Biology subjects

Hare, D.

Publications and source records attributed to Hare, D..

7 recordsLinked to original sources

bioRxiv2026

TLR3 Expression in Villus-Like Enterocytes Drives IFN-III Responses to Enteroviruses

Enteroviruses initiate infection at the intestinal epithelium but can spread systemically to cause severe disease. Although both MDA5 and TLR3 have been implicated in enterovirus sensing, the mechanisms by which the intestinal epithelium detects these viruses remain poorly defined. To address this, we infected human intestinal organoids (enteroids) with echovirus 11 (E11) and compared responses in models differentiated to mimic either crypt-like or villus-like epithelium. Villus-like enteroids produced significantly more type III interferons (IFN-{lambda}s) following E11 infection or treatment with the dsRNA mimetic poly I:C, and exhibited heightened responsiveness to IFN-{lambda} signaling. Single-cell RNA sequencing (scRNA-seq) of infected enteroids revealed that E11 broadly infected epithelial cell types, but IFN-{lambda} expression was largely restricted to mature enterocytes. Notably, enterocyte differentiation was also associated with upregulation of innate immune genes. Using CRISPR-Cas9 knockout enteroids, we found that TLR3 signaling was essential for intestinal IFN-{lambda} responses to E11 infection, whereas loss of MAVS, the adaptor for MDA5, had no effect. Together, these data support a model in which mature enterocytes serve as key sensors of enterovirus infection via TLR3, triggering a localized IFN-{lambda} response that may help restrict viral spread. ImportanceEnteroviruses are commonly circulating viruses that can cause a broad spectrum of disease, particularly in pediatric populations. Innate immune sensing in the intestinal epithelium likely plays a critical role in determining the outcome of enterovirus infections. Deficiencies in TLR3 signaling, IFN-{lambda} responses, or crypt-villus architecture may contribute to severe disease presentations. Our findings highlight the importance of TLR3-mediated sensing in mature enterocytes, which may also have broader implications for other intestinal viruses, as well as for inflammatory conditions like inflammatory bowel disease. A deeper understanding of how TLR3 sensing and IFN-{lambda} production are regulated in the intestine could inform new therapeutic strategies aimed at modulating mucosal sensitivity to viral nucleic acids and enhancing antiviral defense.

immunology↗

bioRxiv2024

Improving the integration of AI into existing ecological inference workflows

O_LIArtificial Intelligence (AI) has revolutionised the process of identifying species and individuals in audio recordings and camera trap images. However, despite developments in sensor technology, machine learning, and statistical methods, a general AI-assisted data-to-inference pipeline has yet to emerge. C_LIO_LIWe argue that this is, in part, due to a lack of clarity around several decisions in existing workflows, including: the choice of classifier used (e.g., semi- vs. fully automated); how classifier confidence scores are used and interpreted; and the availability and selection of appropriate statistical methods for drawing ecological inferences. C_LIO_LIHere, we attempt to conceptualise a general workflow associated with automated tools in ecology. We motivate this perspective using our experiences with occupancy modelling using monitoring data collected through passive acoustic monitoring and camera trapping, identifying priority areas for future developments. C_LIO_LIWe offer an accessible guide to support the ecological community in navigating and capitalising on rapid technological and methodological advances. We describe how different error types arise from both sensor-based monitoring and from classifiers themselves; how different error types are handled at each stage of the workflow; and finally, implications and opportunities associated with deciding on methods used at each step of the pipeline. C_LIO_LIWe recommend that "black box" tools like neural network classification algorithms should be embraced in ecology, but widespread uptake requires more formal integration of AI into the existing ecological inference workflows. Like ecological AI more broadly, however, successful development of new data-to-inference pipelines is a multidisciplinary endeavour that requires input from everyone invested in collecting, processing, analysing, and using ecological monitoring data. C_LI

ecology↗

bioRxiv2024

Interferon Epsilon Protects Epithelial Barriers from Viral Infection through Autocrine Intracellular Signaling

Antiviral defenses at mucosal barriers are essential for preventing viral entry and systemic infection. Interferon epsilon (IFN{varepsilon}) is a unique type I IFN that, unlike other family members, is not induced by infection but is constitutively expressed in epithelial tissues. IFN{varepsilon} was initially characterized in the female reproductive tract (FRT), where it provides broad antiviral protection, but its roles outside the FRT remain poorly defined. Here, we used Ifn{varepsilon}-/- mice and single-cell RNA sequencing to delineate IFN{varepsilon} function across distinct mucosal surfaces. In the FRT, Ifn{varepsilon} expression was restricted to specific epithelial subsets, was independent of estrous stage, and maintained basal ISG expression. IFN{varepsilon} was also retained intracellularly in primary human FRT-derived cells. Extending these analyses to the intestine, we found that IFN{varepsilon} is highly expressed in villous-tip enterocytes of the small intestine in vivo, where it sustains inflammatory enterocyte subsets and maintains type III IFN expression. Loss of Ifn{varepsilon} depleted these subsets and rendered mice more susceptible to enteric viral infection. Together, these findings establish IFN{varepsilon} as a constitutively expressed, spatially restricted IFN that coordinates mucosal antiviral defenses across both reproductive and gastrointestinal epithelial tissues.

immunology↗

bioRxiv2024

Disproportionate regulation of wildlife trade

An increasing number of countries in the Global North have enacted, or are considering, import bans on hunting trophies with the aim of protecting wildlife. We interrogate key arguments used to characterize trophy hunting and associated trade by proponents of such bans, using data from the Convention on International Trade in Endangered Species of Wild Fauna and Flora (CITES) over 25 years (2000-2024), the International Union for Conservation of Nature (IUCN) Red List of Threatened Species, and empirical research. Contrary to claims by proponents of bans, we show that trophy hunting is not a major threat to any CITES-listed species traded as a hunting trophy in 2000-2024. Arguments used to support bans often mischaracterize trophy hunting and its impacts and fail to recognize the benefits it can, and does, have for wildlife and people. Countries that have enacted or are considering import bans account for 64% of global trade in hunting trophies of CITES-listed species taken from the wild. Combined, these policies would restrict approximately one-fifth of this trade, likely with significant implications for conservation. We question whether these legislative actions are proportionate and discuss policy solutions. Wildlife trade solutions may appear simple, but evidence-based, just policies are needed to conserve biodiversity and avoid harming people.

ecology↗

bioRxiv2024

ARTIC RSV amplicon sequencing reveals global RSV genotype dynamics.

Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infections (LTRIs) in young children and adults over 65, contributing significantly to global healthcare burdens. With the recent approval of multiple pharmacological interventions for RSV, there is an increased demand for efficient, high-throughput sequencing methods to monitor RSV genetic diversity and any potential impact these interventions may have. Here we introduce two novel amplicon-based sequencing schemes designed for RSV A and B, optimised for integration with widespread existing ARTIC sequencing workflows. We demonstrate that these primer schemes can produce high quality genomes from RSV samples across the globe, with eight laboratories in five countries generating complete genomes on both Nanopore and Illumina sequencing platforms. The ability to effectively multiplex these RSV A and B primer schemes, enables streamlined, high-throughput sequencing without prior subtyping. Furthermore, these results provide a snapshot of the circulating diversity of RSV. Phylogenetic analysis of the 882 samples sequenced for this study suggests only minimal geographic clustering of RSV sequences, underscoring the global nature of RSV spread. It also highlights the distinct lineage dynamics seen between RSV A and B. This study represents an advancement in RSV genomics, providing robust tools for global sequencing efforts aimed at tracking RSV evolution and assessing the efficacy of new therapeutic interventions both rapidly and at scale.

genomics↗

bioRxiv2023

Evaluating key evidence and formulating regulatory alternatives regarding the UK Hunting Trophies (Import Prohibition) Bill

Public policy addressing biodiversity loss is most likely to be effective when it is informed by appropriate evidence and considers potential unintended consequences. We evaluate key evidence relating to the Hunting Trophies (Import Prohibition) Bill that was discussed in the UK Parliament between 2022 and 2024. We characterize the UKs role in international hunting trophy trade by analyzing CITES trade data for 2000-2021 and 2015-2021. For CITES-listed species imported to/exported from the UK as hunting trophies in these periods we use data from the International Union for Conservation of Nature Red List of Threatened Species to determine whether hunting designated as "trophy hunting" is i) likely a major threat contributing to species being of elevated conservation concern, ii) likely or possibly causing localized declines, or iii) not a threat. We then use the Red List to determine whether such hunting provides, or potentially provides, benefits for species and/or people. Finally, we evaluate the UK Governments impact assessment of the bill. In 2000-2021 an estimated 3494 hunting trophies from 73 CITES-listed species and subspecies were exported to the UK involving an estimated 2549 whole organism equivalents (WOEs), i.e. individual animals. Imports involved 158.86 {+/-} 66.53 (mean {+/-} SD) trophies/year (115.83 {+/-} 32.27 WOEs/year). In 2015-2021, 79% of imports were from countries where populations of the hunted species are stable, increasing, or abundant. Legal hunting for trophies is not a major threat to any of the species or subspecies imported to the UK, but likely or possibly represents a local threat to some populations of nine species. This hunting does, or could potentially, benefit 20 species and subspecies, and people. Among other concerns, the impact assessment failed to adequately consider the costs and benefits to local communities in countries where such hunting occurs. Informed by these analyses we discuss alternative regulatory options.

ecology↗

bioRxiv2018

The expendable male hypothesis

Matrilineal descent confers lineage membership via the female line. In matrilineal descent systems, men share lineage membership not with their own children, but with their sisters children. The theoretically influential concept of the matrilineal puzzle posits that men experience tension between the desire to exert control over their natal kin (i.e., the lineage to which they belong) and over their affinal kin (i.e., their spouses and their biological children). The rationale for this puzzle rests on two fundamental assumptions: (i) that men are always in positions of authority over women; and (ii) that men are interested in the outcomes of parenting. In this paper, we suggest that the matrilineal puzzle does not exist from an evolutionary perspective. Instead, we examine what ecological conditions might render men expendable within local kinship configurations-specifically when (i) women, without significant assistance from men, are capable of meeting the subsistence needs of their families; and (ii) men have little to gain from parental investment in children. We conclude that the expendable male hypothesis may explain the evolution of matrilineal descent in numerous cases, and by noting that female-centered approaches that call into doubt assumptions inherent to male-centered models of kinship are justified in evolutionary perspective.\n\nO_QD\"...for some females there exist important advantages for male care ... For many females male parental care has small or negligible effects on female reproductive success, suggesting that as a general explanation for social monogamy, the Male Care is Essential Hypothesis is inadequate.\" - Gowaty 1996 [1]\n\nC_QD

animal behavior and cognition↗