Biology subjects

Johnson, P. J.

Publications and source records attributed to Johnson, P. J..

7 recordsLinked to original sources

bioRxiv2025

Cautious explorers: comparing movement patterns of wild and rewilded solitary predators

Many rewilding projects emphasize recovering trophic networks through species translocation. Understanding the behaviour and movement patterns of rewilded animals is central to evaluating the success of rewilding efforts. In this study, we compared the behaviour of rewilded Persian leopards (Panthera pardus tulliana) in Russia with their wild counterparts in Iran to assess how they compare in terms of exploratory and cautious movement in new environments. We used Behavioural Change Point Analysis with selection procedures to identify points where individuals switched between movement modes. We analysed intrinsic movement metrics (speed, persistence velocity, turning velocity) and spatiotemporal attributes (duration, net squared displacement, distance travelled). Time spent in each behavioural mode differed between wild and rewilded leopards: on average, rewilded leopards spent more time in the "Ranging" mode and less time "Encamped" compared to wild leopards. Rewilded leopards were also slower than wild leopards, particularly in the "Encamped" state while wild leopards exhibited similar speeds across modes. Importantly, rewilded leopards had larger displacement and spent longer in the "Ranging" mode, a pattern not seen in wild leopards. These findings highlight distinct spatial behaviour patterns between wild and rewilded leopards. Accordingly, rewilded leopards adopted both exploratory and cautious behavioural strategies, reflecting their tendency to range more widely over extended periods, plausibly to gather information from large parts of their environments, albeit at lower speed, arguably to avoid potential risks, suggesting that they are in the process of adapting to new environments. These differences are likely to reflect different ecological circumstances, but even more so the previous experiences and thus different social circumstances of the two samples of Persian leopards. OPEN RESEARCH STATEMENTAll locational data from Iran are publicly available on Movebank: https://www.movebank.org/panel_embedded_movebank_webapp. Project: Persian leopard Tandoureh Iran (accession number 270329098). All the data are available for download as .csv file.

animal behavior and cognition↗

bioRxiv2025

Pharmacological inhibition of V-ATPase targets mode-switching but not the proton transport cycle

Vacuolar-type adenosine triphosphatases (V-ATPases) are rotary proton pumps that establish proton gradients across cellular membranes1,2. Their pharmacological inhibition is currently under active investigation as a therapeutic strategy for cancer, infectious diseases, and autophagy-related disorders3,4. However, the molecular mechanism underlying V-ATPase inhibition remains poorly understood. Based on ensemble average measurements, it is widely assumed that inhibitors suppress activity by slowing the catalytic transport cycle and reducing proton transport rates5-7. Here, we tested this popular notion by directly measuring single-molecule proton pumping in the presence of three potent V-ATPase inhibitors: bafilomycin A1, concanamycin A, and diphyllin. Although all compounds abolish proton gradients in a canonical concentration-dependent manner (IC50 of 0.2 nM, 0.6 nM, and 41 nM, respectively), they leave the proton transport rate of active V-ATPases essentially unchanged. Instead, inhibitors modulate the reversible switching kinetics between ultralong-lived active (pumping) and inactive modes. Distinct inhibitors modulate mode lifetimes in a mode-specific and differentially efficient manner, altering the probability of the pump being in the active mode. Given that mode-switching has been documented across diverse primary8,9 and secondary10-13 active transporters, our results suggest a novel strategy for therapeutic intervention that targets mode occupancy rather than the canonical transport cycle.

biophysics↗

bioRxiv2024

A novel dataset of 2,362 equine fecal microbiomes from eight veterinary teaching hospital on three continents reveals dominant effects of geography, breed, and disease

Horses and other equids are reliant on the gut microbiome for health, and studies have reported associations between certain clinical conditions and features of the fecal microbiome. However, research to date on the equine fecal microbiome has often relied on small sample sizes collected from single and relatively localized geographic regions. Previous work largely employs single timepoint analyses, or horses selected based on limited health criteria. To address these issues and expand our understanding of the core microbiome in health, and the changes associated with adverse outcomes, the Equine Gut Group (EGG) has collected and performed 16S rRNA sequencing on 2,362 fecal samples from 1,190 healthy and affected horses. Here we present the EGG database and demonstrate its utility in characterizing the equine microbiome in health and acute gastrointestinal disease. The EGG 16S rRNA database is a valuable resource to study the equine microbiome and its role in equine health.

microbiology↗

bioRxiv2024

Comparative neuroimaging of the carnivoran brain: Neocortical sulcal anatomy

Carnivorans are an important study object for comparative neuroscience, as they exhibit a wide range of behaviours, ecological adaptations, and social structures. Previous studies have mainly examined relative brain size, but a comprehensive understanding of brain diversity requires the investigation of other aspects of their neuroanatomy. Here, we obtained primarily post-mortem brain scans from twenty-six species of the order Carnivora, spanning across eight families with diverse representatives and including additional individuals for selected species, to create the largest Carnivoran brain collection to date. We then reconstructed their cortical surfaces, and examined neocortical sulcal anatomy to establish a framework for systematic inter-species comparisons. We observed distinct regional variations in sulcal anatomy, potentially related to the species behaviour and ecology. Arctoidea species with pronounced forepaw dexterity exhibited complex sulcal configurations in the presumed somatosensory cortex but low sulcal complexity in the presumed visual and auditory occipitotemporal cortex. Canidae had the largest number of unique major sulci with a unique sulcus in the occipital cortex and highly social canids featuring an additional frontal cortex sulcus. We also observed differentially complex occipito-temporal sulcal patterns in Felidae and Canidae, indicative of changes in auditory and visual areas that may be related to foraging strategies and social behaviour. In conclusion, this study presents an inventory of the sulcal anatomy of a number of rarely studied carnivoran brains including detailed digital atlases and establishes a framework and novel avenues for further investigations employing a variety of neuroimaging modalities to reveal more about carnivoran brain diversity.

neuroscience↗

bioRxiv2022

ULTRAFAST STRUCTURAL CHANGES DIRECT THE FIRST MOLECULAR EVENTS OF VISION

Vision is initiated by the rhodopsin family of light-sensitive G protein-coupled receptors (GPCRs). A photon is absorbed by the 11-cis retinal chromophore of rhodopsin which isomerises within 200 femtoseconds to the all-trans conformation, thereby initiating the cellular signal transduction processes that ultimately lead to vision. However, the intramolecular mechanism by which the photoactivated retinal induces the activation events inside rhodopsin remains elusive. In this work, we use ultrafast time-resolved crystallography at room temperature to determine how an isomerised twisted all-trans retinal stores the photon energy required to initiate protein conformational changes associated with the formation of the G protein-binding signalling state. The distorted retinal at 1 ps time-delay of photoactivation has pulled away from half of its numerous interactions with its binding pocket, and the excess of the photon energy is released through an anisotropic protein breathing motion in the direction of the extracellular space. Strikingly, the very early structural motions in the protein side chains of rhodopsin appear in regions involved in later stages of the conserved Class A GPCR activation mechanism. Our work sheds light on the earliest stages of vision in vertebrates and points to fundamental aspects of the molecular mechanisms of agonist-mediated GPCR activation.

biochemistry↗

bioRxiv2022

Regulation of the mammalian-brain V-ATPase via ultra-slow mode-switching

Summary paragraphVacuolar-type adenosine triphosphatases (V-ATPases)1-3 are electrogenic rotary mechanoenzymes structurally related to F-type ATP synthases4,5. They hydrolyze ATP to establish electrochemical proton gradients for a plethora of cellular processes1,3. In neurons, the loading of all neurotransmitters into synaptic vesicles is energized by ~1 V-ATPase molecule per synaptic vesicle6,7. To shed light into this bona fide single-molecule biological process, we investigated electrogenic proton pumping by single mammalian-brain V-ATPases, using individual synaptic vesicles fused with immobilized liposomes. We show V-ATPases do not pump continuously in time, as hypothesized by observing the rotation of bacterial homologs8 and assuming strict ATP/proton coupling. Instead, they stochastically switch between three novel ultra-long-lived proton-pumping, inactive, and proton-leaky modes. Upending conventional wisdom, direct observation of pumping revealed that physiologically relevant concentrations of ATP do not regulate the intrinsic pumping rate. Instead, ATP regulates V-ATPase activity via the switching probability of the proton-pumping mode. In contrast, electrochemical proton gradients regulate the pumping rate and the switching of the pumping and inactive modes. This work reveals and emphasises the mechanistic and biological importance of mode-switching in protein regulation.

biophysics↗

bioRxiv2020

Diffusion MRI Changes in the Healthy Aging Canine Brain

White matter dysfunction and degeneration have been a topic of great interest in healthy and pathological aging. While ex vivo studies have investigated age-related changes in canines, little in vivo canine aging research exists. Quantitative diffusion MRI such as diffusion tensor imaging (DTI) has demonstrated aging and neurodegenerative white matter changes in humans. However, this method has not been applied and adapted in vivo to canine populations. This study aimed to test the hypothesis that white matter diffusion changes frequently reported in human aging are also found in aged canines. The study used Tract Based Spatial Statistics (TBSS) and a region of interest (ROI) approach to investigate age related changes in fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AxD) and radial diffusivity (RD). The results show that, compared to younger animals, aged canines have significant decreases in FA in parietal and temporal regions as well as the corpus callosum and fornix. Additionally, AxD decreases were observed in parietal, frontal and midbrain regions. Similarly, an age-related increase in RD was observed in the right parietal lobe while MD decreases were found in the midbrain. These findings suggest that canine samples offer a model for healthy human aging as they exhibit similar white matter diffusion tensor changes with age.

neuroscience↗