Biology subjects

Jeffery, K. J.

Publications and source records attributed to Jeffery, K. J..

12 recordsLinked to original sources

bioRxiv2026

Non-invasive genomic sampling uncovers novel connectivities and origins of confiscated gorillas

BackgroundGorillas are a group of African great apes with two species and four subspecies that are currently critically endangered or endangered. Previous studies that analysed the genetics of wild gorillas from non-invasive samples, such as faeces or hair, analysed short mitochondrial or nuclear markers, which may not reflect the wider nuclear genome. Recent technical advances in target capture hybridisation, enrich the endogenous DNA content of non-invasive samples, allowing contiguous genomic regions to be sequenced. ResultsHere, we generated georeferenced genetic data from faecal and hair samples of 280 wild gorillas, sampled from three of the four gorilla subspecies, across large parts of their present-day distributions. With this expanded representation of gorilla genetic diversity in the wild, we detected three population clusters in western lowland gorillas, with the Sangha River and its affluents acting as significant barriers to gene flow. We reconstructed patterns of past population connectivity between western lowland gorillas in the north-eastern distribution range and Cross River gorillas, which may have been facilitated by a migration corridor also used by the Central and Nigeria-Cameroon chimpanzee subspecies. Finally, we predicted the geographic origins of wild-born gorillas, achieving a mean prediction error of 65 km, with a population-level resolution for mountain gorillas and some populations of western lowland gorillas. ConclusionOur work characterises fine-scale population structure in western lowland gorillas, which will be informative for future conservation strategies. This proof of concept in predicting geographic locations of wild gorillas, will be useful for future applications to geolocalise trafficked or rescued gorillas.

evolutionary biology↗

bioRxiv2024

Local genetic adaptation to habitat in wild chimpanzees

How populations adapt to their environment is a fundamental question in biology. Yet we know surprisingly little about this process, especially for endangered species such as non-human great apes. Chimpanzees, our closest living relatives, are particularly interesting because they inhabit diverse habitats, from rainforest to woodland-savannah. Whether genetic adaptation facilitates such habitat diversity remains unknown, despite having wide implications for evolutionary biology and conservation. Using 828 newly generated exomes from wild chimpanzees, we find evidence of fine-scale genetic adaptation to habitat. Notably, adaptation to malaria in forest chimpanzees is mediated by the same genes underlying adaptation to malaria in humans. This work demonstrates the power of non-invasive samples to reveal genetic adaptations in endangered populations and highlights the importance of adaptive genetic diversity for chimpanzees. One-Sentence SummaryChimpanzees show evidence of local genetic adaptation to habitat, particularly to pathogens, such as malaria, in forests.

evolutionary biology↗

bioRxiv2024

The dorsal thalamic lateral geniculate nucleus is required for visual control of head direction cell firing direction in rats

Head direction (HD) neurons, signalling facing direction, generate a signal that is primarily anchored to the outside world by visual inputs. We investigated the route for visual landmark information into the HD system in rats. There are two candidates: an evolutionarily older, larger subcortical (retino-tectal) pathway specialised for coarse vision, and a smaller cortical (retino-geniculo-striate) pathway for higher acuity vision. We disrupted the cortical pathway by lesioning the dorsal lateral geniculate (dLGN) thalamic nuclei bilaterally, and recorded HD cells in postsubicular (PoS) cortex as rats foraged in a visual-cue-controlled enclosure. In dLGN-lesioned rats we found the expected number of PoS HD cells. Although directional tuning curves were broader across a trial, this was due to increased instability of otherwise normal-width tuning curves. Tuning curves were also poorly responsive to polarizing visual landmarks, and did not distinguish cues based on their visual pattern. Thus, the retino-geniculo-striate pathway is not critical for generation of an underlying, tightly-tuned directional signal, but does provide the main route for vision-based anchoring of the signal to the outside world, even when visual cues are high-contrast and low in detail. Key pointsO_LIHead direction (HD) cells indicate the facing direction of the head, using visual landmarks to distinguish directions C_LIO_LIIn rats, we investigated whether this visual information is routed through the thalamus to visual cortex or arrives via the superior colliculus: a phylogenetically older and (in rodents) larger pathway, but not known for pattern vision. C_LIO_LIWe lesioned the thalamic dorsal lateral geniculate nucleus (dLGN) in rats and recorded the responsiveness of cortical HD cells to visual cues. C_LIO_LIWe found that cortical HD cells had normal tuning curves but these were slightly more unstable during a trial. Most notably, HD cells in dLGN-lesioned animals showed little ability to distinguish highly distinct cues and none to distinguish more similar cues. C_LIO_LIThese results suggest that directional processing of visual landmarks in mammals requires the geniculo-cortical pathway, which raises questions about when and how visual directional landmark processing appeared during evolution. C_LI

neuroscience↗

bioRxiv2023

Three separable roles for context in breaking environmental symmetries for place cells

Effective self-localization requires that the brain can resolve ambiguities in incoming sensory information arising from self-similarities (symmetries) in the environment structure. We investigated how place cells use environmental cues to resolve the ambiguity of a rotationally symmetric environment, by recording from hippocampal CA1 in rats exploring a 2-box. This apparatus comprises two adjacent rectangular compartments, identical but with directionally opposed layouts (cue card at one end and central connecting doorway) and distinguished by their odor contexts (lemon vs. vanilla). Despite the structural and visual rotational symmetry of the boxes, no place cells rotated their place fields. The majority remapped their fields between boxes but some repeated them, maintaining a translational symmetry and thus adopting a relationship to the layout that was conditional on the odor. In general, the place field ensemble maintained a stable relationship to environment orientation as defined by the odors, but sometimes the whole ensemble rotated its firing en bloc, decoupling from the odor context cues. While the individual elements of these observations - odor remapping, place field repetition, ensemble rotation and decoupling from context - have been reported in isolation, the combination in the one experiment is incompletely explained within current models. We redress this by proposing a model in which odor cues enter into a three-way association with layout cues and head direction, creating a configural context signal that facilitates two separate processes: place field orientation, and place field positioning. This configuration can subsequently still function in the absence of one of its components, explaining the ensemble decoupling from odor. We speculate that these interactions occur in retrosplenial cortex, because it has previously been implicated in context processing, and all the relevant signals converge here.

neuroscience↗

bioRxiv2021

Environment symmetry drives a multidirectional code in rat retrosplenial cortex

A class of neurons showing bidirectional tuning in a two-compartment environment was recently discovered in dysgranular retrosplenial cortex (dRSC). We investigated here whether these neurons possess a more general environmental symmetry-encoding property, potentially useful in representing complex spatial structure. We report that directional tuning of dRSC neurons reflected environment symmetry in onefold, twofold and fourfold-symmetric environments: this was the case not just globally, but also locally within each sub-compartment. Thus, these cells use environmental cues to organize multiple directional tuning curves, which perhaps sometimes combine via interaction with classic head direction cells. A consequence is that both local and global environmental symmetry are simultaneously encoded even within local sub-compartments, which may be important for cognitive mapping of the space beyond immediate perceptual reach. One Sentence SummaryRetrosplenial directionally tuned neurons encode global environment symmetry even in local sub-compartments.

neuroscience↗

bioRxiv2021

Evidence for two distinct thalamocortical circuits in retrosplenial cortex

Retrosplenial cortex (RSC) lies at the interface between perceptual and memory networks in the brain and mediates between these, although it is not yet known how. It has two distinct subregions, granular (gRSC) and dysgranular (dRSC). The present study investigated how these subregions differ with respect to their electrophysiology and connections, as a step towards understanding their functions. gRSC is more closely connected to the hippocampal system, in which theta-band local field potential oscillations are prominent. We therefore compared theta-rhythmic single-unit activity between the two RSC subregions and found, mostly in gRSC, a subpopulation of non-directional cells with spiking activity strongly entrained by theta oscillations, suggesting a stronger coupling of gRSC to the hippocampal system. We then used retrograde tracers to examine whether differences in neural coding between RSC subregions might reflect differential inputs from the anterior thalamus, which is a prominent source of RSC afferents. We found that gRSC and dRSC differ in their afferents from two AV subfields: dorsomedial (AVDM) and ventrolateral (AVVL). AVVL targets both gRSC and dRSC, while AVDM provides a selective projection to gRSC. These combined results suggest the existence of two distinct but interacting RSC subcircuits: one connecting AVDM to gRSC that may comprise part of the cognitive hippocampal system, and the other connecting AVVL to both RSC regions that may link hippocampal and perceptual regions. We suggest that these subcircuits are distinct to allow for differential weighting during integration of converging sensory and cognitive computations: an integration that may take place in thalamus, RSC or both. HighlightsO_LIThe two retrosplenial cortex subregions, gRSC and dRSC, differ in their temporal firing characteristics and relation to theta oscillations. C_LIO_LIThere are differential afferents from the anteroventral thalamic nucleus to gRSC and dRSC, with the dorsomedial subnucleus projecting selectively to gRSC. C_LIO_LIThe anteroventral thalamus-retrosplenial cortex circuitry thus comprises two functionally and anatomically distinct but connected circuits, differentially connected to the hippocampal system, that may support the integration of cognitive and perceptual information. C_LI

neuroscience↗

bioRxiv2020

Grid cell firing fields in a volumetric space

We investigated how entorhinal grid cells represent volumetric (three-dimensional) space. On a flat surface, grid cell firing fields are circular and arranged in a close-packed hexagonal array. In three dimensions, theoretical and computational work suggests that the most efficient configuration would be a regular close packing of spherical fields. We report that in rats exploring a cubic lattice, grid cells were spatially stable and maintained normal directional modulation, theta modulation and spike dynamics. However, while the majority of grid fields were spherical, they were irregularly arranged, even when only fields abutting the lower surface (equivalent to the floor) were considered. Thus, grid organization is shaped by the environments movement affordances, and may not need to be regular to support spatial computations. One Sentence SummaryIn rats exploring a volumetric space, grid cells are spatially modulated but their firing fields are irregularly arranged.

neuroscience↗

bioRxiv2020

Hippocampal place cells encode global location but not changes in environmental connectivity in a 4-room navigation task

Flexible navigation relies on a cognitive map of space, thought to be implemented by hippocampal place cells: neurons that exhibit location-specific firing. In connected environments, optimal navigation requires keeping track of ones location and of the available connections between subspaces. We examined whether the dorsal CA1 place cells of rats encode environmental connectivity in four geometrically-identical boxes arranged in a square. Rats moved between boxes by pushing saloon-type doors that could be locked in one or both directions. While rats demonstrated knowledge of environmental connectivity, their place cells did not respond to connectivity changes, nor did they represent doorways differently from other locations. Importantly, place cells coded the space in a global frame, expressing minimal repetitive fields despite the repetitive geometry (global coding). These results suggest that CA1 place cells provide a spatial map that does not explicitly include connectivity.

neuroscience↗

bioRxiv2020

Optimised use of Oxford Nanopore Flowcells for Hybrid Assemblies

Hybrid assemblies are highly valuable for studies of Enterobacteriaceae due to their ability to fully resolve the structure of mobile genetic elements, such as plasmids, which are involved in the carriage of clinically important genes (e.g. those involved in AMR/virulence). The widespread application of this technique is currently primarily limited by cost. Recent data has suggested that non-inferior, and even superior, hybrid assemblies can be produced using a fraction of the total output from a multiplexed nanopore (Oxford Nanopore Technologies [ONT]) flowcell run. In this study we sought to determine the optimal minimal running time for flowcells when acquiring reads for hybrid assembly. We then evaluated whether the ONT wash kit might allow users to exploit shorter running times by sequencing multiple libraries per flowcell. After 24 hours of sequencing, most chromosomes and plasmids had circularised and there was no benefit associated with longer running times. Quality was similar at 12 hours suggesting shorter running times are likely to be acceptable for certain applications (e.g. plasmid genomics). The ONT wash kit was highly effective in removing DNA between libraries. Contamination between libraries did not appear to affect subsequent hybrid assemblies, even when the same barcodes were used successively on a single flowcell. Utilising shorter run-times in combination with between-library nuclease washes allows at least 36 Enterobacteriaceae isolates to be sequenced per flowcell, significantly reducing the per isolate sequencing cost. Ultimately this will facilitate large-scale studies utilising hybrid assembly advancing our understanding of the genomics of key human pathogens. Data SummaryO_LIRaw sequencing data is available via NCBI under project accession number PRJNA604975. Sample accession numbers are provided in table S1. C_LIO_LIAssemblies are available via Figshare https://doi.org/10.6084/m9.figshare.11816532.v1. C_LI Impact StatementMost existing sequencing data has been acquired from short-read platforms (eg. Illumina). For some species of bacteria, clinically important genes, such as those involved in antibiotic resistance and/or virulence, are carried on plasmids. Whilst Illumina sequencing is highly accurate, it is generally unable to resolve complete genomic structures due to repetitive regions. Hybrid assembly uses long reads to scaffold together short-read contigs, maximising the benefits of both technologies. A major limiting factor to using hybrid assemblies at scale is the cost of sequencing the same isolate with two different technologies. Here we show that high-quality hybrid assemblies can be created for most isolates using significantly shorter run-times than are currently standard. We demonstrate that a simple washing step allows several libraries to be run on the same flowcell, facilitating the ability to take advantage of shorter running times. Adding nuclease means that contamination between libraries is minimal and has no significant effect on the quality of subsequent hybrid assemblies. This approach reduces the cost of acquiring long reads by >30%, paving the way for large-scale studies utilising hybrid assemblies which will likely significantly enhance our understanding of the genomics of important human pathogens.

bioinformatics↗

bioRxiv2020

Multi-omic surveillance of Escherichia coli and Klebsiella spp. in hospital sink drains and patients

Escherichia coli and Klebsiella spp. are important human pathogens that cause a wide spectrum of clinical disease. In healthcare settings, sinks and other wastewater sites have been shown to be reservoirs of antimicrobial-resistant E. coli and Klebsiella spp., particularly in the context of outbreaks of resistant strains amongst patients. Without focusing exclusively on resistance markers or a clinical outbreak, we demonstrate that many hospital sink drains are abundantly and persistently colonised with diverse populations of E. coli, Klebsiella pneumoniae and Klebsiella oxytoca, including both antimicrobial-resistant and susceptible strains. Using whole genome sequencing (WGS) of 439 isolates, we show that environmental bacterial populations are largely structured by ward and sink, with only a handful of lineages, such as E. coli ST635, being widely distributed, suggesting different prevailing ecologies which may vary as a result of different inputs and selection pressures. WGS of 46 contemporaneous patient isolates identified one (2%; 95% CI 0.05-11%) E. coli urine infection-associated isolate with high similarity to a prior sink isolate, suggesting that sinks may contribute to up to 10% of infections caused by these organisms in patients on the ward over the same timeframe. Using metagenomics from 20 sink-timepoints, we show that sinks also harbour many clinically relevant antimicrobial resistance genes including blaCTX-M, blaSHV and mcr, and may act as niches for the exchange and amplification of these genes. Our study reinforces the potential role of sinks in contributing to Enterobacterales infection and antimicrobial resistance in hospital patients, something that could be amenable to intervention. IMPORTANCEEscherichia coli and Klebsiella spp. cause a wide range of bacterial infections, including bloodstream, urine and lung infections. Previous studies have shown that sink drains in hospitals may be part of transmission chains in outbreaks of antimicrobial-resistant E. coli and Klebsiella spp., leading to colonisation and clinical disease in patients. We show that even in non-outbreak settings, contamination of sink drains by these bacteria is common across hospital wards, and that many antimicrobial resistance genes can be found and potentially exchanged in these sink drain sites. Our findings demonstrate that the colonisation of handwashing sink drains by these bacteria in hospitals is likely contributing to some infections in patients, and that additional work is needed to further quantify this risk, and to consider appropriate mitigating interventions.

microbiology↗

bioRxiv2019

The place-cell representation of volumetric space in rats

Place cells are spatially modulated neurons found in the hippocampus that underlie spatial memory and navigation: how these neurons represent 3D space is crucial for a full understanding of spatial cognition. We wirelessly recorded place cells in rats as they explored a cubic lattice climbing frame which could be aligned or tilted with respect to gravity. Place cells represented the entire volume of the mazes: their activity tended to be aligned with the maze axes, and when it was more difficult for the animals to move vertically the cells represented space less accurately and less stably. These results demonstrate that even surface-dwelling animals represent 3D space and suggests there is a fundamental relationship between environment structure, gravity, movement and spatial memory.

animal behavior and cognition↗

bioRxiv2019

Reconciling the potentially irreconcilable? Genotypic and phenotypic amoxicillin-clavulanate resistance in Escherichia coli

Resistance to amoxicillin-clavulanate, a widely used beta-lactam/beta-lactamase inhibitor combination antibiotic, is rising globally, yet susceptibility testing remains challenging. To test whether whole-genome sequencing (WGS) could provide a more reliable assessment of susceptibility than traditional methods, we predicted resistance from WGS for 976 E. coli bloodstream infection isolates from Oxfordshire, UK, comparing against phenotypes from the BD Phoenix (calibrated against EUCAST guidelines). 339/976 (35%) isolates were amoxicillin-clavulanate resistant. Predictions based solely on beta-lactamase presence/absence performed poorly (sensitivity 23% (78/339)) but improved when genetic features associated with penicillinase hyper-production (e.g. promoter mutations, copy number estimates) were considered (sensitivity 82% (277/339); p<0.0001). Most discrepancies occurred in isolates with peri-breakpoint MICs. We investigated two potential causes; the phenotypic reference and the binary resistant/susceptible classification. We performed reference standard, replicated phenotyping in a random stratified subsample of 261/976 (27%) isolates using agar dilution, following both EUCAST and CLSI guidelines, which use different clavulanate concentrations. As well as disagreeing with each other, neither agar dilution phenotype aligned perfectly with genetic features. A random-effects model investigating associations between genetic features and MICs showed that some genetic features had small, variable and additive effects, resulting in variable resistance classification. Using model fixed-effects to predict MICs for the non-agar dilution isolates, predicted MICs were in essential agreement ({+/-}1 doubling dilution) with observed (BD Phoenix) MICs for 691/715 (97%) isolates. This suggests amoxicillin-clavulanate resistance in E. coli is quantitative, rather than qualitative, explaining the poorly reproducible binary (resistant/susceptible) phenotypes and suboptimal concordance between different phenotypic methods and with WGS-based predictions.

microbiology↗