Biology subjects

Wilson, M.

Publications and source records attributed to Wilson, M..

At least 19 recordsLinked to original sources

bioRxiv2026

Longitudinal linear-epitope profiling of SLE identifies novel antigens associated with disease and disease activity

Systemic lupus erythematosus (SLE) is the prototypical systemic autoimmune disease defined by the production of autoantibodies directed against diverse self-antigens. Antinuclear antibodies (ANA) are central to SLE diagnosis, and anti-double-stranded DNA (anti-dsDNA) antibodies are clinically used to track disease activity. However, these biomarkers provide only partial insight into the full spectrum of autoimmune changes in patients. To expand the known landscape of SLE autoreactivity shared among patients and associated with disease activity, we performed an unbiased characterization of 1,268 SLE plasma samples from 695 SLE patients and 301 healthy controls using phage immunoprecipitation and sequencing (PhIP-seq). This technique preferentially displays linear epitopes, and thus provides a complementary set of autoreactivities to previously discovered autoreactive targets. Despite the marked clinical heterogeneity of SLE, machine learning applied to this data surfaced a shared, reproducible signature that robustly discriminates between SLE and healthy controls in two validation cohorts. Autoreactivities in SLE were significantly enriched for RNA-binding protein targets. Autoreactive proteins containing Basic Acidic Dipeptides (BAD) repeat domains, features associated with biomolecular condensate formation, distinguished patients with high disease activity (by SLEDAI score) from patients with no disease activity. Among all shared autoreactivities, a peptide derived from YTHDF2 emerged as the most prevalent target across SLE cohorts occurring in ~25% of SLE patients and displayed striking sequence similarity to a peptide derived from the Epstein Barr virus (EBV) lytic switch protein BZLF1. Competition assays demonstrated higher-affinity binding to the viral peptide, supporting a model in which antiviral humoral responses to EBV may drive secondary epitope spreading toward molecularly mimicked self-antigens. Remarkably, orthogonal validation using the Luminex bead platform containing a panel of only 10 peptides, including BZLF1, demonstrated strong discrimination between SLE and healthy controls (AUC = 0.95). Together, these findings identify a rich, greatly expanded landscape of autoreactivities in SLE, candidate biomarkers associated with high disease activity, and provide mechanistic insight linking EBV-driven immunity to epitope-specific autoimmunity in lupus.

immunology↗

bioRxiv2026

Neuroinflammation and metabolic dysfunction in POLG-related mitochondrial epilepsy

Super-refractory status epilepticus is a common neurological manifestation of mitochondrial disease caused by bi-allelic pathogenic variants in POLG. Epilepsy in POLG-related disease typically presents with an explosive onset of status epilepticus, often from an occipital focus, and is associated with extensive neurodegeneration. The neuropathological mechanisms underlying POLG-related mitochondrial epilepsy remain poorly understood, however, neuroinflammation and glial dysfunction are hypothesised to play a significant role. In this study, we performed a neuropathological and proteomic investigation of post-mortem brain tissues from 12 patients with POLG-related mitochondrial epilepsy (age range: 3 - 28 years) and matched control cases. Given that the primary visual cortex is prominently involved in this epileptic disorder, occipital cortical tissues (Brodmann area 17) were compared to frontal cortical tissues (Brodmann area 9). Liquid chromatography-mass spectrometry (LC-MS/MS) analysis identified a distinct immunometabolic signature in the occipital cortex, and to a lesser extent in the frontal cortex, in POLG-related epilepsy. This was characterised by decreased abundance of mitochondrial proteins coupled to an increased expression of innate immune and inflammatory proteins, consistent with neuroinflammation. To validate these observations, we confirmed an increased density of cells immunoreactive for acute phase proteins (C-reactive protein, osteopontin and serpin A3), immune co-receptors (CD14 and HLA-DR), the inflammatory glycoprotein YKL40, the cytokine TNF-alpha, and mitochondrial translocator protein (TSPO). We also demonstrate a decreased expression of mitochondrial oxidative phosphorylation (OXPHOS) subunits within POLG patient microglia, indicative of mitochondrial dysfunction. Finally, we show enrichment of mitochondrial OXPHOS and interneuron proteins in the control primary visual cortex compared with the frontal cortex, which may underlie the selective regional vulnerability observed in POLG-related mitochondrial disease. Overall, these findings provide strong neuropathological evidence implicating neuroinflammation and glial dysfunction in POLG-related epilepsy.

neuroscience↗

bioRxiv2026

Widespread introgression and a potential role for a neo-sex chromosome in booby diversification and speciation

Speciation in marine taxa is dynamic and complex, often occurring in the absence of absolute geographic barriers to gene flow. Boobies comprise a clade of seven highly mobile seabird species with high diversity in the eastern Pacific Ocean, where no land barriers separate extant sister species and hybridization is widespread. They exhibit striking diversity in bare-part coloration, an important signal of mate quality, and possess a novel multiple sex chromosome system (Z1Z2Z1Z2 / Z1Z2W), likely resulting from a fusion between an ancestral autosomal microchromosome and the W chromosome. To understand speciation processes in the context of gene flow, we sequenced and analyzed 29 short-read booby genomes and assembled a reference northern gannet genome to (1) test for introgression, (2) characterize genomic patterns of divergence across species, and (3) investigate the gene content and evolution of the neo-sex chromosome. We found that divergence among eastern Pacific sister taxa is temporally associated with periods of glacial maxima. Between periods of glacial maxima, two pairs of sister species (blue-footed and Peruvian boobies; masked and Nazca boobies) exhibit strong signatures of episodic introgression, indicating that speciation has occurred over multiple periods of divergence followed by gene flow. However, in the third pair of sister species, genomic signatures showed higher divergence within brown booby populations than between brown and Cocos boobies. We also identified the epidermal differentiation complex - a gene cassette involved in skin, feather, beak, and claw development - on the neo-sex region of the W chromosome, where it spans the boundary between the putatively recombining and non-recombining regions, with interspecific variation in the exact recombination suppression boundary. We inferred that this complex may contribute to diversity in feather and bare part coloration across boobies. Together, these results reveal that diversification and speciation in a clade of highly mobile seabirds emerged from a complex evolutionary history involving historical climate dynamics, introgression, and sex chromosome evolution.

evolutionary biology↗

bioRxiv2026

Diverse root fungal endophytes mediate plant access to soil nutrients

Plant roots are broadly colonized by endophytic fungi with saprotrophic capabilities, but our understanding of whether they function in ways that are beneficial or detrimental to the host remains limited to model organisms. We hypothesized that endophytic fungi broadly affect plant access to soil nutrients, particularly organic forms that are typically not directly available to the plant. To address this, we paired 41 fungal endophytes with switchgrass (Panicum virgatum L.) and provided either inorganic or organic forms of nitrogen (N) and phosphorus (P). We evaluated how the fungi affected plant tissue N and P as well as plant growth. We also examined if these outcomes could be predicted from fungal phylogenetic relationships, in vitro traits of the fungi, or characteristics of the habitat from which fungi were isolated. There was substantial variation in both plant N (0.05-0.63%) and P (0.02-0.10%) acquisition that depended on the interaction of fungus and nutrient treatment. More fungi were beneficial for plant N than for P and shoot nutrients generally increased more than root nutrients from fungal associations. However, fungal effects on plant nutrients were not predicted by fungal traits, habitat traits, or fungal phylogenetic relationships. This unpredictability highlights a key challenge for incorporating endophytes into nutrient management strategies. Improving our ability to predict endophyte impacts on host nutrient acquisition will require identifying the mechanisms underlying observed beneficial effects and scaling up to realistic, diverse root microbial communities.

ecology↗

bioRxiv2026

Population-scale Y chromosome assemblies reveal recurrent remodeling within constrained architectures

The human Y chromosome is among the most structurally dynamic chromosomes in the human genome, yet much of its diversity remains unresolved because of extensive palindromes, ampliconic gene families, satellite-rich heterochromatin and large segmental duplications. What remained unclear was how these diverse forms of variation fit together across the full chromosome, how often similar structures recur in different lineages, and which aspects of organization remain constrained despite rapid sequence turnover. Here, we generated and analyzed 142 nearly complete human Y chromosome assemblies from 17 major haplogroups spanning approximately 180,000 years of evolution, creating a population-scale resource for studying Y chromosome biology and diversity. These assemblies show that structural change on the Y chromosome is recurrent but constrained, even in its most repetitive regions. In the fertility-associated azoospermia factor c (AZFc) region, recurrent inversions, deletions, and complex rearrangements generate a limited repertoire of structural haplotypes. Multicopy ampliconic gene families follow distinct evolutionary paths: DAZ paralogues differ in structural constraint, RBMY evolves within a modular array, and TSPY copy number varies mainly through local expansion and contraction. The centromere and Yq12 heterochromatin vary greatly in size but retain a stable higher-order organization, including a single hypomethylated centromeric core and conserved Yq12 repeat composition and orientation. Methylation across palindromic and ampliconic regions is likewise structured by repeat class, copy order and local architecture. Together, these results provide a population-scale resource for the human Y chromosome and show that its rapid structural evolution is repeatedly funneled into a limited set of architectural outcomes.

genomics↗

bioRxiv2026

Interconnecting ADC Structure with Tumor Cell Biology with Multimodal Learning

Antibody-drug conjugates (ADCs) represent a significant advancement in cancer therapy, yet their development remains constrained by high attrition rates driven by an incomplete understanding of how ADC chemical design interconnects with tumor biology. Compounding this challenge, the field has converged on a narrow set of redundant structural components, and current linker-payload systems that do not share a single mechanism of action. Existing drug response prediction frameworks cannot resolve this multidimensional complexity, relying predominantly on genomic inputs while protein-level biology is challenging to integrate. To address this, we developed a multimodal machine learning platform interconnecting ADC structural parameters with tumor cell biology across thousands of curated structure-activity datapoints, including multi-omics profiles from 1,479 human tumor cell lines and protein-level inputs from a unique model (GENCEP) that derives complete proteomic signatures. The model was validated through blinded retrospective evaluation and, critically, large coverage prospective prediction of cytotoxicity across 159 ADC-cell line combinations spanning five antigens, four mechanistically distinct linker-payload systems, and eight tumor types, most with no prior published associated ADC data. Performance surpassed industry benchmarks established for small molecule therapeutic modalities, demonstrating that protein-informed multimodal integrated framework is effective at capturing cytotoxic determinants at scale.

pharmacology and toxicology↗

bioRxiv2026

The Impact of BOLD Induced Linewidth Modulation on Functional 1H MRS Analysis

Functional MRS can measure the neurometabolic response to neuronal activation, therapeutic interventions and changes in physiology. Substantial technical challenges currently present a barrier to reproducible findings and broader adoption by the neuroscientific community. One such challenge is the conflation between genuine metabolic changes and bias caused by subtle spectral lineshape changes associated with the BOLD response. Previous studies have demonstrated an approximately 1% bias for glutamate estimates at 7T based on experimentally acquired data and a single conventional fitting algorithm. In this study, we use synthetic MRS data to estimate the bias for two conventional fitting methods (LCModel and ABfit-reg) at 3T and 7T and evaluate the efficacy of dynamic lineshape adjustment, during preprocessing and fitting analysis stages, to reduce bias. Using the same dataset, we also explore the potential bias in 2D fitting approaches, comparing several fitting models implemented in FSL-MRS. Bias between two conventional fitting methods without explicit linewidth correction was similar ([~]1% for glutamate) and in good agreement with previous experimental studies at 7T. Lineshape changes from the BOLD response cause similar bias in conventional and 2D fitting packages for 3T and 7T data, resulting in an overestimation of metabolic changes associated with neuronal activation. This bias may be significantly reduced (<0.2%) by incorporating a BOLD linewidth matching step for conventional analysis or by direct modelling for 2D analysis. We therefore recommend explicit BOLD lineshape correction or modelling for future task-based fMRS studies at 3T and above.

neuroscience↗

bioRxiv2026

Autoantibody Repertoires in Healthy Individuals Vary According to HLA Class II Genotype

The link between HLA genotype and the presence of pathogenic autoantibodies has previously been established across different autoimmune disorders. However, the functional process linking specific antibodies to specific HLA remains unclear. Additionally, autoantibodies - usually associated with autoimmune disease - are also present in healthy individuals. To this end, we sought to determine the spectrum of self-antigen antibody specificity (the "autoreactome") in healthy individuals, stratified by HLA genotypes. We utilized Phage ImmunoPrecipitation Sequencing (PhIP-Seq), a programmable phage display for interrogation of antibody specificity, which encompasses over 700,000 peptides tiled across the entire human proteome. Serum from 741 donors without diagnosed autoimmune disease were grouped by their five homozygous HLA-DRB1 genotypes and analyzed for differences in autoreactivity profiles. We applied a custom filter to the PhIP-Seq normalized data and obtained a set of enriched peptides for each HLA-DRB1 genotype. We found that the autoreactome in healthy individuals with different HLA-DRB1 genotypes are generally distinct. Binary logistic regression successfully identified whether a sample belongs to a specific HLA-DRB1 genotype (HLA-DRB1*01, HLA-DRB1*03, HLA-DRB1*04, HLA-DRB1*07, and HLA-DRB1*15) with the following accuracies: 96%, 92%, 90%, 94%, and 90%, and multinomial models predicted HLA-DRB1 genotype with up to 90% accuracy. Finally, gene-level analysis suggests that individuals with specific HLA autoimmune risk alleles may harbor potentially pathogenic autoantibodies in the absence of, or prior to the establishment of, overt disease. Our analysis demonstrates that autoreactivity profiles in healthy people vary according to HLA class II genotype, and may provide insight into the pathological processes associated with development of autoimmune and other immune-mediated diseases.

immunology↗

bioRxiv2026

Structure-guided design of a targeted autoantibody degrader for neurologic disease

Despite rapid progress in the diagnosis of autoantibody-mediated neurologic diseases, standard-of-care therapeutic options remain limited to nonspecific immunosuppression. Here, we report an alternative therapeutic strategy using targeted protein degradation to eliminate pathogenic autoantibodies while leaving the rest of the immune system intact. We previously discovered autoimmune vitamin B12 central deficiency (ABCD), a neurologic condition in which autoantibodies targeting the transcobalamin receptor (CD320) impair the transport of cobalamin (B12) from the blood into the central nervous system (CNS). Combining scanning alanine mutagenesis by phage display, cryo-electron microscopy, and computational modeling, we elucidated a highly conserved anti-CD320 epitope and defined the structural determinants of antigen-autoantibody binding. Next, we synthesized a lysosome-targeting chimera (LYTAC) comprising the lysosome targeting glycan, triGalNAc, fused to the antigenic epitope of CD320 as autoantibody bait. In vitro, this LYTAC promoted the specific lysosomal internalization and extracellular clearance of anti-CD320, restoring homeostatic cellular uptake of B12. In a passive transfer mouse model of ABCD, LYTAC treatment rapidly cleared anti-CD320 from circulation and prevented penetration of anti-CD320 into the CNS. These findings uncover the mechanism of autoantibody-antigen binding in ABCD and demonstrate targeted autoantibody degradation as a therapeutic strategy that may be generalizable to other autoimmune neurologic diseases.

neuroscience↗

bioRxiv2025

A neurorecording toolkit for longitudinal assessments of transplanted human cortical organoids in vivo

Human cortical organoids (hCOs) are three-dimensional neural cell aggregates that recapitulate certain structural and functional aspects of the developing human cortex. Xenotransplantation of hCOs into the rodent brain enables human-centric modeling of neurodevelopmental processes in a physiologically relevant environment. Here, we present a neurorecording toolkit for longitudinal structural and functional assessment of hCO xenografts as they mature in vivo. Single hCOs were implanted into the retrosplenial cortex of adult immunodeficient mice and monitored for up to 8 months. Optical coherence tomography was used for label-free imaging of xenograft vascularization and structure, enabling quantitative assessments of capillary density and graft volume. To probe neuronal activity, human neurons were labeled with a calcium sensor before implantation using either adeno-associated or lentivirus for sparse or dense neuronal labeling, respectively. Fluorescent imaging was conducted using two-photon, widefield, and swept confocally-aligned planar excitation microscopy for single cell, whole-graft, and volumetric calcium imaging, respectively. Results from these modalities indicate an increase in neuronal activity and synchronicity over time during in vivo graft maturation. Further, we chronically implanted surface graphene microelectrode arrays (gMEAs) and performed recordings of xenograft and host local field potential signals simultaneously with 2P calcium imaging, confirming the spatial localization and human origin of electrical signals recorded at the xenograft surface.

neuroscience↗

bioRxiv2025

Genomics of Irish swine-derived Streptococcus suis: Population structure, prophages, and anti-viral defence mechanisms

Streptococcus suis is a major pig pathogen with zoonotic potential, posing an occupational risk to farmers and meat handlers. We characterised 110 S. suis strains from diseased pigs in Ireland (2005-2022) using whole-genome sequencing to investigate population structure and phage-host dynamics. We identified fifteen distinct serotypes, with serotypes 9 and 2 being the most dominant. In silico multi-locus sequence typing revealed high diversity within the collection, identifying several sequence types (STs), including 26 novel STs. Investigation of strain-level genomic clustering using PopPUNK against global S. suis genomes showed that the Irish isolates were phylogenetically dispersed across the broader global S. suis population rather than clustering in a single clonal group. The majority of Irish isolates fall within the ten established pathogenic lineages, including the highly virulent zoonotic lineage 1. A stable endemic clonal lineage was identified among Irish isolates, showing minimal genetic variation over a decade. Prophage analysis revealed novel viral taxa that were interspersed among known streptococcal phages, rather than clustering distinctly. Restriction-modification systems were the predominant anti-viral defence systems identified across genomes. CRISPR-Cas systems were present in limited strains but showed substantial targeting bias toward full-length prophages, indicating ongoing phage pressure. CRISPR spacers matched non-S. suis streptococcal phages, and phylogenomic analysis revealed that Vansinderenvirus phages clustered with S. suis rather than other S. thermophilus phages, suggesting evolutionary connections between phage lineages infecting different streptococci. This study presents the first comprehensive genomic characterisation of S. suis in Ireland, revealing a diverse population with significant implications for animal and human health.

microbiology↗

bioRxiv2025

A Descriptive Analysis of Streptococcus suis-Associated Disease in Irish Pigs from 2010 to 2024: Serotypes, Pathology, and Antimicrobial Resistance

Streptococcus suis is a major cause of respiratory and systemic diseases in post-weaned pigs, leading to significant production losses and animal welfare concerns. This study provides the first long-term national level analysis of Streptococcus suis-associated disease (SSAD) in the Republic of Ireland. We examined the pig diagnostic submissions, characterised serotype distribution, antimicrobial susceptibility, and co-infection patterns from 2010 to 2024. The findings confirm that serotypes 9 and 2 or 1/2 were most frequently associated with disease. We observed a significant shift in recent years where serotype 9 has surpassed serotype 2 or 1/2 in number of occurrences. S. suis was frequently co-detected with viral pathogens including porcine reproductive and respiratory syndrome virus (PRRSV), porcine circovirus type 2, and swine influenza virus (SIV), as well as bacterial pathogens such as Actinobacillus pleuropneumonia and Pasteurella multocida, typically from pneumonic lungs. While resistance to tetracycline and erythromycin was high (44.4% to 65.8%), isolates remained susceptible to first-line beta-lactam antibiotics such as penicillin (7.9% resistance), ampicillin (5.5% resistance) and amoxycillin/clavulanate (0% resistance). The observed heterogeneity between and within herds challenges successful implementation of vaccination and highlights the need for ongoing disease monitoring. These findings provide the first in-depth assessment of SSAD in Irelands pig population which will offer valuable insights for future surveillance efforts, including genomic studies and supporting evidence-based strategies and vaccine selection for controlling S. suis in Irish pig sector.

microbiology↗

bioRxiv2025

Refined cell transfer model reveals roles for Ascl2 and Cxcr3 in splenic localization of mouse NK cells during virus infection

Cell transfer experiments complement the rigorous investigation of antiviral and antitumor functions of natural killer (NK) cells. Success in these endeavors is enhanced by expansion of small numbers of input NK cells driven by viral antigens or homeostatic proliferation in immunodeficient hosts. In contrast, analysis of other NK-cell functions, including immunoregulation, are non-proliferative and require an intact immune system in recipient mice. We reveal poor persistence of conventional congenic (CD45.1) BoyJ NK cells following adoptive transfer in comparison to CRISPR-generated CD45.1+ (JAXBoy) NK cells. Reciprocal transfers between C57BL/6 and JAXBoy mice substantially improve seeding and maintenance of donor NK cells. Using this system, we confirm that CXCR3 re-positions NK cells in the white pulp of the spleen after infection, which is vital for immunoregulation. Moreover, we discovered that the transcription factor ASCL2 is required for recruitment of NK cells into the spleen and white pulp. These results provide improved tools and novel insights into NK cell biology. Key pointsO_LIJAXBoy are superior to conventional BoyJ mice for NK cell persistence after transfer. C_LIO_LICXCR3 repositions donor NK cells in T/B-zones of the spleen after infection. C_LIO_LIThe transcription factor ASCL2 is required for NK-cell recruitment to spleen white pulp. C_LI

immunology↗

bioRxiv2025

Age- and estrous-dependent effects of psilocybin in rats

Psilocybin, a psychedelic compound in "magic" mushrooms, has promise as a novel treatment for psychiatric disorders, many of which are more prevalent in females and have onsets during adolescence. However, there is a lack of research about how factors such as sex and age affect responses to psilocybin, as well as potential safety concerns with developmental exposure. The primary objectives of this preclinical study were to determine if psilocybin-induced head twitch responses differ between adolescent and adult rats, and if estrous phase contributes to variation in female head twitch responses. Secondarily, this study sought to determine if treatment with psilocybin during adolescence has long-term effects on anxiety-associated behaviors and behavioral flexibility. Results showed that 1 mg/kg intraoral psilocybin failed to elicit head twitch responses in adolescents (P35 and P45) but elicited robust responses in adult rats. Further, adolescent psilocybin exposure did not cause long-term differences in performance on the elevated zero maze or probabilistic reversal learning tasks. Lastly, adult females in diestrus showed increased head twitch responses after 1 mg/kg psilocybin compared to females in proestrus. Head twitch responses are thought to be mediated by 5-HT2A receptors, but no age-or estrous-related differences in 5-HT2A receptor expression were observed in the medial prefrontal cortex. Collectively, these results highlight the existence of age-and sex-dependent differences in the effects of psychedelics, while finding no long-term effects on selected behaviors after adolescent exposure. These findings have implications on psychedelic study design, emphasizing the need for inclusive research considering age, sex, and hormonal status.

pharmacology and toxicology↗

bioRxiv2025

Permissive central tolerance plus defective peripheral checkpoints licence pathogenic memory B cells in CASPR2-antibody encephalitis

Autoimmunity affects 10% of the population. Within this umbrella, autoantibody-mediated diseases targeting one autoantigen provide a unique opportunity to comprehensively understand the developmental pathway of disease-causing B cells and autoantibodies. While such autoreactivities are believed to be generated during germinal centre reactions, the roles of earlier immune checkpoints in autoantigen-specific B cell tolerance are poorly understood. We address this concept in patients with CASPR2-autoantibody encephalitis and healthy controls. In both groups, comparable and high ([~]0.5%) frequencies of unmutated CASPR2-reactive naive B cells were identified. By contrast, CASPR2-reactive memory B cells were exclusive to patients, and their B cell receptors demonstrated affinity-enhancing somatic mutations with heterogenous binding kinetics. These effector molecules possessed epitope-dependent pathogenic effects in vitro neuronal cultures and in vivo. The unmutated common ancestors of these memory B cells showed a distinctive balance between strong CASPR2 reactivity and very limited binding across the remaining human proteome. Our results are the first to propose mechanisms underlying autoantigen-specific tolerance in humans. We identify permissive central tolerance, defective peripheral tolerance and heterogenous autoantibody binding properties as sequential pathogenic steps which licence CASPR2-directed pathology. By leveraging the basic immunobiology, we rationally direct tolerance-restoring approaches in CASPR2-antibody diseases. This paradigm is applicable across autoimmune conditions.

immunology↗

bioRxiv2025

Isolation of phages infecting the zoonotic pathogen Streptococcus suis reveals novel structural and genomic characteristics

Bacteriophage research has experienced a renaissance in recent years, owing to their therapeutic potential and versatility in biotechnology, particularly in combating antibiotic resistant-bacteria along the farm-to-fork continuum. However, certain pathogens remain underexplored as targets for phage therapy, including the zoonotic pathogen Streptococcus suis which causes infections in pigs and humans. Despite global efforts, the genome of only one infective S. suis phage has been described. Here, we report the isolation of two phages that infect S. suis: Bonnie and Clyde. The phages infect 58% of 100 S. suis strains tested, including representatives of seven different serotypes and thirteen known sequence types from diverse geographical origins. Clyde suppressed bacterial growth in vitro within two multi-strain mixes designed to simulate a polyclonal S. suis infection. Both phages demonstrated stability across various temperatures and pH levels, highlighting their potential to withstand storage conditions and maintain viability in delivery formulations. Genome comparisons revealed that neither phage shares significant nucleotide identity with any cultivated phages in the NCBI database and thereby represent novel species belonging to two distinct novel genera. This study is the first to investigate the adhesion devices of S. suis infecting phages. Structure prediction and analysis of adhesion devices with AlphaFold2 revealed two distinct lineages of S. suis phages: Streptococcus thermophilus-like (Bonnie) and S. suis-like (Clyde). The structural similarities between the adhesion devices of Bonnie and S. thermophilus phages, despite the lack of nucleotide similarity and differing ecological niches, suggest a common ancestor or convergent evolution, highlighting evolutionary links between pathogenic and non-pathogenic streptococcal species. These findings provide valuable insights into the genetic and phenotypic characteristics of phages that can infect S. suis, providing new data for the therapeutic application of phages in a One Health context.

microbiology↗

bioRxiv2025

Chemical shift and relaxation regularisation improve the accuracy of 1H MR spectroscopy analysis

PurposeAccurate analysis of metabolite levels from 1H MRS data is a significant challenge, typically requiring the estimation of approximately 100 parameters from a single spectrum. Signal overlap, spectral noise and common artefacts further complicate analysis, leading to instability and reports of poor agreement between different analysis approaches. One inconsistently used method to improve analysis stability is known as regularisation, where poorly determined parameters are partially constrained to take a predefined value. In this study we examine how regularisation of frequency and linewidth parameters influences analysis accuracy. MethodsThe accuracy of three MRS analysis methods was compaired: 1) ABfit, 2) ABfit-reg and 3) LCModel, where ABfit-reg is a modified version of ABfit incorporating regularisation. Accuracy was assessed on synthetic MRS data generated with random variability in the frequency shift and linewidth parameters applied to each basis signal. Spectra (N=1000) were generated across a range of SNR values (10, 30, 60, 100) to evaluate the impact of variable data quality. ResultsComparison between ABfit and ABfit-reg demonstrates a statistically significant (p < 0.0005) improvement in accuracy associated with regularisation for each SNR regime. An approximately 10% reduction in the mean squared metabolite errors were found for ABfit-reg compared to LCModel for SNR >10 (p < 0.0005). Furthermore, Bland-Altman analysis shows that incorporating regularisation into ABfit enhances its agreement with LCModel. ConclusionRegularisation is beneficial for MRS fitting and accurate characterisation of the frequency and linewidth variability in vivo may yield further improvements.

biochemistry↗

bioRxiv2024

Individual Alpha Frequency Predicts the Sensitivity of Time Perception

A growing body of research links individual differences in the alpha-band frequency to temporal aspects of perception. However, whether the human alpha rhythm is a correlate of time perception itself has remained controversial. This study combined EEG with multiple duration perception tasks to evaluate whether individual alpha frequency (IAF) is associated with sensitivity or bias in judging visual durations across a range of peri-second durations (spanning 100-1200ms). In a temporal estimation task, participants (n = 55; 38 female, 13 male, 4 non-binary) reported the duration of a single stimulus between 300-1200ms. In a temporal discrimination task, participants reported which of two stimuli was longer: a standard (100, 600, or 1200ms) or comparison (50-150% of the standard). Stimuli also varied in whether their luminance was static or dynamically varying over time. We found that IAF was significantly related to the variance of duration estimates, a precision measure, but not average duration estimates, a bias measure. Further supporting this relationship, psychometric function slopes obtained from the independent duration discrimination tasks were positively correlated with IAF, particularly for the static stimulus conditions. These individual differences effects held when controlling for participant age. We also explored trial-level variability in alpha frequency and found it was predictive of shifts in the point of subjective equality (PSE) during discrimination of very short (100ms). Taken together, these results suggest that IAF plays a role in shaping individual differences in the sensitivity of time perception and that spontaneous variations around ones IAF can lead to a bias in temporal representations. Significance StatementBrain waves in the 8-13 Hz range, known as alpha waves, have long been hypothesized to modulate our perception of time, yet the evidence remains unclear. This study investigates the relationship between an individuals alpha frequency (IAF) and temporal sensitivity using a wide range of time perception tasks and stimulus durations to address gaps in the literature. We demonstrate that IAF is significantly associated with the precision of duration estimates and sensitivity in duration discrimination, particularly for static unchanging stimuli. These findings provide novel evidence that IAF shapes individual differences in time perception, emphasizing its role as a neural marker of temporal sensitivity.

neuroscience↗