Biology subjects

Fox, N.

Publications and source records attributed to Fox, N..

14 recordsLinked to original sources

bioRxiv2026

First detected incursions of avian influenza H5N1 clade 2.3.4.4b into mainland Australia from the Southern Ocean

High pathogenicity avian influenza H5N1 clade 2.3.4.4b has caused a panzootic of devastating impact to poultry and wildlife globally. The Australian continent and broader Oceania until recently remained the last major region without confirmed detections. Here we report the first H5N1 clade 2.3.4.4b detections from two live seabirds - a brown skua and a southern giant petrel - found on the south coast of Western Australia in June 2026. Virus genome sequencing showed that both viruses were most closely related to H5N1 viruses detected recently on sub-Antarctic islands in the Southern Indian Ocean. In time-calibrated phylogeographic analyses, both viruses sampled in Western Australia clustered with viruses from Heard Island, a sub-Antarctic external territory of Australia. Ancestral location reconstruction also identified Heard Island as the most probable source location, although unsampled intermediate locations cannot be excluded. The two Western Australian detections were estimated to be independent incursions from Heard Island, rather than local transmission on mainland Australia. There was no evidence of reassortment with endemic avian influenza viruses in Australia, and both virus sequences retained key avian-like genetic markers and lacked known substitutions for reduced antiviral susceptibility. These detections revealed a Southern Ocean pathway of recurrent H5N1 incursions into Australia, highlighting the risk of potential establishment on the mainland and the need for heightened surveillance and rapid, nationally-coordinated, virus genomic characterisation.

microbiology↗

bioRxiv2026

bifrost: an R package for scalable inference of phylogenetic shifts in multivariate evolutionary dynamics

O_LIHigh-dimensional comparative datasets, including geometric morphometric landmarks, functional traits, and other large trait datasets, are increasingly common in biology. When these datasets include a large number of traits relative to the number of taxa, they pose significant challenges for phylogenetic comparative analysis. In addition, evolutionary dynamics are often heterogeneous across phylogenies, challenging researchers to develop tools that can localize and account for such variation when investigating hypotheses of evolutionary change. C_LIO_LIWe present bifrost, an R package for detecting and characterizing shifts in multivariate trait evolution across phylogenetic trees. bifrost implements a stepwise greedy search over alternative macroevolutionary regime configurations on a phylogeny. Candidate shifts are proposed and assessed at internal nodes, accelerated with parallel model fitting where possible, and aggregated sequentially when they exceed a user-defined information-criterion acceptance threshold. C_LIO_LIThe underlying model is a scalar-rate multivariate Brownian motion process fit by generalized least squares using mvMORPH::mvgls [1]. Our framework also provides support estimates for individual shifts using information-criterion weights. C_LIO_LIWe illustrate the workflow using a fossil-tip-dated phylogeny and high-dimensional landmark data for early bony fish jaws (32,508 scalar coordinate values), and discuss tuning, outputs, and limitations. bifrost extends existing phylogenetic comparative frameworks for evolutionary analysis and provides a scalable pipeline for exploring the phylogenetic natural history of large multivariate datasets. C_LI

evolutionary biology↗

bioRxiv2025

Independent Generation of Amyloid-β via Novel APP Transcripts

The amyloid precursor protein (APP) is processed by multiple enzymes to generate biologically active peptides, including amyloid-{beta} (A{beta}), which aggregates to form the hallmark pathology of Alzheimers disease (AD). A{beta} is produced through an initial {beta}-secretase cleavage of APP, generating a 99-amino acid C-terminal fragment (APP-C99). Subsequent cleavage of APP-C99 by {gamma}-secretase produces A{beta} peptides of varying lengths. To better understand the transcriptional regulation of A{beta} production, we employed long-read RNA sequencing and identified previously unannotated transcripts encoding APP-C99 with an additional methionine residue (APP-C100), generated independently of {beta}-secretase cleavage. These transcripts are expressed separately from full-length APP, and we observed that cells lacking full-length APP can still produce A{beta} through these shorter isoforms. Importantly, mass spectrometry analysis of cerebrospinal fluid (CSF) revealed peptides consistent with the methionine-extended A{beta} species, supporting the in vivo translation of these transcripts. Our findings reveal an alternative pathway for A{beta} generation and aggregation, highlighting a potential new target for modulating A{beta} accumulation in AD.

neuroscience↗

bioRxiv2025

GI-NemaTracker - A farm system-level mathematical model to predict the consequences of gastrointestinal parasite control strategies in sheep

Gastro-intestinal nematode infections are considered one of the major endemic diseases of sheep on the grounds of animal health and economic burden, both in the British Isles and globally. Parasites are increasingly developing resistance to commonly used anthelmintic treatments meaning that alternative control strategies that reduce or replace the use of anthelmintics are required. We present GI-NemaTracker, a systems-level mathematical model of the full host-parasite-environment system governing gastro-intestinal nematode transmission on a sheep farm. The model is based on a series of time-varying delay-differential equations that explicitly capture environmentally-driven time delays in nematode development. By taking a farm systems-level approach we represent both in-host and environmentally-driven free-living parasite dynamics and their interaction with a population of individually modelled lambs with diverse trait parameters assigned at birth. Thus we capture seasonally varying rates of parasite transmission and consequently variable weight gain of individual lambs throughout the season. The model is parameterised for Teladorsagia circumcincta, although the framework described could be applied to a range of nematode parasite species. We validate the model against experimental and field data and apply it to study the efficacy of four different anthelmintic treatment regimes (neo-suppresive treatment, strategic prophylactic treatment, treatment based on faecal egg counts and a regime which leaves 10% of the animals untreated) on lamb weight gain and pasture contamination. The model predicts that similar body weights at a flock level can be achieved while reducing the number of treatments administered, thus supporting a health plan that reduces anthelmintic treatments. As the model is capable of combining parasitic and free-living stages of the parasite with host performance, it is well suited to predict complex system responses under non-stationary conditions. The implications of the model and its potential as a tool in the development of sustainable control strategies in sheep are discussed.

systems biology↗

bioRxiv2025

Powerful flowers: Public perception of grassland aesthetics is strongly related to management and biodiversity

Temperate grasslands provide various cultural ecosystem services that are appreciated in diverse ways. Capturing these diverse appreciations requires different methodological approaches, such as questionnaire surveys and social media analyses. In this study, we combined the potential of both approaches to capture two aspects of what people appreciate in agricultural grasslands, i.e., the aesthetic quality of differently managed plant communities and the objects frequently found in grassland-based social media images. The two complementary approaches showed that people preferred colourful flower- and species-rich grasslands over grass-dominated and fertilised swards. Social media analysis highlighted that people mainly photographed flowers, followed by livestock and/or wildlife, but this depended also on the social media platform used. In conclusion, peoples appreciation was clearly related to the intensity of grassland management and to the level of biodiversity, with a preference for extensively managed grasslands with diverse flowers and wildlife. Yet, we also found significant differences between (i) conservationists and agricultural professionals in the aesthetic appreciation of the plant communities, and (ii) between common visitors and naturalists in their social media content. Our results suggest that extensive management and ecological restoration can be used to increase cultural grassland ecosystem services by enhancing the richness of forbs, flowers and other attractive wildlife. Thus, targeted management is necessary to maintain and enhance the attractiveness of grassland landscapes and subsequently increase the health benefits that can be associated with these cultural grassland ecosystem services and human-nature contacts.

ecology↗

bioRxiv2024

Biological changes, political ideology, and scientific communication shape human perceptions of pollen seasons

Climate change is changing the timing and intensity of pollen seasons, thereby increasing human exposure to allergenic pollen. Climate-driven changes in pollen seasons present a unique opportunity to craft messaging aimed at communicating climate change impacts on public health through changes in the biological systems. However, it is unclear how pollen seasons are experienced and understood by the public, including how well we detect pollen seasons or what factors we view as responsible for changes in pollen seasons. Here, we use social media data in the United States from 2012 to 2022 to assess public perceptions of pollen seasons at large spatiotemporal scales. We show that pollen seasons detected by social media (Twitter) users align well with natural pollen seasons. Attribution of changing pollen seasons, however, varies based on political ideology: liberal users, compared to conservative users, are more likely to attribute changing pollen seasons to climate change. Mass media and scientific experts play a key role in communicating how climate change drives changing pollen seasons. Our findings reveal how changes in biological systems, political ideology, and scientific communications collectively shape public perceptions of pollen seasons under climate change. Our findings constitute a step towards more effective climate change impact communication and public health intervention design.

scientific communication and education↗

bioRxiv2023

Bursting with potential: How sensorimotor beta bursts develop from infancy to adulthood

Beta activity is thought to play a critical role in sensorimotor processes. However, little is known about how activity in this frequency band develops. Here, we investigated the developmental trajectory of sensorimotor beta activity from infancy to adulthood. We recorded electroencephalography (EEG) from adults, 12-month-olds, and 9-month-olds while they observed and executed grasping movements. We analysed beta burst activity using a novel method that combines time-frequency decomposition and principal component analysis (PCA). We then examined the changes in burst rate and waveform motifs along the selected principal components. Our results reveal systematic changes in beta activity during action execution across development. We found a decrease in beta burst rate during movement execution in all age groups, with the greatest decrease observed in adults. Additionally, we identified four principal components that defined waveform motifs that systematically changed throughout the trial. We found that bursts with waveform shapes closer to the median waveform were not rate-modulated, whereas those with waveform shapes further from the median were differentially rate-modulated. Interestingly, the decrease in the rate of certain burst motifs occurred earlier during movement and was more lateralized in adults than in infants, suggesting that the rate modulation of specific types of beta bursts becomes increasingly refined with age.

neuroscience↗

bioRxiv2022

A global high-density chromatin interaction network reveals functional long-range and trans-chromosomal relationships

Chromatin contacts are essential for gene-expression regulation, however, obtaining a high-resolution genome-wide chromatin contact map is still prohibitively expensive owing to large genome sizes and the quadratic scale of pairwise data. Chromosome conformation capture (3C) based methods such as Hi-C have been extensively used to obtain chromatin contacts. However, since the sparsity of these maps increases with an increase in genomic distance between contacts, long-range or trans chromatin contacts are especially challenging to sample. Here, we created a high density reference genome-wide chromatin contact map using a meta-analytic approach. We integrate 3600 Human, 6700 Mouse, and 500 Fly 3C experiments to create species-specific meta-3C contact maps with 304 billion, 193 billion, and 19 billion contacts in respective species. We validate that meta-3C are uniquely powered to capture functional chromatin contacts in both cis and trans. Unlike individual experiments, meta-3C gene contacts predict gene coexpression for long-range and trans chromatin contacts. Similarly, for long-range cis-regulatory interactions, meta-3C contacts outperform all individual experiments, providing an improvement over the conventionally used linear genomic distance-based association. Assessing between species, we find patterns of chromatin contacts conservation in both cis and trans and strong associations with coexpression even in species for which 3C data is lacking. We have generated an integrated chromatin interaction network which complements a large number of methodological and analytic approaches focused on improved specificity or interpretation. This high-depth "super-experiment" is surprisingly powerful in capturing long-range functional relationships of chromatin interactions, which are now able to predict coexpression, expression quantitative trait loci (eQTL), and cross-species relationships.

genomics↗

bioRxiv2021

Retinoic acid exerts sexually dimorphic effects over muscle energy metabolism and function

The retinol dehydrogenase Rdh10 catalyzes the rate-limiting reaction that converts retinol into retinoic acid (RA), an autacoid that regulates energy balance and suppresses adiposity. Relative to WT, Rdh10+/- males experienced reduced fatty-acid oxidation, glucose intolerance and insulin resistance. Running endurance decreased 40%. Rdh10+/- females increased reliance on fatty acid oxidation and did not experience glucose intolerance nor insulin resistance. Running endurance improved 2.2-fold. Estrogen increased, revealed by a 40% increase in uterine weight. Because skeletal muscle energy use restricts adiposity and insulin resistance, we assessed the mixed fiber type gastrocnemius muscle (GM) to determine the effects of endogenous RA on muscle metabolism in vivo. RA in Rdh10+/- male GM decreased 38% relative to WT. TAG content increased 1.7-fold. Glut1 mRNA and glucose decreased >30%. Rdh10+/- male GM had impaired electron transport chain activity, and a 60% reduction in fasting ATP. The share of oxidative fibers increased, as did expression of the myogenic transcription factors Myog and Myf5. Centralized nuclei increased 5-fold in fibers--indicating muscle malady or repair. In Rdh10+/- female GM, RA decreased only 17%, due to a 1.8-fold increase in the estrogen-induced retinol dehydrogenase, Dhrs9. Rdh10+/- female GM did not amass TAG, increase oxidative fibers, decrease Glut1 mRNA or glucose, nor increase centralized nuclei. Expression of Myog and Myf5 decreased. Electron transport chain activity increased, elevating fasting ATP >3-fold. Thus, small decreases in skeletal muscle RA affect whole body energy use, insulin resistance and adiposity, in part through estrogen-related sexual dimorphic effects on mitochondria function.

biochemistry↗

bioRxiv2020

Molecular and cellular pathology of monogenic Alzheimer's disease at single cell resolution

Cell and molecular biology analyses of sporadic Alzheimers disease brain are confounded by clinical variability, ageing and genetic heterogeneity. Therefore, we used single-nucleus RNA sequencing to characterize cell composition and gene expression in the cerebral cortex in early-onset, monogenic Alzheimers disease. Constructing a cellular atlas of frontal cortex from 8 monogenic AD individuals and 8 matched controls, provided insights into which neurons degenerate in AD and responses of different cell types to AD at the cellular and systems level. Such responses are a combination of positively adaptive and deleterious changes, including large-scale changes in synaptic transmission and marked metabolic reprogramming in neurons. The nature and scale of the transcriptional changes in AD emphasizes the global impact of the disease across all brain cell types. One Sentence SummaryAlzheimers disease brain atlas provides insights into disease mechanisms

neuroscience↗

bioRxiv2019

Transcranial magnetic stimulation during British Sign Language production reveals monitoring of discrete linguistic units in left superior parietal lobule

Successful human hand and arm movements are typically carried out by combining visual, motoric, and proprioceptive information in planning, initiation, prediction, and control. The superior parietal lobule (SPL) has been argued to play a key role in integrating visual and motoric information particularly during grasping of objects and other such tasks which prioritise visual information. However, sign language production also engages SPL even though fluent signers do not visually track their hands or fixate on target locations. Does sign language production simply rely on the motoric/ proprioceptive processes engaged in visually guided action, or do the unique characteristics of signed languages change these processes? Fifteen fluent British Sign Language users named pictures while we administered transcranial magnetic stimulation (TMS) to left SPL, a control site, or no TMS. TMS to SPL had very specific effects: an increased rate of (sign-based) phonological substitution errors for complex two-handed signs (those requiring hand contact), but TMS did not slow or otherwise impair performance. Thus, TMS decreased the likelihood of detecting or correcting phonological errors during otherwise successful bimanual coordination, but it did not noticeably alter fine movement control. These findings confirm that for fluent signers SPL has adapted to monitor motor plans for discrete hand configurations retrieved from memory as well as more fine-grained aspects of visually guided actions.

neuroscience↗

bioRxiv2019

Data Resource Profile:The Dementias Platform UK (DPUK) Data Portal

The Dementias Platform UK (DPUK) Data Portal is a data repository facilitating access to data for 3 370 929 individuals in 42 cohorts. The Data Portal is an end-to-end data management solution providing a secure, fully auditable, remote access environment for the analysis of cohort data. All projects utilising the data are by default collaborations with the cohort research teams generating the data. The Data Portal uses UK Secure eResearch Platform (UKSeRP) infrastructure to provide three core utilities: data discovery, access, and analysis. These are delivered using a 7 layered architecture comprising: data ingestion, data curation, platform interoperability, data discovery, access brokerage, data analysis and knowledge preservation. Automated, streamlined, and standardised procedures reduce the administrative burden for all stakeholders, particularly for requests involving multiple independent datasets, where a single request may be forwarded to multiple data controllers. Researchers are provided with their own secure lab using VMware which is accessed using two factor authentication. Over the last 2 years, 160 project proposals involving 579 individual cohort data access requests were received. These were received from 268 applicants spanning 72 institutions (56 academic, 13 commercial, 3 government) in 16 countries with 84 requests involving multiple cohorts. Project are varied including multi-modal, machine learning, and Mendelian randomisation analyses. Data access is usually free at point of use although a small number of cohorts require a data access fee.

neuroscience↗

bioRxiv2018

Neural Dynamics of Executive Function in Cognitively-able Kindergarteners with Autism Spectrum Disorders (ASD) as Predictors of Concurrent Academic Achievement: Preliminary Study

Although electrophysiological (EEG) measures of executive functions (EF) (e.g. error monitoring) have been used to predict academic achievement in typically developing (TD) children, work investigating a link between error monitoring, and academic skills in children with autism spectrum disorder (ASD) is limited. In the current study, we employed traditional electrophysiological and advanced time-frequency methods, combined with principal components analyses, to extract neural activity related to error monitoring, and tested their relations to academic achievement in cognitively-able kindergarteners with ASD. Thirty-five cognitively-able kindergarteners with ASD completed academic assessments and the child-friendly \"Zoo Game\" Go/No-go task at school entry. The Go/No-go task successfully elicited an error-related negativity (ERN) and error positivity (Pe) in children with ASD as young as 5 years at medio-frontal and posterior electrode sites, respectively. We also observed increased response-related theta power during errors relative to correct trials at medio-frontal sites. Both larger Pe and theta power significantly predicted concurrent academic achievement after controlling for behavioral performance on the Zoo Game and IQ. These results suggest that the use of time frequency EEG analyses, combined with traditional ERP measures, may provide new opportunities to investigate neurobiological mechanisms of EF and academic achievement in young children with ASD.

neuroscience↗

bioRxiv2017

Improving data availability for brain image biobanking in healthy subjects: practice-based suggestions from an international multidisciplinary working group

Brain imaging is now ubiquitous in clinical practice and research. The case for bringing together large amounts of image data from well-characterised healthy subjects and those with a range of common brain diseases across the life course is now compelling. This report follows a meeting of international experts from multiple disciplines, all interested in brain image biobanking. The meeting included neuroimaging experts (clinical and non-clinical), computer scientists, epidemiologists, clinicians, ethicists, and lawyers involved in creating brain image banks. The meeting followed a structured format to discuss current and emerging brain image banks; applications such as atlases; conceptual and statistical problems (e.g. defining normality); legal, ethical and technological issues (e.g. consents, potential for data linkage, data security, harmonisation, data storage and enabling of research data sharing). We summarise the lessons learned from the experiences of a wide range of individual image banks, and provide practical recommendations to enhance creation, use and reuse of neuroimaging data. Our aim is to maximise the benefit of the image data, provided voluntarily by research participants and funded by many organisations, for human health. Our ultimate vision is of a federated network of brain image biobanks accessible for large studies of brain structure and function.

neuroscience↗