Biology subjects

Reynolds, C.

Publications and source records attributed to Reynolds, C..

10 recordsLinked to original sources

bioRxiv2026

Older Adults Show Preserved Neural Signatures of Audiovisual Integration but Altered Links to Speech Comprehension

Older adults often experience difficulty understanding speech in noisy environments despite relatively preserved hearing. Although visual speech cues can improve speech perception, it remains unclear whether the neural mechanisms supporting audiovisual integration are preserved in healthy ageing. We addressed this question using magnetoencephalography (MEG) combined with Rapid Invisible Frequency Tagging (RIFT) during challenging audiovisual speech task. Forty younger and forty older adults attended to one of two competing speech streams while the speaker's lip movements were frequency tagged, with the visual modulation driven by either the attended or unattended speech envelope. Task-Relevant amplitude modulation of frequency tagging in visual speech improved speech comprehension in younger adults as previously reported for this cohort; this accuracy benefit was absent in older adults. Auditory and visual tagging responses were modulated by task relevance similarly across age groups, indicating largely preserved modality-specific sensory processing in older adults. Intermodulation responses, reflecting nonlinear interactions between auditory and visual speech signals, also remained sensitive to task relevance and did not differ in their condition-dependent modulation between age groups. Greater Task-Relevant versus Task-Irrelevant differences in intermodulation coherence were also associated with greater comprehension benefits in younger adults; no significant association was found in older adults, and this relationship differed significantly between age groups. These findings suggest that the absence of a comprehension benefit in older adults is linked to a change in the relationship between audiovisual intermodulation and behaviour, despite largely preserved task-sensitive brain responses.

neuroscience↗

bioRxiv2026

Regulatory architecture tunes gene expression noise in the plant heat shock response

Cells within the same tissue can respond differently to the same stress, yet how gene regulatory networks generate and control this variability remains unclear. Here, we show that cell-to-cell variation in the Arabidopsis heat shock response is coordinated across the heat shock regulon and that the distribution of responses is tuned by the underlying regulatory network. Imaging of an HSP70 promoter reporter revealed basal activity in a subset of root cells and heterogeneous induction after heat shock, with some cells remaining near pre-stress expression levels. Dual reporters showed strong coordination between independently integrated HSP70 reporter loci, consistent with substantial shared upstream regulatory variation. Single-nucleus RNA sequencing confirmed heterogeneous but coordinated activation of heat shock genes across root cell types. Stronger heat shock states at both ambient and heat stress temperatures were associated with a recurrent thermoprotective programme across root cell populations, whereas weak responders after heat shock were associated with distinct cell-type specific transcriptional programmes, including defence- and jasmonate-associated states in some root cell types. Stochastic modelling suggested that HSFA2-dependent amplification could broaden the distribution of HSP70 expression across cells. Consistent with this prediction, experiments showed that loss of HSFA2 reduced HSP70 induction and lowered cell-to-cell variability after controlling for differences in mean expression. Together, these results show that the plant heat shock network controls both the magnitude and distribution of stress-responsive gene expression across cells.

plant biology↗

bioRxiv2026

Augmenting Speech Comprehension using Rapid Frequency Tagging

Speech comprehension under adverse listening conditions benefits from visual speech, but whether visual input can be modulated to improve listening remains unclear. Here we used rapid frequency tagging, a non-invasive sensory stimulation technique, in which the visual tag at 55 Hz over the mouth region of a talking face was amplitude-modulated by the envelope of either the task-relevant or task-irrelevant speech stream. When the visual modulation followed the task-relevant speech envelope, comprehension improved relative to task-irrelevant modulation and to an unmodulated tagging control. MEG responses showed enhanced 55 Hz visual tagging, altered 40 Hz auditory tagging and a non-linear 15 Hz intermodulation. Individual comprehension gains were associated with intermodulation responses in left inferior frontal cortex, linking behavioural benefit to audiovisual interaction. These findings show that task-relevant visual stimulation can improve comprehension by strengthening audiovisual interaction, establishing amplitude-modulated frequency tagging as a tool for probing and supporting comprehension in challenging environments.

neuroscience↗

bioRxiv2026

Genomic footprints of selfing, introduction history, and long-distance dispersal in an invasive alien plant

Biological invasions are natural experiments for studying the evolutionary and ecological processes underlying colonization success and range expansion. Using genome-wide data -- generated via genotyping-by-sequencing (GBS) from 30 populations spanning Europe and South Africa-- we investigated the colonization history and successful spread of the invasive buttonweed Cotula coronopifolia, an annual plant introduced into Europe from South Africa about 300 years ago. Our analyses identified three major lineages in Europe distributed across the continent, often co-occurring without evidence of admixture. Phylogenomic dating revealed that these lineages diverged > 2,000 years ago --well before the earliest European records-- suggesting divergence within the native range and either multiple introductions or a single introduction with multiple lineages. Mating-system inference shows that reproduction occurs primarily via self-fertilization ([~]70% on average), although outcrossing predominates in some populations, revealing a facultative mating system. This high selfing rate has led to extremely low heterozygosity in most populations and a strong genetic structure. Genetic clustering also revealed admixed individuals resulting from rare inter-lineage outcrossing; comparisons of empirical and simulated data indicate that increased diversity after sporadic admixture events decays rapidly under subsequent selfing. Both the introduction history and long-distance dispersal facilitated by waterbirds likely explain the scattered distribution of lineages across Europe. Altogether, these results provide an empirical demonstration of Bakers "ideal weed" concept, highlighting the role of a flexible mating system in providing reproductive assurance during colonization and showing how predominant selfing shapes the genomic landscape of an invasive species. SIGNIFICANCE STATEMENTUnderstanding how reproductive strategies influence colonization and spread of alien species is central to invasion biology. By combining population genomics and phylogenomic inference, this study provides key insights into the colonization history and successful invasion of the self-fertilizing plant C. coronopifolia, introduced from South Africa to Europe in the 18th century. We show that the species invasion success relies on the introduction of multiple lineages and the predominance of selfing, which has drastically reduced genetic diversity yet contributed to reproductive assurance and spread across diverse habitats. Occasional outcrossing and long-distance dispersal by waterbirds or through horticultural transport have further shaped the species genetic landscape. These findings illustrate how self-compatibility and ecological generalism can overcome genetic constraints during range expansion and provide the basis for understanding the evolutionary dynamics of selfing plant invasions.

genomics↗

bioRxiv2024

Wnt activation in mature dermal adipocytes leads to lipodystrophy and skin fibrosis via ATGL-dependent lipolysis.

ObjectiveAccumulation of extracellular matrix (ECM) and dermal adipocyte lipodystrophy occurs during skin fibrosis, which compromises the skins flexibility and function. We recently showed that sustained Wnt activation in dermal progenitor cells leads to fibrotic ECM thickening in the dermis and lipodystrophy of dermal white adipose tissue (DWAT). The aim of this study was to test if Wnt/{beta}-catenin signaling in mature dermal adipocytes directly leads to lipodystrophy and impact skin fibrosis. MethodsWe developed a genetically lineage traceable, DWAT specific, inducible and reversible mouse model of Wnt activation (Adipo-{beta}-catistab) in the dorsal skin. We analyzed the DWAT lipid droplet size, cell identity, and affect on ECM accumulation and remodeling in skin fibrosis. Adipocyte triglyceride lipase (ATGL) is the key rate limiting enzyme of the lipolysis pathway, which is a biological process of breaking down triglyceride stores in adipocytes. The Atgl gene was conditionally deleted in mature dermal adipocytes to test the requirement of the lipolysis pathway in the Wnt-induced lipodystrophy (Adipo-{beta}-catistab; Atglfl/fl). ResultsHere, we utilize mouse genetic models with lineage tracing to show that Wnt activation in mature dermal adipocytes is sufficient to induce adipocyte lipodystrophy and fibrotic collagen remodeling. Upon withdrawal of adipocyte-restricted Wnt activation, lipodystrophy and fibrosis were reversed. Mechanistically, we find that Wnt activation stimulates Adipose Triglyceride Lipase (ATGL)-mediated lipolysis pathway. We found Atgl in dermal adipocytes is functionally required for Wnt-induced lipodystrophy in the DWAT and fibrotic remodeling. ConclusionCollectively, this study demonstrates that Wnt activation in dermal adipocytes promotes lipolysis and may be a novel therapeutic avenue for preventing and reversing lipodystrophy and skin fibrosis.

cell biology↗

bioRxiv2024

Machine learning models reveal environmental and genetic factors associated with the plant circadian clock

The circadian clock of plants contributes to their survival and fitness. However, understanding clock function at the transcriptome level and its response to the environment requires assaying across high resolution time-course experiments. Generating these datasets is labour-intensive, costly and, in most cases, performed under tightly controlled laboratory conditions. To overcome this barrier, we have developed ChronoGauge: an ensemble model which can reliably estimate the endogenous circadian time of plants using the expression of a handful of time-indicating genes within a single time-pointed transcriptomic sample. ChronoGauge can predict a plants circadian time with high accuracy across unseen Arabidopsis bulk RNA-seq and microarray samples, and can be further applied across samples in non-model species, including field samples. Finally, we demonstrate how ChronoGauge can be applied to test hypotheses regarding the response of the circadian transcriptome to specific genotypes or environmental conditions.

plant biology↗

bioRxiv2021

Circadian regulation of the transcriptome in a complex polyploid crop

The circadian clock is a finely balanced time-keeping mechanism that coordinates programmes of gene expression. It is currently unknown how the clock regulates expression of homoeologous genes in polyploids. Here, we generate a high-resolution time-course dataset to investigate the circadian balance between sets of three homoeologous genes (triads) from hexaploid bread wheat. We find a large proportion of circadian triads exhibit imbalanced rhythmic expression patterns, with no specific sub-genome favoured. In wheat, period lengths of rhythmic transcripts are found to be longer and have a higher level of variance than in other plant species. Expression of transcripts associated with circadian controlled biological processes are largely conserved between wheat and Arabidopsis, however striking differences are seen in agriculturally critical processes such as starch metabolism. Together, this work highlights the ongoing selection for balance versus diversification in circadian homoeologs, and identifies clock-controlled pathways that might provide important targets for future wheat breeding.

plant biology↗

bioRxiv2019

Pupillary dilation responses as a midlife indicator of risk for Alzheimer’s Disease: Association with Alzheimer’s disease polygenic risk

Pathological changes in Alzheimers disease (AD) begin decades before dementia onset. Because locus coeruleus tau pathology is the earliest occurring AD pathology, targeting indicators of locus coeruleus (dys)function may improve midlife screening for earlier identification of AD risk. Pupillary responses during cognitive tasks are driven by the locus coeruleus and index cognitive effort. Several findings suggest task-associated pupillary response as an early marker of AD risk. Requiring greater effort suggests being closer to ones compensatory capacity, and adults with mild cognitive impairment (MCI) have greater pupil dilation during digit span tasks than cognitively normal individuals, despite equivalent task performance. Higher AD polygenic risk scores (AD-PRSs) are associated with increased odds of MCI and tau positivity. We hypothesized that AD-PRSs would be associated with pupillary responses in cognitively normal middle-aged adults. We demonstrated that pupillary responses during digit span tasks were heritable (h2=.30-.36) in 1119 men ages 56-66. We then examined associations between AD-PRSs and pupillary responses in a cognitively normal subset who all had comparable span capacities (n=539). Higher AD-PRSs were associated with greater pupil dilation/effort in a high (9-digit recall) cognitive load condition; Cohens d=.36 for the upper versus lower quartile of the AD-PRS distribution. Results held up after controlling for APOE genotype. The results support pupillary response--and by inference, locus coeruleus dysfunction--as a genetically-mediated biomarker of early MCI/AD risk. In some studies, cognition predicted disease progression earlier than biomarkers. Pupillary responses might improve screening and early identification of genetically at-risk individuals even before cognitive performance declines.

genetics↗

bioRxiv2019

Within-family studies for Mendelian randomization: avoiding dynastic, assortative mating, and population stratification biases

Mendelian randomization (MR) is a widely-used method for causal inference using genetic data. Mendelian randomization studies of unrelated individuals may be susceptible to bias from family structure, for example, through dynastic effects which occur when parental genotypes directly affect offspring phenotypes. Here we describe methods for within-family Mendelian randomization and through simulations show that family-based methods can overcome bias due to dynastic effects. We illustrate these issues empirically using data from 61,008 siblings from the UK Biobank and Nord-Trondelag Health Study. Both within-family and population-based Mendelian randomization analyses reproduced established effects of lower BMI reducing risk of diabetes and high blood pressure. However, while MR estimates from population-based samples of unrelated individuals suggested that taller height and lower BMI increase educational attainment, these effects largely disappeared in within-family MR analyses. We found differences between population-based and within-family based estimates, indicating the importance of controlling for family effects and population structure in Mendelian randomization studies.

genetics↗

bioRxiv2019

Complexity measures of the electroencephalograph capture loss and recovery of consciousness in patients anesthetized with propofol

Propofol is one of the most widely used anesthetics for routine surgical anesthesia. Propofol administration alone produces EEG spectral characteristics similar to most hypnotics; however, inter-individual variation can make spectral measures inconsistent. Complexity measures of EEG signals could offer universal measures to better capture anesthetic depth as brain activity exhibits nonlinear behavior at several scales. We tested the potential of nonlinear dynamics analyses to identify loss and recovery of consciousness at clinically relevant timepoints. Patients undergoing propofol general anesthesia for various surgical procedures were identified as having changes in states of consciousness by the loss and recovery of response to verbal stimuli after induction and upon cessation of anesthesia, respectively. Nonlinear dynamics analyses showed more significant differences between consciousness states than most spectral measures. Thus, complexity measures could provide a means for reliably capturing depth of consciousness based on subtle EEG changes at the beginning and end of anesthesia administration.

neuroscience↗