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Girard, A.

Publications and source records attributed to Girard, A..

7 recordsLinked to original sources

Adaptive motility and feeding strategies of deep-branching predatory protists

Heterotrophic flagellates play a major role in nutrient recycling and shaping aquatic microbial communities. Many motile species have evolved diverse predatory strategies to exploit microbial prey, from bacteria to small eukaryotes. Excavates, deep-branching eukaryotic lineages with distinctive biflagellate morphology and conserved cytoskeletal features, exhibit varied feeding behaviours, including grazing, raptorial feeding, and filter-feeding. However, the temporal dynamics of their motility, feeding, and spatial distribution in relation to bacterial population density remain under-explored. Here, we quantify the behavioural ecology of excavates using high-resolution, single-cell tracking and quantitative analysis. Focussing on two Discoba species - the marine Jakoba libera and freshwater Reclinomonas americana - we identify different behavioural patterns: J. libera swims, forages and feeds, while R. americana swims and feeds. Prey availability differentially affects motility: J. libera increases the number of swimming cells when food is scarce, while R. americana shows the opposite trend. Spatial statistics reveal fundamental differences in their feeding and redistribution strategies. J. libera acts as an active forager, whereas R. americana behaves as a strict filter feeder. A third species, the anaerobic Kipferlia bialata (from a different clade), adopts a foraging strategy similar to J. libera. Together, these results elucidate the adaptive relationship between prey availability, feeding modes, and motility in bacteriovorous excavate flagellates, offering new insights into the ecological and evolutionary dynamics of microbial predators.

biophysics↗

Lipoprotein(a) promotes thrombosis through platelet activation and promotion of a lysis-resistant thrombus architecture

Elevated levels of lipoprotein(a) (Lp(a)) are an independent risk factor for the development of atherothrombotic diseases. However, it is unknown if Lp(a) directly promotes thrombus formation, inhibits thrombus clearance, or merely accelerates the underlying atherosclerotic processes that culminate in plaque rupture. While numerous studies indicate that the apolipoprotein(a) (apo(a)) component of Lp(a) can inhibit plasminogen activation and fibrinolysis, recent evidence suggests that these effects may not be retained in Lp(a). An alternative mechanism through which Lp(a) may promote atherothrombotic events is by impacting platelet function. However, the effects of Lp(a) on platelet function and thrombosis have never been directly assessed in blood clots formed from flowing whole blood. Using a transgenic mouse model expressing high plasma concentrations of apo(a), we showed using a laser-induced mesenteric vessel injury model employing intravital microscopy that apo(a) increased platelet and fibrin volumes in the thrombi without affecting fibrinolysis. In a ferric chloride-induced mouse carotid artery thrombosis model, we found that apo(a) substantially reduced occlusion times and led to more stable thrombi; importantly, we also demonstrated that the effects of Lp(a) could be mitigated by low-dose aspirin therapy. We evaluated the prothrombotic potential of Lp(a) in human blood clots formed under arterial flow conditions using a Chandler loop apparatus. In these studies, we showed that the presence of Lp(a) during thrombogenesis inhibited lysis of the thrombi, without directly impacting fibrinolysis. Lp(a) promoted platelet accumulation in the Chandler thrombi and facilitated the development of fibrin networks that displayed features of fibrinolysis resistance. In an analysis of the UK Biobank, participants with Lp(a) [≥]125 nmol/L had a higher risk for arterial thrombosis of non-atherosclerotic etiology but not a higher risk for venous thromboembolism. Collectively, these findings demonstrate that Lp(a) is inherently prothrombotic and likely promotes arterial thrombosis in vivo in part through promoting platelet activation. These findings explain how elevated Lp(a) is an important risk factor for arterial thrombosis either with or without an atherosclerotic etiology as well as observational primary prevention data suggesting that aspirin reduces atherothrombotic risk specifically in patients with elevated Lp(a).

biochemistry↗

IL-6 is a Key Factor in the Formation of Gut Tissue Resident Memory T Cells from Naïve T cells

Tissue resident memory CD4+ T cells (TRMs) populate mucosal sites and play a critical role in local immune responses. Gut TRM cells persist for extended periods in the gut mucosa where they rapidly respond to invading pathogens and provide long lasting protection. This study investigates the factors that mediate differentiation of naive CD4+ T cells into cells presenting a gut TRM phenotype. Naive CD4+ T cells were cultured under conditions that mimicked mucosal environments. This included signaling through MAdCAM-1 in the presence of Retinoic Acid (RA) and TGF-{beta}. This combination of stimuli primed naive CD4+ T cells to adopt a TRM phenotype. However, to fully differentiate into TRMs an additional soluble factor provided by memory T cells was required. Our results identified IL-6 as a key factor that induces the expression of TRM -associated markers, including CD69, CD103 and CCR5. This unique combination of stimuli promoted TRM differentiation despite low level proliferation. TRM differentiation was mediated through JAK/STAT signaling, and antagonists that target JAK/STAT pathways suppressed MAdCAM-1 mediated TRM cell formation. Our findings revealed that MAdCAM-1 works together with TGF-{beta}, RA and IL-6 in this process. Such information may aid in the design of next generation adjuvants and effective mucosal vaccines. Additionally, each of these factors may be targeted to treat excessive gut inflammation associated with conditions like inflammatory bowel disease. Overall, these findings provide new strategies aimed at modulating immune responses to invading pathogens and identify therapeutic approaches toward regulating gut inflammation. Author SummaryImmunologists and vaccinologists have long been interested in strategies aimed at boosting immune responses in mucosal tissues where pathogens are first encountered. Gut Tissue resident memory T cells (TRMs) play a central role in gut homeostasis and immunity. They provide a rapid long-lasting protection against pathogens. TRMs must target harmful pathogens and at the same time tolerate harmless commensal bacteria. This balance between immunity and tolerance in the complex environment of gut tissues is essential to the maintenance of gut homeostasis. In this study we have identified key factors present in the gut tissue milieu that are involved in TRM differentiation from naive T cells. These findings point to new therapeutic approaches that can potentially target immune responses in gut tissues and may help in developing effective mucosal vaccines. Conversely, these factors may be targeted in excessive gut inflammation involved in conditions like inflammatory bowel disease (IBD). Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=145 SRC="FIGDIR/small/660664v1_ufig1.gif" ALT="Figure 1"> View larger version (65K): org.highwire.dtl.DTLVardef@14e6015org.highwire.dtl.DTLVardef@860b93org.highwire.dtl.DTLVardef@61f8c8org.highwire.dtl.DTLVardef@142b48_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗

Interleukin-17 drives sex-dependent weight loss and changes in feeding behaviour during Trypanosoma brucei infection

In the skin, Trypanosoma brucei colonises the subcutaneous white adipose tissue (scWAT) and harbours a pool of parasites that are proposed to be competent for forward transmission. The interaction between parasites, adipose tissue, and the local immune system is likely to drive the adipose tissue wasting and weight loss observed in cattle and humans infected with T. brucei. However, mechanistically, the events leading to scWAT wasting are not fully understood. Here, using several complementary approaches, including mass cytometry by time of flight, bulk and single cell transcriptomics, and in vivo genetic models, we found that T. brucei infection drives local expansion of several IL-17A-producing cells in the murine WAT, including TH17 and V{gamma}6+ T cells. We also found that global IL-17 deficiency, or mice lacking IL-17 receptor expression exclusively in adipocytes, were protected from infection-induced WAT wasting and weight loss. Unexpectedly, we found that abrogation of IL-17 signalling in adipocytes results in a significant accumulation of Dpp4+ Pi16+ interstitial preadipocytes and a higher burden of extravascular parasites in the WAT, highlighting a critical role for IL-17 signalling in controlling preadipocyte fate, scWAT tissue dynamics, and local parasite burden. Taken together, our study highlights the central role of adipocyte IL-17 signalling in controlling WAT responses to infection, suggesting that adipocytes are a critical coordinator of the tissue dynamics and immune responses to T. brucei infection.

immunology↗

Automatic detection, identification and counting of anguilliform fish using in situ acoustic camera data: development of a cross-camera morphological analysis approach

Acoustic cameras are increasingly used in monitoring studies of diadromous fish populations, even though analyzing them is time-consuming. In complex in situ contexts, anguilliform fish may be especially difficult to identify automatically using acoustic camera data because the undulation of their body frequently results in fragmented targets. Our study aimed to develop a method based on a succession of computer vision techniques, in order to automatically detect, identify and count anguilliform fish using data from multiple models of acoustic cameras. Indeed, several models of cameras, owning specific technical characteristics, are used to monitor fish populations, causing major differences in the recorded data shapes and resolutions. The method was applied to two large datasets recorded at two distinct monitoring sites with populations of European eels with different length distributions. The method yielded promising results for large eels, with more than 75% of eels automatically identified successfully using datasets from ARIS and BlueView cameras. However, only 42% of eels shorter than 60 cm were detected, with the best model performances observed for detection ranges of 4-9 m. Although improvements are required to compensate for fish-length limitations, our cross-camera method is promising for automatically detecting and counting large eels in long-term monitoring studies in complex environments.

ecology↗

Predicting leaf traits across functional groups using reflectance spectroscopy

O_LIPlant ecologists use functional traits to describe how plants respond to and influence their environment. Reflectance spectroscopy can provide rapid, non-destructive estimates of leaf traits, but it remains unclear whether general trait-spectra models can yield accurate estimates across functional groups and ecosystems. C_LIO_LIWe measured leaf spectra and 22 structural and chemical traits for nearly 2000 samples from 104 species. These samples span a large share of known trait variation and represent several functional groups and ecosystems. We used partial least-squares regression (PLSR) to build empirical models for estimating traits from spectra. C_LIO_LIWithin the dataset, our PLSR models predicted traits like leaf mass per area (LMA) and leaf dry matter content (LDMC) with high accuracy (R2>0.85; %RMSE<10). Models for most chemical traits, including pigments, carbon fractions, and major nutrients, showed intermediate accuracy (R2=0.55-0.85; %RMSE=12.7-19.1). Micronutrients such as Cu and Fe showed the poorest accuracy. In validation on external datasets, models for traits like LMA and LDMC performed relatively well, while carbon fractions showed steep declines in accuracy. C_LIO_LIWe provide models that produce fast, reliable estimates of several widely used functional traits from leaf reflectance spectra. Our results reinforce the potential uses of spectroscopy in monitoring plant function around the world. C_LI

ecology↗

Polygenic risk scores of several subtypes of epilepsies in a founder population

ImportanceEpilepsy is defined as a group of neurological disorders characterized by epileptic seizures, brief episodes of symptoms that are caused by abnormal or excessive neuronal activity in the brain. Epilepsy affects around 3 percent of individuals. In the past 10 years, many groups have been working to better understand the complex genetic mechanisms underlying epilepsy. Together, they studied many different genetic mechanisms, but there is still a substantial missing heritability component in epilepsy genetics.\n\nObjectiveHere, we used polygenic risk scores (PRS) to quantify the cumulative effects of a number of variants, which may individually have a very small effect on susceptibility.\n\nDesignWe calculated PRS in 522 French-Canadian epilepsy patients divided into seven subtypes and French-Canadian controls.\n\nSettingAll study participants (cases and controls) were selected based on their French-Canadian ancestry.\n\nParticipantsThe epilepsy cohort was composed of families of at least three affected individuals with Idiopathic Generalized Epilepsy (IGE) or Non-acquired Focal Epilepsy (NAFE) previously collected and diagnosed by neurologists following the International League Against Epilepsy (ILAE) criteria.\n\nExposuresAll samples were processed on a common genotyping array.\n\nMain outcomes and ResultsWe show that the area under the curve (AUC) is almost always slightly greater than 0.5, especially in patients with IGE and subtypes. We also looked at the association of the PRS with the different phenotypes using a linear mixed effects model estimated by generalized estimating equation (GEE) with the pairwise identity-by-descent (IBD) matrix as a random effect. P-values of GEE were consistent with AUC calculations.\n\nConclusions and RelevanceGlobally, we support the notion that PRS and SNP-based heritability provide reliable measures to rightfully estimate the contribution of genetic factors to the pathophysiological mechanism of epilepsies, but further studies are needed on PRS before they can be used clinically.

genetics↗