Biology subjects

Stephenson, A.

Publications and source records attributed to Stephenson, A..

6 recordsLinked to original sources

bioRxiv2026

Sensory neurons shape γδ T cell effector programs to control Psoriasiform Inflammation.

Psoriasis is a chronic autoimmune skin disorder marked by IL-17 producing gamma delta T cell ({gamma}{delta}T17) and pruritus, but immunoregulatory roles of itch-inducing neurons in this context remain unclear. This study addressed whether non-peptidergic (NP) afferents bearing the Mas-related G protein-coupled receptor D (MrgprD/NP1) and MrgprA3/NP2 subsets had differential effects on psoriasiform immunopathology. Data show human NP1 and NP2 neurons basally expressed an array of pattern recognition and cytokine receptor genes and psoriatic human skin had a profound dysregulation of neuropeptides and their receptors. In mice, imiquimod (IMQ) application reduced the density of MrgprD+ skin afferents, whereas NP1 neuron ablation exacerbated IMQ-induced disease. Strikingly, NP1 activation using either optogenetics or {beta}-alanine before IMQ exposure significantly reduced epidermal thickness, psoriatic clinical score and {gamma}{delta}T17 cell accumulation. In stark contrast, NP2 activation increased the numbers of {gamma}{delta}T17 cells that co-expressed amphiregulin (Areg) and exacerbated IMQ-driven skin pathology. Instead, pre-emptive NP1 stimulation shifted {gamma}{delta} T cell profiles away from being IL-17 and Areg dominant to IL-13+ {gamma}{delta} T cells expressing the transcription factor GATA3 accompanied by IL-10 secretion. Importantly, IL-10 signaling blockade reversed NP1-mediated suppression of IMQ-induced dermatitis. These data show that inflammatory skin disease can be distinctly modulated by sensory neuron subsets.

immunology↗

bioRxiv2025

TRPV1+ neurons promote cutaneous immunity against Schistosoma mansoni.

Immunity against skin-invasive pathogens requires mechanisms that rapidly detect, repel or immobilize the infectious agent. While bacteria often cause painful cutaneous reactions, host skin invasion by the human parasitic helminth Schistosoma mansoni often goes unnoticed. This study investigated the role of pain-sensing skin afferents that express the ion channel Transient Receptor Potential Vanilloid 1 (TRPV1) in the detection and initiation of skin immunity against S. mansoni. Data show that mice infected with S. mansoni have reduced behavioral responses to painful stimuli and sensory neurons exposed from infected mice have significantly less calcium influx and neuropeptide release in response to the TRPV1 agonist capsaicin. Using both gain- and loss-of-function approaches, data show that TRPV1+ neurons are critical regulators of S. mansoni survival during migration from the skin into the pulmonary tract. Moreover, TRPV1+ neurons were both necessary and sufficient to promote proliferation and cytokine production from dermal {gamma}{delta} T cells as well as neutrophil and monocyte skin accumulation post-infection. These results suggest a model in which S. mansoni may have evolved to inhibit TRPV1+ neuron activation as a countermeasure that limits IL-17-mediated inflammation, facilitating systemic dissemination and chronic parasitism. One sentence summaryThe parasitic helminth Schistosoma mansoni averts IL-17-dependent protective immunity by suppressing skin-innervating TRPV1+ neurons.

immunology↗

bioRxiv2023

TidyGEO: Preparing analysis-ready datasets from Gene Expression Omnibus

TidyGEO is a Web-based tool for downloading, tidying, and reformatting data series from Gene Expression Omnibus (GEO). As a freely accessible repository with data from over 4 million biological samples across more than 4,000 organisms, GEO provides diverse opportunities for secondary research. Transcriptomic data are most common in GEO, but other measurement types are also prevalent, including DNA methylation levels, genotypes, and chromatin-accessibility profiles. GEOs diversity and expansiveness present opportunities and challenges. Although scientists may find assay data relevant to a given research question, most analyses require sample annotations, such as a samples treatment group, disease subtype, or age. In GEO, such annotations are stored alongside assay data in delimited, text-based files. However, the structure and semantics of the annotations vary widely from one series to another, and many annotations are not useful for analysis purposes. Thus, every GEO series must be tidied before it can be analyzed. Manual approaches may be used, but these are error prone and take time away from other research tasks. Custom computer scripts can be written, but many scientists lack the computational expertise to create such scripts. To address these challenges, we created TidyGEO, which supports essential data-cleaning tasks for sample-level annotations, such as selecting informative columns, renaming columns, splitting or merging columns, standardizing data values, and filtering samples. Additionally, users can integrate annotations with assay data, restructure assay data, and generate code that enables others to reproduce these steps. The source code for TidyGEO is at https://github.com/srp33/TidyGEO.

bioinformatics↗

bioRxiv2022

A highly sensitive LC-MS/MS method for quantitative determination of 7 vitamin D metabolites in mouse brain tissue

Despite its critical role in neurodevelopment and brain function, vitamin-D (vit-D) homeostasis, metabolism and kinetics within the central nervous system remain largely undetermined. Thus, it is of critical importance to establish an accurate, highly sensitive and reproducible method to quantitate vit-D in brain tissue. Here, we present a novel liquid chromatography tandem mass spectrometry (LC-MS/MS) method and for the first time, demonstrate detection of seven major vit-D metabolites in brain tissues of C57BL/6J wild-type mice, namely: 1,25(OH)2D3, 3-epi-1,25(OH)2D3, 1,25(OH)2D2, 25(OH)D3, 25(OH)D2, 24,25(OH)2D3, and 24,25(OH)2D2. Chromatographic separation was achieved on a pentaflurophenyol column 3 mM ammonium formate with water/methanol [A] and methanol/isopropanol [B] phases. Detection was by positive-ion electrospray tandem mass spectrometry. We used calibration standards of each metabolite prepared in brain matrices to validate the detection range, precision, accuracy and recovery. Isotopically labelled analogues, 1,25(OH)2D3-d3, 25(OH)D3-C5 and 24,25(OH)2D3-d6, served as the internal standards for the closest molecular related metabolite in all measurements. The calibration range was between 1 fg/mL to 10 ng/mL with an LLOD and LLOQ of 10 fg/mL and 3 fg/mL, respectively. The intra-/inter-day precision and accuracy for measuring brain vit-D metabolites ranged between 0.12-11.53% and 0.28-9.11%, respectively. Recovery ranged between 99.06% and 106.9% for all metabolites. Collectively, the sensitivity and efficiency of our method supersedes previously reported protocols used to measure vit-D and to our knowledge, the first protocol to reveal the abundance of 25(OH)D2, 1,25(OH)D2 and 24,25(OH)2D2, in brain tissue of any species. This technique may be important in supporting the future advancement of pre-clinical research into the function of vit-D in neurophysiological, neuropsychiatric, and neurodegeneration.

physiology↗

bioRxiv2020

The evolution of red colour vision is linked to coordinated rhodopsin tuning in lycaenid butterflies

Colour vision is largely mediated by changes in number, expression, and spectral properties of rhodopsins, but the genetic mechanisms underlying adaptive shifts in spectral sensitivity remain largely unexplored. Using in vivo photochemistry, optophysiology, and in vitro functional assays, we link variation in eye spectral sensitivity at long wavelengths to species-specific absorbance spectra for LW opsins in lycaenid butterflies. In addition to loci specifying an ancestral green-absorbing rhodopsin with maximum spectral sensitivity ({lambda}max) at 520-530 nm in Callophrys sheridanii and Celastrina ladon, we find a novel form of red-shifted LW rhodopsin at {lambda}max = 565-570 nm in Arhopala japonica and Eumaeus atala. Furthermore, we show that Ca. sheridanii and Ce. ladon exhibit a smaller bathochromic shift at BRh2 (480-489 nm), and with the ancestral LW rhodopsin, cannot perceive visible red light beyond 600 nm. In contrast, molecular variation at the LW opsin in A. japonica and E. atala is coordinated with tuning of the blue opsin that also shifts sensitivity to longer wavelengths enabling colour discrimination up to 617 nm. We then use E. atala as a model to examine the interplay between red and blue spectral sensitivity. Owing to blue duplicate expression, the spatial distribution of opsin mRNAs within an ommatidium defines an expanded retinal stochastic mosaic of at least six opsin-based photoreceptor classes. Our mutagenesis in vitro assays with BRh1 ({lambda}max = 435 nm) chimeric blue rhodopsins reveal four main residues contributing to the 65 nm bathochromic shift towards BRh2 ({lambda}max = 500 nm). Adaptations in this four-opsin visual system are relevant for discrimination of conspecific reflectance spectra in E. atala. Together, these findings illustrate how functional changes at multiple rhodopsins contribute to the evolution of a broader spectral sensitivity and adaptation in visual performance. Significance StatementRhodopsins are photosensitive protein molecules that absorb specific wavelengths of incoming light and convey colour information in the visual system. We show that molecular evolution in a green insect opsin gene resulted in a shift in its maximal absorbance peak, enabling some lycaenid butterflies to use spectral energy of longer wavelengths (LW) to discriminate colours in the red spectrum better than relatives bearing ancestral green LW rhodopsins. Lycaenids also evolved a duplicate blue opsin gene, and we illustrate an example where species equipped with red LW rhodopsins shifted their blue sensitivity peak to longer wavelengths due to changes in several blue-tuning residues that have evolved repeatedly in different insect lineages. We demonstrate how changes at multiple vision genes in the insect eye effectively create a coordinated mechanism expanding spectral sensitivity for visually guided behaviours such as selecting host plants and mates.

evolutionary biology↗

bioRxiv2018

Measuring narrative engagement: The heart tells the story

Stories play a fundamental role in human culture. They provide a mechanism for sharing cultural identity, imparting knowledge, revealing beliefs, reinforcing social bonds and providing entertainment that is central to all human societies. Here we investigated the extent to which the delivery medium of a story (audio or visual) affected conscious and subconscious engagement with the narrative. Although participants self-reported greater involvement for watching video relative to listening to auditory scenes, stronger physiological responses were recorded for auditory stories. Sensors placed at their wrists showed higher and more variable heart rates, greater electrodermal activity, and even higher body temperatures. We interpret these findings as physiological evidence that the stories were more cognitively and emotionally engaging when presented in an auditory format. This may be because listening to a story, rather than watching a video, is a more active process of co-creation, and that this imaginative process in the listeners mind is detectable on the skin at their wrist.

neuroscience↗