Biology subjects

Foley, J.

Publications and source records attributed to Foley, J..

13 recordsLinked to original sources

bioRxiv2026

Cognitive robustness in a new insect model of extended longevity

Human life expectancy has jumped by several decades in the last century, but the healthspan has not followed suit. The ageing population has come with an increased prevalence of neurodegenerative disease, and insects have proven to be valuable models of these conditions and their associated cognitive decline. The Heliconius butterfly genus is an emerging system in insect cognition, having recently evolved a significant expansion in neural centres of learning and memory, alongside enhanced stability of visual long-term memory in comparison with their close relatives in the Heliconiini tribe. This is linked to the cognitive demands imposed by Heliconius spatially-faithful foraging behaviour for a protein-rich diet of pollen, and co-occurs with a dramatic lifespan extension in this genus over the other Heliconiini outgroups. Here, we investigate whether the Heliconius cognitive healthspan is similarly discrepant, or if any cognitive decline is instead delayed in accordance with their lifespan extension. We first report evidence that investment in learning and memory circuits co-evolves with Heliconiini lifespan. We then conduct learning and memory assays across the lifespans of a representative longer-lived Heliconius, H. hecale, and the shorter-lived Heliconiini outgroup, Dryas iulia. Across both species, and particularly in H. hecale, we find evidence for cognitive robustness in late life, in contrast to evidence for widespread cognitive declines in insects. Our results add a new taxonomic order to the study of age-related memory impairment, and suggest Heliconius as a valuable model system for mechanistic studies of the maintenance of neurological health in the context of extended life.

animal behavior and cognition↗

bioRxiv2025

Evolution of increased longevity and slowed ageing in a genus of tropical butterfly

Evolution has given rise to lifespans in extant species ranging from days to centuries. Given that mechanisms of ageing are highly conserved, studying long-lived lineages across the animal kingdom could yield insights relevant for healthy ageing in humans. However, typical models of extended lifespan often live for decades, making them impractical for longitudinal studies. Ideal model systems would be organisms that are naturally long-lived compared to their close relatives, but have lifespans on experimentally tractable scales. Here, we present the Neotropical butterfly genus Heliconius as a novel model system for the evolution of extended longevity. We collate data from 27 species across the Heliconiini tribe to reveal a 25-fold variation in lifespan within the group, with our 348-day maximum for Heliconius hewitsoni longer than any butterfly species previously recorded in the scientific literature. While previous work has attributed this lifespan extension to a plastic response to enhanced nutrition, we conduct detailed survival and functional senescence analyses on two species representative of shorter- and longer-lived clades to show evidence of evolved, heritable mechanisms of slowed ageing in Heliconius. Our results add a new case study to the canon of noteworthy agers, and provide valuable insights into the evolution of increased longevity.

evolutionary biology↗

bioRxiv2025

A multidimensional analysis of the risk of infection with Ehrlichia canis among urban dogs in Iquitos, Peru.

Ehrlichia canis is a tick-borne bacterium that causes a potentially fatal disease in dogs called Canine Monocytic Ehrlichiosis. In this cross-sectional study, we used a One Health framework to identify statistical associations between E. canis infection in dogs and multiple dog-related, human and environmental factors in Iquitos, Peru. Due to the lack of consensus regarding the positivity threshold for E. canis qPCR assays, we also evaluated if the factors associated with infection remained conserved regardless of the Ct value cut-off used: Ct<35, a conservative but commonly accepted Ct cut-off for bacterial screening, or Ct [≤]40, which has been used in several E. canis studies. Under the more conservative scenario, we found that the prevalence of E. canis among dogs was 19.6% (95% CI 15.8-23.9%). Additionally, we showed that risk factor analyses utilizing a qPCR Ct cut-off of 35 or 40 (with conventional PCR confirmation for samples with a Ct>35) yield comparable results in statistical models, although some differences should be considered. Our findings suggest that in Iquitos, Peru, interventions to prevent E. canis infection should prioritize dogs living in houses with corrugated iron walls. Additionally, comprehensive strategies targeting dogs that have recently traveled and incorporating neutering/spaying and widespread acaricide programs may also prove beneficial. We also discuss the challenges encountered during molecular testing for E. canis detection, highlighting the broader difficulties of studying poorly understood intracellular pathogens in Global South countries.

ecology↗

bioRxiv2024

Electric charge controls plasmodesma conductivity

While plant cells are enclosed by rigid cell walls that counteract intracellular hydrostatic pressure1, their plasma membrane, cytosol, and endoplasmic reticulum (ER) remain connected through plasmodesmata, nanoscopic cell wall pores2. Plasmodesmal cell-to-cell transport occurs in the cytosolic sleeve between the plasma membrane and the ER membrane3-5, and is generally thought to be limited by the size of the moving particle alone6. Given that biological membranes carry negative electric surface charges7-9, this steric notion conflicts with physical theory of ion diffusion in nanometer-sized pores with charged walls10. Quantifying the movements of differently sized and charged fluorescent dyes in Tradescantia stamen hairs, we found that anionic fluorophores of up to 1 kDa traversed plasmodesmata whereas much smaller cationic ones did not. While this agrees with theoretical expectations of different size exclusion limits for cations and anions, it questions current dogma concerning plasmodesma function and also structure, as it implies positively rather than negatively charged surfaces within plasmodesmal pores. Our findings call for re-evaluations of current models of symplasmic transport, especially of charged molecules like the phytohormone auxin (indole-acetic acid) and certain amino acids.

cell biology↗

bioRxiv2023

Cerebellum-Midbrain Reward Circuitry in Humans: an in vivo dissection

Emerging research in non-human animals implicates cerebellar projections to the ventral tegmental area (VTA) in appetitive behaviors, but these circuits have not been characterized in humans. Here, we mapped cerebello-VTA white-matter connectivity in humans using probabilistic tractography on diffusion imaging data from the Human Connectome Project. We uncovered the topographical organization of these connections by separately tracking from parcels of cerebellar lobule VI, crus I/II, vermis, paravermis, and cerebrocerebellum. Results revealed that connections from the cerebellum to the VTA predominantly originate in the right hemisphere, interposed nucleus, and paravermal cortex, and terminate mostly ipsilaterally. Paravermal crus I sends the most connections to the VTA compared to other lobules. We discovered a medial-to-lateral gradient of connectivity, such that the medial cerebellum has the highest connectivity with the VTA. Individual differences in microstructure were associated with measures of negative affect and social functioning. By splitting the tracts into quarters, we found that the socio-affective effects were driven by the third quarter of the tract, corresponding to the point at which the fibers leave the deep nuclei. Taken together, we produced detailed maps of cerebello-VTA structural connectivity for the first time in humans and established their relevance for trait differences in socio-affective regulation.

neuroscience↗

bioRxiv2023

Enhanced long-term memory and increased mushroom body plasticity in Heliconius butterflies

As highly labile structures on both individual and evolutionary time-scales, the mushroom bodies, a key site of learning and memory in insects, are an excellent model for investigating the evolution of cognitive variation. We explored the behavioural consequences of mushroom body expansion in Heliconius butterflies, which possess greatly expanded mushroom bodies relative to their closest outgroups. We conducted long-term visual memory assays across three Heliconius and three other Heliconiini species using trained food-colour associations. We confirm robust differences between clades, with Heliconius exhibiting greater fidelity to the trained colour after 8 days without reinforcement compared to other Heliconiini, with further evidence of stable preferences at 13 days. We extended this analysis to consider the plastic response of the mushroom body calyces over this time period, measuring the volume of the mushroom body calyx, and the number of neurons and synapses it contains. We find substantial post-eclosion expansion and synaptic pruning in calyx of Heliconius erato, but not in Dryas iulia. In Heliconius erato, visual associative learning experience specifically is associated with a greater retention of calyceal synapses. At an individual level, fidelity to the trained colour in Heliconius erato was also positively correlated with synapse number. These results point to an enhanced visual long-term memory across Heliconius, facilitated not only by phylogenetic expansion of the mushroom body, but also changes in its developmental response to learning experience. The co-evolution of mushroom body expansion, plasticity and specific behaviours provides an important case study in the evolution of cognition. Significance StatementHow are cognitive differences between species supported by evolutionary changes in the brain? We investigated this question using Heliconius butterflies which have expanded mushroom bodies, a region of the insect brain involved in learning and memory. We show that Heliconius have more stable visual long-term memories and exhibit more substantial age- and experience-related plasticity than a closely related genus with smaller mushroom bodies. Recall accuracy was also predicted by synapse number in Heliconius erato, but not Dryas iulia, suggesting functional importance. These results suggest that increases in the size of specific brain regions and changes in their plastic response to experience may co-evolve to shape the evolution of cognition.

animal behavior and cognition↗

bioRxiv2021

Profiling Transcription Initiation in Peripheral Leukocytes Reveals Severity-Associated Cis-Regulatory Elements in Critical COVID-19

The contribution of transcription factors (TFs) and gene regulatory programs in the immune response to COVID-19 and their relationship to disease outcome is not fully understood. Analysis of genome-wide changes in transcription at both promoter-proximal and distal cis-regulatory DNA elements, collectively termed the active cistrome, offers an unbiased assessment of TF activity identifying key pathways regulated in homeostasis or disease. Here, we profiled the active cistrome from peripheral leukocytes of critically ill COVID-19 patients to identify major regulatory programs and their dynamics during SARS-CoV-2 associated acute respiratory distress syndrome (ARDS). We identified TF motifs that track the severity of COVID- 19 lung injury, disease resolution, and outcome. We used unbiased clustering to reveal distinct cistrome subsets delineating the regulation of pathways, cell types, and the combinatorial activity of TFs. We found critical roles for regulatory networks driven by stimulus and lineage determining TFs, showing that STAT and E2F/MYB regulatory programs targeting myeloid cells are activated in patients with poor disease outcomes and associated with single nucleotide genetic variants implicated in COVID-19 susceptibility. Integration with single-cell RNA-seq found that STAT and E2F/MYB activation converged in specific neutrophils subset found in patients with severe disease. Collectively we demonstrate that cistrome analysis facilitates insight into disease mechanisms and provides an unbiased approach to evaluate global changes in transcription factor activity and stratify patient disease severity.

genomics↗

bioRxiv2021

Sarcoptic mange outbreak decimates South American camelid populations in San Guillermo National Park, Argentina

Sarcoptic mange epidemics can devastate wildlife populations. In 2014, mange was first detected in vicuna (Vicugna vicugna) and guanaco (Lama guanicoe) in San Guillermo National Park (SGNP), Argentina. This study characterized the potential source and the impacts of the outbreak in 2017-2019. Transect surveys indicated a sharp decrease in the density of live vicuna and guanaco by 68% and 77%, respectively, from May 2017 to June 2018. By April 2019 no vicuna or guanaco were recorded on transect surveys, suggesting a near-extinction at the local level. Clinical signs consistent with mange (e.g. intense pruritus, hyperkeratosis, alopecia) were observed in 24% of live vicuna (n = 478) and 33% of live guanaco (n = 12) during surveys, as well as in 94% of vicuna carcasses (n = 124) and 85% of guanaco carcasses (n = 20) opportunistically examined during the study period. Histological examination (n = 15) confirmed sarcoptic mange as the cause of the cutaneous lesions. Genetic characterization revealed that Sarcoptes scabiei recovered from seven vicuna (n = 13) and three guanaco (n = 11) shared the same genotype, which is consistent with a single source and recent origin of the epidemic. A governmental livestock incentive program introduced llama (Lama glama) in areas adjacent to SGNP in 2009, some of which reportedly had alopecic scaling consistent with sarcoptic mange. We hypothesize that the introduction of mange-infected llama may have triggered the outbreak in wild camelids which has now put them at a high risk of local extinction. This unprecedented event highlights that the accidental introduction of disease may be underestimated at the onset yet can have devastating effects on native ungulate populations with potentially profound effects at the community and ecosystem levels.

zoology↗

bioRxiv2020

The gene cortex controls scale colour identity in Heliconius

In Heliconius butterflies, wing pattern diversity is controlled by a few genes of large effect that regulate colour pattern switches between morphs and species across a large mimetic radiation. One of these genes, cortex, has been repeatedly associated with colour pattern evolution in butterflies. Here we carried out CRISPR knock-outs in multiple Heliconius species and show that cortex is a major determinant of scale cell identity. Chromatin accessibility profiling and introgression scans identified cis-regulatory regions associated with discrete phenotypic switches. CRISPR perturbation of these regions in black hindwing genotypes recreated a yellow bar, revealing their spatially limited activity. In the H. melpomene/timareta lineage, the candidate CRE from yellow-barred phenotype morphs is interrupted by a transposable element, suggesting that cis-regulatory structural variation underlies these mimetic adaptations. Our work shows that cortex functionally controls scale colour fate and that its cis-regulatory regions control a phenotypic switch in a modular and pattern-specific fashion.

evolutionary biology↗

bioRxiv2020

The ΔF508 CFTR defect: molecular mechanism of suppressor mutation V510D and the contribution of transmembrane helix unraveling

Cystic fibrosis (CF) results from mutations within the gene encoding the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR), a transmembrane chloride channel found on the apical surface of epithelial cells. The most common CF-causing mutation results in a deletion of phenylalanine 508 ({Delta}F508-CFTR), a residue normally found within the NBD1 domain. Loss of F508 causes NBD1 to be less thermodynamically stable and prevents proper tertiary folding of CFTR. As a result, CFTR is not properly trafficked to the cell surface. Recently, progress has been made towards the development of small molecule "correctors" that can restore CFTR tertiary structure and stabilize the channel to overcome the instability inherent in {Delta}F508-CFTR. However, the resultant improvement in channel activity has been modest, and the need for potent correctors remains. To fully inform such efforts, a better understanding of the molecular pathology associated with {Delta}F508-CFTR is required. Here we present a comprehensive study of the impact of F508 deletion on both purified NBD1 and full-length CFTR. Through the use of homology modeling, molecular dynamics simulations, mutational analysis, biochemical, biophysical and functional characterization studies, we obtained insight into how the {Delta}F508 mutation may lead to helical unraveling of transmembrane domains 10 and 11 (TM10, TM11), and how the known suppressor mutations V510D and R1070W, as well as novel second site suppressor mutations (SSSMs) identified in this work, may act to rescue {Delta}F508-CFTR maturation and trafficking.

biochemistry↗

bioRxiv2019

Micronutrient intake and prevalence of micronutrient inadequacy among women (15-49 y) and children (6-59 mo) in South Kivu and Kongo Central, Democratic Republic of Congo (DRC)

Iron biofortified beans and carotenoid enriched cassava are proposed as a solution to combat iron and vitamin A deficiencies, respectively, in the Democratic Republic of Congo (DRC). To inform the need for biofortified foods we conducted a survey in 2014, in two provinces of the DRC, South Kivu and Kongo Central. Unexpectedly, women of reproductive age (WRA; 15-49 y) and their children (6-59 m) had a low prevalence of biochemical iron and vitamin A deficiency, based on ferritin and retinol binding protein, respectively. However, to better understand the lack of biochemical deficiency of these nutrients we examined the prevalence of inadequate intake for these and other select nutrients. Dietary intake was assessed using 24-hour recalls (with repeats) among 744 mother-child dyads. In WRA the prevalence of inadequate iron intakes was 32% (10% bioavailability). The prevalence of inadequate vitamin A intakes was low in South Kivu (18%) and negligible in Kongo Central (1%). The prevalence of inadequate iron intake was 74% in infants (6-11 m) and ~22% in the older children (12-59 months). There was a high prevalence of inadequate zinc intake in women and children (i.e. 83% WRA) consistent with our findings of a high prevalence of low serum zinc in the same sample. Dietary data here corroborate the low prevalence of biochemical vitamin A deficiency but not iron. However, any change to the supply of red palm oil would dramatically reduce population vitamin A intakes, thus a carotenoid enriched cassava program may be beneficial as a safety net measure. Additionally, iron biofortified beans may be warranted given the high rates of dietary inadequacy and uncertainty around the validity of iron biomarkers. Crops biofortified with zinc also appear warranted. We caution that our findings cannot be extrapolated to the entire Congo where diverse agro-ecological landscape exist or when political and environmental shocks occur which challenge food production.

physiology↗

bioRxiv2019

Bocaparvovirus, Erythroparvovirus and Tetraparvovirus in New World Monkeys from Central America

Parvoviruses in the genera Bocaparvovirus (HBoV), Erythroparvovirus (B19) and Tetraparvovirus (PARV4) are the only autonomous parvoviruses known to be associated with human and non-human primates based on studies and clinical cases in humans worldwide and non-human primates in Asia and Africa. Here, the presence of these pathogenic agents was assessed by PCR in blood and feces from 55 howler monkeys, 112 white-face monkeys, 3 squirrel monkeys, and 127 spider monkeys in Costa Rica and El Salvador. Overall, 3.7% of the monkeys had HboV DNA, 0.67% had B19 DNA, and 14.1% had PARV4 DNA, representing the first detection of these viruses in New World monkeys. Sex was significantly associated with the presence of HBoV, males having risk up to nine times compared with females. Captivity was associated with increased prevalence for PARV4 and when all viruses were analyzed together. This work underscores the importance of future research aimed at understanding how these viruses behave in natural environments of the Neotropics, and what variables may favor their presence and transmission.

epidemiology↗

bioRxiv2018

Identification of a Novel Neutralizing and Two Non-Neutralizing Epitopes on Epstein-Barr Virus gp350 Protein

Prevention of Epstein-Barr virus (EBV) primary infection has focused on generating neutralizing antibodies (nAbs) targeting the major envelope glycoprotein gp350/220 (gp350). To date, eight gp350 epitopes have been identified, but only one has elicited nAbs. In this study, we generated 23 hybridomas that produced anti-gp350 antibodies. We compared the candidate anti-gp350 antibodies to nAb-72A1 by: (1) testing their ability to detect gp350 using ELISA, flow cytometry, and immunoblot; (2) sequencing their heavy and light chain complementarity-determining regions (CDRs); (3) measuring the ability of each monoclonal antibody (mAb) to neutralize EBV infection in vitro; and (4) mapping the gp350 amino acids bound by the mAbs using RepliTope peptide microarrays. Eight antibodies recognized both denatured and non-denatured gp350, whereas five failed to react with denatured gp350 but recognized native gp350, suggesting they recognized conformational epitope(s). Sequence analysis of the heavy and light chain variable regions of the hybridomas identified 15 as mAbs with novel CDR regions unique from those of nAb-72A1. Seven of the new mAbs neutralized EBV in vitro, with HB20 and HB17 reducing EBV infection by 40% and >60%, and >30% and 80%, at 10 g/ml and 50 g/ml, respectively. Epitope mapping identified nine epitopes and defined their core residues, including two unique immunodominant epitopes, 253TPIPGTGYAYSLRLTPRPVSRFL253 and 875LLLLVMADCAFRRNLSTSHTYTTPPY899, and a novel nAb epitope 381GAFASNRTFDIT392. This study provides comprehensive in vitro mapping of the exact residues defining nine epitopes of EBV gp350. Our findings will inform novel strategies to design optimal EBV vaccines capable of conferring broader protection against the virus.\n\nImportanceNeutralizing antibodies (nAbs) directed against Epstein-Barr virus envelope glycoprotein gp350/220 (gp350) are generated in humans upon infection or immunization, and are thought to prevent neonatal infection. However, clinical use of exogenous nAbs (passive immunization) is limited to a single study using the only well-characterized nAb, 72A1. The gp350 ectodomain contains at least eight unique B-cell binding epitopes; two of these epitopes are recognized by nAb-72A1. The exact amino acid residues of the other six epitopes and their role in generating nAbs has not been elucidated. We used our 15 newly generated and fully characterized monoclonal antibodies and a peptide-overlapping RepliTope array to provide a comprehensive map of the core amino acid residues that define epitopes of gp350 and to understand their role in generating nAbs. These results will inform design of better-targeted gp350 peptide vaccines that contain only protective epitopes, which will focus the B-cell response to produce predominantly nAbs.

immunology↗