Biology subjects

Treacy, C.

Publications and source records attributed to Treacy, C..

5 recordsLinked to original sources

bioRxiv2026

Multiphoton tomographic fluorescence lifetime imaging microscopy -TomoFLIM

Fluorescence lifetime imaging microscopy provides quantitative, concentration-independent contrast for probing molecular interactions, biochemical environments and cellular physiology. However, the requirement to acquire sufficient time-resolved photon statistics makes FLIM inherently slow, limiting its application to dynamic biological processes. In live-cell applications, including calcium signalling and vesicular trafficking, acquisition times can exceed the timescale of the underlying biology, causing temporal averaging, motion artefacts and loss of transient information. Methods that increase FLIM acquisition speed while preserving quantitative lifetime accuracy are therefore required. We report on a high-speed, compressive, multiphoton fluorescence lifetime imaging technique (TomoFLIM). Two-photon fluorescence is excited using a line focus projected tomographically across the sample, while time-tagged fluorescence is acquired using time-correlated single-photon counting. Time-resolved fluorescence data are reconstructed using Lucy-Richardson deconvolution followed by a computationally efficient centre-of-mass method lifetime estimator. In addition, TomoFLIM Net, a physics-informed neural-network, directly reconstructs fluorescence intensity and lifetime from compressed time-resolved tomographic data. TomoFLIM was benchmarked against raster-scanned fluorescence lifetime measurements using calibrated fluorescence lifetime beads and biological specimens. We demonstrate imaging at compression ratios exceeding 90%, with Pearson correlation coefficients above 80% relative to reference images. A raster-scanned FLIM dataset acquired in 60 s was reproduced using TomoFLIM in 3.75 s, representing a 16-fold increase in frame rate and equivalent reduction in accumulated dark counts. TomoFLIM Net recovered distinct experimental bead lifetime populations, demonstrating a direct route from compressed measurements to quantitative lifetime maps. TomoFLIM therefore offers significant potential for rapid live-cell imaging of dynamic biological processes, including deep within turbid biological specimens.

biophysics↗

bioRxiv2025

Relationships between GABA+ and Glx concentrations with age and inhibition in healthy older adults

Inhibition represents a core executive function which underlies the ability to suppress interfering and/or distracting stimuli, thereby building resistance against task-irrelevant information. However, the impact of ageing on inhibitory functioning and the potential role of neuroplasticity - largely driven by predominant excitatory (glutamatergic) and inhibitory (GABAergic) neurochemicals - remains poorly understood. In this study, we investigated age relationships with neurochemical concentrations (GABA+ and Glx) and examined the associations between these neurochemicals and inhibitory sub-components in the context of healthy ageing. To this end, participants completed three inhibition tasks (i.e., flanker, Stroop and go/no-go), each measuring a different sub-component process, via the PsyToolkit platform. MRS data was acquired in the sensorimotor (SM1; n=71, mean age (SD) = 68.3 ({+/-}9.7) years, 39 females) and prefrontal (PFC; n=58, mean age (SD) = 67.6 ({+/-}9.6) years, 30 females) regions using a HERMES sequence and analysed using OSPREYs pipeline. After correcting for gender and education, semi-partial correlations (rho) revealed no significant relationships between age and GABA+ or Glx concentrations in either the SM1 or PFC regions. Furthermore, through partial correlations (rho), after correcting for age, gender and education, we identified a significant negative relationship between SM1 Glx concentrations and go/no-go error rates, such that greater concentrations of Glx in the SM1 region were associated with greater accuracy on the go/no-go task. The null age-neurochemical results suggest that GABA+ and Glx may not uniformly decline during healthy ageing. This finding suggests that the relationship between older age and neurochemistry may be more nuanced than previously reported. In addition, our neurochemical-behavioural findings provide neurochemically-and-spatially specific evidence that SM1 Glx concentrations may be important for response inhibition. This result indicates a role for the glutamatergic system in supporting inhibition over the normal course of ageing.

neuroscience↗

bioRxiv2025

Neurophysiological Correlates of Modifiable Dementia Risk Factors in Cognitively Unimpaired Older Adults

The 2024 Lancet Commission on Dementia estimates that up to 45% of dementia cases could be prevented by addressing modifiable risk factors, emphasising both prevention opportunities and the need to understand the biological mechanisms. This study investigated neurophysiological mechanisms underlying modifiable dementia risk factors in cognitively unimpaired older adults. Seventy-nine cognitively unimpaired older adults underwent MRI brain scans, with spectroscopy measurements taken from the sensorimotor cortex (SMC) and prefrontal cortex (PFC), using a Hadamard Encoding and Reconstruction of MEGA-Edited Spectroscopy (HERMES) sequence, optimised for measuring GABA+. Modifiable dementia risk scores were calculated using the Assessment for Cognitive Health and Dementia Risk (CogDrisk). Hierarchical linear regression analyses revealed a significant negative relationship within the SMC, with lower GABA+ ({beta} = -0.249, p = 0.009) associated with higher risk scores. In the PFC, lower tNAA and tCho concentrations significantly predicted higher risk scores ({beta} = -0.168 and -0.170, respectively). These findings suggest that GABAergic system alterations may underlie the pathophysiology of modifiable dementia risk in healthy ageing, whilst changes in tNAA and tCho may reflect early alterations in neuronal integrity. These region-specific neurochemical findings may help identify potential early biomarkers for dementia risk, and suggest new therapeutic pathways for preventive interventions.

neuroscience↗

bioRxiv2025

Age-related Inhibitory Decline: Examining Inhibition Sub-Components and their Impact on Sustained Attention in Healthy Ageing

ObjectiveThe inhibition deficit hypothesis postulates that inhibitory functioning declines with age, which negatively impacts other cognitive abilities. Yet still, the impact of healthy ageing on inhibitory functioning remains unclear, with the multifaceted nature of inhibition often an overlooked factor. Moreover, no prior study has empirically tested whether inhibitory sub-components explain differential age-effects in sustained attention - an open question that this work aims to address. MethodIn this cross-sectional study, we investigated the inhibition deficit hypothesis in a sample of eighty healthy older adults (mean age = 67.78 years, 44f). We utilised the PsyToolkit platform to administer three inhibition tasks (i.e., flanker, Stroop, and go/no-go), each targeting a distinct sub-component process, along with the Sustained Attention to Response Task (SART). ResultsSemi-partial correlations (rho) of the three inhibition sub-component measures (correcting for gender and education) with age resulted in significant positive relationships with task performance on the Stroop and go/no-go, such that older individuals had more pronounced Stroop effects and worse go/no-go accuracy, respectively. Lastly, go/no-go performance completely mediated the relationship between ageing and sustained attention performance, whilst Stroop effects partially mediated this association. ConclusionAge-related declines were observed in specific inhibition tasks, which speaks against a general inhibition deficit in healthy ageing and cautions against conflating these sub-components into a generalised concept of inhibition. The mediation findings demonstrate that inhibitory sub-components account for age-related declines in sustained attention, over and beyond ageing itself via an indirect path, representing an important cognitive domain to maintain throughout ageing. Key pointsO_ST_ABSQuestionC_ST_ABSAre different inhibitory sub-components associated with age, and do they mediate age-related changes in sustained attention? FindingsDifferent inhibition tasks were uncorrelated, demonstrating specific relationships with age and providing evidence that select inhibition tasks can explain differential age-effects in sustained attention. ImportanceThis study lends support for the inhibition deficit hypothesis and underlines the importance of considering inhibitions multifaceted nature. Next stepsFuture research should adopt longitudinal designs to examine causal relationships

animal behavior and cognition↗

bioRxiv2018

Structural basis for isoform-specific kinesin-1 recognition of Y-acidic cargo adaptors

The light chains (KLCs) of the heterotetrameric microtubule motor kinesin-1, that bind to cargo adaptor proteins and regulate its activity, have a capacity to recognize short peptides via their tetratricopeptide repeat domains (KLCTPR). Here, using X-ray crystallography, we show how kinesin-1 recognizes a novel class of adaptor motifs that we call Y-acidic (tyrosine flanked by acidic residues), in a KLC-isoform specific manner. Binding specificities of Y-acidic motifs (present in JIP1 and in TorsinA) to KLC1TPR are distinct from those utilized for the recognition of W-acidic motifs found in adaptors that are KLC-isoform non-selective. However, a partial overlap on their receptor binding sites implies that adaptors relying on Y-acidic and W-acidic motifs must act independently. We propose a model to explain why these two classes of motifs that bind to the concave surface of KLCTPR with similar low micromolar affinity can exhibit different capacities to promote kinesin-1 activity.

biochemistry↗