Biology subjects

Low, K.

Publications and source records attributed to Low, K..

10 recordsLinked to original sources

bioRxiv2026

Regional cerebral arterial elasticity is associated with cardiovascular health in cognitively healthy older adults

Ageing is often associated with a decline in cardiovascular and cerebrovascular health. This study examines the relationship between cerebral arterial elasticity and measures of cardiovascular health, as well as longitudinal changes in cerebral arterial elasticity over a 1.5 year interval. The pulse relaxation function (PReFx) is a measure of regional cerebral arterial elasticity derived using diffuse optical tomography (pulse-DOT). PReFx was measured over the anterior brain, including the frontal lobes and anterior sections of temporal and parietal regions that are especially vulnerable to vascular and cognitive ageing. We examined relationships between PReFx and measures of four cardiovascular risk factors (CVRF; i.e., hypertension, cholesterol, diabetes, obesity), as well as CVRF burden (i.e., number of CVRFs) in the highly active and cognitively healthy ACTIVate cohort (60-70 years). We replicated the well-established relationship between PReFx and both age and cardiorespiratory fitness, and examined associations between PReFx, measures of cardiovascular health and CVRF burden. Higher CVRF burden was linearly associated with lower cerebral arterial elasticity. The relationship between age and cerebral arterial elasticity was partially mediated by pulse pressure, an index of hypertension. PReFx declined significantly in as little as 1.5 years, and the effect did not vary with baseline level of any of the four CVRFs. We conclude that PReFx shows promise as a putative biomarker for monitoring cerebrovascular ageing in healthy older adults.

neuroscience↗

bioRxiv2025

Prion shedding is reduced by chronic wasting disease vaccination

Chronic wasting disease (CWD) is a strictly fatal and highly contagious prion disease of wild and farmed cervids currently expanding in North America. Prion diseases are caused by conversion of the cellular prion protein to its pathological isoform PrPSc. Vaccination is considered a promising strategy to contain CWD, even though prion diseases do not show classical immune responses. For CWD containment, it is important that vaccines reduce shedding of prions in excreta, a major contributor to transmission. Here, we tested the effect of vaccines on prion shedding in feces and urine by vaccinating and prion infecting knock-in mice that recapitulate CWD pathogenesis as found in cervids. Vaccination reduced or even prevented CWD shedding in feces and urine collected between 30-90% of incubation time to disease. This is the first report showing that prion shedding can be blocked in a prion disease. For CWD specifically it may reduce the environmental prion burden and break the disease transmission cycle.

neuroscience↗

bioRxiv2025

Region-specific associations between cerebral arterial elasticity and grey matter volume: Evidence for lateral prefrontal vulnerability

BackgroundAgeing is associated with increased cardiovascular health risks and disproportionate atrophy in frontotemporal brain. Regional cerebral arterial elasticity correlates with regional grey matter volume, with stronger associations frontally and in older adults. Cardiorespiratory fitness (CRF) is linked to preserved brain structure and greater arterial elasticity, while sex differences exist in the timing of vascular versus structural changes. This study examines whether regional cerebral arterial elasticity in frontotemporal cortex mediates the association between age and corresponding grey matter volume decline, and whether sex and/or CRF moderate this relationship. MethodsWe analysed data from 162 healthy adults (60-70 years) with structural MRI and diffuse optical tomography of the cerebral arterial pulse (Pulse-DOT) from the ACTIVate cohort. CRF was estimated from demographic and physiological measures. Pulse Relaxation Function (PReFx), an optical index of regional arterial elasticity, was measured across 28 frontal, temporal, and parietal regions of interest (ROI). Grey matter (GM) volume was quantified for corresponding ROIs. Mediation and moderated mediation models tested whether PReFx mediated the relationship between age and GM volume at bilateral frontal and temporal ROIs, and whether biological sex or CRF moderated this relationship. ResultsRegional bivariate correlations identified associations between age, PReFx and GM volume across multiple ROIs, which PReFx and GM volume being associated primarily in left frontal and temporal areas. PReFx partially mediated the effect of age on GM volume in a left mid-inferior frontal ROI, accounting for approximately 16% of the total age effect and this relationship was only evident in females. Although higher CRF was associated with greater PReFx, it did not moderate the relationship between age, PReFx and GM volume. ConclusionsConsistent with cascade models of neurovascular aging, cerebral arterial stiffening was found to partially explain the effect of increasing age on frontal GM volume, even in this highly age-restricted and high functioning cohort. This effect was only significant over the left prefrontal cortex, consistent with greater vulnerability of frontal brain and associated cognitive functions. It was also exclusively present in females, who had better cardiovascular health, larger grey matter volume and greater arterial elasticity than males. These findings are consistent with pulse-DOT measures of cerebral arterial elasticity being more sensitive to subclinical brain structural variability.

neuroscience↗

bioRxiv2025

How to Improve the Reliability of Aperiodic Parameter Estimates in M/EEG: A Method Comparison and Recommendations for Best Practices

Interest in broadband aperiodic brain activity (1/f phenomenon) has increased exponentially over recent years, partly fueled by the development of tools to parameterize it (i.e., estimate its offset/intercept and exponent/slope) using the M/EEG power spectrum. Broadband aperiodic activity needs to be separated from narrowband periodic activity before its parameters are computed. A popular method, the fooof toolbox (Donoghue et al., 2020), is based on the data-driven detection of narrowband-periodic peaks, whose maximum number is set by the user. While increasing analytic flexibility, variability in the number of detected peaks may increase sensitivity to noise and reduce the reliability of aperiodic parameter estimates and the power of analytic pipelines. Here, we present an investigation of the effects of analytic choices (e.g., number of peaks, spectral estimation method) on metrics indicating the adequacy of spectral parametrization. These include the internal consistency (odd-even reliability) of aperiodic estimates, the number of outliers generated, and their ability to detect effects. Across two different data sets (resting state and task-based) we found a decrease in the reliability of intercept and slope estimates as more peaks were allowed to be extracted. To ameliorate this problem, we propose a theory-driven modification of fooof labelled censored regression, whereby a theory-driven range of frequencies expected to contain periodic activity is removed from all spectra, and the remaining power values are regressed on the remaining frequencies to obtain parameter estimates. This method shows more reliable and robust estimates compared to fooof, while avoiding overfitting.

neuroscience↗

bioRxiv2025

Cardiorespiratory fitness and cardiometabolic health are associated with distinct cognitive domains in cognitively healthy older adults.

BackgroundAging is associated with progressive cognitive decline, as well as increased prevalence of cardiometabolic risk factors and reduced cardiorespiratory fitness. In fact, reduced cardiometabolic health and cardiorespiratory fitness are both associated with a decline in cognitive functioning. This study examines the common and distinct contributions of these cardiovascular health factors on cognitive variability across different domains in cognitively healthy older adults. Methods and ResultsWe apply structural equation modelling (SEM) to model cross-sectional relationships between cardiometabolic health, cardiorespiratory fitness and performance across multiple cognitive domains in an age-restricted sample of healthy older adults from the ACTIVate Study (n=345; 60-70 yrs). Participants completed a series of cognitive and clinical assessments (including brachial blood pressure, heart rate, blood-based metabolic markers). We designed a cognitive model (Model 1) with four latent factors that are differentially impacted by aging (Processing Speed, Executive Function, Verbal Memory and Crystallized Ability) and used it to test effects on cognition of two theory-driven dimensions of cardiovascular health: Cardiorespiratory Fitness (Model 2) and Cardiometabolic Health (Model 3). Model 4 included both predictors and examined their joint and distinct effects on these cognitive domains. When controlling for their joint variance, Cardiometabolic Health and Cardiorespiratory Fitness showed evidence consistent with a double dissociation on cognitive domains. Specifically, cardiorespiratory fitness significantly predicted processing speed (r=0.28, p<0.05) and executive function (r=0.66, p<0.05), but not verbal memory and crystallized ability. In contrast, cardiometabolic health predicted crystallized ability (r=0.31, p<0.05) and verbal memory (r=0.28, p<0.05), but not executive function and processing speed. ConclusionsThis study shows the first evidence that cardiorespiratory fitness and cardiometabolic health are associated with distinct cognitive domains in a large cross-sectional, age-restricted and high functioning cohort. These findings emphasize the importance of healthy aging approaches that target both health literacy and lifestyle behaviors to promote functional capacity across the lifespan.

neuroscience↗

bioRxiv2025

NeuroDISK: An AI Approach to Automate Continuous Inquiry-Driven Discoveries in Neuroimaging Genetics

Collaborative and multi-site neuroimaging studies have greatly accelerated the rate at which new and existing data can be aggregated to answer a neuroscientific question. New research initiatives are continuously collecting more data, allowing opportunities to refine previous published findings through continuous and dynamic updates. Yet, we lack a practical framework for researchers to systematically, automatically, and continuously update published findings. We developed NeuroDISK, an automated artificial intelligence based framework that: 1) performs automated and inquiry-driven analyses, and 2) continuously updates these analyses as new data becomes available. NeuroDISK was evaluated using published results from the ENIGMA consortiums work on the genetic architecture of the cerebral cortex. We incorporate both meta-analysis and meta-regression options to showcase our framework on the effect of specific genotypes and moderators on select brain regions. Initial NeuroDISK meta-analysis results replicate the original publication, and we show result updates after adding new data. The NeuroDISK framework can be generalized for users to define question(s), run corresponding workflow(s) and access results interactively and continuously.

bioinformatics↗

bioRxiv2024

Identification of novel fructo-oligosaccharide bacterial consumers by pulse metatranscriptomics in a human stool sample

Dietary fibres influence the composition of the human gut microbiota and directly contribute to its downstream effects on host health. As more research supports the use of glycans as prebiotics for therapeutic applications, the need to identify the gut bacteria that metabolize glycans of interest increases. Fructooligosaccharide (FOS) is a common diet-derived glycan that is fermented by the gut microbiota and has been used as a prebiotic. Despite being well studied, we do not yet have a complete picture of all FOS-consuming gut bacterial taxa. To identify new bacterial consumers, we used a short exposure of microbial communities in a stool sample to FOS or galactomannan as the sole carbon source to induce glycan metabolism genes. We then performed metatranscriptomics, paired with whole metagenomic sequencing (WMS), and 16S amplicon sequencing. The short incubation induced genes involved in carbohydrate metabolism, like carbohydrate-active enzymes (CAZymes), including glycoside hydrolase family 32 genes, which hydrolyze fructan polysaccharides like FOS and inulin. Interestingly, FOS metabolism transcripts were notably overexpressed in Blautia species not previously reported to be fructan consumers. We therefore validated the ability of different Blautia species to ferment fructans by monitoring their growth and fermentation in defined media. This pulse metatranscriptomics approach is a useful method to find novel consumers of prebiotics and increase our understanding of prebiotic metabolism by CAZymes in the gut microbiota. SignificanceComplex carbohydrates are key contributors to the composition of the human gut microbiota and play an essential role in the microbiotas effects on host health. Understanding which bacteria consume complex carbohydrates, or glycans, provides a mechanistic link between dietary prebiotics and their beneficial health effects, an essential step for their therapeutic application. Here, we used a pulse metatranscriptomics pipeline to identify bacterial consumers based on glycan metabolism induction in a human stool sample. We identified novel consumers of FOS among Blautia species, expanding our understanding of this well-known glycan. Our approach can be applied to identify consumers of understudied glycans and expand our prebiotic repertoire. It can also be used to study prebiotic glycans directly in stool samples in distinct patient populations to help delineate the prebiotic mechanism.

microbiology↗

bioRxiv2023

Proteomic Features of Adolescents and Young Adults with Soft Tissue Tumours

Adolescents and young adult (AYA) patients with soft tissue tumours (STT) including sarcomas are an underserved group with disparities in treatment outcomes. To define the molecular features between AYA and older adult (OA) patients, we analysed the proteomic profiles of a large cohort of STT across 10 histological subtypes (AYA n=66, OA n=243). AYA tumours are enriched in proteins involved in mitochondrial metabolism while OA patients have elevated inflammatory and cell cycle signalling. By integrating the patient-level proteomic data with functional genomic profiles from sarcoma cell lines, we show that the mRNA splicing pathway is an intrinsic vulnerability in cell lines from OA patients and that components of the spliceosome complex are independent prognostic factors for metastasis free survival in AYA patients. Our study highlights the importance of performing age-specific molecular profiling studies to identify risk stratification tools and targeted agents tailored for the clinical management of AYA patients.

cancer biology↗

bioRxiv2023

Pseudomonas aeruginosa AlgF is a protein-protein interaction mediator required for acetylation of the alginate exopolysaccharide

Enzymatic modifications of bacterial exopolysaccharides enhance immune evasion and persistence during infection. In the Gram-negative opportunistic pathogen Pseudomonas aeruginosa, acetylation of alginate reduces opsonic killing by phagocytes and improves reactive oxygen species scavenging. Although it is well-known that alginate acetylation in P. aeruginosa requires AlgI, AlgJ, AlgF, and AlgX, how these proteins coordinate polymer modification at a molecular level remains unclear. Here, we describe the structural characterization of AlgF and its protein interaction network. We characterize direct interactions between AlgF and both AlgJ and AlgX in vitro, and demonstrate an association between AlgF and AlgX, as well as AlgJ and AlgI, in P. aeruginosa. We determine that AlgF does not exhibit acetylesterase activity and is unable to bind to polymannuronate in vitro. Therefore, we propose that AlgF functions to mediate protein-protein interactions between alginate acetylation enzymes, forming the periplasmic AlgJFXK (AlgJ-AlgF-AlgX-AlgK) acetylation and export complex required for robust biofilm formation.

microbiology↗

bioRxiv2021

Liquid-Liquid Phase Separation Protects Amyloidogenic and Aggregation-Prone Peptides in Heterologous Expression Systems

Studying pathogenic effects of amyloids requires homogeneous amyloidogenic peptide samples. Recombinant production of these peptides is challenging due to their susceptibility to aggregation and chemical modifications. Thus, chemical synthesis is primarily used to produce amyloidogenic peptides suitable for high resolution structural studies. Here, we exploited the shielded environment of protein condensates formed via liquid-liquid phase separation (LLPS) as a protective mechanism against premature aggregation. We designed a fusion protein tag undergoing LLPS in E. coli and linked it to highly amyloidogenic peptides, including A{beta} amyloid. We find that the fusion proteins form membraneless organelles during overexpression and remain soluble. We also developed a facile purification method of functional A{beta} peptides free of chromatography steps. The strategy exploiting LLPS can be applied to other amyloidogenic, hydrophobic, and repetitive peptides that are otherwise difficult to produce.

molecular biology↗