Biology subjects

Roux, M.

Publications and source records attributed to Roux, M..

9 recordsLinked to original sources

bioRxiv2026

A 4,000-year genomic history of Bantu speakers from the Congo rainforest

The Congo rainforest was the heartland of the Bantu Expansion, yet its demographic history remains partially understood. We inferred past population dynamics using genomes from 960 sub-Saharan Africans, including four newly sequenced ancient individuals from Iroungou cave and 176 present-day individuals from Gabon. Bantu-speaking populations began differentiating ~4,000 years ago, preceding explosive population growth by a millennium. Distinct southward dispersals contributed to the ancestry of Bantu speakers in Gabon and elsewhere in sub-Saharan Africa, with the ~700-year-old Iroungou individuals providing the closest genetic proxies for the latter. Both Bantu speakers and hunter-gatherers from the Congo rainforest experienced a major demographic crisis ~1,500 years ago, coinciding with an archaeological hiatus. These findings illuminate early Bantu dispersals and the subsequent, unexplained collapse of rainforest populations.

genomics↗

bioRxiv2026

miR-10a-5p as a critical molecular regulator of dopaminergic impulsivity in the nucleus accumbens

Impulsive-compulsive disorders (ICDs), including pathological gambling, hypersexuality, and compulsive buying, are frequently precipitated by dopamine D2/3 receptor agonists such as pramipexole (PPX), yet the molecular mechanisms that confer individual vulnerability remain poorly understood. Impulsive choice, a core dimension of ICDs, is modulated by dopaminergic signaling within corticostriatal circuits, but the microRNAs (miRs) that potentially translate this signaling into persistent behavioral change have not been identified. Here, we combined a delay discounting task (DDT) with high-throughput miR sequencing in the dorsal striatum and nucleus accumbens (NAcc) of rats stratified by baseline impulsivity and subchronic PPX treatment. PPX increased impulsive choice selectively in low- and mid-impulsive rats, whereas high-impulsive rats remained unaffected, consistent with a ceiling effect. Among the differentially expressed miRs, miR-10a-5p emerged as the strongest candidate: it was constitutively elevated in high-impulsive rats and upregulated by PPX in low- and mid-impulsive animals in both regions, thereby paralleling the trait-dependent behavioral effect of the drug. In vivo viral-mediated overexpression of miR-10a-5p confirmed its predicted downregulation of the PI3K-AKT-mTOR and BDNF pathways in the striatum, and, critically, overexpression restricted to the NAcc, but not the dorsal striatum, was sufficient to increase impulsive choice, recapitulating the pro-impulsive effect of PPX. These findings identify miR-10a-5p as a critical molecular regulator of impulsivity through its activity in the NAcc, providing a mechanistic link between dopaminergic perturbation, trait vulnerability, and ICDs, and opening new avenues for the development of miR-directed therapeutic strategies for these disorders.

neuroscience↗

bioRxiv2025

A moss N-Acetyltransferase-MAPK protein controls 2D to 3D developmental transition via acetylation and phosphorylation changes

Post-translational modifications (PTMs) finetune plant responses to developmental and environmental cues by impacting protein activity, stability, localization and interaction landscape. In this study we identified a moss specific protein which combines two common PTMs: acetylation and phosphorylation. This protein originated from the fusion of a MAPK with an N-acetyltransferase, for which we named it Rosetta NATD-MAPK 1 (RAK1). Using biochemical methods, we demonstrated that RAK1 has acetyltransferase activity that is enhanced by activation of its MAPK domain. Phenotypical studies of rak1 knockout mutants revealed a role for RAK1 in the regulation of the 2D-to-3D growth transition. Through Mass Spectrometry we verified that defective 2D-to-3D transition in the mutants was caused by differentially regulated acetylation and phosphorylation events associated to metabolic reprogramming and 3D differentiation. Collectively, this study uncovers a previously unknown multidomain protein and provides insights into the interplay of PTMs during developmental reprogramming. TeaserAcetylation and phosphorylation changes modulate the 2D to 3D developmental transition in Physcomitrium patens.

plant biology↗

bioRxiv2022

The genomic landscape of contemporary western Remote Oceanians

The Vanuatu archipelago served as a gateway to Remote Oceania during one of the most extensive human migrations to uninhabited lands, ~3,000 years ago. Ancient DNA studies suggest an initial settlement by East Asian-related peoples that was quickly followed by the arrival of Papuan-related populations, leading to a major population turnover. Yet, there is uncertainty over the population processes and the sociocultural factors that have shaped the genomic diversity of ni-Vanuatu, who present nowadays among the worlds highest linguistic and cultural diversity. Here, we report new genome-wide data for 1,433 contemporary ni-Vanuatu from 29 different islands, including 287 couples. We find that ni-Vanuatu derive their East Asian- and Papuan-related ancestry from the same source populations and descend from relatively synchronous, sex-biased admixture events that occurred ~1,700-2,300 years ago, indicating a peopling history common to all the archipelago. However, East Asian-related ancestry proportions differ markedly across islands, suggesting that the Papuan-related population turnover was geographically uneven. Furthermore, we detect Polynesian ancestry arriving ~600-1,000 years ago to South Vanuatu in both Polynesian- and non-Polynesian-speaking populations. Lastly, we provide evidence for a tendency of spouses to carry similar genetic ancestry, when accounting for relatedness avoidance. The signal is not driven by strong genetic effects of specific loci or trait-associated variants, suggesting that it results instead from social assortative mating. Altogether, our findings provide insight into both the genetic history of ni-Vanuatu populations and how sociocultural processes have shaped the diversity of their genomes.

genomics↗

bioRxiv2021

Brain virtual histology with X-ray phase-contrast tomography Part II: 3D morphologies of amyloid-β plaques in Alzheimer's disease models

While numerous transgenic mouse strains have been produced to model the formation of amyloid-{beta} (A{beta}) plaques in the brain, efficient methods for whole-brain 3D analysis of A{beta} deposits are lacking. Moreover, standard immunohistochemistry performed on brain slices precludes any shape analysis of A{beta} plaques. The present study shows how in-line (propagation-based) X-ray phase-contrast tomography (XPCT) combined with ethanol-induced brain sample dehydration enables hippocampus-wide detection and morphometric analysis of A{beta} plaques. Performed in three distinct Alzheimer mouse strains, the proposed workflow identified differences in signal intensity and 3D shape parameters: 3xTg displayed a different type of A{beta} plaques, with a larger volume and area, greater elongation, flatness and mean breadth, and more intense average signal than J20 and APP/PS1. As a label-free non-destructive technique, XPCT can be combined with standard immunohistochemistry. XPCT virtual histology could thus become instrumental in quantifying the 3D spreading and the morphological impact of seeding when studying prion-like properties of A{beta} aggregates in animal models of Alzheimers disease. This is Part II of a series of two articles reporting the value of in-line XPCT for virtual histology of the brain; Part I shows how in-line XPCT enables 3D myelin mapping in the whole rodent brain and in human autopsy brain tissue. HighlightsO_LIX-ray phase-contrast tomography (XPCT) enables whole brain detection of A{beta} plaques C_LIO_LIMorphometric parameters of A{beta} plaques may be readily retrieved from XPCT data C_LIO_LINew shape parameters were successfully extracted from three Alzheimers disease models C_LIO_LIA Fiji-based "biologist-friendly" analysis workflow is proposed and shared C_LIO_LIXPCT is a powerful virtual histology tool that requires minimal sample preparation C_LI O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=120 SRC="FIGDIR/small/436908v2_ufig1.gif" ALT="Figure 1"> View larger version (39K): org.highwire.dtl.DTLVardef@7c3167org.highwire.dtl.DTLVardef@18f689eorg.highwire.dtl.DTLVardef@1d9c72org.highwire.dtl.DTLVardef@a027a_HPS_FORMAT_FIGEXP M_FIG Graphical abstract C_FIG

neuroscience↗

bioRxiv2020

MORFEE: a new tool for detecting and annotating single nucleotide variants creating premature ATG codons from VCF files

SummaryVariants in 5UTR regions that create upstream translation initiation AUG codons are a class of neglected non coding variations. When they associate with a premature stop codon and create upstream open reading frames (uORFs) whose translation competes with that of natural proteins, they can have strong impact on human diseases. We here describe MORFEE, a new bioinformatics tool that detects, annotates and predicts, from a standard VCF file, the creation of uORF by any 5UTR variants on uORF creation. MORFEE was applied to two genomic resources and identified candidate functional variants that could explain statistical association signals observed in the context of Genome Wide Association Studies or could be responsible for rare forms of diseases. In conclusion MORFEE is an easy-to-use tool complementary to existing ones that can help resolving genetic investigations that remained so far unfruitful. Availability and implementationMORFEE is written in R with code and package available at https://github.com/daissi/MORFEE. Contactdavid-alexandre.tregouet@inserm.fr; david-alexandre.tregouet@u-bordeaux.fr

bioinformatics↗

bioRxiv2020

A novel rare c. -39C>T mutation in the PROS1 5'UTR causing PS deficiency by creating a new upstream translation initiation codon and inhibiting the production of the natural protein.

Inherited Protein S deficiency (PSD) (MIM176880) is a rare automosal dominant disorder caused by rare mutations, mainly located in the coding sequence of the structural PROS1 gene, and associated with an increased risk of venous thromboembolism. To identify the molecular defect underlying PSD observed in an extended French pedigree with 7 PSD affected members in who no candidate deleterious PROS1 mutation was detected by Sanger sequencing of PROS1 exons and their flanking intronic regions or via a MLPA approach, a whole genome sequencing strategy was adopted. This led to the identification of a never reported C to T substitution at c.-39 from the natural ATG codon of the PROS1 gene that completely segregates with PSD in the whole family. This substitution ACG->ATG creates a new start codon upstream of the main ATG. We experimentally demonstrated that the variant generates a novel overlapping ORF and inhibits the translation of the wild type protein from the main ORF in HeLa cells. This work describes the first example of 5UTR PROS1 mutation causing PSD through the creation of an upstream ORF, a mutation that is not predicted to be deleterious by standard annotation softwares.

genetics↗

bioRxiv2018

OPTIMIR, a novel algorithm for integrating available genome-wide genotype data into miRNA sequence alignment analysis.

Next-generation sequencing is an increasingly popular and efficient approach to characterize the full set of microRNAs (miRNAs) present in human biosamples. MiRNAs detection and quantification still remain a challenge as they can undergo different post transcriptional modifications and might harbor genetic variations (polymiRs) that may impact on the alignment step. We present a novel algorithm, OPTIMIR, that incorporates biological knowledge on miRNA editing and genome-wide genotype data available in the processed samples to improve alignment accuracy. OPTIMIR was applied to 391 human plasma samples that had been typed with genome-wide genotyping arrays. OPTIMIR was able to detect genotyping errors, suggested the existence of novel miRNAs and highlighted the allelic imbalance expression of polymiRs in heterozygous carriers. OPTIMIR is written in python, and freely available on the GENMED website (http://www.genmed.fr/index.php/fr/) and on Github (github.com/FlorianThibord/OptimiR).

bioinformatics↗

bioRxiv2016

Analgesic effects of neurotensin agonists in a rat bone cancer pain model

Bone metastases are a source of intractable pain, resistant to conventional opioid and non-opioid analgesics. The neurotensin system represents a potential pathway toward bone cancer pain (BCP) relieve via the inhibition of its receptors NTS1 and NTS2. Capitalizing on our recent results using neurotensin analogs in inflammatory and neuropathic pain models, we here show, for the first time, a potential role for neurotensin receptors agonists in the treatment of BCP. The novel non-selective agonist JMV-2009 (300 g/kg) reversed mechanical allodynia in our rodent BCP model at both early and late stages of the disease. The NTS2-selective agonist JMV-431 (90 g/kg), in addition to anti-allodynia, also had an effect on weight bearing deficits. In parallel, we tested proven analgesics from several classes to put the effect of neurotensin analogs in perspective and found that morphine (3 mg/kg), tramadol (15 mg/kg) and amitriptyline (10 mg/kg) had mild effects on BCP while the cannabinoid nabilone (1 mg/kg) significantly reversed both allodynia and weight bearing deficits. Taken together, our results affirm the potential of the modulation of the neurotensin system for the development of new analgesics for the treatment of bone cancer pain.

pharmacology and toxicology↗