Biology subjects

Reid, A. T.

Publications and source records attributed to Reid, A. T..

6 recordsLinked to original sources

bioRxiv2026

Graph-theoretic comparisons of structural covariance networks: quantifying the false discovery rate

Structural covariance networks (SCNs) represent spatial patterns of covariation in brain morphology, often as a network of connections between nodes representing correlations in grey matter volume or cortical thickness measured by magnetic resonance imaging (MRI). SCNs have been suggested to reveal differences in functional organisation that are reflected in coordinated alterations to brain structure, and often these differences are sought in graph-theoretic measures such as the degree of clustering, segregation into distinct modules, or the characteristic path length between nodes. A common practice is to calculate SCNs for groups of interest, and use permutation testing to determine if they are significantly different for the measure of interest. However, the statistical validity of group comparisons using SCN-derived graph measures remains poorly understood. Here, we systematically evaluate the reliability of SCN estimation and downstream graph-theoretic analyses using structural MRI data from the Human Connectome Project (n = 1,096). We use simulations to show the effects of sample size and atlas dimensionality on SCN reliability. Using bootstrapping to characterise the distribution of SCN graph measures, we establish that small sample sizes systematically bias graph-theoretic measures including clustering, characteristic path length and modularity. Finally, we use simulations based on extrema from the bootstrapping distribution to characterise the statistical power and false discovery rate (FDR) for graph-theoretic between-group comparisons of SCNs, showing that at small sample sizes (n [≤] 30) permutation testing is no better than chance. These findings suggest that many significant SCN group differences, particularly those using small samples and high-dimensional parcellations, may reflect sampling noise rather than true biological differences. We recommend that future SCN studies use larger samples, coarser parcellations, and explicitly evaluate reliability before interpreting group differences.

neuroscience↗

bioRxiv2026

Light on Broken Networks: Resting-State fNIRS as a Tool for Connectivity Mapping

Resting-state functional connectivity (RSFC) and networks (RSNs) provide insight into large-scale brain organization and its disruption in neurological disease. RSNs are most commonly assessed using fMRI, yet its translational use is constrained by high cost, motion sensitivity, and limited feasibility for repeated measurements. Functional near-infrared spectroscopy (fNIRS) offers a portable alternative, but its reliability for RSFC and RSN mapping remains insufficiently established. Near whole-head fNIRS data and fMRI-BOLD signals of corresponding cortical regions were extracted, based on which RSN organization was compared across two independent cohorts of 31 participants each. Cross-modal convergence and divergence were assessed using bivariate and partial correlations across multiple network levels. Edgewise analyses revealed substantial modality differences with bivariate correlations (50-61% of edges), which were markedly reduced using partial correlations (<3%). Group-level connectivity patterns showed moderate cross-modal similarity (r {approx} 0.37). At nodal level, net strength, local efficiency, and path-length differed substantially between modalities, while normalized strength and assortativity were largely comparable. Across nodes, group-level graph-metric distributions were broadly similar for normalized strength, assortativity, local efficiency, and path length (rho {approx} 0.27-0.5). At network-level, fNIRS-derived modules significantly overlapped with fMRI modules, particularly based on bivariate correlations, identifying default mode, attentional, executive, salience, sensorimotor, and visual networks (Jaccard {approx} 0.27-0.5). Overall, fNIRS captured key features of large-scale RSFC and RSN organization observed with fMRI, supporting meaningful cross-modal correspondence and translational utility. While partial correlations enhanced edge-level agreement, they attenuated nodal and modular recovery, suggesting greater suitability for targeted connectivity analyses rather than whole-network characterization.

neuroscience↗

bioRxiv2023

Comparison of commercially available differentiation media on morphology, function, and virus-host interaction in conditionally reprogrammed human bronchial epithelial cells

IntroductionPrimary air liquid interface (ALI) cultures of bronchial epithelial cells are used extensively to model airway responses. A recent advance is the development of conditional reprogramming that enhances proliferative capability. Several different media and protocols are utilized, yet even subtle differences may influence cellular responses. We compared the morphology and functional responses, including innate immune responses to rhinovirus infection in conditionally reprogrammed primary bronchial epithelial cells (pBECs) differentiated using two commonly used culture media. MethodspBECs from healthy participants (n = 5) were CR using {gamma}-irradiated 3T3 fibroblasts and Rho Kinase inhibitor. CRpBECs were differentiated at ALI in either PneumaCult (PN-ALI) or Bronchial Epithelial Growth Medium (BEGM)-based differentiation media (BEBM:DMEM, 50:50, Lonza) - (AB-ALI) for 28 days. Transepithelial electrical resistance (TEER), immunofluorescence, histology, cilia activity, ion channel function, and expression of cell markers were analyzed. Viral load was assessed by RT-qPCR and anti-viral factors quantified by Legendplex following Rhinovirus-A1b (RVA1b) infection. ResultsCRpBECs differentiated in PneumaCult were smaller and had a lower TEER and cilia beat frequency (CBF) compared to BEGM media. PneumaCult media cultures exhibited significantly increased FOXJ1 expression, more ciliated cells with a larger active area, increased intracellular mucins, and increased calcium-activated chloride channel current. However, there were no significant changes in viral RNA or host antiviral responses. ConclusionThere are distinct structural and functional differences in CRpBECs cultured in the two commonly used ALI differentiation media. Such factors need to be taken into consideration when designing and comparing CRpBECs ALI experiments.

cell biology↗

bioRxiv2021

Tract-specific statistics based on diffusion-weighted probabilistic tractography

Diffusion-weighted neuroimaging approaches provide rich evidence with which to estimate the structural integrity of white matter in vivo. Tract-based spatial statistics (TBSS), for instance, allows us to assess the spatial distribution of statistical tests performed on diffusion properties such as fractional anisotropy, which are proposed to reflect the integrity of white matter tracts. However, such methods do not provide a direct assessment of white matter integrity for connections between two specific regions of the brain. Here, we present a novel method for deriving tract-specific diffusion statistics, based upon arbitrarily-defined regions of interest. Our approach makes use of an empirically-derived population distribution based on probabilistic tractography, using the Nathan Kline Institute (NKI) Enhanced Rockland sample. We use a heuristic method to determine the most likely geometry of a path between two regions, if one exists, and express this as a spatial distribution. We then estimate the average orientation of streamlines traversing this path, at discrete distances along its trajectory, and compute the fraction of diffusion directed along this orientation for each participant. This allows us to obtain participant-wise metrics along the specific tract (tract-specific anisotropy; TSA), which can then be used to perform statistical analysis on any comparable population. Based on this method, we report both negative and positive associations between age and TSA for two networks derived from published meta-analytic studies (the "default mode" and "what-where" networks), along with more moderate sex differences and age-by-sex interactions in both networks.

neuroscience↗

bioRxiv2020

SARS-CoV-2 Spike protein promotes hyper-inflammatory response that can be ameliorated by Spike-antagonistic peptide and FDA-approved ER stress and MAP kinase inhibitors in vitro

SARS-CoV-2 infection causes an inflammatory cytokine storm and acute lung injury. Currently there are no effective antiviral and/or anti-inflammatory therapies. Here we demonstrate that 2019 SARS-CoV-2 spike protein subunit 1 (CoV2-S1) induces high levels of NF-{kappa}B activations, production of pro-inflammatory cytokines and mild epithelial damage, in human bronchial epithelial cells. CoV2-S1-induced NF-{kappa}B activation requires S1 interaction with human ACE2 receptor and early activation of endoplasmic reticulum (ER) stress, and associated unfolded protein response (UPR), and MAP kinase signalling pathways. We developed an antagonistic peptide that inhibits S1-ACE2 interaction and CoV2-S1-induced productions of pro-inflammatory cytokines. The existing FDA-approved ER stress inhibitor, 4-phenylburic acid (4-PBA), and MAP kinase inhibitors, trametinib and ulixertinib, ameliorated CoV2-S1-induced inflammation and epithelial damage. These novel data highlight the potentials of peptide-based antivirals for novel ACE2-utilising CoVs, while repurposing existing drugs may be used as treatments to dampen elevated inflammation and lung injury mediated by SARS-CoV-2.

immunology↗

bioRxiv2019

Anti-microbial immunity is impaired in COPD patients with frequent exacerbations

BackgroundPatients with frequent exacerbations represent a chronic obstructive pulmonary disease (COPD) sub-group requiring better treatment options. The aim of this study was to determine the innate immune mechanisms that underlie susceptibility to frequent exacerbations in COPD.\n\nMethodsWe measured sputum expression of immune mediators and bacterial loads in samples from patients with COPD at stable state and during virus-associated exacerbations. Ex vivo immune responses to rhinovirus infection in differentiated bronchial epithelial cells (BECs) sampled from patients with COPD were additionally evaluated. Patients were stratified as frequent exacerbators ([≥]2 exacerbations in the preceding year) or infrequent exacerbators (<2 exacerbations in the preceding year) with comparisons made between these groups.\n\nResultsFrequent exacerbators had reduced sputum cell mRNA expression of the anti-viral immune mediators type I and III interferons and reduced interferon-stimulated gene (ISG) expression when clinically stable and during virus-associated exacerbation. RV-induction of interferon and ISGs ex vivo was also impaired in differentiated BECs from frequent exacerbators. Frequent exacerbators also had reduced sputum levels of the anti-microbial peptide mannose-binding lectin (MBL)-2 with an associated increase in sputum bacterial loads at 2 weeks following virus-associated exacerbation onset. MBL-2 levels correlated negatively with bacterial loads during exacerbation.\n\nConclusionThese data implicate deficient airway innate immunity in the increased propensity to exacerbations observed in some patients with COPD. Therapeutic approaches to boost innate antimicrobial immunity in the lung could be a viable strategy for prevention/treatment of frequent exacerbations.

immunology↗