Biology subjects

Curry, A.

Publications and source records attributed to Curry, A..

5 recordsLinked to original sources

bioRxiv2026

Prefrontal activation predicts response latency and is shaped by age and lifestyle

Neurological and neuropsychiatric conditions affect 43% of the global population, many shaped by modifiable lifestyle exposures, yet their relationship to cortical haemodynamics is poorly characterised. The dorsolateral prefrontal cortex (dlPFC) is a particularly tractable target: it underpins executive function, is disrupted across neuropsychiatric and age-related conditions, and lies on the cortical surface, within reach of scalable, wearable-grade optical neuroimaging. We present LUCID, a longitudinal study of 92 healthy adults combining consumer wearable sleep and physical activity metrics with task-evoked dlPFC haemodynamics, measured by time-domain functional near-infrared spectroscopy (TD-fNIRS). Log-transformed peak dlPFC activation was negatively associated with reaction time (RT) across the 2N-Back and Stroop tasks and both hemispheres (r = -0.37 to -0.53), greater activation accompanying faster responses, consistent with a capacity/recruitment account. Activation showed moderate test-retest reliability (intraclass correlation coefficient, ICC = 0.56-0.71), with between-person variance exceeding within-person fluctuation, indicating stable individual differences. Demographic and lifestyle features incrementally predicted activation, with age the strongest predictor and modest contributions from sleep and physical activity. These findings establish TD-fNIRS dlPFC activation as a longitudinally stable, behaviourally relevant functional neural marker for scalable tracking of modifiable risk.

neuroscience↗

bioRxiv2025

Differential Regulation of SIRT5 Activity by Reduced Nicotinic Acid Riboside (NARH)

SIRT5, one of the human sirtuins, catalyzes the removal of acyl substitutions from lysine residues in a NAD+-dependent manner. In addition to the deacetylase activity, SIRT5 also demonstrates strong desuccinylase, demalonylase, and deglutarylase activity. Through deacylating a broad spectrum of cellular proteins and enzymes, SIRT5 is heavily involved in the regulation of energy metabolism, reactive oxygen species (ROS) reduction, and ammonia detoxification. Accumulating evidence also suggest SIRT5 as a potential therapeutic target for the treatment of neurodegenerative diseases, metabolic disorders, and cancer. In the current study, we report the identification and characterization a SIRT5 modulator, reduced nicotinic acid riboside (NARH). It shows differential regulation of the distinct activities of SIRT5: activates desuccinylation, but mildly suppresses deacetylation. NARH binds to SIRT5 in the absence of NAD+, and demonstrates cellular target engagement and activity. The potential NARH binding site is further investigated using a suite of biochemical and computational approaches. The current study provides greatly-needed mechanistic understanding of SIRT5 regulation, as well as a novel chemical scaffold for further activator development.

biochemistry↗

bioRxiv2024

Biochemical Characterization and Inhibitor Discovery for PfSir2A -- New Tricks for An Old Enzyme

The Sir2 enzyme from Plasmodium falciparum (PfSir2A) is essential for the antigenic variation of this parasite, and its inhibition is expected to have therapeutic effects for malaria. Selective PfSir2A inhibitors are not available yet, partially due to the fact that this enzyme demonstrates extremely weak in vitro deacetylase activity, making the characterization of its inhibitors rather challenging. In the current study, we report the biochemical characterization and inhibitor discovery for this enzyme. PfSir2A exhibits greater enzymatic activity in the presence of DNA for both the peptide and histone protein substrates, suggesting that nucleosomes may be the real substrates of this enzyme. Indeed, it demonstrates robust deacetylase activity against nucleosome substrates, stemming primarily from the tight binding interactions with the nucleosome. In addition to DNA/nucleosome, free fatty acids (FFAs) are also identified as endogenous PfSir2A regulators. Myristic acid, a biologically relevant FFA, shows differential regulation of the two distinct activities of PfSir2A: activates deacetylation, but inhibits defatty-acylation. The structural basis of this differential regulation was further explored. Moreover, synthetic small molecule inhibitors of PfSir2A were discovered through the screening of a library of human sirtuin regulators. The mechanism of inhibition of the lead compounds were investigated. Collectively, the mechanistic insights and inhibitors described in this study will facilitate the future development of small molecule PfSir2A inhibitors as antimalarial agents.

biochemistry↗

bioRxiv2021

Hydraulic synchrony of spawning sites amongst Earth's riverine fishes

Earths riverine fishes utilize a suite of reproductive guilds, broadly following four guilds: nest guarders, broadcast pelagic spawners, broadcast benthic spawners and nest non-guarders 1,2, and these guilds utilize different mechanisms to aerate eggs 3,4. Globally, river fishes populations are declining5, and spawning habitat rehabilitation has become a popular tool to counter these declines6. However, there is a lack of understanding as to what classifies suitable spawning habitats for riverine fishes, thereby limiting the efficacy of these efforts and thus the restoration of the target species. Using data from n = 220 peer-reviewed papers and examining n = 128 unique species, we show the existence of a hydraulic pattern (defined by Froude number (Fr), a non-dimensional hydraulic parameter) that characterizes the reproductive guilds of riverine fishes. We found nest guarders, broadcast pelagic spawners, benthic spawners, and nest non-guarders selected sites with mean Fr = 0.05, 0.11, 0.22, and 0.28, respectively. Some of the fishes in this study are living fossils, suggesting that that these hydraulic preference patterns may be consistent across time. Our results suggest this hydraulic pattern can guide spawning habitat rehabilitation for all riverine fish species globally in absence of specific spawning habitat information for a species, where resource managers can establish the reproductive guild of the species of interest, and then apply the specific hydraulic requirements (Fr range) of that reproductive guild, as presented herein, in the rehabilitation of the target species.

ecology↗

bioRxiv2021

The salmon-peloton: hydraulic habitat shifts of adult Atlantic salmon (Salmo salar) due to behaviour thermoregulation

In recent decades there has been an increase in conservation and restoration projects targeting Atlantic salmon (Salmo salar - AS), as populations in eastern Canada decline. Missing however, is an understanding of thermo-hydraulic habitat use by adult AS during summer, and thus the actual benefits of altering in-river physical structures. Here, we illustrated how optical and thermal infrared (TIR) imagery acquired from a UAV can be used in concert with in-situ depth and velocity data to map adult AS and develop models of thermo-hydraulic habitats in the Miramichi River, New Brunswick. We found during optimal thermal conditions (< 19 {degrees}C) proximity to boulders and Froude numbers, a non-dimensional hydraulic metric, were key parameters that characterized adult AS habitat. However, during behavioural thermoregulation events (>19 {degrees}C), proximity to the cool thermal plume and Froude number, a non-dimensional hydraulic parameter, were critical controls on habitat use. We also observed AS formed a distinct geometric formation during behavioural thermoregulation events, and term this formation a thermal-peloton. The primary function of the peloton is undoubtedly to reduce thermally induced stressed; however, we conceptualize the geometry of the peloton attenuates hydraulic-drag, and reduces energetic expenditure of individuals practicing behavioural thermoregulation. These data provide an unrivaled viewpoint of thermo-hydraulic habitat selection by adult AS, and a blue print for restoration work. The use of UAV-based sensors has the potential to instigate a paradigm shift for river sciences. The age of applying hyper-resolution, remote sensing for river science and aquatic ecology is immensely exciting.

ecology↗