Biology subjects

Fulton, D.

Publications and source records attributed to Fulton, D..

4 recordsLinked to original sources

bioRxiv2025

Adult organotypic brain slice cultures recapitulate extracellular matrix remodelling in haemorrhagic stroke

1.Haemorrhagic stroke is a devastating condition characterised by vessel rupture and free blood within the brain parenchyma or cerebrospinal fluid (CSF) filled spaces. Across the major subtypes of haemorrhagic stroke (subarachnoid, intracerebral, and intraventricular haemorrhages), the presence of blood in the CSF generates significant tissue damage in the first 72 hours after the event, known as early brain injury (EBI). EBI includes neuroinflammation, blood-brain barrier breakdown and dysregulation of extracellular matrix (ECM) dynamics. ECM dysfunction has been shown to trigger fibrosis of the cortical blood vessels, limiting normal CSF circulation and resulting in the buildup of metabolic waste or the development of post-haemorrhagic hydrocephalus. Limiting or preventing this fibrosis may therefore reduce the rate of morbidity experienced by survivors, providing a potential avenue for non-surgical treatment to reduce secondary brain injury post-stroke. Despite this, current in vivo approaches fail to differentiate between the effect of blood products and secondary consequences including intracranial pressure (ICP) elevation and mass effect. Here, we describe an adult rat organotypic brain slice culture (OBSC) model of haemorrhagic stroke which enables the identification of the effect of blood products on ECM dysregulation. We demonstrate the distribution of key cell types across a time course of 0, 3 and 7 days in culture, indicating that such cultures are viable for a minimum of 7 days. Using immunofluorescence staining, Western blotting and RNA sequencing, we show that exposure of OBSCs to lysed blood markedly increases ECM deposition around cortical blood vessels. This is accompanied by dysregulation of ECM regulatory genes and upregulation of inflammation and oxidative stress-related genes, successfully recapitulating the changes seen in human stroke survivors. This versatile ex vivo model provides a translational platform to further understanding of haemorrhagic stroke pathophysiology and develop or trial novel therapeutics prior to progression to in vivo stroke studies.

neuroscience↗

bioRxiv2022

Recording animal-view videos of the natural world

Plants, animals, and fungi display a rich tapestry of colors. Animals, in particular, use colors in dynamic displays performed in spatially complex environments. In such natural settings, light is reflected or refracted from objects with complex shapes that cast shadows and generate highlights. In addition, the illuminating light changes continuously as viewers and targets move through heterogeneous, continually fluctuating, light conditions. Although traditional spectrophotometric approaches for studying colors are objective and repeatable, they fail to document this complexity. Worse, they miss the temporal variation of color signals entirely. Here, we introduce hardware and software that provide ecologists and filmmakers the ability to accurately record animal-perceived colors in motion. Specifically, our Python codes transform photos or videos into perceivable units (quantum catches) for any animal of known photoreceptor sensitivity. We provide the plans, codes, and validation tests necessary for end-users to capture animal-view videos. This approach will allow ecologists to investigate how animals use colors in dynamic behavioral displays, the ways natural illumination alters perceived colors, and other questions that remained unaddressed until now due to a lack of suitable tools. Finally, our pipeline provides scientists and filmmakers with a new, empirically grounded approach for depicting the perceptual worlds of non-human animals.

animal behavior and cognition↗

bioRxiv2019

A morphological analysis of activity-dependent myelination and myelin injury in transitional oligodendrocytes

Neuronal activity is established as a driver of oligodendrocyte (OL) differentiation and myelination. The concept of activity-dependent myelin plasticity, and its role in cognition and disease, is gaining support. Methods capable of resolving changes in the morphology of individual myelinating OL would advance our understanding of myelin plasticity and injury, thus we adapted a labelling approach involving Semliki Forest Virus (SFV) vectors to resolve and quantify the 3-D structure of OL processes and internodes in cerebellar slice cultures. We first demonstrate the utility of the approach by studying changes in OL morphology after complement-mediated injury. SFV vectors injected into cerebellar white matter labelled transitional OL (TOL), whose characteristic mixture of myelinating and non-myelinating processes exhibited significant degeneration after complement injury. The method was also capable of resolving finer changes in morphology related to neuronal activity. Prolonged suppression of neuronal activity, which reduced myelination, increased the number of TOL processes, while decreasing both the length of putative internodes, and the proportion of myelinating terminal branches. Overall this approach provides novel information on the morphology of TOL, and new opportunities to study the response of OL to conditions that alter circuit function or induce demyelination.

neuroscience↗

bioRxiv2018

Transfer RNA Genes Affect Chromosome Structure and Function via Local Effects

The genome is packaged and organized in an ordered, non-random manner and specific chromatin segments contact nuclear substructures to mediate this organization. While transfer RNA genes (tDNAs) are essential for the generation of tRNAs, these loci are also binding sites for transcription factors and architectural proteins and are thought to play an important role in the organization of the genome. In this study, we investigate the role of tDNAs in genomic organization and chromosome function by editing a chromosome so that it lacks any tDNAs. Surprisingly our analyses of this tDNA-less chromosome show that loss of tDNAs does not grossly affect chromosome folding or chromosome tethering. However, loss of tDNAs affects local nucleosome positioning and the binding of SMC proteins at these loci. The absence of tDNAs also leads to changes in centromere clustering and a reduction in the frequency of long range HML-HMR heterochromatin clustering. We propose that the tDNAs primarily affect local chromatin structure that result in effects on long-range chromosome architecture.

molecular biology↗