Biology subjects

McClure, J.

Publications and source records attributed to McClure, J..

13 recordsLinked to original sources

bioRxiv2026

A Multi-Scale Ecological Approach to Assessing Antimicrobial Resistance in a Freshwater Fish

Antimicrobial resistance (AMR) genes are increasingly recognized as an emerging environmental contaminant. Yet, the ecological mechanisms shaping their distribution across natural landscapes remain poorly understood. Here, we quantified AMR gene abundances in microbial communities sampled from wild fish from eight freshwater lakes on Vancouver Island and paired these gene-level measurements with fine-scale limnological and land-use data. Using droplet digital PCR, field surveys, and an iterative spatial forecasting framework that integrates Random Forest models with regression kriging, we explored how watershed-scale processes relate to variation in AMR genes across lakes. Our analyses reveal potential associations between elevated AMR gene levels, changes in water quality, deforestation, and geographic proximity to salmon aquaculture. By integrating data across biological and spatial scales, from genes within microbial communities to lake-level conditions and landscape patterns, this study illustrates the value of combining quantitative molecular measurements with geospatial modeling to identify environmental factors that may promote antimicrobial resistance in natural systems. Our approach provides a proof-of-concept and a general predictive framework for generating hypotheses and informing future monitoring efforts aimed at understanding, managing, and forecasting environmental reservoirs of resistance. SignificanceAntimicrobial resistance (AMR) genes are ancient components of environmental microbiomes. Yet, the mechanisms that generate modern hotspots of resistance across natural landscapes remain unclear. Here, we reveal how watershed-scale environmental change, including water quality metrics linked with deforestation and proximity to salmon aquaculture, predicts elevated AMR gene levels in the microbiomes of wild fish populations. By combining quantitative droplet digital PCR with ecological data and geospatial modeling, we move beyond isolated surveillance data to identify ecological mechanisms that promote antimicrobial resistance in freshwater ecosystems. This integrative approach provides mechanistic insight into why certain habitats, and the organisms within them, become reservoirs of resistance while others do not. Our findings highlight the importance of ecological context in understanding resistance evolution and offer a predictive tool for informing proactive monitoring and management strategies.

ecology↗

bioRxiv2025

A summary of intraspecific size variation for large mysticetes

Following existing work on odontocetes, an extensive survey of literature was conducted to summarize the growth and body mass of nine mysticete species along with analyses of adult size distributions using data from the International Whaling Commission catch database. Relationships uncovered between length parameters in mysticetes are combined with results previously obtained for odontocetes. On average, the mean adult length was 4% below the asymptotic size and its relative variability appeared to be very similar across most species (CV=4-5%). This value was expectedly higher in species with more prolonged growth throughout adulthood (CV=6-8%). Total body mass relationships between mysticete species appear to align with feeding strategies, as generalists and skim-feeders are notably heavier than lunge-feeding specialists.

zoology↗

bioRxiv2024

A summary of intraspecific size variation for large odontocetes

The study of cetacean size and growth aids in research about their energetics, ecology, evolution, and taxonomy. Data on total body length and mass of large cetaceans is retained in an overwhelming amount of literature and previous reviews are limited in discussing the variation of both length and mass. Nearly all the known published literature was examined to provide a brief but comprehensive summary of the adult size of four large odontocetes. To supplement the existing literature, data from the International Whaling Commission catch database were reviewed and incorporated into analyses to improve descriptions of intraspecific variation in adult size for Physeter macrocephalus. Regional comparisons of commercial data for P. macrocephalus revealed apparent differences in adult size that are likely more attributable to catch biases rather than a diagnostic difference in size between populations.

zoology↗

bioRxiv2023

MGAT5 (GnTase-V) products are overexpressed in primary osteoblastic osteogenic sarcoma

It is well documented that MGAT5 (Glycosyltransferase V) products are over expressed in carcinomas and likely accelerate metastasis by promoting neoangiogenesis. We now report a similar over expression in primary osteoblastic osteogenic sarcoma and demonstrate new intratumoural blood vessels. Expansion of the tumours is by osteoclastic resorption of both trabecular and cortical bone with the latter by cutting channels similar to physiological cutting cones. Osteoclasts, adjacent capillaries, and related mast cells also overexpress MGAT5 products and we speculate that this facilitates neoangiogenesis.

pathology↗

bioRxiv2023

The intraosseous expansion of primary chondrosarcoma is achieved by osteoclasts expressing GnTase V (MGAT5) activity to drive neoangiogenesis.

We have studied the impact of primary central conventional chondrosarcoma on the bone tissues (trabecular, endosteal and cortical) of the proximal femur. A combination of macroscopy, contact radiography, histology, lectin histochemistry and immunohistochemistry techniques were employed. The tumours expanded by driving the resorption of bone tissue progressively removing trabecular, endosteal and cortical bone ultimately causing pathological fracture of the latter. Resorption of all tissue types was by osteoclasts invariably accompanied by companion mesenchymal tissue containing capillaries, mononuclear cells and mast cells. There were no new pathological mechanisms in play, rather the usurpation of normal physiological mechanisms of bone tissue remodelling and modelling. Lectin histochemistry showed that osteoclasts, endothelial cells and mast cells expressed GnTase V (MGAT5) which has been implicated in neoangiogenesis. The linkage of osteoclasts and new blood vessels we believe is key to successful bone resorption.

pathology↗

bioRxiv2023

Chondro/osteoclasts and mast cells are co-villains in the joint destruction of rheumatoid arthritis

Chondro/osteoclasts and mast cells are cells of interest in the cartilage and bone destruction of joints affected by rheumatoid arthritis (RA). Both are major cellular components of the vascular synovial pannus proliferation characteristic of this disease. Chondroclasts degrade calcified cartilage and osteoclasts degrade bone tissue. Chondroclasts and osteoclasts are identical cell types and differentiate from monocyte precursors. Our studies show a close microanatomical relationship between these cells and new capillary formation (shown by the lectin Psophocarpus tetragonolobus - PTL-11) in the resorption sites of the mineralized tissues. Clast and mast cells express receptors for the lectin lPHA indicating beta1,6-acetylglucosaminal transferase V (GNTase V/MGAT5) activity providing a mechanism for neoangiogenesis. In addition to an angiogenetic function for mast cells it is probable that their products control monocyte differentiation and chondro/osteoclastogenesis.

pathology↗

bioRxiv2023

Glycoprofiling of Cartilage Matrix-Forming Tumours.

Lectin staining of benign and malignant cartilage proliferations indicates restricted glycoprofiles and significant differences. In general terms benign lesions show less cellular binding and more matrical binding than malignant lesions. This suggests that in the benign category cells are less metabolically active and the matrix more structurally stable. Chondrosarcoma cells stain with the lectin lPHA indicating increased {beta}1-6 branching linkages in complex N-linked glycans which is also a known feature of carcinoma cells. Increased angiogenesis and increased mast cell numbers are present in the connective tissue septa separating lobules of chondrosarcoma. The blood vessels stain with the lectins PTL-II and lPHA. Mast cells stain with lPHA. {beta} 1-6 linkage is initiated by the Golgi-bound glycosyltransferase GnTase V. Increased {beta}1-6 linkages are believed to enhance the metastatic potential of a malignant cell by angiogenesis. LPHA ligand is present not only in chondrosarcoma cells but also in endothelial cells and mast cells of the septa. The ligand for the lectin PTL-II is a core 1 O-linked glycans produced under the auspices of the galactosyltransferase T synthase. Production of this glycans by endothelial cells is believed to be obligatory for the formation of these cells into tubes as part of the construction of functioning blood vessels. There are, therefore, two candidate genes in chondrosarcoma worthy of further study viz those for GnTase V and T synthase. Targeted disruption of the activities of these genes has therapeutic possibilities.

pathology↗

bioRxiv2022

Study of the glycome of synovial mast cells in normal tissues, osteoarthritis and rheumatoid arthritis reveals MGAT5 activity in these and endochondral cells.

Mast cells and angiogenesis play roles in the synovium of both osteoarthritis and rheumatoid disease but precise mechanisms are unclear. In a study of the glycome of human synovial biopsies from normal, osteoarthritic and rheumatoid disease cases mast cell numbers were increased in both osteoarthritic and rheumatoid disease synovial samples (the latter more than the former). Both mast cells and endothelial cells expressed receptors for the lectin Phaseolus vulgaris leukagglutinin (lPHA). Endothelial cells only expressed receptors for Psophocarpus tetragonolobus (PTL-II). Mast cells and angiogenesis are, therefore, likely to have a common pathogenetic mechanism in osteoarthritis and rheumatoid synovitis, the difference being one of degree. lPHA receptor expression in both mast cells and endothelial cells indicates {beta}l,6N-acetylglucosaminyl (GlcNAc) - transferase V (GnTaseV/MGAT5) activity. This provides a linkage between mast cells and endothelial cell proliferation. Endothelial cells show core 1 O-glycosylation (positive PTL-II staining) which is probably necessary for the formation of competent tubular structures and for continuing vascular integrity.

pathology↗

bioRxiv2022

Aspects of the glycome of endochondral ossification

Comparatively little is known about the glycome (the set of glycans and glycoconjugates made by the cell, tissue or organism) of bone and cartilage. The glycome has a high-density coding capacity and is important in post-translational modification. Lectin histochemistry provides insights into the glycome and we applied this technique to an ectopic ossification site in human bronchial cartilages. Our results show that cartilage matrix at the site of erosion by chondroclasts has a limited but definite glycoprofile. In contrast, bone matrix does not express many lectin ligands. Chondroclasts have an extensive glycoprofile similar to that of, but not identical to, osteoclasts. N and O glycans are both expressed in the zone of presumptive mineralization and are relevant to that process. Bone trabecular lining cells communicate with osteocytes via intracanalicular processes and some lectin ligands were expressed by these three components. Mast cells and angiogenesis were prominent. Since cartilage normally resists vascular penetration by the secretion of antiangiogenesis factors it is postulated that the hypertrophic chondrocytes in the mineralization zone produce proteases which inhibit antiangiogenesis and facilitate angiogenesis by mast cells.

molecular biology↗

bioRxiv2019

Transforming growth factor-beta signaling via ALK1 and ALK5 regulates distinct functional pathways in vein graft intimal hyperplasia

RationaleTransforming growth factor-beta (TGF{beta}) is tightly regulated at multiple levels, with regulation at the receptor level now recognized as a key determinant of the cellular response to this pleiotropic cytokine. TGF{beta} promotes saphenous vein graft neointima formation after coronary artery bypass graft (CABG) surgery, inducing smooth muscle cell (SMC) hyperplasia and fibrosis by signaling via activin receptor-like kinase 5(ALK5). However, the role of the alternate TGF{beta} receptor ALK1 remains completely unknown. ObjectiveTo define the receptor pathways activated by TGF{beta} in SMCs and their mechanistic importance during CABG neointima formation. Methods and resultsRadioligand co-IP assays revealed direct interactions between TGF{beta}, ALK5 and ALK1 in primary saphenous vein graft SMC (HSVSMC) from patients undergoing CABG. Knockdown and pharmacological inhibition of ALK5 or ALK1 in HSVSMC significantly attenuated TGF{beta}-induced phosphorylation of receptor-regulated (R)-Smads 2/3 and 1/5, respectively. Microarray profiling followed by qRT-PCR validation showed that TGF{beta} induced distinct transcriptional networks downstream of ALK5 or ALK1, associated with HSVSMC contractility and migration, respectively and confirmed using migration assays as well as qRT-PCR and western blot assays of contractile SMC markers. scRNAseq analysis of TGF{beta}-treated HSVSMC identified distinct subgroups of cells showing ALK5 or ALK1 transcriptional responses, while RNA velocity analyses indicated divergence in differentiation towards ALK5 or ALK1-dominant lineages. ALK1, ALK5 and their downstream effectors pSmad1/5 and pSmad2/3 were localized to SMA+ neointimal SMCs in remodelled mouse vein grafts. Pharmacological inhibition or genetic ablation of Smad1/5 substantially reducing neointima formation following acute vascular injury. Notably, expression and activation of ALK1, ALK5 and their respective downstream R-Smads was already evident in hyperplastic saphenous veins prior to grafting. ConclusionsWhilst canonical TGF{beta} signaling via ALK5 promotes a contractile HSVSMC phenotype, transactivation of ALK1 by TGF{beta} induces neointima formation by driving cell migration. Restoring the balance between ALK1 and ALK5 in HSVSMC may represent a novel therapeutic strategy for vein graft failure.

cell biology↗

bioRxiv2019

Towards development of a statistical framework to evaluate myotonic dystrophy type 1 mRNA biomarkers in the context of a clinical trial

Myotonic dystrophy type 1 (DM1) is a rare genetic disorder, characterised by muscular dystrophy, myotonia, and other symptoms. DM1 is caused by the expansion of a CTG repeat in the 3-untranslated region of DMPK. Longer CTG expansions are associated with greater symptom severity and earlier age at onset. The primary mechanism of pathogenesis is thought to be mediated by a gain of function of the CUG-containing RNA, that leads to trans-dysregulation of RNA metabolism of many other genes. Specifically, the alternative splicing (AS) and alternative polyadenylation (APA) of many genes is known to be disrupted. In the context of clinical trials of emerging DM1 treatments, it is important to be able to objectively quantify treatment efficacy at the level of molecular biomarkers. We show how previously described candidate mRNA biomarkers can be used to model an effective reduction in CTG length, using modern high-dimensional statistics (machine learning), and a blood and muscle mRNA microarray dataset. We show how this model could be used to detect treatment effects in the context of a clinical trial.

bioinformatics↗

bioRxiv2018

Analysis of a large data set reveals haplotypes carrying putatively recessive lethal alleles with pleiotropic effects on economically important traits in beef cattle

BackgroundDeleterious recessive alleles can result in reduced economic performance in livestock in multiple ways in homozygous individuals: from early embryonic death, death soon after birth, to being non-lethal but causing reduced viability. While death is an easy phenotype to score, reduced viability is not as easy to identify. However, it can sometimes be observed as reduced artificial insemination (AI) conception rates, longer calving intervals, or higher hazard for live born animals.\n\nMethodsIn this paper, we searched for haplotypes carrying putatively recessive lethal alleles in 132,725 genotyped Irish beef cattle from five breeds: Aberdeen Angus, Charolais, Hereford, Limousin, and Simmental. We phased the genotypes in sliding windows along the genome and used five tests to identify haplotypes with absence of or reduced homozygosity. We then corroborated the identified haplotypes with reproduction records, indicating early embryonic death, and postnatal survival records. Finally, we assessed haplotype pleiotropy by estimating substitution effects on national estimates of breeding values for 15 economically important traits in beef production.\n\nResultsWe found support for three haplotypes with carrying putatively recessive lethal alleles. The haplotypes were located on chromosome 14 in Aberdeen Angus, chromosome 19 in Charolais and chromosome 16 in Simmental. Their population frequencies is 15.2%, 14.4%, and 8.8%, respectively. All of the haplotypes showed pleiotropic effects on economically important traits for beef production. Their allele substitution effects are {euro}3.23, {euro}1.47, and {euro}2.30 for the terminal index and -{euro}3.15, -{euro}0.75, and {euro}1.12 for the replacement index, where one standard deviations are {euro}18.32, {euro}22.54, and {euro}22.33 for terminal index and {euro}29.52, {euro}35.62, and {euro}30.97 for the replacement index. We identified ZFAT as the candidate gene for lethality in Aberdeen Angus, several candidate genes for the Simmental haplotype, and no candidate genes for the Charolais haplotype.\n\nConclusionsWe analysed genotype, reproduction, survival, and production data to discover haplotypes carrying putatively recessive lethal alleles in Irish beef cattle. We found support for three haplotypes. All three haplotypes have pleiotropic effects on economically important traits in beef production.

genetics↗

bioRxiv2017

SNP Data Quality Control in a National Beef and Dairy Cattle System and Highly Accurate SNP Based Parentage Verification and Identification

A major use of genetic data is parentage verification and identification as inaccurate pedigrees negatively affect genetic gain. Since 2012 the international standard for single nucleotide polymorphism (SNP) based verification in Bos taurus cattle has been the ISAG 100 and 200 SNP panels. While these SNP sets have provided an increased level of parentage accuracy over microsatellite markers (MS), they can validate the wrong parent for an animal at [≤]1% misconcordance rate levels, indicating that more SNP are needed if a more accurate pedigree is required. With rapidly increasing numbers of cattle being genotyped in Ireland that represent 61 Bos taurus breeds from a wide range of farm types: beef/dairy, AI/pedigree/commercial, purebred/crossbred, and large to small herd size the Irish Cattle Breeding Federation (ICBF) analysed different SNP densities to determine that at a minimum [≥]500 SNP are needed to consistently predict only one set of parents at a [≤]1% misconcordance rate. For parentage validation and prediction ICBF uses 800 SNP selected based on SNP clustering quality, ISAG200 inclusion, call rate (CR), and minor allele frequency (MAF) in the Irish cattle population. Large datasets require sample and SNP quality control (QC). Most publications only deal with SNP QC via CR, MAF, parent-progeny conflicts, and Hardy-Weinberg deviation, but not sample QC. We report here a genomic sample QC pipeline to deal with the unique challenges of >1,000,000 genotypes from a national herd such as SNP genotype errors from mis-tagging of animals, lab errors, farm errors, and multiple other issues that can arise.

genetics↗