Search bioRxiv⌕ Search

Biology subjects

Whyte, C.

Publications and source records attributed to Whyte, C..

6 recordsLinked to original sources
bioRxiv2025

Cerebellar and Subcortical Contributions to Working Memory Manipulation

Working memory enables us to temporarily store and manipulate information, a crucial function for problem-solving. However, most working memory models emphasize cortical interactions ignoring contributions from subcortical and cerebellar regions. Given the dense connectivity between the cerebellum, subcortex, and cortex, we hypothesize that these regions provide unique contributions during working memory manipulation. We tested this hypothesis using functional Magnetic Resonance Imaging (fMRI) to measure blood oxygen-level dependent (BOLD) activity during a mental rotation task, where participants judged whether rotated pairs of three-dimensional stimuli were identical. Our results revealed a distributed network spanning the cortex, subcortex, and cerebellum that differentiates rotated from non-rotated stimuli and correct from incorrect responses. BOLD recruitment in these regions increased with larger angles of rotation. We observed delayed responses in premotor, subcortical, and cerebellar regions during incorrect trials. These findings suggest that cerebellar and subcortical regions support working memory manipulation, highlighting a broader mechanism by which distributed brain regions interact to coordinate higher cognitive functions.

neuroscience↗
bioRxiv2023

The tissue-resident regulatory T cell pool is shaped by transient multi-tissue migration and a conserved residency program

The tissues are the site of many of the most important immunological reactions, yet the immunology of the tissues has remained relatively opaque. Recent studies have identified Foxp3+ regulatory T cells (Tregs) in several non-lymphoid tissues. These tissue-resident populations have been ascribed unique characteristics based on comparisons to lymphoid Tregs. Here we performed a systematic analysis of the Treg population residing in non-lymphoid organs throughout the body, revealing shared phenotypes, transient residency and common molecular dependencies. Further, tissue Tregs from different non-lymphoid organs shared T cell receptor (TCR) sequences, with functional capacity to drive multi-tissue Treg entry. Finally, tissue Tregs extracted from non-lymphoid organs were tissue-agnostic on re-entry, without homing preference for their tissue of origin. Together these results demonstrate that the tissue-resident Treg pool in most non-lymphoid organs, other than the gut, is largely constituted by broadly self-reactive Tregs, characterised by transient multi-tissue migration and a common residency program.

immunology↗
bioRxiv2022

Astrocyte-targeted gene delivery of interleukin 2 specifically increases brain-resident regulatory T cell numbers and protects against pathological neuroinflammation

The ability of immune-modulating biologics to prevent and reverse pathology has transformed recent clinical practice. Full utility in the neuroinflammation space, however, requires identification of both effective targets for local immune-modulation and a delivery system capable of crossing the blood-brain-barrier. The recent identification and characterization of a small population of regulatory T cells (Tregs) resident in the brain presents one such potential therapeutic target. Here we identified brain IL2 levels as a limiting factor for brain-resident Tregs. We developed a gene-delivery approach for astrocytes, with a small-molecule on-switch to allow temporal control, and enhanced production in reactive astrocytes to spatially-direct delivery to inflammatory sites. Mice with brain-specific IL2 delivery were protected from traumatic brain injury, stroke and multiple sclerosis models, without impacting the peripheral immune system. These results validate brain-specific IL2 gene-delivery as effective protection against neuroinflammation, and provide a versatile platform for delivery of diverse biologics to neuroinflammatory patients.

immunology↗
bioRxiv2020

Word detection in individual subjects is difficult to probe with fast periodic visual stimulation

Measuring cognition in single subjects presents unique challenges. Yet individually sensitive measurements offer extraordinary opportunities, from informing theoretical models to enabling truly individualised clinical assessment. Here, we test the robustness of fast, periodic, visual stimulation (FPVS), an emerging method proposed to elicit detectable responses to written words in the electroencephalogram (EEG) of individual subjects. The method is non-invasive, passive, and requires only a few minutes of testing, making it a potentially powerful tool to test comprehension in those who do not speak or who struggle with long testing procedures. In an initial study, Lochy et al. (2015) used FPVS to detect word processing in 8 out of 10 fluent French readers. Here, we attempted to replicate their study in a new sample of ten fluent English readers. Participants viewed rapid streams of pseudo-words with words embedded at regular intervals, while we recorded their EEG. Based on Lochy et al., we expected that words would elicit a steady-state response at the word-presentation frequency (2 Hz) over parieto-occipital electrode sites. However, across 40 datasets (10 participants, two conditions, and two regions of interest - ROIs), only four datasets met the criteria for a unique response to words. This corresponds to a 10% detection rate. We conclude that FPVS should be developed further before it can serve as an individually-sensitive measure of written word processing.

animal behavior and cognition↗
bioRxiv2019

Artificial Intelligence for Bioinformatics: Applications in Protein Folding Prediction

AI recently shows great promise in the field of bioinformatics, such as protein structure prediction. The Critical Assessment of protein Structure Prediction (CASP) is a nationwide experiment that takes place biannually, which centered around analyzing the best current systems for predicting protein tertiary structures. In this paper, we research on available AI methods and features, and then explore novel methods based on reinforcement learning. Such method will have profound implications for R&D in bioinformatics and add an additional platform to the management of innovation in biotechnology.

bioinformatics↗