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Michaud, C.

Publications and source records attributed to Michaud, C..

10 recordsLinked to original sources

Effects of aging on multiple object tracking under normal and altered viewing conditions

Multiple object tracking (MOT) is a core function of dynamic visual attention that relies on the ability to simultaneously monitor several moving objects. Although MOT performance is known to decline with age, and to depend on efficient oculomotor strategies, how these processes interact across the adult lifespan and under degraded visual input remains poorly understood. Here, we examined the effects of aging on MOT under normal and gaze-contingent viewing conditions simulating central and peripheral visual field loss. Sixty participants aged 20-80 years completed a MOT task while eye movements were recorded, enabling characterization of performance and oculomotor behavior across five viewing conditions. Behavioral results revealed a continuous decline in tracking performance across adulthood, indicating a graded rather than categorical effect of age. Performance was strongly reduced by visual-field restrictions, with the largest impairments under central vision occlusion. Eye-tracking analyses showed that better performance was associated with greater reliance on centroid-based gaze strategies, consistent with distributed monitoring of target configurations. Critically, older adults relied more on focal, target-based tracking under conditions simulating peripheral vision loss, and less on centroid-based strategies; this shift was associated with poorer performance. In contrast, oculomotor behavior during full-field viewing was largely preserved across age. Together, these findings suggest that aging affects multiple object tracking through combined sensory, attentional, and oculomotor mechanisms. Beyond a reduction in capacity, age-related decline also reflects systematic changes in visual sampling strategies during dynamic tracking.

animal behavior and cognition↗

Connecting gene expression and cytokinin signaling during meristem determinacy transition in the rice panicle

Structural complexity in the rice inflorescence (panicle) is determined by the activity of indeterminate meristems, which allow sequential branching events to occur but later acquire a determinate character that precludes the initiation of new growth axes. To better understand the underlying regulatory processes, we combined a detailed time-course of panicle development with tissue-specific sampling of meristems before and after the determinacy switch, monitoring global gene expression programs and hormone accumulation. This allowed the delineation of three dynamic transcriptional modules and the inference of gene regulatory networks highlighting hormone regulatory hubs associated with the indeterminate-to-determinate meristem transition. Our data confirm the importance of known regulators of inflorescence development and identify novel actors, notably genes encoding transcription factors, that were not previously described in the regulation of flowering. The combined biochemical and transcriptomic data support a model in which cytokinin signalling is particularly active during the proliferative branching phase, during which meristem maintenance is promoted while a feedback mechanism is also triggered, ultimately leading to the acquisition of determinate meristem fate later in development. HighlightInvestigating the molecular nature of rice inflorescence meristem determinacy, we studied temporal and spatial gene expression alongside hormone accumulation, identifying novel regulatory interactions and a key role for cytokinins.

plant biology↗

Motion processing in visual cortex of maculopathy patients

Previous studies on animal models suggested that visual areas involved in motion processing could undergo important cortical reorganizations following retinal damages. This could have major implications for patients suffering from macular degeneration (MD), one leading cause of vision loss. Here, we performed fMRI recordings in a group of maculopathy patients (including individuals suffering from age-related macular degeneration or from Stargardts Disease) and a control group to characterize the motion processing cortical network in MD patients and determine whether this network is modified following the onset of the scotoma. We used an experimental protocol based on random-dot kinematograms (RDKs) classically employed to characterize motion-selective areas in the brain. To ensure that the visual information processed by the two groups was equivalent, the visual field in each control participant was masked using an artificial scotoma directly derived from clinical measurements in their paired patient. We found that in MD patients, translational motion elicited significant and robust activations in a restricted cortical network which included the human V5/MT+ complex (hMT+), areas V3A and V6, and a portion of primary visual areas (V1, V2 and V3) connected to peripheral vision. Importantly, the same patterns of responses were also observed in control participants. Moreover, the extent and strength of activation within these motion-selective areas did not differ significantly between the two groups. Altogether, these results suggest that in humans, the motion-selective network does not undergo significant large-scale cortical reorganizations following the onset of MD. Significance statementMotion processing in the visual cortex of patients with macular degeneration has never been characterized. Here, we performed fMRI recordings in 7 maculopathy patients and found robust motion-selective activations in a cortical network which included the human V5/MT+ complex (hMT+), areas V3A and V6, and a portion of primary visual areas connected to peripheral vision. These activations closely align with those reported in participants with normal vision in the literature and do not significantly differ from those measured in a group of age and gender-matched control participants who viewed the motion stimuli with a matched artificial scotoma. Altogether, our results suggest that the motion-selective network does not undergo significant large-scale reorganizations in maculopathy patients following the onset of the scotoma.

neuroscience↗

Point contact-restricted cAMP signaling controls ephrin-A5-induced axon repulsion

Signal transduction downstream of axon guidance molecules is essential to steer developing axons. Second messengers including cAMP are key molecules shared by a multitude of signaling pathways and are required for a wide range of cellular processes including axon pathfinding. Yet, how these signaling molecules achieve specificity for each of their downstream pathways remains elusive. Subcellular compartmentation emerged as a flexible strategy to reach such a specificity. Here, we show that point contact-restricted cAMP signals control ephrin-A5-evoked axon repulsion in vitro by modulating Focal Adhesion Kinase phosphorylation and the assembly and disassembly rate of point contacts. Consistently, preventing point contact-specific cAMP signals, in developing retinal ganglion cells in vivo alters the refinement of their terminal axonal arbor in the brain. Altogether, our study identifies point contacts as a compartment containing a local cAMP signal required for ephrin-A5-dependent axon guidance and highlights the crucial role of such subcellularly restricted second messenger signals in the wiring of neuronal circuits.

developmental biology↗

Lesion-specific suppression of YAP/TAZ by biomimetic nanodrug ameliorates atherosclerosis development

Atherosclerosis, characterized by the buildup of lipid-rich plaque on the vessel wall, is the primary cause of myocardial infarction and ischemic stroke. Recent studies have demonstrated that dysregulation of yes-associated protein 1 (YAP) and transcriptional coactivator with PDZ-binding domain (TAZ) contributes to plaque development, making YAP/TAZ potential therapeutic targets. However, systemic modulation of YAP/TAZ expression or activities risks serious off-target effects, limiting clinical applicability. To address the challenge, this study develops monocyte membrane-coated nanoparticles (MoNP) as a drug delivery vehicle targeting activated endothelium lining the plaque surface and utilizes MoNP to deliver verteporfin (VP), a potent YAP/TAZ inhibitor, for lesion-specific treatment of atherosclerosis. The results reveal that MoNP significantly enhance payload delivery to inflamed endothelial cells (EC) while avoiding phagocytic cells, and preferentially accumulate in atherosclerotic regions. MoNP-mediated delivery of VP substantially reduces YAP/TAZ expression, suppressing inflammatory gene expression and macrophage infiltration in cultured EC and mouse arteries exposed to atherogenic stimuli. Importantly, this lesion-targeted VP nanodrug effectively decreases plaque development in mice without causing noticeable histopathological changes in major organs. Collectively, these findings demonstrate a plaque-targeted and pathway-specific biomimetic nanodrug, potentially leading to safer and more effective treatments for atherosclerosis.

bioengineering↗

Cell-cycle status of male and female gametes during Arabidopsis reproduction

Fertilization in Arabidopsis thaliana is a highly coordinated process that begins with a pollen tube delivering the two sperm cells into the embryo sac. Each sperm cell can then fertilize either the egg or the central cell to initiate embryo or endosperm development, respectively. The success of this double fertilization process requires a tight cell cycle synchrony between the male and female gametes to allow karyogamy (nuclei fusion). However, the cell cycle status of the male and female gametes during fertilization still remains elusive as DNA quantification and DNA replication assays have given conflicting results1-4. Here, to reconcile these results, we quantified the DNA replication state by DNA sequencing and performed microscopic analyses of fluorescent markers covering all the phases of the cell cycle. We show that male and female gametes in Arabidopsis are both arrested prior to DNA replication at maturity and initiate their DNA replication only during fertilization.

plant biology↗

Toxoplasma gondii-s basal complex: the other apicomplexan business end is multifunctional

The Apicomplexa are famously named for their apical complex, a constellation of organelles at their apical end dedicated to invasion of their host cells. In contrast, at the other end of the cell, the basal complex (BC) has been in the limelight since it is much less prominent and specific functions were not immediately obvious. However, in the past decade a staggering array of functions have been associated with the BC, and strides have been made in understanding its structure. Here, these collective insights are supplemented with new data to provide an overview of the understanding of the BC in Toxoplasma gondii. The emerging picture is that the BC is a dynamic and multifunctional complex, with a series of (putative) functions. The BC has multiple roles in cell division: it is the site where building blocks are added to the cytoskeleton scaffold; it exerts a two-step stretch and constriction mechanism as contractile ring; and it is key in organelle division. Furthermore, the BC has numerous putative roles in import, such as the recycling of mother cell remnants, the acquisition of host-derived vesicles, possibly the uptake of lipids derived from the extracellular medium, and the endocytosis of micronemal proteins. The latter process ties the BC to motility, whereas an additional role in motility is conferred by Myosin C. Furthermore, the BC acts on the assembly and/or function of the intravacuolar network, which may directly or indirectly contribute to the establishment of chronic tissue cysts. Here we provide experimental support for molecules acting in several of these processes, and identify several new BC proteins critical to maintaining the cytoplasmic bridge between divided parasites. However, the dispensable nature of many BC components leaves many questions unanswered regarding its function. In conclusion, the BC in T. gondii is a dynamic and multifunctional structure at the posterior end of the parasite.

cell biology↗

Eoulsan 2: an efficient workflow manager for reproducible bulk, long-read and single-cell transcriptomics analyses

AO_SCPLOWBSTRACTC_SCPLOWO_ST_ABSMotivationC_ST_ABSCore sequencing facilities produce huge amounts of sequencing data that need to be analysed with automated workflows to ensure reproducibility and traceability. Eoulsan is a versatile open-source workflow engine meeting the needs of core facilities, by automating the analysis of a large number of samples. Its core design separates the description of the workflow from the actual commands to be run. This originality simplifies its usage as the user does not need to handle code, while ensuring reproducibility. Eoulsan was initially developed for bulk RNA-seq data, but the transcriptomics applications have recently widened with the advent of long-read sequencing and single-cell technologies, calling for the development of new workflows. ResultWe present Eoulsan 2, a major update that (i) enhances the workflow manager itself, (ii) facilitates the development of new modules, and (iii) expands its applications to long reads RNA-seq (Oxford Nanopore Technologies) and scRNA-seq (Smart-seq2 and 10x Genomics). The workflow manager has been rewritten, with support for execution on a larger choice of computational infrastructure (workstations, Hadoop clusters, and various job schedulers for cluster usage). Eoulsan now facilitates the development of new modules, by reusing wrappers developed for the Galaxy platform, with support for container images (Docker or Singularity) packaging tools to execute. Finally, Eoulsan natively integrates novel modules for bulk RNA-seq, as well as others specifically designed for processing long read RNA-seq and scRNA-seq. Eoulsan 2 is distributed with ready-to-use workflows and companion tutorials. Availability and implementationEoulsan is implemented in Java, supported on Linux systems and distributed under the LGPL and CeCILL-C licenses at: http://outils.genomique.biologie.ens.fr/eoulsan/. The source code and sample workflows are available on GitHub: https://github.com/GenomicParisCentre/eoulsan. A GitHub repository for modules using the Galaxy tool XML syntax is further provided at: https://github.com/GenomicParisCentre/eoulsan-tools Contacteoulsan@bio.ens.psl.eu

bioinformatics↗

A more complex basal complex: novel components mapped to the Toxoplasma gondii cytokinesis machinery portray an expanded hierarchy of its assembly and function

The basal complex (BC) of Toxoplasma gondii has an essential role in cell division but details on the mechanism are lacking. To promote insights in this process, reciprocal proximity based biotinylation was used to map the basal complex proteome. An assembled protein map was interrogated by spatiotemporal characterization of critical components as well as functionally by disrupting the expression of the components. Spatially, this revealed four proteins sub-complexes with distinct sub-structural BC localization. Temporally, several patterns were differentiated based on their first appearance and/or disappearance from the BC corresponding with different steps in BC development (initiation, expansion, constriction, maturation). We also identified a protein pre-ceding BC formation (BCC0) laid out in a 5-fold symmetry. This symmetry marks the apical annuli and site of alveolar suture formation. From here, it was determined that the apical cap is assembled in the apical direction, whereas the rest of the IMC expands in the basal direction, inspiring a new bi-directional daughter budding process. Furthermore, we discovered BCC4, an essential protein exclusively localizing to the BC during cell division. Although depletion of BCC4 did not prevent BC formation, it led to BC fragmentation at the mid-point of cell division. Based on these data, a model is presented wherein BCC4 and MORN1 stabilize each other and form a rubber band that implies an essential role for the BC in preventing the fraying of the basal end of the assembling daughter cytoskeleton scaffolds. Furthermore, one new component of the Myosin J and Centrin2 cluster was BCC1, a hypothetical protein whose depletion prevents the non-essential last step of BC constriction. Overall, the BC is a highly dynamic, multi-functional structure that is critical to the hierarchical assembly of the daughter parasites.

microbiology↗

Experimental evolution of virulence and associated traits in a Drosophila melanogaster - Wolbachia symbiosis

AO_SCPLOWBSTRACTC_SCPLOWEvolutionary theory predicts that vertically transmitted symbionts are selected for low virulence, as their fitness is directly correlated to that of their host. In contrast with this prediction, the Wolbachia strain wMelPop drastically reduces its Drosophila melanogaster host lifespan at high rearing temperatures. It is generally assumed that this feature is maintained because the D. melanogaster-wMelPop symbiosis is usually not exposed to environmental conditions in which the symbiont is virulent. To test this hypothesis, we submitted wMelPop-infected D. melanogaster lines to 17 generations of experimental evolution at a high temperature, while enforcing late reproduction by artificial selection. The fly survival was measured at different time points, as well as two traits that have been proposed to be causally responsible for wMelPop virulence: its relative density and the mean number of copies of octomom, an 8-genes region of the Wolbachia genome. We hypothesised that these conditions (high temperature and late reproduction) would select for a reduced wMelPop virulence, a reduced wMelPop density, and a reduced octomom copy number. Our results indicate that density, octomom copy number and virulence are correlated to each other. However, contrary to our expectations, we could not detect any reduction in virulence during the course of evolution. We discuss the significance of our results with respect to the evolutionary causes of wMelPop virulence.

evolutionary biology↗