Biology subjects

Matthews, I.

Publications and source records attributed to Matthews, I..

7 recordsLinked to original sources

bioRxiv2026

Guardians of our Rivers: transforming river health assessment through macroinvertebrate monitoring with citizen scientists

Freshwater ecosystems in Scotland are increasingly threatened by multiple interacting stressors, including pollution, hydrological alteration, land use change, and climate-driven pressures. Scotland's rivers are amongst the most physically diverse and dynamic in the UK, contributing significantly to the country-s economy and natural heritage. Monitoring 125,000 km of waterways presents an issue, with limited funding and capacity of environmental agencies creating an environmental monitoring deficit at a time when robust data are essential for delivering national and global biodiversity targets. Citizen science offers a scalable, community driven approach to strengthening environmental evidence. This study evaluates the development, implementation, and outcomes of Guardians of our Rivers (GooR), a nationwide citizen science programme using macroinvertebrate-based river health assessments based on the Anglers' Riverfly Monitoring Initiative (RMI) established by the Riverfly Partnership. Between 2022 and 2025, GooR trained more than 850 volunteers, established 123 monitoring sites across Scotland, and generated over 860 surveys-surpassing the previous 16 years of aquatic invertebrate monitoring efforts. Standardised field training, full equipment provision, and structured support enabled high-quality data collection across diverse catchments. The establishment of nationally applied trigger and target thresholds created a consistent mechanism for detecting ecological deterioration and ensured that verified trigger breaches (n = 39 in 2025) resulted in formal investigation or follow-up. Analysis of national abundance patterns revealed ecological and biogeographic trends across the eight RMI taxa, confirming data sensitivity to habitat differences, water quality, and regional pressures. A detailed case study of the Lothian Esk catchment demonstrated the programme's capacity to detect seasonal macroinvertebrate dynamics and site level ecological trajectories over time. Overall, GooR illustrates how well-designed and well-supported citizen science can deliver high resolution spatiotemporal datasets, enhance early warning systems, empower communities, and make a meaningful contribution to promoting river health. Importantly, GooR forged a working partnership with Scottish Environmental Protection Agency (SEPA) that allowed communities to not only gather data but also transformed the way citizen science is recognized as contributing to freshwater conservation. Continued investment and long-term support will be essential to sustain these gains and realise the full potential of citizen-driven freshwater stewardship.

ecology↗

bioRxiv2026

Single-nuclei RNA-sequencing uncovers sexually divergent exercise signatures partially mimicked by TFEB overexpression in mouse skeletal muscle

Exercise induces extensive, cell-type-specific transcriptional remodeling in skeletal muscle to support metabolic flexibility and adaptation. However, the regulatory mechanisms underlying these transcriptional programs, and the extent to which they differ between sexes, remain poorly defined. We previously reported that lifelong, muscle-specific overexpression of human Transcription Factor E-B (cTFEB;HSACre transgenic mice) recapitulates many adaptive features of endurance training in both sexes, leading to profound geroprotective effects during aging even in the absence of exercise. Here, we profile transcriptional adaptations to voluntary wheel running (VWR) and TFEB-overexpression at single-nucleus resolution in young male and female mouse tibialis anterior muscle. This represents, to our knowledge, the first integrated analysis of exercise and TFEB signaling using sex as a biological variable. Using robust bioinformatic and single-nuclei RNA-sequencing approaches, we profiled six muscle-resident cell populations and uncover previously unrecognized, sex-dependent signaling nodes governing exercise-associated metabolic plasticity. TFEB activation and endurance training by VWR elicit strongly correlated transcriptional programs enriched for lipid metabolism, mitochondrial remodeling, and immune modulation, establishing TFEB-overexpression as a partial exercise mimetic. In general, female muscle exhibited enhanced extracellular matrix and lipid-associated responses to endurance training and TFEB overexpression, whereas males preferentially engaged in angiogenic and oxidative networks, revealing distinct sex-specific, sex-dimorphic, or sex-agnostic regulatory routes to metabolic flexibility. Integration with independent multi-omics datasets from endurance-trained rats (MoTrPAC) confirms the conservation of TFEB-exercise transcriptional convergence in skeletal muscle across species and potentially muscle types. Together, these findings define TFEB as a regulator of exercise transcriptional programs and reveal sex-specific molecular frameworks that drive metabolic adaptation in skeletal muscle. Furthermore, the resulting sex-resolved, single-nucleus transcriptional atlas provides a unique resource for the field, enabling comparative, mechanistic, and hypothesis-driven exploration of exercise-responsive skeletal muscle regulatory networks across sexes.

physiology↗

bioRxiv2025

Convergent Skeletal Muscle Cytokine Responses to TFEB Overexpression and Voluntary Wheel Running Reflect Sex-Based Variability in Exercise Adaptations

Endurance exercise (running) promotes skeletal muscle remodeling through metabolic and inflammatory signaling cascades. However, the extent to which these responses are sex-dependent remains unclear. Here, we profiled cytokine responses in quadriceps muscle lysates from sedentary, voluntary wheel-running (VWR; 5 weeks), and muscle-specific TFEB-overexpressing (cTFEB;HSACre) male and female mice. Cytokine analysis revealed 40 differentially expressed factors associated with exercise and/or TFEB overexpression, many displaying sex-dimorphic expression patterns. In males, VWR induced significant increases in interleukins (e.g., IL-1, IL-1{beta}, IL-2, IL-5, IL-17) and chemokines (e.g., MCP-1, CCL5, CXCL9), as well as cytokines involved in TNF signaling (e.g., TNF, sTNFR1/2, Fas ligand). TFEB overexpression in sedentary males recapitulated many of these cytokine elevations. In contrast, female runner muscle showed limited cytokine activation, with significant changes restricted to IL-3, IL-3Rb, IL-13, and CXCL16. Both sexes exhibited a reduction in IL-4 and an increase in IGFBP-5 with running. Several additional male-specific cytokine profiling responses, including increases in IFN{gamma}, SCF, TPO, VCAM1A, and leptin, further underscored the sex-specificity of exercise-related inflammatory adaptations. These findings demonstrate that skeletal muscle cytokine responses to endurance-like stimuli are profoundly influenced by sex and suggest that male muscle exhibits a broader and/or later remodeling profile than female muscle. Our data also implicate skeletal muscle TFEB-overexpression as a partial molecular mediator of the cytokine shifts observed with exercise, particularly in males, and highlights their potential use as a new prioritization platform for exercise-associated phenotypes.

physiology↗

bioRxiv2024

Activation of the muscle-to-brain axis ameliorates neurocognitive deficits in an Alzheimer disease mouse model via enhancing neurotrophic and synaptic signaling

INTRODUCTIONSkeletal muscle regulates central nervous system (CNS) function and health, activating the muscle-to-brain axis through the secretion of skeletal muscle originating factors ( myokines) with neuroprotective properties. However, the precise mechanisms underlying these benefits in the context of Alzheimers disease (AD) remain poorly understood. METHODSTo investigate muscle-to-brain axis signaling in response to amyloid {beta} (A{beta})- induced toxicity, we generated 5xFAD transgenic female mice with enhanced skeletal muscle function (5xFAD;cTFEB;HSACre) at prodromal (4-months old) and late (8-months old) symptomatic stages. RESULTSSkeletal muscle TFEB overexpression reduced A{beta} plaque accumulation in the cortex and hippocampus at both ages and rescued behavioral neurocognitive deficits in 8- months-old 5xFAD mice. These changes were associated with transcriptional and protein remodeling of neurotrophic signaling and synaptic integrity, partially due to the CNS-targeting myokine prosaposin (PSAP). DISCUSSIONOur findings implicate the muscle-to-brain axis as a novel neuroprotective pathway against amyloid pathogenesis in AD.

neuroscience↗

bioRxiv2022

Inhibition of Phosphodiesterase 12 results in Antiviral Activity against several RNA Viruses including SARS-CoV-2.

Phosphodiesterase 12 (PDE12) is a negative regulator of the type 1 interferon (IFN) response and here we show that PDE12 inhibitors (lead compounds 63 and 17) are associated with increased RNAseL activity, are well tolerated at the therapeutic range and inhibit, both in vitro and in vivo, the replication of several RNA viruses including hepatitis C virus (HCV), dengue virus (DENV), West Nile Virus (WNV) and SARS-CoV-2.

microbiology↗

bioRxiv2022

Skeletal Muscle Proteostasis Promotes Central Nervous System Rejuvenation and Reduces Neuroinflammation during Aging and Neurodegenerative Disease

Skeletal muscle has recently arisen as a novel regulator of Central Nervous System (CNS) function and aging, secreting bioactive molecules known as myokines with metabolism-modifying functions in targeted tissues, including the CNS. Here we report the generation of a novel transgenic mouse with enhanced skeletal muscle lysosomal and mitochondrial function via targeted overexpression of Transcription Factor E-B (TFEB). We have discovered that the resulting geroprotective effects in skeletal muscle reduce neuroinflammation and the accumulation of tau-associated pathological hallmarks in a mouse model of tau pathology. Muscle-specific TFEB overexpression also significantly ameliorates proteotoxicity, reduces neuroinflammation and promotes transcriptional remodeling of the aged CNS, preserving cognition and memory in aged mice. Our results implicate the maintenance of skeletal muscle function throughout aging to direct regulation of CNS health and disease, and suggest that skeletal-muscle originating factors may act as novel therapeutic targets against age-associated neurodegenerative disorders.

neuroscience↗

bioRxiv2020

Distinct recruitment of feed-forward and recurrent pathways across higher-order areas of mouse visual cortex

Cortical visual processing transforms features of the external world into increasingly complex and specialized neuronal representations. These transformations arise in part through target-specific routing of information; however, within-area computations may also contribute to area-specific function. Here, we sought to determine whether higher-order visual cortical areas LM, AL, PM, and AM have specialized anatomical and physiological properties by using a combination of whole-cell recordings and optogenetic stimulation of V1 axons in vitro. We discovered area-specific differences in the strength of recruitment of interneurons through feed-forward and recurrent pathways, as well as differences in cell-intrinsic properties and interneuron densities. These differences were most striking when comparing across medial and lateral areas, suggesting that these areas have distinct profiles for net excitability and integration of V1 inputs. Thus, cortical areas are not defined simply by the information they receive, but also by area-specific circuit properties that enable specialized filtering of these inputs.

neuroscience↗