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Reid, M.

Publications and source records attributed to Reid, M..

6 recordsLinked to original sources

Cerebral microthrombi promote focal Cav-1-dependent blood-brain barrier impairment, triggering neuroinflammation and neuronal damage after traumatic brain injury

Traumatic brain injury (TBI) is frequently accompanied by blood-brain barrier (BBB) dysfunction, yet the microvascular events that initiate barrier failure and secondary neural injury remain poorly understood. Using highly sensitive fluorescent nanoscale tracers, correlative light and electron microscopy, single-cell transcriptomics, and genetic manipulation of Caveolin-1 (Cav-1), we show that BBB leakage after TBI in mice occurs focally at sites of cerebral microthrombus formation. Endothelial cells adjacent to microthrombi remain structurally intact, but exhibit a distinct transcriptional program enriched in both thrombosis- and transcytosis-related genes, including Cav-1. Microthrombi promote Cav-1-dependent transcytosis and size-selective extravasation of blood-borne proteins, exposing the surrounding parenchyma to circulating factors and inducing focal microglia activation and neuronal damage in vivo. In human induced pluripotent stem cell-derived neurons, these proteins directly impaired neuronal structure and network function. Genetic deletion of Cav-1 markedly reduces microthrombus-associated BBB leakage, immune-cell diapedesis, microglial activation and neuronal loss, whereas endothelial re-expression of Cav-1 using AAVs restores leakage. Human TBI data reveal early dynamic coagulation dysregulation associated with adverse clinical outcome, focal cerebral vascular injury and endothelial transcriptional signatures consistent with reduced barrier integrity and increased caveolae-associated transport. Together, these findings identify cerebral microthrombi as focal sites of Cav-1-dependent BBB dysfunction and establish pathological endothelial transcytosis as a mechanistic link between post-traumatic microvascular thrombosis, blood protein extravasation and secondary neuronal injury. Targeting Cav-1-dependent transcytosis may therefore provide a strategy to limit pathological BBB permeability and secondary injury after TBI.

neuroscience↗

ezscore-f: A Set of Freely Available, Validated Sleep Stage Classifiers for Forehead EEG

The increasing availability of wearable forehead EEG devices, such as the Hypnodyne ZMax, open-source DCM, CGX PatchEEG, and many others, has significantly expanded opportunities for convenient, at-home sleep monitoring. However, most publicly available sleep classifiers are trained on scalp EEG from traditional polysomnography (PSG) data, and thus generalize poorly to forehead EEG due to differences in electrode placement, referencing montages, and higher susceptibility to artifacts from user movements and electrode displacement. Conventional classifiers typically do not explicitly account for these artifacts, resulting in inaccurate and misleading sleep stage scoring. To address this gap, we developed a suite of artifact-aware sleep stage classifiers trained specifically using forehead EEG data, leveraging two comprehensive datasets--Wearanize+ and Donders2022--that contain concurrent forehead EEG and clinical PSG recordings. We further introduce two classifier variants: one optimized for real-time applications that operates directly on raw EEG amplitudes, and another optimized for offline analysis utilizing normalized EEG signals. Validation results indicate robust and reliable classification performance across standard sleep stages (Wake, N1, N2, N3, REM), along with effective identification of artifact epochs. Importantly, the developed classifiers generalize well to forehead EEG devices beyond the original training platform. These validated classifiers are freely available to the sleep research community through the open-source ezscore-f package, providing versatile and practical tools for forehead EEG-based sleep stage analysis.

neuroscience↗

Using fisheries risk assessment to inform precautionary and collaborative management in a declining coho salmon fishery

The conservation and management of Pacific salmon in Canada faces an uncertain future. While fisheries policies, like Canadas Wild Salmon Policy, increasingly emphasize conservation, salmon continue to decline due to cumulative pressures of climate change, habitat loss, and overfishing, requiring precautionary management. We quantified population dynamics for 52 coho salmon populations along the North and Central Coast of British Columbia since 1980 to determine population status, assess risks posed by a mixed-stock fishery spanning U.S., Canadian, and Indigenous jurisdictions, and implemented forward simulations of alternative productivity trends and harvest scenarios to inform collaborative management tables. We found declining abundances for 51% of coho populations since 2017, driven by productivity regime shifts associated with recent marine heatwaves. Although long-term coho recovery depended on future productivity trends, reduced harvest rates across U.S. and Canadian fisheries can improve short-term recovery prospects. While rebuilding coho will depend largely on whether productivity improves, harvest management remains one of the few tools available to provide a safe operating space for coho populations, and their fisheries, to adapt to ongoing ecosystem changes.

ecology↗

Loss of RREB1 reduces adipogenesis and improves insulin sensitivity in mouse and human adipocytes

There are multiple independent genetic signals at the Ras-responsive element binding protein 1 (RREB1) locus associated with type 2 diabetes risk, fasting glucose, ectopic fat, height, and bone mineral density. We have previously shown that loss of RREB1 in pancreatic beta cells reduces insulin content and impairs islet cell development and function. However, RREB1 is a widely expressed transcription factor and the metabolic impact of RREB1 loss in vivo remains unknown. Here, we show that male and female global heterozygous knockout (Rreb1+/-) mice have reduced body length, weight, and fat mass on high-fat diet. Rreb1+/- mice have sex- and diet-specific decreases in adipose tissue and adipocyte size; male mice on high-fat diet had larger gonadal adipocytes, while males on standard chow and females on high-fat diet had smaller, more insulin sensitive subcutaneous adipocytes. Mouse and human precursor cells lacking RREB1 have decreased adipogenic gene expression and activated transcription of genes associated with osteoblast differentiation, which was associated with Rreb1+/- mice having increased bone mineral density in vivo. Finally, human carriers of RREB1 T2D protective alleles have smaller adipocytes, consistent with RREB1 loss-of-function reducing diabetes risk.

physiology↗

The effect of sleep continuity disruption on multimodal emotion processing and regulation: a laboratory-based, randomized, controlled experiment in good sleepers

Previous research shows that experimental sleep deprivation alters emotion processing, suggesting a potential mechanism linking sleep disruption to mental ill-health. Extending previous work, we experimentally disrupted sleep continuity in good sleepers and assessed next-day emotion processing and regulation using tasks with established sensitivity to depression. In a laboratory-based study, 51 good sleepers (37 female; mean age = 24 years, SD= 3.63) were randomized to one night (23:00-07:00) of uninterrupted sleep (n=24) or sleep continuity disruption (n=27). We assessed emotion perception, attention, and memory the following day. Participants also completed an emotion regulation task and measures of self-reported affect, anxiety, sleepiness, overnight declarative memory consolidation, and psychomotor vigilance. Confirming the effects of the manipulation, sleep continuity disruption led to a marked decrease in polysomnography-defined total sleep time (229.98 mins vs 434.57 mins), increased wake-time after sleep onset (260.66 mins vs 23.84 mins) and increased sleepiness (d=0.81). Sleep continuity disruption led to increased anxiety (d=0.68), decreased positive affect (d=-0.62), reduced overnight declarative memory consolidation (d=-1.08) and reduced psychomotor vigilance [longer reaction times (d=0.64) and more lapses (d=0.74)], relative to control. However, contrary to our hypotheses, experimental sleep disruption had no effect on perception of, or bias for, emotional facial expressions, emotional memory for words, or emotion regulation following worry induction. In conclusion, one night of sleep continuity disruption had no appreciable effect on objective measures of emotion processing or emotion regulation in response to worry induction, despite clear effects on memory consolidation, vigilance, and self-reported affect and anxiety.

neuroscience↗

Timing of water limitations affects source to sink differences in δ13C composition in apple

Deficit irrigation is used to reduce vegetative vigor, increase fruit quality, and conserve water resources. However, physiological responses to deficit irrigation can vary depending on soil and environmental conditions. Although physiological measurements are often made at single points in time, responses are often longer lasting and a measurement that integrates responses over time would have greater value in assessing the effectiveness of deficit irrigation practices. Carbon isotope composition has long been used as a proxy measurement for water-use efficiency, stomatal conductance, and carbon dioxide exchange with the atmosphere and is heavily influenced by water status. Potentially, fruit, leaves, or other tissues could be used as samples for carbon isotope measurements. However, it is not well known how irrigation practices can influence both source and sink tissue carbon isotope composition in perennial systems. Here, we used two experiments to determine how irrigation timing affects both source and sink {delta}13C at the end of the season. Irrigation limitations were initiated after bloom for either the whole season or for early, middle, or late season and compared to a well-watered control. For both experiments, leaves were poor indicators of irrigation deficit treatments that were applied during the season. There were no significant differences in leaf {delta}13C between deficit treatments and the control for both experiments. However, all sink tissues including roots and stems in experiment one for both years and for fruits in experiment two for both years were significantly more enriched compared to the well-watered control. Environmental conditions during the season also appeared to influence the magnitude of difference in {delta}13C between deficit irrigation treatments and the control. These results indicate that the use of sink tissues are more sensitive for measuring signals associated with in-season water deficits. Carbon isotope composition can be an effective proxy to measure efficacy of irrigation treatments at the physiological level.

plant biology↗