Biology subjects

Chevalier, R.

Publications and source records attributed to Chevalier, R..

5 recordsLinked to original sources

bioRxiv2022

Magnetic resonance imaging datasets with anatomical fiducials for quality control and registration

Tools available for reproducible, quantitative assessment of brain correspondence have been limited. We previously validated the anatomical fiducial (AFID) placement protocol for point-based assessment of image registration with millimetric (mm) accuracy. In this data descriptor, we release curated AFID placements for some of the most commonly used structural magnetic resonance imaging templates and datasets. The release of our accurate placements allows for rapid quality control of image registration, teaching neuroanatomy, and clinical applications such as disease diagnosis and surgical targeting. We release placements on individual subjects from four datasets (n = 132 subjects for a total of 15,232 fiducials) and more than 10 brain templates (4,288 fiducials), compiling over 300 human rater hours of annotation. We also validate human rater accuracy of released placements to be within 1-2 mm (using a total of 50,336 Euclidean distances), consistent with prior studies. Our data is compliant with the Brain Imaging Data Structure (BIDS) allowing for facile incorporation into modern neuroimaging analysis pipelines. Data is accessible on GitHub (https://github.com/afids/afids-data).

neuroscience↗

bioRxiv2022

Telomere Position Effect Over Long Distance acts as a genome-wide epigenetic regulator through a common cis- element.

Among epigenetic modifiers, telomeres, represent attractive modulators of the genome in part through position effects. Telomere Position Effect - Over Long Distances (TPE-OLD) modulates genes expression by changes in telomere-dependent long-distance loops, with a reach of 10Mb from a telomere. However, TPE-OLD remains poorly defined. To gain further insights into the genome-wide impact of telomere length on genomic and epigenomic regulation through TPE-OLD, we used cells with controlled telomere length combined to a genome wide transcriptome and methylome analysis. By integrating omics data, we identified a common cis-acting motif that behaves as an insulator or enhancer. Using reporter assays integrating this element, we uncovered the trans partners regulating this activity. Further exploiting our cellular model, we observed the depletion of one candidate factor, RBPJ, at TPE-OLD associated loci upon telomere shortening. We concluded that, at the genome-wide level, TPE-OLD is relayed by RBPJ binding Alu-like elements to telomeres that acts as enhancers. In response to external stimuli (i.e., Aging), TPE-OLD might act by coordinating telomere length to the action of Alu newly evolved enhancers in association with RBPJ.

molecular biology↗

bioRxiv2021

SMCHD1 variants may induce variegated expression in Facio Scapulo Humeral Dystophy and Bosma Arhinia and microphtalmia syndrome

An expanding number of genetic syndromes are linked to mutations in genes encoding factors that guide chromatin organization. Recently, distinct genetic syndromes have been linked to mutations in the SMCHD1 gene. However, the function of this non-canonical SMC protein remains partly defined in Human tissues. To address this question, we determined its epi-signature in type 2 Facio Scapulo Humeral Dystrophy (FSHD2) and Bosma Arhinia and Microphtalmia Syndrome (BAMS) linked to heterozygous mutations in this gene. By combining RNA-Seq, DNA methylation profiling and ChIP-Seq, we showed that SMCHD1 regulates repressed chromatin but also cis-regulatory elements and enhancers. Our results emphasize dual functions for SMCHD1, in chromatin compaction, chromatin insulation and gene regulation with variable outcomes and targets depending on tissues. We propose that altered DNA methylation and long-range chromatin organization at a number of loci required for development and tissue differentiation, trigger variegated gene expression in rare genetic diseases linked to heterozygous SMCHD1 mutations.

genetics↗

bioRxiv2020

Application of the Anatomical Fiducials Framework to a Clinical Dataset of Patients with Parkinsons Disease

Establishing spatial correspondence between subject and template images is necessary in neuroimaging research and clinical applications such as brain mapping and stereotactic neurosurgery. Our anatomical fiducials (AFIDs) framework has recently been validated to serve as a quantitative measure of image registration based on salient anatomical features. In this study, we sought to apply the AFIDs protocol to the clinic, focusing on structural magnetic resonance images obtained from patients with Parkinsons Disease (PD). We confirmed AFIDs could be placed to millimetric accuracy in the PD dataset with results comparable to those in normal control subjects. We evaluated subject-to-template registration using this framework by aligning the clinical scans to standard template space using a robust open preprocessing workflow. We found that registration errors measured using AFIDs were higher than previously reported, suggesting the need for optimization of image processing pipelines for clinical grade datasets. Finally, we examined the utility of using point-to-point distances between AFIDs as a morphometric biomarker of PD, finding evidence of reduced distances between AFIDs that circumscribe regions known to be affected in PD including the substantia nigra. Overall, we provide evidence that AFIDs can be successfully applied in a clinical setting and utilized to provide localized and quantitative measures of registration error. AFIDs provide clinicians and researchers with a common, open framework for quality control and validation of spatial correspondence and the location of anatomical structures, facilitating aggregation of imaging datasets and comparisons between various neurological conditions.

neuroscience↗

bioRxiv2018

Penetration Assessment of Dietary Supplements and Drugs through the Blood-Brain Barrier for Potential Treatment of Parkinson ‘s disease

Parkinsons disease (PD) is a progressive neurodegenerative disorder, affecting 2% of the population over the age of 60. To date, there is no disease modifying drugs to prevent dopaminergic neuron loss and abnormal protein deposition in the brains. There is a strong demand for neuroprotective therapies to prevent or slow down dopaminergic neuron degeneration. An essential prerequisite for a compound designed to affect the central nervous system (CNS) is a satisfactory transport through the blood brain barrier (BBB). Numerous posts on the net suggest that both repositioned drugs molecules and active molecules present in dietary supplements may slow down PDs progression. The logBB is an index of BBB permeability. Starting from quantitative and qualitative permeability data, this study tries to predict logBB values from various physicochemical properties of molecules, including, among others, molecular size, polar surface area (PSA) and logP values. Quantitative logBB models were implemented using MLP (multiple linear regression), PLS (Partial Least Square), AAKR (Auto Associative Kernel Regression) and ECM (Evolving Cluster Method). Qualitative models were carried out with SVM (Support Vector Method).\n\nThe paper estimates the BBB permeability of 39 molecules potentially able to slow down PDs progression and compares the performances of qualitative and quantitative machine learning method used. For information, the current study also gives a short overview of the state of the art on the potential impact of dietary supplements on PD.

neuroscience↗