Biology subjects

Hayes, J.

Publications and source records attributed to Hayes, J..

At least 19 recordsLinked to original sources

bioRxiv2026

Optimizing an avian influenza vaccine using a novel Bacterial Enzymatic Combinatorial Chemistry (BECC) TLR4 adjuvant

The development of broadly protective and dose-sparing influenza vaccines remains a critical challenge, particularly for zoonotic H5N1 strains with pandemic potential. This study evaluates BECC470s, a synthetic TLR4 adjuvant, for its ability to enhance the immunogenicity and protective efficacy of recombinant H5 hemagglutinin (rHA) vaccination in murine models. BECC470s-adjuvanted rHA elicited robust IgG1/IgG2a antibody responses and complete survival following homologous 2004 H5N1 challenge in a prime-boost model. Although BECC470s broadened antibody binding to both variable HA head and conserved stalk domains by ELISA, functional neutralizing antibody responses were restricted to the matched 2004 H5N1 isolate, with no detectable neutralization of H5N1 viruses isolated in 2022 or 2024. These data indicate that BECC470s enhances the magnitude and apparent breadth of binding antibody responses while maintaining strain-specific neutralizing activity, supporting its potential as an adjuvant for next-generation influenza vaccines while underscoring the need for further optimization to achieve true cross-neutralizing protection.

immunology↗

bioRxiv2025

Low levels of H5N1 HA and NA antibodies in the human population are boosted by seasonal A/H1N1 infection but not by A/H3N2 infection or influenza vaccination

An increase in the number of human cases of influenza A/H5N1 infection in the US has raised concerns about the pandemic potential of the virus. Preexisting population immunity is a key determinant for risk assessment and pandemic potential for any virus. Antibody responses against the bovine A/H5N1 hemagglutinin (HA) and neuraminidase (NA) proteins were measured among a population of influenza-vaccinated or influenza-infected individuals. Modest titers of bovine A/H5N1 HA-binding antibodies and low to undetectable neutralizing antibody responses were detected in a cohort of 73 individuals. Conversely, bovine A/H5N1 NA binding and neuraminidase-inhibiting antibody responses were comparable to those against a human A/H1N1 NA at baseline. Seasonal influenza vaccination failed to significantly increase antibody titers against both HA and NA glycoproteins of bovine A/H5N1. Recent infection with human A/H1N1 but not A/H3N2 viruses induced significant increases in bovine A/H5N1 neutralizing antibody, as well as increases in NA-binding and NA-inhibiting antibodies to bovine A/H5N1 NA. While the degree of protection afforded by these A/H5N1 cross-reactive antibodies is not known, incorporating NA or enhancing current seasonal vaccine formulations to increase NA-specific antibody responses may increase antibody breadth and protection against both seasonal and pandemic influenza viruses.

immunology↗

bioRxiv2025

Structural implications of glycosylation on the voltage-gated sodium channel β3-subunit

Voltage-gated sodium (NaV) channel -subunits are modulated by associated {beta}-subunits that affect their localization, trafficking and gating behaviour. The {beta}-subunits are members of the immunoglobulin (Ig) domain family of cell-adhesion molecules and the interactions between their extracellular Ig-domains may modify channel clustering. The full-length {beta}3-subunit can form cis trimers on the plasma membrane. The atomic resolution structure of a deglycosylated trimeric {beta}3-subunit Ig-domain has been solved by X-ray crystallography. However, it is not clear whether this particular trimeric Ig-domain structure is plausible for cell-expressed, glycosylated {beta}3-subunits. Here we use glycan profiling to confirm an extensive and heterogeneous pattern of {beta}3-subunit glycosylation, with the majority of glycans being bi- and tri-antennary structures with one or two terminal sialic acids. Two tryptic peptides of the {beta}3 Ig-domain are predicted to contain potential N-linked glycosylation sites. When the isolated, glycosylated full-length {beta}3-subunit was trypsin-digested and analysed by LC-MS/MS, only one of these peptides - containing an N-linked glycosylation site at residue N95 and located close to the trimer interface - was identified in its unmodified form, suggesting that residue N95 is under-glycosylated. All-atom molecular dynamics simulations of the glycosylated, membrane-bound full-length {beta}3 trimer confirmed that glycans can be accommodated with the Ig-domain trimer and indeed, may contribute to protein-membrane and inter-protomer interactions within the full-length, membrane-embedded trimer. Further biochemical studies are warranted to explore the interactions between oligomeric {beta}-subunits with corresponding -subunit sodium channels.

biochemistry↗

bioRxiv2025

Development of a Transcriptional Biosensor for Hydrogen Sulfide that Functions under Aerobic and Anaerobic Conditions

Hydrogen sulfide (H2S) is a gaseous gut metabolite with disputed effects on gastrointestinal health. Monitoring H2S concentration in the gut would provide insight into its role in disease, but is complicated by sulfides reactivity and volatility. Here we develop a transcriptional sulfide biosensor in E. coli. The sensor relies on enzymatic oxidation of sulfide catalyzed by a sulfide:quinone reductase (Sqr) to polysulfides, which bind to the repressor SqrR, triggering unbinding from the promoter and transcription of the reporter. Through promoter engineering and improving soluble SqrR expression, we optimized the system to provide an operational range of 50 {micro}M - 750 {micro}M and dynamic range of 18 aerobically. To enable sensing in anaerobic environments, we identified an Sqr from Wolinella succinogenes that uses menaquinone, facilitating reoxidation through the anaerobic electron transport chain by fumarate or nitrate. Use of this homolog resulted in an anaerobic H2S response up to 750 {micro}M. This sensor could ultimately enable spatially and temporally resolved measurements of H2S in the gastrointestinal tract to elucidate the role of this metabolite in disease, and potentially as a non-invasive diagnostic.

synthetic biology↗

bioRxiv2024

Linking phenology, harvest index and genetics to improve chickpea grain yield

Phenology is critical to crop adaptation. We grew 24 chickpea genotypes in 12 environments to analyse: the environmental and genotypic drivers of phenology; associations between phenology and yield; and phenotypes associated with allelic variants of three flowering related candidate loci: CaELF3a; a cluster of three FT genes on chromosome 3; and a region on chromosome 4 with an orthologue of the floral promoter GIGANTEA. A simple model with 3 genotype-specific parameters explained the differences in flowering response to daylength. Environmental factors causing flower abortion, such as low temperature and radiation and high humidity, led to a longer flowering-to-podding interval. Late podding associated with poor partition to grain, limiting yield in favourable environments. Sonali, carrying the early allele of Caelf3a (elf3a), was generally the earliest to set pod, had low biomass but the highest harvest index. Genotypes combining the early variants of GIGANTEA and FT orthologues FTdel, where a deletion in the intergenic region of FTa1-FTa2 was associated with slow development, usually featured early reproduction and high harvest index, returning high yield in favourable environments. We emphasise the importance of pod set, rather than flowering, as a target for breeding, agronomic, and modelling applications. HighlightThis paper analyses the environmental and genetic controls of chickpea phenology and its effects on grain yield, in a multi-environment trial including 24 genotypes with varying combinations of flowering related genes.

plant biology↗

bioRxiv2023

Integrating Patient Metadata and Genetic Pathogen Data: Advancing Pandemic Preparedness with a Multi-Parametric Simulator

Training and practice are needed to handle an unusual crisis quickly, safely, and effectively. Functional and table-top exercises simulate anticipated CBRNe (Chemical, Biological, Radiological, Nuclear, and Explosive) and public health crises with complex scenarios based on realistic epidemiological, clinical, and biological data from affected populations. For this reason, the use of anonymized databases, such as those from ECDC or NCBI, are necessary to run meaningful exercises. Creating a training scenario requires connecting different datasets that characterise the population groups exposed to the simulated event. This involves interconnecting laboratory, epidemiological, and clinical data, alongside demographic information. The sharing and connection of data among EU member states currently face shortcomings and insufficiencies due to a variety of factors including variations in data collection methods, standardisation practices, legal frameworks, privacy, and security regulations, as well as resource and infrastructure disparities. During the H2020 project PANDEM-2 (Pandemic Preparedness and Response), we developed a multi-parametric training tool to artificially link together laboratory data and metadata. We used SARS-CoV-2 and ECDC and NCBI open-access databases to enhance pandemic preparedness. We developed a comprehensive training procedure that encompasses guidelines, scenarios, and answers, all designed to assist users in effectively utilising the simulator. Our tool empowers training managers and trainees to enhance existing datasets by generating additional variables through data-driven or random simulations. Furthermore, it facilitates the augmentation of a specific variables proportion within a given set, allowing for the customization of scenarios to achieve desired outcomes. Our multi-parameter simulation tool is contained in the R package Pandem2simulator, available at https://github.com/maous1/Pandem2simulator. A Shiny application, developed to make the tool easy to use, is available at https://uclouvain-ctma.Shinyapps.io/Multi-parametricSimulator/. The tool runs in seconds despite using large data sets. In conclusion, this multi-parametric training tool can simulate any crisis scenario, improving pandemic and CBRN preparedness and response. The simulator serves as a platform to develop methodology and graphical representations of future database-connected applications.

bioengineering↗

bioRxiv2022

Patterns and determinants of the global herbivorous mycobiome

In spite of their indispensable role in host nutrition, the anaerobic gut fungal (AGF) component of the herbivorous gut microbiome remains poorly characterized. To examine global patterns and determinants of AGF diversity, we generated and analyzed an amplicon dataset from 661 fecal samples from 34 animal species, 9 families, and 6 continents. We identified 56 novel genera, greatly expanding AGF diversity beyond current estimates. Both stochastic (homogenizing dispersal and drift) and deterministic (homogenizing selection) processes played an integral role in shaping AGF communities, with a higher level of stochasticity observed in foregut fermenters. Community structure analysis revealed a distinct pattern of phylosymbiosis, where host-associated (animal species, family, and gut type), rather than ecological (domestication status and biogeography) factors predominantly shaped the community. Hindgut fermenters exhibited stronger and more specific fungal-host associations, compared to broader mostly non-host specific associations in foregut fermenters. Transcriptomics-enabled phylogenomic and molecular clock analyses of 52 strains from 14 genera indicated that most genera with preferences for hindgut hosts evolved earlier (44-58 Mya), while those with preferences for foregut hosts evolved more recently (22-32 Mya). This pattern is in agreement with the sole dependence of herbivores on hindgut fermentation past the Cretaceous-Paleogene (K-Pg) extinction event through the Paleocene and Eocene, and the later rapid evolution of animals employing foregut fermentation strategy during the early Miocene. Only a few AGF genera deviated from this pattern of co-evolutionary phylosymbiosis, by exhibiting preferences suggestive of post-evolutionary environmental filtering. Our results greatly expand the documented scope of AGF diversity and provide an ecologically and evolutionary-grounded model to explain the observed patterns of AGF diversity in extant animal hosts.

microbiology↗

bioRxiv2022

Resolution doubling in light-sheet microscopy via oblique plane structured illumination

Structured illumination microscopy (SIM) doubles the spatial resolution of a fluorescence microscope without requiring high laser powers or specialized fluorophores. However, the excitation of out-of-focus fluorescence can accelerate photobleaching and phototoxicity. In contrast, light-sheet fluorescence microscopy (LSFM) largely avoids exciting out-of-focus fluorescence, thereby enabling volumetric imaging with low photo-bleaching and intrinsic optical sectioning. Combining SIM with LSFM would enable gentle 3D imaging at doubled resolution. However, multiple orientations of the illumination pattern, which are needed for isotropic resolution doubling in SIM, are challenging to implement in a light-sheet format. Here we show that multidirectional structured illumination can be implemented in oblique plane microscopy, a LSFM technique that uses a single objective for excitation and detection, in a straightforward manner. We demonstrate isotropic lateral resolution below 150nm, combined with lower photo-toxicity compared to traditional SIM systems and volumetric acquisition speed exceeding 1Hz.

biophysics↗

bioRxiv2022

Incertohypothalamic A13 dopaminergic neurons are involved in fine forelimb movements but not reward

Tyrosine hydroxylase (TH)-containing neurons of the dopamine (DA) cell group A13 are well-positioned to impact known dopamine-related functions since their descending projections innervate target regions that regulate vigilance, sensorimotor integration and execution. Despite this known connectivity little is known regarding the functionality of A13-DA circuits. Using TH-specific loss-of-function methodology and techniques to monitor population activity in transgenic rats in vivo we investigated the contribution of A13-DA neurons in reward and movement-related actions. Our work demonstrates a role for A13-DA neurons in grasping and handling of objects that is independent from reward. A13-DA neurons respond strongly when animals grab and manipulate food items while their inactivation or degeneration prevents animals from successfully doing so - a deficit partially attributed to a reduction in grip strength. In contrast, there was no relation between A13-DA activity and food-seeking behavior when animals were tested on a reward-based task that did not include a reaching/grasping response. Moreover, motivation for food was unaffected as goal-directed behavior for food items was in general intact following A13 neuronal inactivation/degeneration. These results demonstrate a functional role for A13-DA neurons in prehensile actions that are uncoupled from reward and as such position A13-DA neurons into the functional framework regarding centrally-located DA populations and their ability to coordinate movement.

neuroscience↗

bioRxiv2022

Emergent periodicity in the collective synchronous flashing of fireflies

In isolation from their peers, Photinus carolinus fireflies flash with no intrinsic period between successive bursts. Yet, when congregating into large mating swarms, these fireflies transition into predictability, synchronizing with their neighbors with a rhythmic periodicity. Here we propose a mechanism for emergence of synchrony and periodicity, and formulate the principle in a mathematical framework. Remarkably, with no fitting parameters, analytic predictions from this simple principle and framework agree strikingly well with data. Next, we add further sophistication to the framework using a computational approach featuring groups of random oscillators via integrate-and-fire interactions controlled by a tunable parameter. This agent-based framework of P. carolinus fireflies interacting in swarms of increasing density also shows quantitatively similar phenomenology and reduces to the analytic framework in the appropriate limit of the tunable coupling strength. We discuss our findings and note that the resulting dynamics follow the style of a decentralized follow-the-leader synchronization, where any of the randomly flashing individuals may take the role of the leader of any subsequent synchronized flash burst.

animal behavior and cognition↗

bioRxiv2022

Microbial Community Dynamics Provide Evidence for Hypoxia During a Coral Reef Mortality Event

In July 2016, a severe coral reef invertebrate mortality event occurred approximately 200km southeast of Galveston, Texas at the East Flower Garden Bank wherein upwards of 80% of corals in a 0.06 km2 area died. Based on surveys of dead corals and other invertebrates shortly after this mortality event, responders hypothesized that localized hypoxia was the most likely direct cause. However, no dissolved oxygen data were available to test this hypothesis because oxygen is not continuously monitored within the Flower Garden Banks sanctuary. Here we quantify microbial plankton community diversity based on four cruises over two years at the Flower Garden Banks, including a cruise just 5-8 days after the mortality event was first observed. In contrast with observations collected during baseline conditions, microbial plankton communities in the thermocline were differentially enriched with taxa known to be active and abundant in oxygen minimum zones or that have known adaptations to oxygen limitation shortly after the mortality event (e.g. SAR324, Thioglobaceae, Nitrosopelagicus, and Thermoplasmata MGII). Unexpectedly, these enrichments were not localized to the East Bank, but were instead prevalent across the entire study area, suggesting there was a widespread depletion of dissolved oxygen concentrations in the thermocline around the time of the mortality event. Hydrographic analysis revealed the southern East Bank coral reef (where the localized mortality event occurred) was uniquely within the thermocline at this time. Our results demonstrate how temporal monitoring of microbial communities can be a useful tool to address questions related to past environmental events. IMPORTANCEIn the northwestern Gulf of Mexico in July 2016, upwards of 80% of corals in a small area of the East Flower Garden Bank coral reef suddenly died without warning. Oxygen depletion is believed to have been the cause. However, there was considerable uncertainty as no oxygen data is available from the time of the event. Microbes are sensitive to changes in oxygen and can be used as bioindicators of oxygen loss. In this study, we analyze microbial communities in water samples collected over several years at the Flower Garden Banks, including shortly after the mortality event. Our findings indicate that compared to normal conditions, oxygen depletion was widespread in the deep-water layer during the mortality event. Hydrographic analysis of water masses further revealed some of this low oxygen water likely upwelled onto the coral reef.

microbiology↗

bioRxiv2021

Sex-specific transcriptome of spinal microglia in neuropathic pain due to peripheral nerve injury

Recent studies have suggested a sexually dimorphic role of microglia in the maintenance of neuropathic pain in rodents. Here, we utilized RNA sequencing analysis and in vitro primary cultures of microglia to characterize the sex differences in microglia in pain-related regions in nerve injury and chemotherapy-induced peripheral neuropathy mouse models. Whilst mechanical allodynia and behavioral changes were observed in all models, transcriptomic analysis revealed a substantial change in microglial gene expression only within the ipsilateral lumbar spinal cord 7-days after nerve injury. Both sexes upregulated genes associated with inflammation, phagosome, and lysosome activation, though males revealed a prominent global transcriptional shift not observed in female mice, reflecting acute activation. Further, in vitro studies revealed that only male microglia from nerve-injured mice developed a reactive phenotype with increased phagocytotic activity. This study indicates distinct sex differences in spinal microglia and suggests they contribute to the sex-specific pain processing following nerve injury.

neuroscience↗

bioRxiv2021

Predictive and motivational factors influencing anticipatory contrast: A comparison of contextual and gustatory predictors in food restricted and free-fed rats

In anticipation of palatable food, rats can learn to restrict consumption of a less rewarding food type resulting in a binge on the preferred food when it is made available. This construct is known as anticipatory negative contrast (ANC) and can help elucidate the processes that underlie binge-like behavior as well as self-control in rodent motivation models. In the current investigation we aimed to shed light on the ability of distinct predictors of a preferred food choice to generate contrast effects and the motivational processes that underlie this behavior. Using a novel set of rewarding solutions, we directly compared contextual and gustatory ANC predictors in both food restricted and free-fed Sprague-Dawley rats. Our results indicate that, despite being food restricted, rats are selective in their eating behavior and show strong contextually-driven ANC and do so after fewer training sessions than free-fed animals. These differences mirrored changes in palatability for the less preferred solution across the different sessions as measured by lick microstructure analysis. Moreover, in contrast to previous research, gustatory cues in both food restricted and free-fed rats were sufficient for ANC to develop although this flavor-driven ANC did not relate to a corresponding change in lick patterning. These differences in the lick microstructure between context- and flavor-driven ANC indicate that the motivational processes underlying ANC generated by the two predictor types are distinct.

animal behavior and cognition↗

bioRxiv2021

Itaconate and its derivatives repress C2C12 myogenesis via succinate dehydrogenase inhibition

A Krebs cycle intermediate metabolite, itaconate, has gained attention as a potential antimicrobial and autoimmune disease treatment due to its anti-inflammatory effects. While itaconate and its derivatives pose an attractive therapeutic option for the treatment of inflammatory diseases, the effects outside the immune system still remain limited, particularly in the muscle. Therefore, we endeavored to determine if itaconate signaling impacts muscle differentiation. Utilizing the well-established C2C12 model of in vitro myogenesis, we evaluated the effects of itaconate and its derivatives on transcriptional and protein markers of muscle differentiation as well as mitochondrial function. We found itaconate and the derivatives dimethyl itaconate and 4-octyl itaconate disrupt differentiation media-induced myogenesis. A primary biological effect of itaconate is a succinate dehydrogenase (SDH) inhibitor. We find the SDH inhibitors dimethyl malonate and harzianopyridone phenocopie the anti-myogenic effects of itaconate. Furthermore, we find treatment with exogenous succinate results in blunted myogenesis. Together our data indicate itaconate and its derivatives interfere with in vitro myogenesis, potentially through inhibition of SDH and subsequent succinate accumulation. More importantly, our findings suggest the therapeutic potential of itaconate and its derivatives could be limited due to deleterious effects on myogenesis.

cell biology↗

bioRxiv2021

Self-organization in natural swarms of Photinus carolinus synchronous fireflies

Fireflies flashing in unison is a mesmerizing manifestation of animal collective behavior and an archetype of biological synchrony. To elucidate synchronization mechanisms and inform theoretical models, we recorded the collective display of thousands of Photinus carolinus fireflies in natural swarms, and provide the first spatiotemporal description of the onset of synchronization. At low firefly density, flashes appear uncorrelated. At high density, the swarm produces synchronous flashes within periodic bursts. Using three-dimensional reconstruction, we demonstrate that flash bursts nucleate and propagate across the swarm in a relay-like process. Our results suggest that fireflies interact locally through a dynamic network of visual connections defined by visual occlusion from terrain and vegetation. This model illuminates the importance of the environment in shaping self-organization and collective behavior.

animal behavior and cognition↗

bioRxiv2020

A COVID-19 vaccine candidate using SpyCatcher multimerization of the SARS-CoV-2 spike protein receptor-binding domain induces potent neutralising antibody responses

There is dire need for an effective and affordable vaccine against SARS-CoV-2 to tackle the ongoing pandemic. In this study, we describe a modular virus-like particle vaccine candidate displaying the SARS-CoV-2 spike glycoprotein receptor-binding domain (RBD) using SpyTag/SpyCatcher technology (RBD-SpyVLP). Low doses of RBD-SpyVLP in a prime-boost regimen induced a strong neutralising antibody response in mice and pigs that was superior to convalescent human sera. We evaluated antibody quality using ACE2 blocking and neutralisation of cell infection by pseudovirus or wild-type SARS-CoV-2. Using competition assays with a monoclonal antibody panel, we showed that RBD-SpyVLP induced a polyclonal antibody response that recognised all key epitopes on the RBD, reducing the likelihood of selecting neutralisation-escape mutants. The induction of potent and polyclonal antibody responses by RBD-SpyVLP provides strong potential to address clinical and logistic challenges of the COVID-19 pandemic. Moreover, RBD-SpyVLP is highly resilient, thermostable and can be lyophilised without losing immunogenicity, to facilitate global distribution and reduce cold-chain dependence.

immunology↗

bioRxiv2020

Spatiotemporal reconstruction of emergent flash synchronization in firefly swarms via stereoscopic 360-degree cameras

During mating season, males of synchronous firefly species flash in unison within swarms of thousands of individuals. These strongly-correlated collective displays have inspired numerous mathematical models to explain how global synchronous patterns emerge from local interactions. Yet, experimental data to validate these models remains sparse. To address this gap, we develop a method for three-dimensional tracking of firefly flashes, using a stereoscopic setup of 360-degree cameras. We apply this method to record flashing displays of the North American synchronous species Photinus carolinus in its natural habitat as well as within controlled environments, and obtain the 3D reconstruction of flash occurrences in the swarm. Our results show that even a small number of interacting males synchronize their flashes; however, periodic flash bursts only occur in groups larger than 15 males. Moreover, flash occurrences are correlated over several meters, indicating long-range interactions. While this suggests emergent collective behaviour and cooperation, we identify distinct individual trajectories that hint at additional competitive mechanisms. These reveal possible behavioural differentiation with early flashers being more mobile and flashing longer than late followers. Our experimental technique is inexpensive and easily implemented. It is extensible to tracking light communication in various firefly species and flight trajectories in other insect swarms.

animal behavior and cognition↗

bioRxiv2020

Studies of human twins reveal genetic variation that affects dietary fat perception

To learn more about the mechanisms of human dietary fat perception, 398 human twins rated fattiness and liking for six types of potato chips that differed in triglyceride content (2.5, 5, 10, and 15% corn oil); reliability estimates were obtained from a subset (n = 50) who did the task twice. Some chips also had a saturated long-chain fatty acid (hexadecanoic acid, 16:0) added (0.2%) to evaluate its effect on fattiness and liking. We computed the heritability of these measures and conducted a genome-wide association study (GWAS) to identify regions of the genome that co-segregate with fattiness and liking. Perceived fattiness and liking for the potato chips were reliable (r = 0.31-0.62, p < 0.05) and heritable (up to h2 = 0.29, p < 0.001, for liking). Adding hexadecanoic acid to the potato chips significantly increased ratings of fattiness but decreased liking. Twins with the G allele of rs263429 near GATA3-AS1 or the G allele of rs8103990 within ZNF729 reported more liking for potato chips than did twins with the other allele (multivariate GWAS, p < 1x10-5), with results reaching genome-wide suggestive but not significance criteria. Person-to-person variation in the perception and liking of dietary fat was (a) negatively affected by the addition of a saturated fatty acid and (b) related to inborn genetic variants. These data suggest liking for dietary fat is not due solely to fatty acid content and highlight new candidate genes and proteins within this sensory pathway.

genetics↗