Biology subjects

Laurent, E.

Publications and source records attributed to Laurent, E..

13 recordsLinked to original sources

bioRxiv2026

Inflections in adolescent cortical maturation signal psychopathology risk

Cerebral cortical maturation supports emotional, social, and cognitive development during adolescence1. Neurodevelopmental theories of psychiatric illnesses, which peak in onset around age 182, implicate subtle alterations in adolescent cortical development3. However, mechanistic links between cortical maturation and emergent psychopathology have remained elusive. This gap likely reflects a need for more nuanced understanding of cortical development4, larger, longitudinal samples powered to detect small effects,5 and more uniform image quality control.6 Using 29,482 structural MRI scans from 11,720 adolescents in the Adolescent Brain Cognitive Development (ABCD) study, we demonstrate reproducible differences in the contour and tempo of maturation across the cortical surface. Regional trajectories are robust to image quality variance and align with increasing functional specialization over time. Thicker cortex in early-maturing sensory regions predicts psychiatric symptoms as early as four years prior to their emergence, a pattern that subsequently spreads to association cortex. Overlap with spatially and temporally organized gene co-expression networks implicates prenatal programming of this sequence of maturation and its links to psychopathology. These findings present a novel, versatile neurodevelopmental framework for cortical maturation during adolescence that sequentially implicates sensory and association cortex in risk for emergent psychiatric symptoms.

neuroscience↗

bioRxiv2026

RNA helicase Drs1 gates 25S rRNA domain III incorporation during early nucleolar pre-60S maturation

Assembly of eukaryotic large ribosomal subunits (LSU) requires coordinated structural and compositional transitions within pre-60S particles, yet the underlying mechanisms remain poorly understood. Here, we show that the DEAD-box helicase Drs1 promotes early maturation across distinct regions of the pre-60S particle. Loss of Drs1 function causes accumulation of co-transcriptional intermediates retaining SSU processome components, indicating that Drs1 promotes timely separation of nascent LSU precursors from the small-subunit assembly pathway. Cryo-EM analyses reveal both a redistribution toward early nucleolar maturation states upon loss of Drs1, including Nsa1-deficient intermediates, and a confinement of Drs1-associated particles to states preceding stable incorporation of 25S rRNA domain III. Drs1 directly engages Erb1 through its unstructured N-terminal extension, promoting stable assembly of the Nop7-Erb1-Ytm1 module associated with domain III maturation. CRAC analysis localizes Drs1 to spatially clustered sites spanning the 5.8S and 25S rRNAs, encompassing domains I-IV. Together, these findings support a model in which Drs1 couples stabilization of assembly-factors with pre-rRNA remodeling across the pre-60S particle, thereby driving ordered early LSU maturation and the timed integration of domain III.

biochemistry↗

bioRxiv2025

Lipid nanoparticle supplementation enhances host metabolism in a model symbiotic cnidarian

Stable cnidarian-dinoflagellate symbiosis provides the trophic foundation of coral reef ecosystems. Understanding nutrient exchange underpinning this symbiosis grows increasingly urgent as reefs face accelerating threats from climate change, and the need for time-critical interventions to improve coral health via aquaculture. Lipid nanoparticles (LNPs), widely used as delivery vehicles in biomedical science, are emerging as a promising tool to supplement coral nutrition. However, physiological impacts of LNPs on cnidarians, including uptake, nutritional value, and holobiont response, remain largely unexplored. Here, we delivered empty, phosphatidylcholine LNPs to both symbiotic and aposymbiotic Exaiptasia diaphana, an anemone model for corals, and analyzed the host proteomic response via mass spectrometry. LNP supplementation elicited broad proteome shifts, with notable overlap between symbiosis- and LNP-induced protein expression. Proteins involved in lipid catabolism, lipid transport, {beta}-oxidation, lysosomal function, and protein translation were significantly more abundant, consistent with enhanced lipid processing and metabolic activity. LNP supplementation, like symbiosis, suppressed both asexual reproduction and the expression of a suite of predation- and digestion-associated venom proteins and proteases, suggesting a conserved "sated" phenotype in response to lipid supply. Variations in feeding frequency with Artemia had minimal impact, indicating that LNPs can be a robust supplement irrespective of primary feeding regime. These data demonstrate that adult Exaiptasia are capable of direct uptake of LNPs, offering a tool for probing lipid metabolism, signaling and symbiotic function in cnidarians. Moreover, the ability to manipulate host physiology using defined lipid formulations holds significant potential for advancing coral aquaculture stress resilience, including reef restoration strategies.

zoology↗

bioRxiv2024

Natural weed seed predators reduce crop yield loss due to weeds by 20% in cereal fields

While many herbicide active substances have been banned and weed infestation is a major threat to crop productivity, it is still unknown to what extent natural weed control provided by seed predators can help farmers manage weed communities. We aim to quantify the contribution of seed predators to crop productivity through weed control and to evaluate whether the magnitude of their influence depends on farming systems such as conservation agriculture. We set up 112 seed predator-exclusion cages in 28 cereal fields in France (14 pairs of conservation and conventional agriculture fields), surveyed weed emergence and biomass, measured crop yield and sampled the main seed predators: carabid beetles and rodents. We found that seed predators activity reduces the yield loss due to weeds by 20%. By extrapolation, it represents an economic gain of 285{euro}/ha. However, the yield loss remains at 60% below the maximum crop yield potential reached in the absence of weeds. Moreover, conservation agriculture enhances weed control, but this does not translate into increased crop yield. This study demonstrates the tangible importance of considering seed predators for weed control but highlights the need to combine this approach with weed control practices or to substantially redesign cropping systems to enhance the beneficial effects of biodiversity on crop productivity. Significance statementAlthough weed biomass is the main driver of decreasing the crop productivity worldwide and the use of herbicides is massively disparaged, we have not yet quantified the role played by on-farm biodiversity to control weeds. Using an experimental design set up in 28 commercial cereal fields in France, we showed that weed seed predators reduce crop yield loss due to weeds by 20%. By extrapolation, it represents an economic gain of 285{euro}/ha. However, in the absence of any other weed control practices, the yield loss remains at 60% below the maximum crop yield potential reached in the absence of weeds. This study demonstrates the quantitative importance of considering seed predators to design pesticide-free systems.

ecology↗

bioRxiv2023

Uncovering and mitigating bias in large, automated MRI analyses of brain development

Large, population-based MRI studies of adolescents promise transformational insights into neurodevelopment and mental illness risk 1, 2. However, MRI studies of youth are especially susceptible to motion and other artifacts 3, 4. These artifacts may go undetected by automated quality control (QC) methods that are preferred in high-throughput imaging studies, 5 and can potentially introduce non-random noise into clinical association analyses. Here we demonstrate bias in structural MRI analyses of children due to inclusion of lower quality images, as identified through rigorous visual quality control of 11,263 T1 MRI scans obtained at age 9-10 through the Adolescent Brain Cognitive Development (ABCD) Study6. Compared to the best-rated images (44.9% of the sample), lower-quality images generally associated with decreased cortical thickness and increased cortical surface area measures (Cohens d 0.14-2.84). Variable image quality led to counterintuitive patterns in analyses that associated structural MRI and clinical measures, as inclusion of lower-quality scans altered apparent effect sizes in ways that increased risk for both false positives and negatives. Quality-related biases were partially mitigated by controlling for surface hole number, an automated index of topological complexity that differentiated lower-quality scans with good specificity at Baseline (0.81-0.93) and in 1,000 Year 2 scans (0.88-1.00). However, even among the highest-rated images, subtle topological errors occurred during image preprocessing, and their correction through manual edits significantly and reproducibly changed thickness measurements across much of the cortex (d 0.15-0.92). These findings demonstrate that inadequate QC of youth structural MRI scans can undermine advantages of large sample size to detect meaningful associations.

neuroscience↗

bioRxiv2021

A novel effective live-attenuated human metapneumovirus vaccine candidate produced in the serum-free suspension DuckCelt-T17 cell platform

Human metapneumovirus (HMPV) is a major pediatric respiratory pathogen for which there is currently no specific treatment or licensed vaccine. Different strategies have been evaluated to prevent this infection, including the use of live-attenuated vaccines (LAVs). However, further development of LAV approaches is often hampered by the lack of highly efficient and scalable cell-based production systems that support worldwide vaccine production. In this context, avian cell lines cultivated in suspension are currently competing with traditional cell platforms used for viral vaccine manufacturing. We investigated whether the DuckCelt(R)-T17 avian cell line (Vaxxel) we previously described as an efficient production system for several influenza strains could also be used to produce a new HMPV LAV candidate (Metavac(R)), an engineered SH gene-deleted mutant of the A1/C-85473 strain of HMPV. To that end, we characterized the operational parameters of multiplicity of infection (MOI), cell density, and trypsin addition to achieve optimal production of the LAV Metavac(R) in the DuckCelt(R)-T17 cell line platform. We demonstrated that the DuckCelt(R)-T17 cell line is permissive and is well adapted to the production of the wild-type A1/C-85473 HMPV and the Metavac(R) vaccine candidate. Moreover, our results confirmed that the LAV candidate produced in DuckCelt(R)-T17 cells conserves its advantageous replication properties in LLC-MK2 and 3D-reconstituted human airway epithelium models, as well as its capacity to induce efficient neutralizing antibodies in a mouse model. Our results suggest that the DuckCelt(R)-T17 avian cell line is a very promising platform for scalable in-suspension serum-free production of the HMPV-based LAV candidate Metavac(R).

immunology↗

bioRxiv2021

Structure-guided glyco-engineering of ACE2 for improved potency as soluble SARS-CoV-2 decoy receptor

Infection and viral entry of SARS-CoV-2 crucially depends on the binding of its Spike protein to angiotensin converting enzyme 2 (ACE2) presented on host cells. Glycosylation of both proteins is critical for this interaction. Recombinant soluble human ACE2 can neutralize SARS-CoV-2 and is currently undergoing clinical tests for the treatment of COVID-19. We used 3D structural models and molecular dynamics simulations to define the ACE2 N-glycans that critically influence Spike-ACE2 complex formation. Engineering of ACE2 N-glycosylation by site-directed mutagenesis or glycosidase treatment resulted in enhanced binding affinities and improved virus neutralization without notable deleterious effects on the structural stability and catalytic activity of the protein. Importantly, simultaneous removal of all accessible N-glycans from recombinant soluble human ACE2 yields a superior SARS-CoV-2 decoy receptor with promise as effective treatment for COVID-19 patients.

biochemistry↗

bioRxiv2021

Making BrainWaves: Portable Brain Technologies in Biology Education

Neuroscience is one of the fastest growing STEM fields, yet its presence in K-12 science education is very limited, partially due to the lack of accessible teaching materials and tools. Here, we describe a new high school neuroscience curriculum ("BrainWaves"), where students utilize recent advances in low-cost, portable Electroencephalography (EEG) technology to investigate their own brain activity. This semester-long curriculum is supported by science mentors and an educational application that guides students through the process of recording and analyzing their own brain activity. Evaluation data collected in 5 public New York City schools in 2018/19 indicate significant positive shifts in content knowledge and self-efficacy among students who participated in BrainWaves compared to students in other courses of the same teacher. The quantitative findings are supported by interviews, where students reported increased appreciation for neuroscience and college readiness and discussed the benefits of collaborating with scientists and using portable brain technology in classrooms.

scientific communication and education↗

bioRxiv2021

Identification of lectin receptors for conserved SARS-CoV-2 glycosylation sites

New SARS-CoV-2 variants are continuously emerging with critical implications for therapies or vaccinations. All 22 N-glycan sites of SARS-CoV-2 Spike remain highly conserved among the variants B.1.1.7, 501Y.V2 and P.1, opening an avenue for robust therapeutic intervention. Here we used a comprehensive library of mammalian carbohydrate-binding proteins (lectins) to probe critical sugar residues on the full-length trimeric Spike and the receptor binding domain (RBD) of SARS-CoV-2. Two lectins, Clec4g and CD209c, were identified to strongly bind to Spike. Clec4g and CD209c binding to Spike was dissected and visualized in real time and at single molecule resolution using atomic force microscopy. 3D modelling showed that both lectins can bind to a glycan within the RBD-ACE2 interface and thus interferes with Spike binding to cell surfaces. Importantly, Clec4g and CD209c significantly reduced SARS-CoV-2 infections. These data report the first extensive map and 3D structural modelling of lectin-Spike interactions and uncovers candidate receptors involved in Spike binding and SARS-CoV-2 infections. The capacity of CLEC4G and mCD209c lectins to block SARS-CoV-2 viral entry holds promise for pan-variant therapeutic interventions.

molecular biology↗

bioRxiv2019

Brain-to-brain synchrony predicts long-term memory retention more accurately than individual brain measures

Little is known about the brain mechanisms that underpin how humans learn while interacting with one another in ecologically-valid environments (1-3). This is because cognitive neuroscientists typically measure one participant at a time in a highly constrained environment (e.g., inside a brain scanner). In the past few years, researchers have begun comparing brain responses across individuals (4-6) demonstrating that brain-to-brain synchrony can predict subsequent memory retention (7-9). Yet previous research has been constrained to non-interacting individuals. Surprisingly, the one study that was conducted in a group setting found that brain synchrony between students in a classroom predicted how engaged the students were, but not how much information they retained (10). This is unexpected because brain-to-brain synchrony is hypothesized to be driven, at least partially, by shared attention (11, 12), and shared attention has been shown to affect subsequent memory (13). Here we used EEG to simultaneously record brain activity from groups of four students and a teacher in a simulated classroom to investigate whether brain-to-brain synchrony, both between students and between the students and the teacher, can predict learning outcomes (Fig. 1A). We found that brain-to-brain synchrony in the Alpha band (8-12Hz) predicted students delayed memory retention. Further, moment-to-moment variation in alpha-band brain-to-brain synchrony discriminated between content that was retained or forgotten. Whereas student-to-student brain synchrony best predicted delayed memory retention at a zero time lag, student-to-teacher brain synchrony best predicted memory retention when adjusting for a [~]200 millisecond lag in the students brain activity relative to the teachers brain activity. These findings provide key new evidence for the importance of brain data collected simultaneously from groups of individuals in ecologically-valid settings.\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=173 SRC=\"FIGDIR/small/644047v2_fig1.gif\" ALT=\"Figure 1\">\nView larger version (43K):\norg.highwire.dtl.DTLVardef@21b335org.highwire.dtl.DTLVardef@7c9823org.highwire.dtl.DTLVardef@1e84b1dorg.highwire.dtl.DTLVardef@19b6f55_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOFigure 1.C_FLOATNO Experimental setup and timeline. (A) Four students and a teacher were concurrently measured with EEG during a science lesson; (B) The lesson comprised four mini-lectures, each followed by a post-test. Pre-test and delayed post-tests were administered one week prior to and one week following the EEG recording session.\n\nC_FIG HighlightsO_LIElectroencephalogram (EEG) was concurrently recorded in a simulated classroom from groups of four students and a teacher.\nC_LIO_LIAlpha-band (8-12Hz) brain-to-brain synchrony predicted students performance in a delayed post-test.\nC_LIO_LIMoment-to-moment variation in alpha-band brain-to-brain synchrony indicated what specific information was retained by students.\nC_LIO_LIWhereas student-to-student brain synchrony best predicted learning at a zero time lag, student-to-teacher brain synchrony best predicted learning when adjusting for a [~]200 millisecond lag in the students brain activity relative to the teachers brain activity.\nC_LI

neuroscience↗

bioRxiv2018

Super-resolution Molecular Map of Basal Foot Reveals Novel Cilium in Airway Multiciliated Cells

Motile cilia are beating machines that play a critical role in airway defense. During airway cell differentiation, hundreds of motile cilia are templated from basal bodies that extend a basal foot, an appendage that links motile cilia together to ensure beating coordination. This assembly has thus far escaped structural analysis because its size is below the resolution limit. Here, we determine the molecular architecture and identify basal foot proteins using a super-resolution-driven approach. Quantitative super-resolution image analysis shows that the basal foot is organized in three main regions linked by elongated coiled-coil proteins. FIB-SEM tomography and comparative super-resolution mapping of basal feet reveal that, among hundreds of motile cilia of an airway cell, a hybrid cilium with features of primary and motile cilia is harbored. The hybrid cilium is conserved in mammalian multiciliated cells and originates from parental centrioles. We further demonstrate that this novel cilium is a signalling centre whose cellular position is dependent on flow.

cell biology↗

bioRxiv2017

Bottom-up and top-down control of dispersal across major organismal groups: a coordinated distributed experiment

Organisms rarely experience a homogeneous environment. Rather, ecological and evolutionary dynamics unfold in spatially structured and fragmented landscapes, with dispersal as the central process linking these dynamics across spatial scales. Because dispersal is a multi-causal and highly plastic life-history trait, finding general drivers that are of importance across species is challenging but highly relevant for ecological forecasting.\n\nWe here tested whether two fundamental ecological forces and main determinants of local population dynamics, top-down and bottom-up control, generally explain dispersal in spatially structured communities. In a coordinated distributed experiment spanning a wide range of actively dispersing organisms, from protozoa to vertebrates, we show that bottom-up control, that is resource limitation, consistently increased dispersal. While top-down control, that is predation risk, was an equally important dispersal driver as bottom-up control, its effect depended on prey and predator space use and whether dispersal occurred on land, in water or in the air: species that routinely use more space than their predators showed increased dispersal in response to predation, specifically in aquatic environments. After establishing these general causes of dispersal, we used a metacommunity model to show that bottom-up and top-down control of dispersal has important consequences for local population fluctuations as well as cascading effects on regional metacommunity dynamics. Context-dependent dispersal reduced local population fluctuations and desynchronized dynamics between communities, two effects that increase population and community stability.\n\nOur study provides unprecedented insights into the generality of the positive resource dependency of dispersal as well as a robust experimental test of current theory predicting that predator-induced dispersal is modulated by prey and predator space use. Our experimental and theoretical work highlights the critical importance of the multi-causal nature of dispersal as well as its cascading effects on regional community dynamics, which are specifically relevant to ecological forecasting.

ecology↗

bioRxiv2017

Efficient genome editing in primary cells and in vivo using viral-derived "Nanoblades" loaded with Cas9/sgRNA ribonucleoproteins

Programmable nucleases have enabled rapid and accessible genome engineering in eukaryotic cells and living organisms. However, their delivery into target cells can be technically challenging when working with primary cells or in vivo. Using engineered murine leukemia virus-like particles loaded with Cas9/sgRNA ribonucleoproteins (\"Nanoblades\"), we were able to induce efficient genome-editing in cell lines and primary cells including human induced pluripotent stem cells, human hematopoietic stem cells and mouse bone-marrow cells. Transgene-free Nanoblades were also capable of in vivo genome-editing in mouse embryos and in the liver of injected mice. Nanoblades can be complexed with donor DNA for \"all-in-one\" homology-directed repair or programmed with modified Cas9 variants to mediate transcriptional up-regulation of target genes. Nanoblades preparation process is simple, relatively inexpensive and can be easily implemented in any laboratory equipped for cellular biology.

cell biology↗