Biology subjects

Hegarty, M.

Publications and source records attributed to Hegarty, M..

8 recordsLinked to original sources

bioRxiv2026

Path Integration and Spatial Updating Recruit Distinct Cognitive-Neural Mechanisms in Humans

Path integration and spatial updating refer to the integration of self-motion information during navigation to update ones start location and the positions of other locations, respectively. Even though path integration has been described as a fundamental process whose output may serve as a building block for other navigational computations like spatial updating, the exact relationship between path integration and spatial updating is unknown. Here we addressed this question with an eye-tracking behavioral experiment and a subsequent fMRI study. Despite experiencing identical self-motion cues, participants showed differential eye fixation patterns and responded more quickly during spatial updating than during path integration, casting doubt on the fundamental role of path integration. Neuroimaging results showed that the precuneus and the dorsal premotor cortex were more activated during spatial updating, but the precuneus had stronger functional connectivity with the thalamus and the frontal cortex during path integration. Further supporting this dissociation, the two tasks invoked distinct brain-wide inter-regional functional networks. Together, the combined findings of both experiments suggest that spatial updating and path integration are dissociable navigation processes supported by distinct behavioral and neural mechanisms, rather than one process operating on the basis of the other.

neuroscience↗

bioRxiv2025

Use of a cytochrome P450 humanised mouse model to refine schistosomiasis drug discovery.

Control of schistosomiasis, a neglected tropical disease caused by infection with Schistosoma spp., remains reliant on a single chemotherapy, praziquantel (PZQ). This strategy presents a risk to global health should PZQ-resistant schistosomes establish in endemic areas and justifies the search for new drugs. However, species-specific metabolic differences between humans and preclinical models hinder the optimisation of next-generation anti-schistosomal therapeutics. Here, to bypass these species-specific limitations, we exploited a humanised mouse model, 8HUM, engineered to express the principal human Phase I cytochrome P450 enzymes (CYP1A1/2, CYP2C9, CYP2D6, CYP3A4/7) as well as the transcription factors constitutive androstane receptor (CAR) and pregnane X receptor (PXR) in place of 35 murine orthologues. We characterised S. mansoni development, immunopathology, hepatic transcriptomic responses, intestinal microbiome changes and PZQ metabolism as well as PZQ efficacy in 8HUM versus wild-type (WT) mice. 8HUM mice supported normal S. mansoni maturation, infection-associated microbiome dysbiosis, Th2-dominant immune responses and characteristic hepatic pathology. PZQ intrinsic clearance in 8HUM hepatic microsomes mirrored human levels and was >10-fold lower than that found for WT microsomes. Oral dosing revealed human-like PZQ exposures of (R)-PZQ and 4OH-PZQ in 8HUM mice at 25 mg/kg bodyweight and >90% reductions in worm burdens at 100 mg/kg bodyweight (equivalent to that seen in WT mice administered PZQ at 400 mg/kg bodyweight). Our results revealed that 8HUM mice recapitulate key features of murine schistosomiasis while exhibiting human-relevant drug metabolism. These findings establish 8HUM as a refined translational platform for anti-schistosomal drug development, improving predictive accuracy and accelerating therapeutic discovery. One Sentence SummaryA cytochrome P450 humanised mouse model is used to study Schistosoma mansoni development, schistosomiasis, drug metabolism and drug efficacy.

pharmacology and toxicology↗

bioRxiv2023

Video gaming, but not reliance on GPS, is associated with spatial navigation performance

Recent evidence suggests that greater reliance on GPS-assisted devices is associated with poorer navigation ability. Contrastingly, studies have shown that video gaming can enhance navigation ability. While gender differences in navigation ability in favour of men are well-reported, it remains unclear if the effects of reliance on GPS and video gaming on navigation performance are influenced by gender. We investigated whether gender would influence the effect of gaming experience and reliance on GPS on navigation ability using the mobile app Sea Hero Quest, which has been shown to predict real-world wayfinding performance. Alongside navigation performance assessment we asked a series of self-report questions relating to reliance on GPS, navigation strategies and gaming experience with a group of US-based participants (n = 822, 280 men, 542 women, mean age = 26.3 years, range = 18-52 years). A multivariate linear regression model found no significant association between reliance on GPS and navigation performance for either gender. There was a significant association between weekly hours of video gaming and navigation performance which was not moderated by gender. After accounting for video game experience, gender was no longer significantly associated with navigation performance. These findings have implications for which daily activities may enhance or disrupt specific cognitive abilities. Future studies applying an interventional design and real-world navigation testing would be useful to determine whether video games playing increases navigation skill, or whether those who are good at navigating tend to play more video games.

neuroscience↗

bioRxiv2023

The relationship between object-based spatial ability and virtual navigation performance

Spatial navigation is a multi-faceted behaviour drawing on many different aspects of cognition. Visuospatial abilities, such as spatial working memory and mental rotation, in particular, may be key factors. A range of tests have been developed to assess visuospatial processing and memory, but how such tests relate to navigation ability remains unclear. This understanding is important to advance tests of navigation for disease monitoring in Alzheimers Disease, where disorientation is an early symptom. Here, we report the use of an established mobile gaming app, Sea Hero Quest, as a measure of navigation ability. We used three separate tests of navigation embedded in the game: wayfinding, path integration and spatial memory in a radial arm maze. In the same participants, we also collected measures of mental rotation (Mental Rotation Test), visuospatial processing (Design Organization Test) and visuospatial working memory (Digital Corsi). We found few strong correlations across our measures. Being good at wayfinding in a virtual navigation test does not mean an individual will rate themself as a confident navigator, be good at path integration, or have a superior memory in a radial arm maze. However, those good at wayfinding tend to perform well on the three visuospatial tasks examined here, and to also use a landmark strategy in the radial maze task. These findings help clarify the inter-relationships between different abilities supporting visuospatial and navigation skills. HighlightsO_LIThree navigation tests embedded in the game Sea Hero Quest were examined in relation to three object-based visuospatial tasks, and self-ratings of navigation ability and stress during navigation. C_LIO_LINo associations were observed among performance on wayfinding, path integration and radial arm maze levels of Sea Hero Quest. C_LIO_LIObject-based visuospatial abilities were selectively correlated with performance on wayfinding levels of Sea Hero Quest. C_LIO_LIGameplay stress and navigation strategy were not associated with performance on Sea Hero Quest navigation tasks. C_LI

neuroscience↗

bioRxiv2022

Cultural determinants of the gap between self-estimated navigation ability and wayfinding performance: evidence from 46 countries.

Cognitive abilities can vary widely. Some people excel in certain skills, others struggle. However, not all those who describe themselves as gifted are. One possible influence on self-estimates is the surrounding culture. Some cultures may amplify self-assurance and others cultivate humility. Past research has shown that people in different countries can be grouped into a set of consistent cultural clusters with similar values and tendencies, such as attitudes to masculinity or individualism. Here we explored whether such cultural dimensions might relate to the extent to which populations in 46 countries overestimate or underestimate their cognitive abilities in the domain of spatial navigation. Using the Sea Hero Quest navigation test and a large sample (N=383,187) we found cultural clusters of countries tend to be similar in how they self-rate ability relative to their actual performance. Across the world population sampled, higher self-ratings were associated with better performance. However, at the national level, higher self-ratings as a nation were not associated with better performance as a nation. Germanic and Near East countries were found to be most overconfident in their abilities and Nordic countries to be most under-confident in their abilities. Gender stereotypes may play a role in mediating this pattern, with larger national positive attitudes to male stereotyped roles (Hofstedes masculinity dimension) associated with a greater overconfidence in performance at the national level. We also replicate, with higher precision than prior studies, evidence that older men tend to overestimate their navigation skill more than other groups. These findings give insight into how culture and demographics may impact self-estimates of our abilities.

neuroscience↗

bioRxiv2019

Illuminating the functional rare biosphere of the Greenland Ice Sheet’s Dark Zone

The Dark Zone of the western Greenland Ice Sheet is the most expansive region of contiguous bare terrestrial ice in the Northern Hemisphere. Microbial processes within the Dark Zone play an important role in driving extensive albedo reduction and amplified melting, yet the composition and function of those consortia have not been fully identified. Here we present the first results from joint 16S rRNA gene and 16S rRNA (cDNA) analysis for the comparison of input (snow), storage (cryoconite), and output (supraglacial stream water) habitats across the Dark Zone over the melt season. Our analysis reveals that all three Dark Zone communities are characterized by a preponderance of rare taxa exhibiting high protein synthesis potential (PSP). Furthermore, taxa with high PSP represent highly connected \"bottlenecks\" within community structure, consistent with roles as metabolic hubs within their communities. Finally, the detection of low abundance-high PSP taxa affiliated with Methylobacterium within snow and stream water indicates a potential role for Methylobacterium in the carbon cycle of Greenlandic snowpacks, and importantly, the export of potentially active methylotrophs to the bed of the Greenland Ice Sheet. By comparing the dynamics of bulk and potentially active microbial communities in the Dark Zone of the Greenland Ice Sheet our study provides insight into the mechanisms and impacts of the microbial colonization of this critical region of our melting planet.

microbiology↗

bioRxiv2018

Pleistocene climate changes explain large-scale genetic variation in a dominant grassland species, Lolium perenne L.

AimGrasslands have been pivotal in the development of herbivore breeding since the Neolithic and are still nowadays the most widespread agricultural land-use across Europe. However, it remains unclear whether the current large-scale genetic variation of plant species found in natural grasslands of Europe is the result of human activities or natural processes.\n\nLocationEurope.\n\nTaxonLolium perenne L (perennial ryegrass).\n\nMethodsWe reconstructed the phylogeographic history of L. perenne, a dominant grassland species, using 481 natural populations including 11 populations from closely related taxa. We combined the Genotyping-by-Sequencing (GBS) and Pool-sequencing (Pool-seq) methods to obtain high-quality allele frequency calls of ~ 500 k SNP loci. We performed genetic structure analyses and demographic reconstructions based on the site frequency spectrum (SFS). We additionally used the same genotyping protocol to assess the genomic diversity of a set of 32 cultivars representative of the L. perenne cultivars widely used for forage purposes.\n\nResultsExpansion across Europe took place during the Wurm glaciation (12-110 kya), a cooling period that decreased the dominance of trees in favour of grasses. Splits and admixtures in L. perenne fit historical sea level changes in the Mediterranean basin. The development of agriculture in Europe (7-3.5 kya), that caused an increase in the abundance of grasslands, did not have an effect on the demographic patterns of L. perenne. We found little differentiation between modern cultivars and certain natural variants. However, modern cultivars do not represent the wide genetic variation found in natural populations.\n\nMain conclusionsDemographic events in L. perenne can be explained by the changing climatic conditions during the Pleistocene. Natural populations maintain a wide genomic variability at continental scale that has been underused by recent breeding activities. This variability constitutes valuable standing genetic variation for future adaptation of grasslands to climate change, safeguarding the agricultural services they provide.

evolutionary biology↗

bioRxiv2018

Temperate grass allergy season defined by spatio-temporal shifts in airborne pollen communities

Grass pollen is the worlds most harmful outdoor aeroallergen and sensitivity varies between species. Different species of grass flower at different times, but it is not known how airborne communities of grass pollen change in time and space. Persistence and high mobility of grass pollen could result in increasingly diverse seasonal pollen communities. Conversely, if grass pollen does not persist for an extended time in the air, shifting pollen communities would be predicted throughout the summer months. Here, using targeted high throughput sequencing, we tracked the seasonal progression of airborne Poaceae pollen biodiversity across Britain, throughout the grass allergy season. All grass genera displayed discrete, temporally restricted peaks of pollen incidence which varied with latitude, revealing that the taxonomic composition of grass pollen exposure changes substantially across the allergy season. By developing more refined aeroallergen profiling, we predict that our findings will facilitate the exploration of links between taxon-specific exposure of harmful grass pollen and disease, with concomitant socio-economic benefits.

ecology↗