Biology subjects

McAllister, C.

Publications and source records attributed to McAllister, C..

4 recordsLinked to original sources

bioRxiv2026

Pathogenic MYBPC3 missense variants alter protein-protein interactions within the sarcomere

BackgroundHypertrophic cardiomyopathy (HCM) is a genetic heart disease that leads to left ventricular hypertrophy, heart failure, and arrhythmias. Pathogenic missense variants in the gene myosin binding protein C (MYBPC3) cluster within its internal subdomains C3 and C6. The protein (MyBP-C), carrying these missense variants, localizes normally to the myofilaments, leaving uncertainty regarding the mechanism(s) by which they cause HCM. MethodsWe probed the molecular pathogenesis of these variants by analyzing (1) their prevalence in an international registry of patients with HCM, (2) total MyBP-C levels and the allelic fraction of mutant MyBP-C in human left ventricular heart tissue, and (3) performing flag-immunoprecipitation and proximity labeling mass spectrometry of wild-type MyBP-C and four pathogenic missense variants (Arg495Gln, Arg502Trp- C3, Trp792Arg, Arg810His- C6) to determine the change in MyBP-C interacting and proximity proteins induced by these variants. ResultsWe found that among patients with HCM who had any MYBPC3 pathogenic variant, 17.9% had a missense variant within the C3 or C6 subdomain. Unlike truncating variants, these C3 or C6 missense variants did not reduce MyBP-C content relative to myosin. The mutant allelic fraction of MyBP-C varied from 10.0-67.0% across samples. Flag-immunoprecipitation mass spectrometry identified 252 MyBP-C interacting proteins. Pathogenic missense variants disrupted 23 MyBP-C protein interactions, including lysosomal Ragulator-Rag complex proteins (RRAGA, RRAGC, LAMTOR4). Proximity labeling mass spectrometry was more sensitive, identifying 3,240 MyBP-C proximity proteins. Pathogenic missense variant(s) altered the proximity to MyBP-C of 789 proteins (69.4% increased and 30.5% decreased). Proteins that were increased in proximity to the missense MyBP-C were enriched for thin-filament proteins. ConclusionPathogenic MYBPC3 missense variants within the C3 and C6 subdomains are present in a substantial subset of patients with HCM. Our findings imply unique mechanisms of these variants distinct from haploinsufficiency, potentially driven by enhanced proximity to the thin filament within myofilaments.

cell biology↗

bioRxiv2025

β-bursting as a sensitive neural marker of inhibitory control in healthy older adults: a linear mixed-effects modelling and threshold-free cluster approach

Inhibitory control is essential for adaptive behaviour and declines with age, yet the underlying neural dynamics remain poorly understood. The {beta}-rhythm (15-29 Hz) is thought to reflect inhibitory signalling within the fronto-basal ganglia network. Recent evidence suggests that transient {beta}-bursts support inhibitory performance, often masked by conventional analyses of trial-averaged {beta}-power. To reveal the link between trial-by-trial {beta}-bursting and inhibition, we applied a recently developed analysis framework combining linear mixed-effects modelling (LMM) with threshold-free cluster enhancement (TFCE) during response inhibition and initiation in older adults. Twenty healthy older adults performed a bimanual anticipatory response inhibition task, while electroencephalography and electromyography were recorded to capture {beta}-activity ({beta}-burst rate/duration; averaged {beta}-power) and muscle bursting dynamics, respectively. Our analysis revealed distinct {beta}-bursting signatures absent in averaged {beta}-power data. Following the stop-signal, parieto-occipital {beta}-bursting presented before a temporal cascade from attentional to inhibitory processes. In addition to expected right fronto-central and bilateral sensorimotor activity, we observed left prefrontal {beta}-bursting, indexing broader inhibitory network engagement during bimanual response inhibition. Moreover, we established a functional link between right sensorimotor {beta}-bursting and muscle bursts during stopping, indicating rapid cortical suppression of initiated motor output. These results help clarify the mechanistic role of {beta}-oscillations and underscore the sensitivity of {beta}-bursting to both the timing and context of inhibitory demands in healthy older adults. Future research will help establish the potential of {beta}-bursting, combined with LMM-TFCE analysis, as a clinically relevant marker of impulse control dysfunction. Significance statementOur novel application of an advanced statistical framework revealed distinct spatiotemporal {beta}-bursting patterns during response inhibition and response withholding in healthy older adults, which were not captured by averaged {beta}-power. Identifying a further link between cortical {beta}-bursting and muscle-level suppression, the findings offer a mechanistic account of how the brain halts action in real time in older adults. This work provides a sensitive, trial-level framework for studying {beta}-bursting measures in general, as well as inhibitory control across aging and clinical populations.

neuroscience↗

bioRxiv2025

Extensive genome evolution distinguishes maize within a stable tribe of grasses

Over the last 20 million years, the Andropogoneae tribe of grasses has evolved to dominate 17% of global land area. Domestication of these grasses in the last 10,000 years has yielded our most productive crops, including maize, sugarcane, and sorghum. The majority of Andropogoneae species, including maize, show a history of polyploidy - a condition that, while offering the evolutionary advantage of multiple gene copies, poses challenges to basic cellular processes, gene expression, and epigenetic regulation. Genomic studies of polyploidy have been limited by sparse sampling of taxa in groups with multiple polyploidy events. Here, we present 33 genome assemblies from 27 species, including chromosome-scale assemblies of maize relatives Zea and Tripsacum. In maize, the after-effects of polyploidy have been widely studied, showing reduced chromosome number, biased fractionation of duplicate genes, and transposable element (TE) expansions. While we observe these patterns within the genus Zea, 12 other polyploidy events deviate significantly. Those tetraploids and hexaploids retain elevated chromosome number, maintain nearly complete complements of duplicate genes, and have only stochastic TE amplifications. These genomes reveal variable outcomes of polyploidy, challenging simple predictions and providing a foundation for understanding its evolutionary implications in an ecologically and economically important clade.

evolutionary biology↗

bioRxiv2022

Ectoparasitism in Polystomatidae (Neodermata, Monogenea): phylogenetic position and mitogenome of Sphyranura euryceae, a parasite of the Oklahoma salamander

BackgroundPolystomatidae represents a monogenean group whose representatives infect mainly (semi)-aquatic tetrapods. Sphyranuridae with its single genus (Sphyranura) exhibits ectoparasitism on salamander hosts and was traditionally considered a sister-group to Polystomatidae based on the presence of a well-developed opisthaptor yet was distinguished due to the presence of a single pair of haptoral suckers, as opposed to the three pairs present in polystomatids. However, more recent molecular work supported its inclusion within Polystomatidae, at an early diverging, yet unresolved, position in the clade of polystomatids that otherwise exhibit endoparasitism of batrachians. Resolving the position of Sphyranura in relation to Polystomatidae is a prerequisite for understanding the factors driving evolution and the shifts between ecto- and endoparasitism in Polystomatidae. MethodsVarious staining methods were used to morphologically characterise collected specimens of Sphyranura. The mitochondrial genome was assembled from WGS data. Based on a combination of nuclear (18S, 28S rRNA) and mitochondrial markers (cox1, 12S) we inferred the phylogeny of Polystomatidae using Bayesian inference and maximum likelihood methods. ResultsBased on morphological examination and comparison with type material, specimens of Sphyranura infecting Oklahoma salamander (Eurycea tynerensis) at Greathouse Spring, Arkansas (USA), were identified as S. euryceae, a new distributional record for the species. Along with an amended diagnosis of Sphyranura we provide the first molecular data for S. euryceae. Mitochondrial level comparison reveals instances of tRNA gene rearrangements in polystomatids. Our phylogeny identifies two clades within polystomatids infecting tetrapods, one infecting exclusively batrachians, the other mainly known from chelonians. Although not fully supported, Sphyranura appears as the earliest branching lineage within the former. ConclusionsWith Sphyranura nested within Polystomatidae, we consider Sphyranuridae invalid. Sphyranuras apparent early branching position indicates ectoparasitism is an ancestral trait with endoparasitism having evolved later in the Polbatrach clade. However, the reduced number of haptoral suckers in representatives of Sphyranura is a derived characteristic potentially resulting from paedomorphic evolution. Whilst there is an indication towards phylogenetic congruence of polystomatids and their batrachian hosts, the same was not true for polystomatid parasites of chelonians with evidence of multiple host switches. Furthermore, geographic distribution of hosts was not found to drive polystomatid phylogeny.

evolutionary biology↗