Biology subjects

Stokes, A.

Publications and source records attributed to Stokes, A..

6 recordsLinked to original sources

bioRxiv2026

Subacute and Chronic Cognitive and Cerebrovascular Functional Consequences of Mild Traumatic Brain Injury in Rats

Traumatic brain injury (TBI) is the main cause of death and disability in the United States in people younger than 35 years old and is a common cause of wartime injuries. Mild TBI (mTBI) is a predisposing factor for later development of dementia and cerebrovascular disease. Aerobic exercise was reported to improve cognitive function in chronic TBI through improved vascular function. The aims of the study are to characterize and correlate the subacute (10 weeks) and chronic (12 months) cognitive and cerebrovascular functional impairment following mTBI and evaluate the modulating effect of exercise early or late following mTBI on these changes. Sprague-Dawley rats received midline fluid percussion injury or sham procedure and followed for 10 weeks or 12 months with a subgroup of mTBI rats undergoing 5-week treadmill aerobic exercise 2 weeks (early) or 10 months (late) post-injury for 6 weeks. Cognitive function was assessed using novel object recognition (NOR) and novel object location (NOL) tests. Regional cerebral blood volume (CBV) and cerebrovascular reactivity following hypercapneic stimulation (CVR) using contrast magnetic resonance imaging (MRI) and ex vivo pial artery vasoreactivity to intraluminal pressure, angiotensin II and diethylenetriamine NONOate (DETA NONOate) were measured. There was no difference in NOR or NOL at 10 weeks between mTBI and sham. NOR, but not NOL, was reduced in mTBI rats at 12 months. CBV at 10 weeks was higher in the primary somatosensory trunk cortex (trunk) and dentate gyrus regions in mTBI, but not at 12 months. CVR was lower in the trunk region of mTBI rats at 12 months. Compared to sham response at 10 weeks, there was impaired arterial constriction response to 90 mm Hg intraluminal pressure in mTBI rats at 10 weeks and in sham and mTBI rats at 12 months, with no difference seen in response to angiotensin II or DETA-NONOate exposure. There was no correlation between cognitive and vascular outcomes at 10 weeks or 12 months. Early or late exercise did not affect 12-month cognitive or vascular function following mTBI. The study showed chronic impairment in short-term memory cognitive function, regional cerebrovascular reactivity and early onset of impaired cerebrovascular myogenic response in rats subjected to mTBI. The findings of persistent cognitive and cerebrovascular impairment in this animal model enhance our understanding of the long-term consequence of mTBI.

neuroscience↗

bioRxiv2024

Flight-Scope: microscopy with microfluidics in microgravity

With the European Space Agency (ESA) and NASA working to return humans to the moon and onwards to Mars, it has never been more important to study the impact of altered gravity conditions on biological organisms. These include astronauts but also useful micro-organisms they may bring with them to produce food, medicine, and other useful compounds by synthetic biology. Parabolic flights are one of the most accessible microgravity research platforms but present their own challenges: relatively short periods of altered gravity ([~]20s) and aircraft vibration. Live-imaging is necessary in these altered-gravity conditions to readout any real-time phenotypes. Here we present Flight-Scope, a new microscopy and microfluidics platform to study dynamic cellular processes during the short, altered gravity periods on parabolic flights. We demonstrated Flight-Scopes capability by performing live and dynamic imaging of fluorescent glucose uptake by yeast, S. cerevisiae, on board an ESA parabolic flight. Flight-Scope operated well in this challenging environment, opening the way for future microgravity experiments on biological organisms.

biophysics↗

bioRxiv2022

Environmental drivers of earthworm communities along an altitudinal gradient in the French Alps

The study of elevational diversity gradients is a central topic in biodiversity research. In this study, we tested for the effect of climate, resource quality and habitat heterogeneity on earthworm communities along an altitudinal gradient and around the treeline in the French Alps. Earthworm communities and environmental properties (i.e. climate, soil properties and vegetation structure and composition) were sampled in six altitudinal stages from 1400 to 2400 m. Results were analysed through multi-table factorial analyses and structural equation modelling. We found average density, biomass and species richness in the range of what is usually reported in comparable ecosystems. We found no monotonic decrease in species richness along the altitudinal gradient, which we explain by the species pool being dominated by taxa with high environmental tolerance and dispersal capacities. Instead, we highlighted the ecotone associated with the treeline as the primary driving factor of earthworm communities: at 1800-2000m altitude, communities were more abundant and diverse, and had a greater variability in body mass. This result was largely explained by the structure and composition of the vegetation, whereas soil and climate appeared to have only indirect effects. Therefore, the treeline effect on earthworm communities can be explained both by the effect of environmental heterogeneity and of trophic resource quality which increases at the ecotone level.

ecology↗

bioRxiv2020

Identifying the spatial and temporal dynamics of molecularly-distinct glioblastoma sub-populations

Glioblastomas (GBMs) are the most aggressive primary brain tumours and have no known cure. Each individual tumour comprises multiple sub-populations of genetically-distinct cells that may respond differently to targeted therapies and may contribute to disappointing clinical trial results. Image-localized biopsy techniques allow multiple biopsies to be taken during surgery and provide information that identifies regions where particular sub-populations occur within an individual GBM, thus providing insight into their regional genetic variability. These sub-populations may also interact with one another through a competitive or cooperative nature; it is important to ascertain the nature of these interactions, as they may have implications for responses to targeted therapies. We combine genetic information from biopsies with a mechanistic model of interacting GBM sub-populations to characterise the nature of interactions between two commonly occurring GBM sub-populations, those with EGFR and PDGFRA genes amplified. We study population levels found across image-localized biopsy data from a cohort of 25 patients and compare this to model outputs under competitive, cooperative and neutral interaction assumptions. We explore other factors affecting the observed simulated sub-populations, such as selection advantages and phylogenetic ordering of mutations, which may also contribute to the levels of EGFR and PDGFRA amplified populations observed in biopsy data.

cancer biology↗

bioRxiv2019

Genetic structure of prey populations underlies the geographic mosaic of arms race coevolution

Reciprocal adaptation is the hallmark of arms race coevolution, but the symmetry of evolutionary change between interacting species is often untested, even in the best-studied battles of natural enemies. We tested whether prey and predator exhibit symmetrical local co-adaptation in the example of a geographic mosaic of coevolution between toxic newts (Taricha granulosa) and resistant garter snakes (Thamnophis sirtalis). Prior work showing a tight correlation between levels of newt toxin and snake resistance is regarded as textbook evidence of the intense arms race between natural enemies. Here, we similarly found that toxin and resistance are functionally matched in prey and predator populations, further suggesting that mosaic variation in the armaments of both species results from the local pressures of reciprocal selection. Contrary to conventional wisdom, however, we found that local variation in newt toxin is best predicted by neutral population divergence rather than the resistance of co-occurring predators. Snake resistance, on the other hand, is clearly explained by local levels of prey toxin. Prey populations seem to structure variation in defensive toxin levels across the geographic mosaic, which in turn determines selection on predator resistance. Exaggerated armaments suggest that coevolution occurs in certain hotspots, but our results imply that neutral processes like gene flow--rather than reciprocal adaptation--structure the greatest source of variation across the landscape. This pattern supports the predicted role of \"trait remixing\" in the geographic mosaic of coevolution, the process by which non-adaptive forces dictate spatial variation in the interactions among species.\n\nSIGNIFICANCE STATEMENTWhen the weapons of natural enemies like prey toxins and predator resistance are matched across the geographic landscape, they are usually presumed to result from arms race coevolution. In the textbook example of an arms race, matched levels of newt toxin and garter snake resistance have long been regarded as evidence of such local co-adaptation. To the contrary, we found that local variation in newt toxicity is best explained by the neutral geographic structure of newt populations. This spatial variation of prey in turn dictates local selection on garter snakes, structuring the geographic pattern of predator resistance. These results demonstrate how landscape patterns of phenotypic variation are determined by a mixture of natural selection, historical biogeography, and gene flow that comprise the geographic mosaic of coevolution.

evolutionary biology↗

bioRxiv2018

The Growth Hormone Secretagogue Receptor, Ghrelin and Biochemical Signaling Molecules in Human Heart Failure

BackgroundCurrently, the early pre-clinical detection of left ventricular (LV) dysfunction is difficult as biomarkers are not specific for the cardiomyopathic process. The underlying molecular mechanisms leading to heart failure remain elusive, highlighting the need for identification of cardiac-specific markers. The growth hormone secretagogue receptor (GHSR) and its ligand ghrelin are present in cardiac tissue and are known to contribute to myocardial energetics. Here, we examined tissue ghrelin-GHSR levels as specific markers of cardiac dysfunction in patients who underwent cardiac transplantation.\n\nMethods and ResultsSamples of cardiac tissue were obtained from 10 cardiac transplant patients at the time of organ harvesting, and during serial post-transplant biopsies. Quantitative fluorescence microscopy using a novel fluorescent ghrelin analog was used to measure levels of GHSR, and immunofluorescence was used to measure levels of ghrelin, b-type natriuretic peptide (BNP) and tissue markers of cardiomyocyte contractility and growth. GHSR and ghrelin expression levels were highly variable in the explanted heart, less in the grafted heart biopsies. GHSR and ghrelin were strongly positively correlated, and both markers were negatively correlated with LV ejection fraction. Ghrelin had stronger positive correlations than BNP with the signaling markers for contractility and growth.\n\nConclusionsThese data suggest that GHSR-ghrelin have potential use as an integrated marker of cardiac dysfunction. Interestingly, tissue ghrelin appeared to be a more sensitive indicator than BNP to the biochemical processes that are characteristic of heart failure. This work allows for further use of ghrelin-GHSR to interrogate cardiac-specific biochemical mechanisms in pre-clinical stages of HF.\n\nPrecisThis study shows the relationships between GHSR, ghrelin, and signaling molecules with relation to heart function in human heart failure with tissue from diseased heart and healthy heart biopsies.

cell biology↗