Biology subjects

Muir, P.

Publications and source records attributed to Muir, P..

12 recordsLinked to original sources

bioRxiv2026

Proximal sesamoid bone fatigue in Thoroughbred racehorses is associated with palmar osteochondral disease in the adjacent third metacarpal bone condyle

Abstract Background: Proximal sesamoid bone (PSB) stress fracture is a common catastrophic injury in racing Thoroughbreds that is associated with bone sclerosis and development of focal osteolysis. Standing computed tomography (sCT) enables sensitive identification of these structural changes and associations with other more common fetlock fatigue injury such as palmar/plantar osteochondral disease lesions affecting the condyles of the third metacarpal/metatarsal (MC3/MT3). Objective: To gain insight into the PSB stress fracture mechanism, we examined associations between fatigue injury prevalence in the three major metacarpophalangeal (MCP) sites: PSB, parasagittal grooves (PSG), and third metacarpal bone MC3 condyles. Study design: Retrospective clinical study. Methods: We studied 22 catastrophically injured Thoroughbred racehorses. Thoracic limbs were examined using computed tomography (CT) (n=29). Subjective CT assessment classified 58 PSBs as 32 control and 26 case PSBs with bone fatigue (transverse fracture, focal osteolysis, or severe sclerosis). Opposing joint surfaces were also studied. PSB bone mineral density (BMD) was estimated. Results: Prevalence of fatigue injury in the PSB, condyle, and PSG was 44.8% (n=26), 43.1% (n=25), and 17.2% (n=10), respectively. For MC3 condyles with POD, 88.0% had fatigue injury in the corresponding PSB (OR = 53.2). Prevalence of PSB fatigue injury was 20.0% when there was PSG fatigue injury. The odds of a PSB having fatigue injury when the opposing MC3 PSG had signs of fatigue injury was 0.25. PSBs with opposing MC3 condyles containing a POD lesion had significantly increased BMD compared with opposing control condyles. BMD was significantly increased in PSBs with structural change associated with cyclic fatigue. Conclusions: Development of PSB fatigue and adaptive PSB sclerosis is associated with POD. Stress fractures in Thoroughbreds commonly affect the MCP joint. Condylar fractures occur from PSG or POD fatigue injury. PSB fractures are also common. Our findings suggest detailed clinical assessment of PSB structural change in racing Thoroughbreds diagnosed with POD is merited as part of routine injury prevention screening.

bioengineering↗

bioRxiv2026

Roles of bacterial growth competition systems in colonization of the murine gut

The gut microbiome is essential for human health. Although the gut microbiota is largely stable at the species level in healthy individuals, strain-level variation remains less understood. Many bacterial strains encode toxin delivery systems that may shape competition within the gut. Here, we investigate how contact-dependent growth inhibition (CDI) and colicins influence intestinal colonization by a competitive murine Escherichia coli isolate, R12. We show that R12 can colonize an intact mouse gut microbiota by displacing resident Enterobacteriaceae, but success depends on multiple interacting factors. CDI systems and colicins provide a competitive advantage against resident E. coli, particularly during early colonization, while metabolic flexibility and access to alternative carbon sources support long-term persistence. Colonization outcomes vary between hosts and are shaped by resident microbiota composition, strain-level competition, and the initial invader-to-resident ratio. Overall, successful gut invasion is determined by the combined effects of bacterial antagonistic systems, metabolic capacity, and ecological context.

microbiology↗

bioRxiv2025

Comparison of two different finite element modeling pipelines for virtual mechanical testing of the distal third metacarpal bone in Thoroughbred racehorses

Condylar stress fracture of the third metacarpal bone (MC3) in Thoroughbred racehorses is a common catastrophic injury and identification of horses at heightened risk remains subjective. Standing computed tomography (sCT) is a practical screening tool that is sensitive to fatigue-induced structural changes. Data from sCT also allows for patient-specific finite element analysis (FEA) of the distal MC3 and prediction of subchondral bone strain, as a potential objective classifier of racehorses at heightened risk. The goal of this study was to compare two independently developed sCT-based subject-specific FEA pipelines for virtual mechanical testing of the distal MC3. One pipeline models the full 3D distal MC3 (UWMSN), while the other uses a simpler approach by using single sCT slices (UMELB). Four (n=4) MC3 condyles from four Thoroughbred racehorses were selected for the study. Models were generated using both pipelines and the predicted subchondral bone strain was compared. UMELB predicted smaller subchondral strain compared to UWMSN, likely due to more limited modes of deformation. Although the UWMSN pipeline can identify elevated subchondral strain in horses with high fatigue damage, it is more labor intensive and computationally expensive. With further tuning and validation, the UMELB pipeline could be used as a simpler and faster approach for prediction of subchondral strain in the distal MC3.

bioengineering↗

bioRxiv2025

Risk assessment for condylar stress fracture in elite racing Thoroughbreds using standing computed tomography-based virtual mechanical testing

BackgroundCondylar stress fracture of the third metacarpal bone is a common catastrophic musculoskeletal injury in Thoroughbred racehorses. Condylar stress fracture is associated with parasagittal groove (PSG) subchondral osteolysis. Standing computed tomography (sCT) imaging allows for sensitive identification of this fatigue-induced structural change, an early form of subchondral bone injury (SBI), but there is not yet an objective method for identifying racehorses at heightened risk of condylar stress fracture. ObjectivesTo estimate PSG first principal strain in elite Thoroughbred racehorses that have undergone subjective risk assessment using sCT fetlock screening. Study designRetrospective clinical study. MethodsWe used fetlock sCT images from 9 thoracic limbs from 7 Thoroughbred racehorses. A tuned, validated 3D finite element (FE) analysis approach was used as a virtual mechanical test to estimate PSG first principal strain in the distal third metacarpal bone (MC3) from these joints. Virtual mechanical testing results were compared with a subjective clinical risk assessment using an established screening approach by Racing Victoria. ResultsMC3 condyles with PSG SBI consistently and significantly displayed increased levels of first principal strain throughout the PSG. We found focal strain concentrations associated with the anatomical location of SBI compared to condyles with no evidence of SBI in the PSG. Clinical diagnosis of SBI with focal osteolysis, FE-predicted strain elevation, and clinical risk assessment were concordant with recall and precision of 0.86. Main limitationsThe sample size was small, and our virtual mechanical testing protocol does not account for whole-joint physiology. ConclusionsRisk assessment through screening with sCT is an established approach to injury prevention in racing Thoroughbreds. Concordance of a current clinical risk assessment approach by Racing Victoria with objective FE analysis of principal strain in sites of SBI in the present study suggests 3D FE analysis using a validated pipeline is an important new approach for routine assessment of risk of MC3 condylar stress fracture in Thoroughbred racehorses.

bioengineering↗

bioRxiv2025

Genetic structure of mesophotic and shallow Acropora aculeus on isolated atolls of Eastern Australia

Acropora is the most diverse and widespread coral genus in the world. Although known for its critical ecological role in shallow-water habitats, its abundance and diversity at upper mesophotic depths have only recently been uncovered. Consequently, little is known about the genetic structuring of mesophotic Acropora populations and their potential ecological and evolutionary relationships with shallow populations. Here, we present the first population genomic evaluation of the depth-generalist coral Acropora aculeus to assess genetic structuring across depths (10 and 40 m) and regions (the Great Barrier Reef (GBR) and the Western Coral Sea (WCS)). We observed strong geographic differentiation between regions, indicating the relative isolation of WCS atolls, with some gene flow occurring from WCS to the GBR, but rarely in the opposite direction. Conversely, we observed no geographic or depth-related genetic structuring within regions, although sample sizes limited the evaluation of local allelic patterns of depth structuring. Our results indicate that widespread connectivity within regions characterizes the broadcast spawning A. aculeus. The lack of depth differentiation should be explored to see whether the wide depth range of some species may be safeguarded against a rapidly changing climate.

genomics↗

bioRxiv2024

Tuning and validation of a virtual mechanical testing pipeline for condylar stress fracture risk assessment in Thoroughbred racehorses

Condylar stress fracture of the third metacarpal/metatarsal bone (MC3/MT3) in Thoroughbred racehorses is a common catastrophic injury, putting racehorse and jockey safety at risk. Microdamage forms in the distal MC3 and may result in strain elevation and higher risk of stress fracture, directly and through focal osteolysis resulting from the associated process of repair by remodeling in the condylar parasagittal grooves (PSG). Standing computed tomography (sCT) is a practical screening tool for detection of fatigue-induced structural changes, but the clinical interpretation remains subjective. The goal of this study was to develop and validate a sCT-based subject-specific finite element analysis (FEA) pipeline for virtual mechanical testing of the distal MC3. Twelve (n=12) MC3 condyles with available ex vivo strain were selected. Half of the specimens were used for tuning of the Youngs modulus in fatigue sites, and the other half to examine validity of the pipeline for prediction of PSG strain. The tuned model improved prediction of strain and predicted higher strain in bones with PSG lysis over the untuned model, which is an essential feature for a diagnostic screening tool. The presented pipeline is expected to assist clinicians with interpretation of sCT-detectable structural changes and ultimately condylar fracture risk assessment.

bioengineering↗

bioRxiv2023

Comparison of radiography and computed tomography for condylar fracture risk assessment in Thoroughbred racehorses

BackgroundCatastrophic injury has a low incidence but leads to the death of many Thoroughbred racehorses annually. Effective screening for injury risk needs to solve the false negative diagnostic sensitivity problem. ObjectivesTo determine sensitivity, specificity, and reliability for condylar stress fracture risk assessment from fetlock digital radiographs (DR) and standing computed tomography (sCT) imaging (Asto CT Equina(R)). Study designControlled ex vivo experiment. MethodsA blinded set of DR and sCT images of the thoracic limb fetlock were prepared from 31 Thoroughbred racehorses and reviewed by four veterinarians. Observers evaluated the condyles and parasagittal grooves (PSG) of the third metacarpal subchondral bone (MC3) for the extent of dense bone and lucency/fissure and assigned a risk assessment grade for condylar stress fracture based on imaging findings. Sensitivity and specificity for detection of subchondral structural changes in the condyles and PSG of the third metacarpal bone and for risk assessment for condylar stress fracture were determined by comparison with a reference assessment. Agreement between each observer and the reference assessment and reliability between observers were determined. Intra-observer repeatability was also assessed. ResultsIntra-observer repeatability was identified for both DR and sCT imaging. Sensitivity for detection of structural change was lower than specificity for both imaging methods and all observers. For horses with a normal level of risk, observer assessment often agreed with the reference assessment. Sensitivity for risk assessment was lower than specificity for all observers. For horses with a high risk of serious injury, observers generally underestimated the level of risk. Diagnostic sensitivity of risk assessment was improved with sCT imaging, particularly for horses with elevated risk of injury. Assessment reliability was better with sCT than DR. Main limitationsThe ex vivo study design influenced DR image sets regarding limb positioning and image contrast compared with in vivo DR imaging. ConclusionsRisk assessment through screening with diagnostic imaging is a promising approach to improve injury prevention in racing Thoroughbreds. Knowledge of sensitivity and specificity of fetlock lesion detection by DR and sCT provides critical guidance regarding development of improved screening programs for racehorses using diagnostic imaging. We found improved detection of MC3 subchondral structural change and risk assessment for condylar stress fracture with sCT ex vivo.

physiology↗

bioRxiv2022

Global phylogenomic assessment of Leptoseris and Agaricia reveals substantial undescribed diversity at mesophotic depths

Mesophotic coral communities are increasingly gaining attention for the unique biological species they host, exemplified by the numerous mesophotic fish species that continue to be discovered. In contrast, many of the photosynthetic scleractinian corals observed at mesophotic depths are assumed to be depth-generalists, with very few species characterised as mesophotic-specialists. This presumed lack of a specialised community remains largely untested, as phylogenetic studies rarely include mesophotic samples and have long suffered from resolution issues associated with traditional sequence markers. Here, we used reduced-representation genome sequencing to provide a phylogenomic assessment of the two dominant mesophotic genera of plating corals in the Indo-Pacific and Western Atlantic, respectively, Leptoseris and Agaricia. While these genome-wide phylogenies broadly corroborated the morphological taxonomy, they also exposed substantial undescribed diversity (at least 24 molecular clades across the 8 species), including deep divergences within genera and current taxonomic species. Five of the eight focal species consisted of at least two sympatrically-occurring, genetically distinct clades, which were consistently detected across different methods. The repeated observation of genetically divergent clades associated with mesophotic depths highlights that there are many more mesophotic-specialist coral species than currently acknowledged, and that an urgent assessment of this largely unstudied biological diversity is warranted.

evolutionary biology↗

bioRxiv2020

Cryptic diversity masks ecologically distinct coral species on tropical reefs

Coral reefs are the epitome of species diversity, yet the number of described scleractinian coral species, the framework-builders of coral reefs, remains moderate by comparison. DNA sequencing studies are rapidly challenging this notion by exposing a wealth of undescribed diversity, but the evolutionary and ecological significance of this diversity remains largely unclear. Here, we present an annotated genome for one of the most ubiquitous corals in the Indo-Pacific (Pachyseris speciosa), and uncover through a comprehensive genomic and phenotypic assessment that it comprises morphologically indistinguishable, but ecologically divergent cryptic lineages. Demographic modelling based on whole-genome resequencing disproved that morphological crypsis was due to recent divergence, and instead indicated ancient morphological stasis. Although the lineages occur sympatrically across shallow and mesophotic habitats, extensive genotyping using a rapid diagnostic assay revealed differentiation of their ecological distributions. Leveraging "common garden" conditions facilitated by the overlapping distributions, we assessed physiological and quantitative skeletal traits and demonstrated concurrent phenotypic differentiation. Lastly, spawning observations of genotyped colonies highlighted the potential role of temporal reproductive isolation in the limited admixture, with consistent genomic signatures in genes related to morphogenesis and reproduction. Overall, our findings demonstrate how ecologically and phenotypically divergent coral species can evolve despite morphological stasis, and provide new leads into the potential mechanisms facilitating such divergence in sympatry. More broadly, they indicate that our current taxonomic framework for reef-building corals may be scratching the surface of the ecologically relevant diversity on coral reefs, consequently limiting our ability to protect or restore this diversity effectively.

evolutionary biology↗

bioRxiv2018

Pseudogenes in the mouse lineage: transcriptional activity and strain-specific history

Pseudogenes are ideal markers of genome remodeling. In turn, the mouse is an ideal platform for studying them, particularly with the availability of developmental transcriptional data and the sequencing of 18 strains. Here, we present a comprehensive genome-wide annotation of the pseudogenes in the mouse reference genome and associated strains. We compiled this by combining manual curation of over 10,000 pseudogenes with results from automatic annotation pipelines. Also, by comparing the human and mouse, we annotated 165 unitary pseudogenes in mouse, and 303 unitaries in human. We make all our annotation available through mouse.pseudogene.org. The overall mouse pseudogene repertoire (in the reference and strains) is similar to human in terms of overall size, biotype distribution (~80% processed/~20% duplicated) and top family composition (with many GAPDH and ribosomal pseudogenes). However, notable differences arise in the pseudogene age distribution, with multiple retro-transpositional bursts in mouse evolutionary history and only one in human. Furthermore, in each strain about a fifth of the pseudogenes are unique, reflecting strain-specific functions and evolution. Additionally, we find that ~15% of the pseudogenes are transcribed, a fraction similar to that for human, and that pseudogene transcription exhibits greater tissue and strain specificity compared to protein-coding genes. Finally, we show that highly transcribed parent genes tend to give rise to processed pseudogenes.

genomics↗

bioRxiv2018

Nearly all new protein-coding predictions in the CHESS database are not protein-coding

In a 2018 paper posted to bioRxiv, Pertea et al. presented the CHESS database, a new catalog of human gene annotations that includes 1,178 new protein-coding predictions. These are based on evidence of transcription in human tissues and homology to earlier annotations in human and other mammals. Here, we reanalyze the evidence used by CHESS, and find that nearly all protein-coding predictions are false positives. We find that 86% overlap transposons marked by RepeatMasker that are known to frequently result in false positive protein-coding predictions. More than half are homologous to only nine Alu-derived primate sequences corresponding to an erroneous and previously withdrawn Pfam protein domain. The entire set shows poor evolutionary conservation and PhyloCSF protein-coding evolutionary signatures indistinguishable from noncoding RNAs, indicating lack of protein-coding constraint. Only four predictions are supported by mass spectrometry evidence, and even those matches are inconclusive. Overall, the new protein-coding predictions are unsupported by any credible experimental or evolutionary evidence of function, result primarily from homology to genes incorrectly classified as protein-coding, and are unlikely to encode functional proteins.

genomics↗

bioRxiv2018

Multiple laboratory mouse reference genomes define strain specific haplotypes and novel functional loci

The most commonly employed mammalian model organism is the laboratory mouse. A wide variety of genetically diverse inbred mouse strains, representing distinct physiological states, disease susceptibilities, and biological mechanisms have been developed over the last century. We report full length draft de novo genome assemblies for 16 of the most widely used inbred strains and reveal for the first time extensive strain-specific haplotype variation. We identify and characterise 2,567 regions on the current Genome Reference Consortium mouse reference genome exhibiting the greatest sequence diversity between strains. These regions are enriched for genes involved in defence and immunity, and exhibit enrichment of transposable elements and signatures of recent retrotransposition events. Combinations of alleles and genes unique to an individual strain are commonly observed at these loci, reflecting distinct strain phenotypes. Several immune related loci, some in previously identified QTLs for disease response have novel haplotypes not present in the reference that may explain the phenotype. We used these genomes to improve the mouse reference genome resulting in the completion of 10 new gene structures, and 62 new coding loci were added to the reference genome annotation. Notably this high quality collection of genomes revealed a previously unannotated gene (Efcab3-like) encoding 5,874 amino acids, one of the largest known in the rodent lineage. Interestingly, Efcab3-like-/- mice exhibit severe size anomalies in four regions of the brain suggesting a mechanism of Efcab3-like regulating brain development.

genomics↗