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Biology subjects

Jean, F.

Publications and source records attributed to Jean, F..

9 recordsLinked to original sources

Multiscale intraspecific variation and coordination of hydraulic traits in silver fir

O_LIIntraspecific variability in hydraulic and morphological traits may alter projections of forest vulnerability to climate change. Recognizing multiscale nature is essential, as trait relationships within populations may not reflect those across the species range. C_LIO_LIWe assessed variability in 11 traits in 10 natural populations of Abies alba across environmental and phylogeographic gradients to evaluate potential impacts on drought vulnerability. We quantified trait variation within and among populations, tested effects of climate, phylogeny and local factors, and evaluated trait coordination across scales. C_LIO_LIHydraulic safety traits and wood density showed low variability, indicating strong constraints. In contrast, water-use and efficiency traits were highly variable. Aridity influenced several traits, but reduced variance was detected only for leaf residual conductance and succulence consisted with stabilising selection. Trait coordination was weak within populations than among populations. C_LIO_LIOverall, A. alba combines constrained hydraulic safety traits with variable water use traits. This may buffer drought impacts but limits shifts in hydraulic safety margins, potentially increasing risks of hydraulic failure, especially in humid environments where populations lack the capacity to tolerate prolonged dry periods. Thus, our findings highlight the need to account for scale-dependent trait variability, coordination, and their underlying drivers when predicting species adaptive capacity to drought. C_LI

plant biology↗

Influence of organs, body size and growth and domoic acid depuration in the king scallop, Pecten maximus.

Since 1995, European fisheries of Pecten maximus faced the presence of Pseudo-nitzschia species, which are able to produce the neurotoxin domoic acid responsible for Amnesic Shellfish Poisoning (ASP). As filter-feeders, scallops can accumulate and retain domoic acid much longer than most of the other bivalves, from months to years. When concentrations exceed the regulatory threshold, fisheries are closed leading to economic crisis. Inter-individual variability increases the difficulty to predict the depuration dynamics. Quantifying the correlations between domoic acid depuration in P. maximus and individual physiological traits, particularly body size, could improve the understanding of contamination and depuration. In this study, toxin dynamics in organs were analysed and the effects of body size and growth were assessed. This analysis was based on two datasets, one experimental and one in situ, of depuration monitoring of P. maximus exposed to a natural bloom of toxic P. australis. Results show that the distribuwtion of domoic acid shifted among organs between the contamination and after two months of depuration. Toxin concentrations negatively correlate with body size during contamination and after two months of depuration, but shift to a positive correlation after 7 months of depuration. This shift suggests that the smaller scallops accumulate more domoic acid and depurate it faster. Thus, dilution by growth can explain the reversal of the correlation between domoic acid and body size throughout depuration. These results yield useful information for modelling such mechanisms, providing valuable tools for scallop fishery management facing ASP. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=60 SRC="FIGDIR/small/708139v3_ufig1.gif" ALT="Figure 1"> View larger version (16K): org.highwire.dtl.DTLVardef@10e61deorg.highwire.dtl.DTLVardef@13b44b9org.highwire.dtl.DTLVardef@1cdba6org.highwire.dtl.DTLVardef@989861_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIExperimental and in situ datasets allowed to quantify DA proportion dynamics in organs of P. maximus C_LIO_LIDA concentration and body size are negatively correlated during contamination phase, but positively correlated after a 7-month depuration C_LIO_LIConsidering dilution by growth is important for young scallops to assess DA depuration dy-namics C_LIO_LIBoth depuration rate and dilution by growth need to be considered to model DA depuration over the whole scallop size range C_LI

ecology↗

A 20-years comparative study of domoic acid depuration in king scallops, Pecten maximus, across French provinces.

Harmful Algal Blooms (HABs) can lead to fishery closures when toxin levels in commercial species exceed regulatory thresholds. Domoic acid (DA), the neurotoxin causing Amnesic Shellfish Poisoning (ASP), is particularly persistent in king scallops (Pecten maximus), a commercially valuable species in France. This species is known for its slow depuration rate compared to other species. As a result, anticipating DA dynamics is therefore a key to managing fishery openings in autumn, especially following spring contamination events. This study used 20 years of data from the French phycotoxin in-situ monitoring programme (REPHYTOX) to identify contamination events along the French Atlantic and English Channel coastlines. Depuration rates were estimated for 104 events; however, no correlation was found between depuration rate and province, time period, initial DA concentration or environmental conditions. Consequently, a median depuration rate was defined and applied in a widely used exponential decay model. In response to professionals needs, we developed a user-friendly predictive tool that estimates DA concentrations in king scallops based on sampling in spring or summer. We recommend performing DA quantification in scallops whenever DA is detected in other shellfish at the same location, and running the predictive model to anticipate DA content at the opening of the fishery season in autumn. This tool will help fishery managers to anticipate bans, to avoid unnecessary licence purchases, or to shift to alternative species. While developed using French data, the methodology is adaptable to other regions, with appropriate adjustments to reflect local ecological, regulatory and fishery contexts.

ecology↗

Beyond Proxies: Towards ecophysiological indicators of drought resistance for forest management

As drought-induced mortality increases globally in forest biomes, it becomes necessary for foresters to have access to reliable predictors of species vulnerability to drought and mortality risk under different climatic scenarios. On the one hand, there exist several "operational" indicators of drought resistance, which are based on observations, expert knowledge and species bioclimate (e.g. Ellenberg, Rameau, ClimEssences). On the other hand, as traits can now be measured at high throughput, functional traits (such as plant hydraulic traits) have been increasingly used to assess species vulnerability to hydraulic failure, a key process of tree mortality under drought. However, this mechanistic approach has never been compared to the operational approach. In this study, we review if indicators commonly used by foresters provide information on Abies species vulnerability to hydraulic failure. We measured a set of traits in a common garden experiment of closely related Mediterranean Abies species. These traits were used as inputs to the SurEau model to compute a single indicator of vulnerability (Time to Hydraulic Failure - THF) and to assess mortality risk in future climate. We found that among circum-Mediterranean firs, a high THF was mainly due to high water losses after stomatal closure. Some operational indicators are good proxies of THF, however they are not available for all species, reduce a species to a single value and have the same limitations as species distribution models. We argue that the ecophysiological approach could help foresters in species selection and in estimating the risk faced by forest tree species in a changing climate. While accounting for the variability of traits, hydraulic models can be forced with different climatic scenarios allowing hydraulic failure risk assessment by the end of the century. HighlightsO_LIIntegrating ecophysiological traits in a process-based model allows the computation of an accurate indicator of vulnerability: the Time to Hydraulic Failure (THF). C_LIO_LIFor Abies species, "operational" indicators, i.e. indicators used by foresters and land managers, are mutually consistent and can be simplified proxies of the vulnerability to hydraulic failure. C_LIO_LIMore research on intra-specific variability is needed to assess the evolutionary potential of Euro-Mediterranean Abies species. C_LI

ecology↗

Co-Contraction Embodies Uncertainty: An Optimal Feedforward Strategy for Robust Motor Control

Despite our environment is often uncertain, we generally manage to generate stable motor behaviors. While reactive control plays a major role in this achievement, proactive control is critical to cope with the substantial noise and delays that affect neuromusculoskeletal systems. In particular, muscle co-contraction is exploited to robustify feedforward motor commands against internal sensorimotor noise as was revealed by stochastic optimal open-loop control modeling. Here, we extend this framework to neuromusculoskeletal systems subjected to random disturbances originating from the environment. The analytical derivation and numerical simulations predict a singular relationship between the degree of uncertainty in the task at hand and the optimal level of anticipatory co-contraction. This prediction is confirmed through a single-joint pointing task experiment where an external torque is applied to the wrist near the end of the reaching movement with varying probabilities across blocks of trials. We conclude that uncertainty calls for impedance control via proactive muscle co-contraction to stabilize behaviors when reactive control is insufficient for task success. Author summaryThis work presents a computational framework for predicting how humans modulate muscle co-contraction to cope with uncertainties of different origins. In our neuromusculoskeletal system, uncertainties have both internal (sensorimotor noise) and external (environmental randomness) origins. The present study focuses on the latter type of uncertainty, which had not been dealt with systematically previously despite its importance in everyday life. Therefore, we thoroughly investigated how random disturbances occurring with some probability in a motor task shape the feedforward control of mechanical impedance through muscle co-contraction. Here we provide theoretical, numerical and experimental evidence that the optimal level of co-contraction steeply increases with the uncertainty of our environment. These findings show that muscle co-contraction embodies uncertainty and optimally mitigates its consequences on task execution when feedback control is insufficient due to sensory noise and delays.

neuroscience↗

A novel highly potent inhibitor of TMPRSS2-like proteases blocks SARS-CoV-2 variants of concern and is broadly protective against infection and mortality in mice

The COVID-19 pandemic caused by the SARS-CoV-2 virus remains a global public health crisis. Although widespread vaccination campaigns are underway, their efficacy is reduced against emerging variants of concern (VOCs) 1,2. Development of host-directed therapeutics and prophylactics could limit such resistance and offer urgently needed protection against VOCs 3,4. Attractive pharmacological targets to impede viral entry include type-II transmembrane serine proteases (TTSPs), such as TMPRSS2, whose essential role in the virus lifecycle is responsible for the cleavage and priming of the viral spike protein 5-7. Here, we identify and characterize a small-molecule compound, N-0385, as the most potent inhibitor of TMPRSS2 reported to date. N-0385 exhibited low nanomolar potency and a selectivity index of >106 at inhibiting SARS-CoV-2 infection in human lung cells and in donor-derived colonoids 8. Importantly, N-0385 acted as a broad-spectrum coronavirus inhibitor of two SARS-CoV-2 VOCs, B.1.1.7 and B.1.351. Strikingly, single daily intranasal administration of N-0385 early in infection significantly improved weight loss and clinical outcomes, and yielded 100% survival in the severe K18-human ACE2 transgenic mouse model of SARS-CoV-2 disease. This demonstrates that TTSP-mediated proteolytic maturation of spike is critical for SARS-CoV-2 infection in vivo and suggests that N-0385 provides a novel effective early treatment option against COVID-19 and emerging SARS-CoV-2 VOCs.

microbiology↗

The Axenfeld-Rieger syndrome gene FOXC1 contributes to left-right patterning

Normal body situs requires precise spatiotemporal expression of the Nodal-Lefty-Pitx2 cascade in the lateral plate mesoderm. The ultimate output of this patterning is establishment of the left-right axis, which provides vital cues for correct organ formation and function. Mutations, deletions and duplications in PITX2 and FOXC1 lead to the rare genetic disease Axenfeld-Rieger syndrome (ARS). While situs defects are not a recognised feature of ARS, partial penetrance of cardiac septal defects and valve incompetence is observed; both of these congenital heart defects (CHDs) also occur following disruption of left-right patterning. Here we investigated whether foxc1 genes have a critical role in specifying organ situs. We demonstrate that CRISPR/Cas9 generated mutants for the zebrafish paralogs foxc1a and foxc1b recapitulate ARS phenotypes including craniofacial dysmorphism, hydrocephalus and intracranial haemorrhage. Furthermore, foxc1a-/-; foxc1b-/- mutant animals display cardiac and gut situs defects. Modelling FOXC1 duplication by transient mRNA overexpression revealed that increased foxc1 dosage also results in organ situs defects. Analysis of known left-right patterning genes revealed a loss in expression of the NODAL antagonist lefty2 in the lateral plate mesoderm. Consistently, LEFTY2 mutations are known to cause human cardiac situs defects. Our data reveal a novel role for the forkhead-box transcription factor foxc1 in patterning of the left-right axis, and provide a plausible mechanism for the incidence of congenital heart defects in Axenfeld-Rieger syndrome patients. Author SummaryThis manuscript investigates the functional consequences of abrogating the activity of Foxc1 (Forkhead Box C1). We demonstrate that loss of zebrafish foxc1a and foxc1b results in phenotypes that resemble human patients with deletions in the FOXC1 locus. Notably, such phenotypes include alterations to the morphology of the heart. Investigations into the mechanisms underlying this phenotype led to the discovery that Foxc1 functions as a regulator of left-right patterning. Most components of left-right specification function normally in foxc1a/b mutants, but there is a pronounced loss of lefty2, a known inhibitor of Nodal signaling. This supports a model in which Foxc1 regulates situs of the heart via the regulation of Lefty2.

genetics↗

SUPER RESOLUTION MICROSCOPY AND DEEP LEARNING IDENTIFY ZIKA VIRUS REORGANIZATION OF THE ENDOPLASMIC RETICULUM

The endoplasmic reticulum (ER) is a complex subcellular organelle composed of diverse structures such as tubules, sheets and tubular matrices. Flaviviruses such as Zika virus (ZIKV) induce reorganization of endoplasmic reticulum (ER) membranes to facilitate viral replication. Here, using 3D super resolution microscopy, ZIKV infection is shown to induce the formation of dense tubular matrices associated with viral replication in the central ER. Viral non-structural proteins NS4B and NS2B associate with replication complexes within the ZIKV-induced tubular matrix and exhibit distinct ER distributions outside this central ER region. Deep neural networks trained to identify ZIKV-infected versus mock-infected cells successfully identified ZIKV-induced central ER tubular matrices as a determinant of viral infection. Super resolution microscopy and deep learning are therefore able to identify and localize morphological features of the ER and may be of use to screen for inhibitors of infection by ER-reorganizing viruses.

cell biology↗

Stochastic optimal open-loop control as a theory of force and impedance planning via muscle co-contraction

Understanding the underpinnings of biological motor control is an important issue in movement neuroscience. Optimal control theory is a leading framework to rationalize this problem in computational terms. Previously, optimal control models have been devised either in deterministic or in stochastic settings to account for different aspects of motor control (e.g. average behavior versus trial-to-trial variability). While these approaches have yielded valuable insights about motor control, they typically fail explain a common phenomenon known as muscle co-contraction. Co-contraction of agonist and antagonist muscles contributes to modulate the mechanical impedance of the neuromusculoskeletal system (e.g. joint stiffness) and is thought to be mainly under the influence of descending signals from the brain. Here we present a theory suggesting that one primary goal of motor planning may be to issue feedforward (open-loop) motor commands that optimally specify both force and impedance, according to the noisy neuromusculoskeletal dynamics and to optimality criteria based on effort and variance. We show that the proposed framework naturally accounts for several previous experimental findings regarding the regulation of force and impedance via muscle co-contraction in the upper-limb. Optimal feedback (closedloop) control, preprogramming feedback gains but requiring on-line state estimation processes through long-latency sensory feedback loops, may then complement this nominal feedforward motor command to fully determine the limbs mechanical impedance. The stochastic optimal open-loop control theory may provide new insights about the general articulation of feedforward/feedback control mechanisms and justify the occurrence of muscle co-contraction in the neural control of movement.\n\nAuthor summaryThis study presents a novel computational theory to explain the planning of force and impedance (e.g. stiffness) in the neural control of movement. It assumes that one main goal of motor planning is to elaborate feedforward motor commands that determine both the force and the impedance required for the task at hand. These feedforward motor commands (i.e. that are defined prior to movement execution) are designed to minimize effort and variance costs considering the uncertainty arising from sensorimotor noise. A major outcome of this mathematical framework is the explanation of a long-known phenomenon called muscle co-contraction (i.e. the concurrent contraction of opposing muscles). Muscle co-contraction has been shown to occur in many situations but previous modeling works struggled to account for it. Although effortful, co-contraction contributes to increase the robustness of motor behavior (e.g. small variance) upstream of sophisticated optimal feedback control processes that require state estimation from delayed sensory feedback to function. This work may have implications regarding our understanding of the neural control of movement in computational terms. It also provides a theoretical ground to explain how to optimally plan force and impedance within a general and versatile framework.

neuroscience↗