S. aureus USA300 ({triangleup}tkt) led to drastic metabolomic changes. Using time-lapse video imaging and mice infection, we observed a major defect of the {triangleup}tkt strain compared to wild-type strain in early intracellular proliferation and in the ability to colonise kidneys. Transcriptional activity of the two master regulators Sigma B and RpiRc was drastically reduced in the {triangleup}tkt mutant during host cells invasion. The concomitant increased RNAIII transcription, suggests that TKT-or a functional PPP-strongly influences the ability of S. aureus to proliferate within host cells by modulating key transcriptional regulators.

microbiology↗

bioRxiv2018

Persistent Staphylococcus aureus infections in children with chronic lung disease: a multi-omics analysis of bacterial adaptation to define novel therapeutic approaches

BackgroundChronic lung infection of cystic fibrosis (CF) patients by Staphylococcus aureus is a well-established epidemiological fact. Indeed, S. aureus is the most commonly identified pathogen in the lungs of CF patients. Strikingly the molecular mechanisms underlying S. aureus persistency are not understood.\n\nMethodsWe selected pairs of sequential S. aureus isolates from 3 patients with CF and from one patient with non-CF chronic lung disease. We used a combination of genomic, proteomic and metabolomic approaches with functional assays for in-depth characterization of S. aureus long-term persistence.\n\nResultsFor the first time, we show that late S. aureus isolates from CF patients have an increased ability for intracellular survival in CFBE-F508del cells compared to ancestral early isolates. Importantly, the increased ability to persist intracellularly was confirmed for S. aureus isolates within the own patient F508del epithelial cells. An increased ability to form biofilm was also demonstrated.\n\nFurthermore, we identified the underlying genetic modifications inducing altered protein expression profiles and notable metabolic changes. These modifications affect several metabolic pathways and virulence regulators that could constitute therapeutic targets.\n\nConclusionsOur results strongly suggest that the intracellular environment might constitute an important niche of persistence and relapse necessitating adapted antibiotic treatments.\n\nSummaryS. aureus persists for years in the lungs of patients with cystic fibrosis despite antibiotic therapies. We demonstrate that S. aureus adaptation leads to increased intracellular persistence suggesting a key role for intracellular niche during S. aureus chronic lung infection.

microbiology↗