Biology subjects

Macdonald, D.

Publications and source records attributed to Macdonald, D..

8 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

Analyzing the miRNA regulatory landscape of OGT identifies evolutionarily conserved upregulation.

O-GlcNAc transferase (OGT) is the key enzyme involved in post-translationally modifying cytoplasmic and nuclear proteins with O-GlcNAc. Maintenance of cellular O-GlcNAcylation levels is critical to cell health and requires precise transcriptional and post-transcriptional control. Herein we examine the miRNA regulation of OGT by the human miRNAome using our high-throughput miRFluR assay. We found >200 miRNA regulators of OGT, including 17 down- and 15 upregulatory miRNAs previously identified in CLIP datasets. We validated the impact of select miRNA on OGT and O-GlcNAc levels using both miRNA mimics and inhibitors that reduce endogenous miRNA levels. We focused our studies on two miRNA families, the downregulatory let-7 family and the upregulatory miR-148/152 family. For the let-7 family, we found that only let-7a-3p and let-7g-3p strongly downregulated OGT. Downregulation required two seed-dependent binding sites. Evolutionary analysis found that the more recent of the two sites emerged in placental mammals. A similar conservation pattern was observed for the site of regulation by the miR-148/152 family, which was previously identified in CLIP datasets. All three miRNA in this family upregulated OGT. Phylogenetic analysis revealed that this upregulatory site has been conserved for the past 98.7 million years. The emergence of these regulatory sites correlates with that of disease states that both OGT and the miRNA are known to impact. Overall, our results provide important insights into OGT, miRNA regulation and conservation through evolution.

molecular biology↗

bioRxiv2024

Screening the human miRNA interactome reveals coordinated upregulation in melanoma, adding bidirectional regulation to miRNA networks.

Cellular protein expression is coordinated post-transcriptionally by an intricate regulatory network. The current presumption is that miRNA work by repression of functionally related targets within a system. In recent work, upregulation of protein expression via direct interactions of mRNA with miRNA has been found in dividing cells, providing an additional mechanism of regulation. Herein, we demonstrate coordinated upregulation of functionally-coupled proteins by miRNA. We focused on CD98hc, the heavy chain of the amino acid transporter LAT1, and -2,3-sialyltransferases ST3GAL1 and ST3GAL2, which are critical for CD98hc stability in melanoma. Profiling miRNA regulation using our high-throughput miRFluR assay, we identified miRNA that upregulated expression of both CD98hc and either ST3GAL1 or ST3GAL2. These co-upregulating miRNAs were enriched in melanoma datasets associated with transformation and progression. Our findings add co-upregulation by miRNA into miRNA regulatory networks and adds a new bidirectional twist to the impact miRNA have on protein regulation and glycosylation.

cell biology↗

bioRxiv2022

miRNA upregulate protein and glycan expression via direct activation in proliferating cells

The dominant paradigm is that miRNA binding to mRNA represses protein expression. Activation by miRNA has been observed in select circumstances (quiescent cells, mitochondria), but is not thought a feature of miRNA action in actively dividing cells. Herein, we comprehensively map the miRNA regulation of -2,6-sialyltransferases ST6GAL1 and ST6GAL2 using a high-throughput assay (miRFluR). We find the majority of miRNA targeting ST6GAL1, the main enzyme controlling -2,6-sialylation, upregulate protein expression. In contrast, those that regulate ST6GAL2 are predominantly downregulatory. We provide evidence that miRNA-mediated upregulation occurs in proliferating cells and is a direct effect. Further, we show that AGO2 and FXR1 are required. Our data expands current understanding of miRNA, providing strong evidence of both upregulatory and downregulatory roles for these non-coding RNA. One-Sentence SummarymiRNA directly activate expression of -2,6-sialyltransferases and sialylation, expanding miRNA actions in dividing cells.

biochemistry↗

bioRxiv2022

Macrocycle-stabilization of its interaction with 14-3-3 increases plasma membrane localization and activity of CFTR

Impaired activity of the chloride channel CFTR is the cause of cystic fibrosis. 14-3-3 proteins have been shown to stabilize CFTR and increase its biogenesis and activity. Here, we report the identification and mechanism of action of a macrocycle stabilizing the 14-3-3/CFTR complex, a first-in-class molecular glue. This molecule rescues plasma membrane localization and chloride transport of F508del-CFTR and works additively with the CFTR pharmacological chaperone corrector lumacaftor (VX-809).

biochemistry↗

bioRxiv2020

Using very high-resolution satellite imagery and deep learning to detect and count African elephants in heterogeneous landscapes

O_LISatellites allow large-scale surveys to be conducted in short time periods with repeat surveys possible <24hrs. Very high-resolution satellite imagery has been successfully used to detect and count a number of wildlife species in open, homogeneous landscapes and seascapes where target animals have a strong contrast with their environment. However, no research to date has detected animals in complex heterogeneous environments or detected elephants from space using very high-resolution satellite imagery and deep learning. C_LIO_LIIn this study we apply a Convolution Neural Network (CNN) model to automatically detect and count African elephants in a woodland savanna ecosystem in South Africa. We use WorldView-3 and 4 satellite data - the highest resolution satellite imagery commercially available. We train and test the model on eleven images from 2014-2019. We compare the performance accuracy of the CNN against human accuracy. Additionally, we apply the model on a coarser resolution satellite image (GeoEye-1) captured in Kenya to test if the algorithm can generalise to an elephant population outside of the training area. C_LIO_LIOur results show the CNN performs with high accuracy, comparable to human detection capabilities. The detection accuracy (i.e., F2 score) of the CNN models was 0.78 in heterogeneous areas and 0.73 in homogenous areas. This compares with the detection accuracy of the human labels with an averaged F2 score 0.77 in heterogeneous areas and 0.80 in homogenous areas. The CNN model can generalise to detect elephants in a different geographical location and from a lower resolution satellite. C_LIO_LIOur study demonstrates the feasibility of applying state-of-the-art satellite remote sensing and deep learning technologies for detecting and counting African elephants in heterogeneous landscapes. The study showcases the feasibility of using high resolution satellite imagery as a promising new wildlife surveying technique. Through creation of a customised training dataset and application of a Convolutional Neural Network, we have automated the detection of elephants in satellite imagery with as high accuracy as human detection capabilities. The success of the model to detect elephants outside of the training data site demonstrates the generalisability of the technique. C_LI

ecology↗

bioRxiv2020

Estimating the density of small population of leopard Panthera pardus using multi-session photographic-sampling data

West Asian drylands host a number of threatened large carnivores, including the leopard (Panthera pardus) which is limited to spatially scattered landscapes with generally low primary productivity. While conservation efforts have focused on these areas for several decades, reliable population density estimates are missing. Spatially-explicit capture-recapture (SECR) methodology, incorporating animal movement in density estimates, is widely used to monitor populations of large carnivores. We employed multi-session SECR modeling to estimate the density of a small population of leopard (Panthera pardus) in a mountainous stretch surrounded by deserts in central Iran. During 6724 camera trap nights, we detected eight and five independent leopards in 2012 and 2016 sessions, respectively. The top performing model demonstrated density estimates of 1.6 (95% CI = 0.9-2.9) and 1.0 (95% CI = 0.6-1.6) independent leopards/100 km2 in 2012 and 2016, respectively. Both sex and season had substantial effects on spatial scale ({sigma}), with larger movements for males and during winter. Currently available estimates in arid regions represent some of the lowest densities across the leopard global range. These small populations are vulnerable to demographic stochasticity. Monitoring temporal changes in population density and composition can inform conservation priorities.

ecology↗

bioRxiv2017

Zebra diel migrations reduce encounter risk with lions over selection for safe habitats

Diel migrations (DMs) undertaken by prey to avoid visual predators during the day have been demonstrated in many taxa in aquatic ecosystems. We reveal that zebras in Hwange National Park (Zimbabwe) employ a similar anti-predator strategy. Zebras forage near waterholes during the day but move away from them at sunset. We demonstrate that this DM, occurring over a few km, dramatically reduces their night-time risk of encountering lions, which generally remain close to waterholes. By contrast, zebra changes in night-time selection for vegetation types marginally reduced their risk of encountering lions. This may arise from a trade-off between encounter risk and vulnerability across vegetation types, with zebras favouring low vulnerability once DM has reduced encounter risk. In summary, here we (1) quantify the effect of a predator-induced DM in a terrestrial system on the likelihood of encountering a predator, (2) distinguish the effects of the DM from those related to day/night changes in selection for vegetation types. We discuss how revealing how prey partition their risk between predator encounter risk and habitat-driven vulnerability is likely critical to understand the emergence of anti-predator behavioural strategies.

ecology↗