👤 Eric Mercier

Pain is one of the leading causes of disability worldwide. Despite the various pharmacological treatments available, patients with chronic pain often remain with significant disabilities and unsatisfactory pain control. Cannabis and cannabinoids are sometimes used in the treatment of chronic pain as they have been shown to be useful in a subset of patients. Some of the adverse effects associated with cannabis use, such as cannabis use disorder (CUD) and cannabis-induced psychosis, have been associated with several genetic variants. Despite this, the paucity of the data or the contradictory results for reported variants limits our ability to use them as genetic markers to personalize cannabis treatment tailored to patients’ genetic background. The aim of this genetic association study was to investigate the link between previously reported genes and cannabinoid response in terms of pain response, CUD and risk of psychotic adverse events in patients with chronic pain. Phone or in person interviews were conducted to document participants’ characteristics, cannabis use and effects, concurrent pharmacotherapy and comorbid conditions. Screening for CUD was performed using the Cannabis Use Disorders Identification Test – Revised. Blood or saliva samples were collected for the genotyping of 18 variants in 11 genes ( One hundred participants were recruited, with blood or saliva samples collected from 77 of them. Two single-nucleotide polymorphisms (SNP) in cannabinoid receptor 1 ( These results suggest alternative allele carriers of rs1049353 and rs2023239 could be at an increased risk of psychotic adverse events related to cannabis use, although additional investigation is required to replicate and confirm these findings. The online version contains supplementary material available at 10.1186/s42238-026-00408-w. Show less

Reading relies on the ability to map written symbols with speech sounds. A specific part of the left ventral occipitotemporal cortex, known as the Visual Word Form Area (VWFA), plays a crucial role in this process. Through the automatization of the mapping ability, this area progressively becomes specialized in written word recognition. Yet, despite its key role in reading, the area also responds to speech. This observation raises questions about the actual nature of neural representations encoded in the VWFA and, therefore, the underlying mechanism of the cross-modal responses. Here, we addressed this issue by applying fine-grained analyses of within- and cross-modal repetition suppression effects (RSEs) and Multi-Voxel Pattern Analyses in fMRI and sEEG experiments. Convergent evidence across analysis methods and protocols showed significant RSEs and successful decoding in both within-modal visual and auditory conditions, suggesting that populations of neurons within the VWFA distinctively encode written and spoken language. This functional organization of neural populations enables the area to respond to both written and spoken inputs. The finding opens further discussions on how the human brain may be prepared and adapted for an acquisition of a complex ability such as reading. Show less

Our use of language, which is profoundly social in nature, essentially takes place in interactive contexts and is shaped by precise coordination dynamics that interlocutors must observe. Thus, language interaction is highly demanding on fast adjustment of speech production. Here, we developed a real-time coupled-oscillators virtual partner (VP) that allows - by changing the coupling strength parameters - to modulate the ability to synchronise speech with a virtual speaker. Then, we recorded the intracranial brain activity of 16 patients with drug-resistant epilepsy while they performed a verbal coordination task with the VP. More precisely, patients had to repeat short sentences synchronously with the VP. This synchronous speech task is efficient to highlight both the dorsal and ventral language pathways. Importantly, combining time-resolved verbal coordination and neural activity shows more spatially differentiated patterns and different types of neural sensitivity along the dorsal pathway. More precisely, high-frequency activity (HFa) in left secondary auditory regions is highly sensitive to verbal coordinative dynamics, while primary regions are not. Finally, while bilateral engagement was observed in the HFa of the inferior frontal gyrus BA44 - which seems to index online coordinative adjustments that are continuously required to compensate deviation from synchronisation - interpretation of right hemisphere involvement should be approached cautiously due to relatively sparse electrode coverage. These findings illustrate the possibility and value of using a fully dynamic, adaptive, and interactive language task to gather deeper understanding of the subtending neural dynamics involved in speech perception, production as well as their interaction. Show less

Sulfur metabolites of methionine (Met) and vitamin E (VE) have antioxidant potential and can maintain liver health in chickens. This study explored the underlying mechanisms of Met sources, the ratio of total sulfur amino acids to lysine (TSAA: Lys), and VE levels on production performances, antioxidant potential, and hepatic oxidation in aged laying hens. Eight hundred and sixty-four, Hy-Line Brown laying hens (70-week age) were divided into 12 treatment groups, each having 6 repeats and 12 birds/each repeat. The dietary treatments consisted of DL-Met (DL-Met), DL-2-hydroxy-4-(methylthio)-butanoic acid (OH-Met), 3 ratios of TSAA: Lys (0.90, 0.95, and 1.00), and 2 levels of VE (20 and 40 g/ton). Albumen height and Haugh unit significantly increased at a lower level of VE (P < 0.05). Triglycerides (TG), total cholesterol (TC), low-density lipoprotein (LDL), and very low-density lipoprotein (VLDL) in serum and superoxide dismutase (SOD) and catalase activities (CAT) in the liver significantly reduced at 0.95 TSAA: Lys ratio (P < 0.05). Fatty acid synthase (FAS), lipoprotein lipase (LPL), nuclear factor erythroid 2-related factor 2 (Nrf2), and carnitine palmitoyltransferase-1 alpha (CPT-1α) also upregulated at this TSAA: Lys ratio (P < 0.05). Compared with the DL-Met group, the OH-Met group had lower Dipeptidyl Peptidase 4 (DPP4) and higher TC, LDL, and VLDL concentrations (P < 0.05).The expression of FAS,CPT-1α), glutathione (GSH), glutathione disulfide (GSSG), glutathione synthetase (GSS), and Nrf2 were significantly higher in OH-Met compared with the DL-Met group (P < 0.05). OH-Met at 0.95 and DL-Met at 0.90 TSAA: Lys ratio showed higher CAT and lower aspartate aminotransferase (AST) activities. Moreover, OH-Met at 0.90 and DL-Met at 0.95 of the TSAA: Lys ratio had a significant reduction of malondialdehyde (MDA) (P < 0.05). Overall, these results suggest that OH-Met source with a lower level of VE positively influenced production performance and improved liver health in aged laying hens through improved lipid metabolism and hepatic antioxidant function. Show less

Cross-language studies suggest more similarities than differences in how dysarthria affects the speech of people with Parkinson's disease (PwPD) who speak different languages. In this study, we aimed to identify the relative contribution of acoustic variables to distinguish PwPD from controls who spoke varieties of two Romance languages, French and Portuguese. This bi-national, cross-sectional, and case-controlled study included 129 PwPD and 124 healthy controls who spoke French or Portuguese. All participants underwent the same clinical examinations, voice/speech recordings, and self-assessment questionnaires. PwPD were evaluated French-speaking and Portuguese-speaking individuals were distinguished from each other with over 90% accuracy by five acoustic variables (the mean fundamental frequency and the shimmer of the sustained vowel /a/ production, the oral diadochokinesis performance index, the relative sound level pressure and the relative sound pressure level standard deviation of the text reading). A distinct set of parameters discriminated between controls and PwPD: for men, maximum phonation time and the oral diadochokinesis speech proportion were the most significant variables; for women, variables calculated from the oral diadochokinesis were the most discriminative. Acoustic variables related to phonation and voice quality distinguished between speakers of the two languages. Variables related to pneumophonic coordination and articulation rate were the more effective in distinguishing PwPD from controls. Thus, our research findings support that respiration and diadochokinesis tasks appear to be the most appropriate to pinpoint signs of dysarthria, which are largely homogeneous and language-universal. In contrast, identifying language-specific variables with the speech tasks and acoustic variables studied was less conclusive. Show less

Mice lacking the bHLH transcription factor (TF) Neurog3 do not form pancreatic islet cells, including insulin-secreting beta cells, the absence of which leads to diabetes. In humans, homozygous mutations of NEUROG3 manifest with neonatal or childhood diabetes. Despite this critical role in islet cell development, the precise function of and downstream genetic programs regulated directly by NEUROG3 remain elusive. Therefore, we mapped genome-wide NEUROG3 occupancy in human induced pluripotent stem cell (hiPSC)-derived endocrine progenitors and determined NEUROG3 dependency of associated genes to uncover direct targets. We generated a novel hiPSC line (NEUROG3-HA-P2A-Venus) where NEUROG3 is HA-tagged and fused to a self-cleaving fluorescent VENUS reporter. We used the CUT&RUN technique to map NEUROG3 occupancy and epigenetic marks in pancreatic endocrine progenitors (PEP) that were differentiated from this hiPSC line. We integrated NEUROG3 occupancy data with chromatin status and gene expression in PEPs as well as their NEUROG3-dependence. In addition, we investigated whether NEUROG3 binds type 2 diabetes mellitus (T2DM)-associated variants at the PEP stage. CUT&RUN revealed a total of 863 NEUROG3 binding sites assigned to 1263 unique genes. NEUROG3 occupancy was found at promoters as well as at distant cis-regulatory elements that frequently overlapped within PEP active enhancers. De novo motif analyses defined a NEUROG3 consensus binding motif and suggested potential co-regulation of NEUROG3 target genes by FOXA or RFX transcription factors. We found that 22% of the genes downregulated in NEUROG3 Mapping NEUROG3 genome occupancy in PEPs uncovered unexpectedly broad, direct control of the endocrine genes, raising novel hypotheses on how this master regulator controls islet and beta cell differentiation. Show less

Preeclampsia is a frequent complication of pregnancy and a leading cause of perinatal mortality. Both genetic and environmental risk factors have been identified. Lipid metabolism, particularly cholesterol metabolism, is associated with this disease. Liver X receptors alpha (NR1H3, also known as LXRalpha) and beta (NR1H2, also known as LXRbeta) play a key role in lipid metabolism. They belong to the nuclear receptor superfamily and are activated by cholesterol derivatives. They have been implicated in preeclampsia because they modulate trophoblast invasion and regulate the expression of the endoglin (CD105) gene, a marker of preeclampsia. The aim of this study was to investigate associations between the NR1H3 and NR1H2 genes and preeclampsia. We assessed associations between single nucleotide polymorphisms of NR1H3 (rs2279238 and rs7120118) and NR1H2 (rs35463555 and rs2695121) and the disease in 155 individuals with preeclampsia and 305 controls. Genotypes were determined by high-resolution melting analysis. We then used a logistic regression model to analyze the different alleles and genotypes for those polymorphisms as a function of case/control status. We found no association between NR1H3 SNPs and the disease, but the NR1H2 polymorphism rs2695121 was found to be strongly associated with preeclampsia (genotype C/C: adjusted odds ratio, 2.05; 95% CI, 1.04-4.05; p = 0.039 and genotype T/C: adjusted odds ratio, 1.85; 95% CI, 1.01-3.42; p = 0.049). This study provides the first evidence of an association between the NR1H2 gene and preeclampsia, adding to our understanding of the links between cholesterol metabolism and this disease. Show less

The aim of this study was to determine: (1) whether the Short Chain Fatty Acids (SCFA) Acetate, Propionate, and Butyrate enhance the synthesis and secretion of intestinal apolipoprotein A-IV-containing lipoproteins and (2) if so, whether these particles are able to promote cholesterol efflux in vitro. For this purpose Caco-2 cells were used for their functional properties of differentiated enterocytes. They were incubated with the three SCFA (2, 4, and 8 mM) for 48 h. Only butyrate stimulated apoA-IV gene expression and this was associated with an increase in apoA-IV secretion. A nondenaturing 2D-PAGE (agarose gel was followed by PAGE) was used to identify apoA-IV-containing lipoproteins in various media, and showed that butyrate stimulated the secretion of two small HDL sized particles. The influence of these secreted particles on cholesterol efflux was investigated using incubation of media with (3)H-cholesterol-labeled Fu5AH cells. The data indicate that conditioned media from Caco-2 cells treated with butyrate resulted in an increase of 20-30% in cholesterol efflux. We conclude that butyrate may regulate apoA-IV secretion and, therefore, modulate reverse cholesterol transport. Show less