Biology subjects

Leroy, E.

Publications and source records attributed to Leroy, E..

8 recordsLinked to original sources

bioRxiv2024

Humans anticipate the consequences of motor control demands when making perceptual decisions between actions

Animals, including humans, are often faced with situations where they must decide between potential actions to perform based on various sources of information, including movement parameters that incur time and energy costs. Consistent with this fact, many behavioral studies indicate that decisions and actions show a high level of integration during goal-directed behavior. In particular, motor costs very often bias the choice process of human and non-human subjects facing successive decisions between actions. However, it appears as well that depending on the design in which the experiment occurs, the effect of motor costs on decisions can vary or even vanish. This suggests a contextual dependence of the influence of motor costs on decision-making. Moreover, it is not currently known whether or not the impact of motor costs on perceptual decisions depend on the difficulty of the decision. We addressed these two important issues by studying the behavior of healthy human subjects engaged in a new perceptual decision-making paradigm in which the constraint level associated with the movement executed to report a choice was volitionally chosen by the participants, and in which the difficulty of the perceptual decision to make continuously evolved depending on their motor performance. The results indicate that the level of constraint associated with a movement executed to express a perceptual decision strongly impacts the duration of these decisions, with a shortening of decisions when these are expressed by demanding movements. This influence appears most important when the decisions are difficult, but it is also present for easy decisions. We interpret this strategy as an adaptive way to optimize the participants overall rate of success at the session level.

neuroscience↗

bioRxiv2024

A bifunctional snoRNA with separable activities in guiding rRNA 2'-O-methylation and scaffolding gametogenesis effectors

Small nucleolar RNAs are non-coding transcripts that guide chemical modifications of RNA substrates and modulate gene expression at the epigenetic and post-transcriptional levels. However, the extent of their regulatory potential and the underlying molecular mechanisms remain poorly understood. Here, we identify a conserved, previously unannotated intronic C/D-box snoRNA, termed snR107, hosted in the fission yeast long non-coding RNA mamRNA and carrying two independent cellular functions. On the one hand, snR107 guides site-specific 25S rRNA 2-O-methylation and promotes pre-rRNA processing and 60S subunit biogenesis. On the other hand, snR107 associates with the gametogenic RNA-binding proteins Mmi1 and Mei2, mediating their reciprocal inhibition and restricting meiotic gene expression during sexual differentiation. Both functions require distinct cis-motifs within snR107, including a conserved 2-O-methylation guiding sequence. Together, our results position snR107 as a dual regulator of rRNA modification and gametogenesis effectors, expanding our vision on the non-canonical functions exerted by snoRNAs in cell fate decisions.

molecular biology↗

bioRxiv2023

A dual, catalytic role for the fission yeast Ccr4-Not complex in gene silencing and heterochromatin spreading

AbstractHeterochromatic gene silencing relies on combinatorial control by specific histone modifications, the occurrence of transcription, and/or RNA degradation. Once nucleated, heterochromatin propagates within defined chromosomal regions and is maintained throughout cell divisions to warrant proper genome expression and integrity. The fission yeast Ccr4-Not complex has been involved in gene silencing, but its relative contribution to distinct heterochromatin domains and its role in nucleation versus spreading have remained elusive. Here, we unveil major functions for Ccr4-Not in silencing and heterochromatin spreading at the mating type locus and subtelomeres. Mutations of the catalytic subunits Caf1 or Mot2, involved in RNA deadenylation and protein ubiquitinylation respectively, result in impaired propagation of H3K9me3 and massive accumulation of nucleation-distal heterochromatic transcripts. Both silencing and spreading defects are suppressed upon disruption of the heterochromatin antagonizing factor Epe1. Overall, our results position the Ccr4-Not complex as a critical, dual regulator of heterochromatic gene silencing and spreading. Author SummaryEukaryotic genomes are partitioned into relaxed, gene-rich regions, and condensed, gene-poor domains called heterochromatin. The maintenance of heterochromatin is crucial for proper genome expression and integrity, and requires multiple factors regulating histone modifications and/or the levels of RNA molecules produced from these regions. Such effectors not only promote heterochromatin assembly but also ensure its propagation from specific nucleation sites to defined domain boundaries. However, while the mechanisms involved in initiation of heterochromatin formation have been well documented, the molecular and biochemical properties underlying its spreading remain largely elusive. By combining genetic and single-cell approaches, we report here that the fission yeast Ccr4-Not complex, a multisubunit complex conserved throughout eukaryotes, is essential for efficient heterochromatin spreading to repress expression of nucleation-distal RNAs. The two catalytic activities of the complex, RNA deadenylation and protein ubiquitinylation, are each critical, thereby defining a dual enzymatic requirement in the process.

genetics↗

bioRxiv2023

Integrated control of non-motor and motor efforts during decision between actions

Humans daily life is characterized by a succession of voluntary actions. Since energy resources are limited, the ability to invest the appropriate amount of effort for selecting and executing these actions is a hallmark of adapted behavior. Recent studies indicate that decisions and actions share important principles, including the exchange of temporal resources when the context requires it. In the present study, we test the hypothesis that the management of energy resources is shared between decision and action too. Healthy human subjects performed a perceptual decision task where they had to choose between two levels of effort to invest in making the decision, and report it with a reaching movement. Crucially, motor difficulty gradually increased from trial to trial depending on participants decision performance. Results indicate a relatively mild impact of the increasing motor difficulty on the choice of the non-motor (decision) effort to invest in each trial and on decision performance. By contrast, motor performance strongly decreased depending on both the motor and decisional difficulties. Together, the results support the hypothesis of an integrated management of energy resources between decision and action. They also suggest that in the context of the present task, the mutualized resources are primarily allocated to the decision-making process to the detriment of movements.

neuroscience↗

bioRxiv2022

African army ants at the forefront of virome surveillance in a remote tropical forest

In this study, we used a predator-enabled metagenomics strategy to sample the virome of a remote and difficult-to-access densely forested African tropical region. Specifically, we focused our study on the use of army ants of the genus Dorylus that are obligate collective foragers and group predators that attack and overwhelm a broad array of animal prey. Using 209 army ant samples collected from 29 colonies and the virion-associated nucleic acid-based metagenomics approach, we showed that a broad diversity of bacterial, plant, invertebrate and vertebrate viral sequences were accumulated by army ants: including sequences from 157 different viral genera in 56 viral families. This suggests that using predators and scavengers such as army ants to sample broad swathes of tropical forest viromes can shed light on the composition and the structure of viral populations of these complex and inaccessible ecosystems.

microbiology↗

bioRxiv2022

Constitutive Activation and Oncogenicity Are Mediated by Loss of Helical Structure at the Cytosolic Boundary of the Thrombopoietin Receptor

Dimerization of the thrombopoietin receptor (TpoR) is necessary for receptor activation and downstream signaling through activated Janus kinase 2. We have shown previously that different orientations of the transmembrane (TM) helices within a receptor dimer can lead to different signaling outputs. Here we addressed the structural basis of activation for receptor mutations S505N and W515K that induce myeloproliferative neoplasms. We show using in vivo bone marrow reconstitution experiments that ligand-independent activation of TpoR by TM asparagine (Asn) substitutions is proportional to the proximity of the mutation to the intracellular membrane surface. Solid-state NMR experiments on TM peptides indicate a progressive loss of helical structure in the juxtamembrane (JM) R/KWQFP motif with either proximity of Asn substitutions to the cytosolic boundary or mutation of W515 in the motif. Mutational studies in the TpoR cytosolic JM region show that the helical loss by itself can induce activation, but is localized to a maximum of 6 amino acids downstream of W515, the rest of the region until Box 1 requiring helicity for receptor function. The constitutive activation of TpoR mutants S505N and W515K can be inhibited by rotation of TM helices within the TpoR dimer, which also restores helicity around W515. Together these data allow us to develop a general model for activation and to explain the critical role of the JM W515 residue in the regulation of receptor activity. (Total manuscript without References and Figure Legends 6507 words, main text (without methods and materials):)

molecular biology↗

bioRxiv2021

Role of Ori in Thermococcus barophilus

The mechanisms underpinning replication of genomic DNA in Archaea have recently been challenged. Species belonging to two different taxonomic orders grow well in the absence of an origin of replication, challenging the role of the replication origin in these organisms. Here, we pursue the investigation of the particular way some archaea manage their DNA replication with Thermococcus barophilus and the role of Ori in this Archaea. Surprisingly we discovered that T. barophilus uses its Ori all along the growth curve with marked increase at the end of exponential phase. Through gene deletion, we show that Ori utilization requires Cdc6, and that origin deletion results in increased time in lag phase and a moderate decrease of growth rate in mutants. The number of chromosomes are quite similar between both strains during exponential and early stationary phases but differs after 24h of growth where {Delta}TbOriC has only 6 chromosomes/cell compared to 10 for the reference strain (WT). Following 1hr of growth in fresh media, {Delta}TbOriC strains contains 3 chromosome copies/cell, whereas the WT contains only 1. We hypothesize that the T. barophilus might degrade DNA to obtain energy to start replication and cell division, whereas the {Delta}TbOriC must maintain more chromosomal copies in order to initiate DNA replication in the absence of an origin or replication. Finally, we analyzed the role of Ori at temperatures above or below the optimal temperature, revealing that Ori is important to start growth at those temperatures, suggesting that replication origins may be involved in stress response.

microbiology↗

bioRxiv2020

At least seven distinct rotavirus genotype constellations in bats with evidence of reassortment and zoonotic transmissions

Bats host many viruses pathogenic to humans, and increasing evidence suggests that Rotavirus A (RVA) also belongs to this list. Rotaviruses cause diarrheal disease in many mammals and birds, and their segmented genomes allow them to reassort and increase their genetic diversity. Eighteen out of 2,142 bat fecal samples (0.8%) collected from Europe, Central America and Africa were PCR-positive for RVA and 11 of those were fully characterized using viral metagenomics. Upon contrasting their genomes with publicly available data, at least 7 distinct bat RVA genotype constellations (GCs) were identified, including evidence of reassortments and 6 novel genotypes. Some of these constellations are spread across the world, whereas others appear to be geographically restricted. Our analyses also suggest that several unusual human and equine RVA strains might be of bat RVA origin, based on their phylogenetic clustering, despite varying levels of nucleotide sequence identities between them. Although SA11 is one of the most widely used reference strains for RVA research and forms the backbone of a reverse genetics system, its origin remained enigmatic. Remarkably, the majority of the genotypes of SA11-like strains were shared with Gabonese bat RVAs, suggesting a potential common origin. Overall, our findings suggest an underexplored genetic diversity of RVAs in bats, which is likely only the tip of the iceberg. Increasing contact between humans and bat wildlife will further increase the zoonosis risk, which warrants closer attention to these viruses. ImportanceThe increased research on bat coronaviruses after SARS-CoV and MERS-CoVallowed the very rapid identification of SARS-CoV-2. This is an excellent example of the importance of knowing viruses harbored by wildlife in general and bats in particular, for global preparedness against emerging viral pathogens. The current effort to characterize bat rotavirus strains from 3 continents shed light on the vast genetic diversity of rotaviruses and also hinted at a bat origin for several atypical rotaviruses in humans and animals, implying that zoonoses of bat rotaviruses might occur more frequently than currently realized.

microbiology↗