Biology subjects

Webster, J.

Publications and source records attributed to Webster, J..

9 recordsLinked to original sources

bioRxiv2026

Tissue retention of dendritic cells drives age-associated protective tolerogenic lymphoid structures

Ectopic lymphoid structures are typically associated with chronic tissue inflammation in autoimmunity and cancer, where they can amplify local immune responses. Similar structures arise spontaneously with age, yet their origin and function remain unclear. Here we identify tissue retention of mature migratory conventional dendritic cells (cDCs) as a driver of age-associated lymphoid organization. Mature cDCs accumulated within lymphoid structures in aged human and mouse tissues. We demonstrate that impaired cDC egress or pharmacological cDC expansion induced de novo structures in mice across multiple otherwise homeostatic organs without associated pathology. Strikingly, senescence-associated tissue cues, which promoted a distinct cDC maturation state, were required for lymphoid niche initiation. Unlike inflammatory structures described in disease, these cDC-driven structures preferentially accumulated tissue-adapted regulatory T cells and protected against inflammatory injury, revealing a previously unrecognized regulatory dimension of age-associated lymphoid organization.

immunology↗

bioRxiv2026

QNPtoVox: A methods pipeline for mapping 2D quantitative neuropathology to 3D MNI voxel space.

1.Quantitative neuropathology has advanced through whole-slide imaging and digital histology platforms. Yet, these measurements rarely align with neuroimaging coordinate frameworks that may be useful for spatial modeling and other applications. QNPtoVox, short for quantitative neuropathology to voxels, is a reproducible, modular pipeline that transforms quantitative metrics generated by digital pathology software (HALO) into voxel-based maps registered to a standard common coordinate (MNI) template. The workflow integrates digital histopathology, gross tissue photography, ex-vivo MRI, and nonlinear registration to generate spatially standardized 3D pathology representations. This Methods article provides a complete procedural description, including required materials, step-wise instructions, operator-dependent checkpoints, expected outputs, reproducibility evaluation, and troubleshooting. QNPtoVox enables voxel-level integration of neuropathology with neuroimaging tools, unlocking existing histopathology datasets for computational modeling and cross-cohort harmonization.

neuroscience↗

bioRxiv2026

Restoration of Keratinocyte Homeostasis Drives Resolution of Skin Inflammation

Chronic skin inflammation is sustained by reciprocal interactions between epidermal dysfunction and immune activation, yet whether epithelial state actively governs restoration of tissue homeostasis remains unclear. Using a murine model of inflammatory skin disease, we modulated epidermal lipid metabolism and examined its effects on tissue organization. Transcriptomic profiling revealed coordinated reversal of inflammatory, metabolic, and structural gene programs accompanied by normalization of epidermal architecture. Single-cell RNA sequencing showed that this remodeling was concentrated in differentiated keratinocytes, with suppression of IL-17 and neutrophil-associated responses and restoration of barrier and mitochondrial-lipid programs, while stromal and myeloid compartments displayed secondary adaptation. Cross-species analysis demonstrated that resolution-associated gene networks are inversely regulated in human psoriasis. Integrated proteomic and transcriptomic analyses further identified a conserved epithelial regulatory triad whose concordant regulation in psoriasis and atopic dermatitis, and whose in vivo silencing, establish mechanistic control of disease severity. Together, these findings indicate that inflammatory resolution reflects reorganization of epidermal transcriptional networks and position epithelial state as a determinant of inflammatory persistence.

cell biology↗

bioRxiv2024

Removal of developmentally regulated microexons has a minimal impact on larval zebrafish brain morphology and function

Microexon splicing is a vertebrate-conserved process through which small, often in-frame, exons are differentially included during brain development and across neuron types. Although the protein sequences encoded by these exons are highly conserved and can mediate interactions, the neurobiological functions of only a small number have been characterized. To establish a more generalized understanding of their roles in brain development, we used CRISPR/Cas9 to remove 45 microexons in zebrafish and assessed larval brain activity, morphology, and behavior. Most mutants had minimal or no phenotypes at this developmental stage. Among previously studied microexons, we uncovered baseline and stimulus-driven phenotypes for two microexons (meA and meB) in ptprd and reduced activity in the telencephalon in the tenm3 B0 isoform. Although mild neural phenotypes were discovered for several microexons that have not been previously characterized, including in ppp6r3, sptan1, dop1a, rapgef2, dctn4, vti1a, and meaf6. This study establishes a general approach for investigating conserved alternative splicing events and prioritizes microexons for downstream analysis.

neuroscience↗

bioRxiv2024

Unraveling Alzheimer's Disease: Investigating Dynamic Functional Connectivity in the Default Mode Network through DCC-GARCH Modeling

Alzheimers disease (AD) has a prolonged latent phase. Sensitive biomarkers of amyloid beta (A{beta}), in the absence of clinical symptoms, offer opportunities for early detection and identification of patients at risk. Current A{beta} biomarkers, such as CSF and PET biomarkers, are effective but face practical limitations due to high cost and limited availability. Recent blood plasma biomarkers, though accessible, still incur high costs and lack physiological significance in the Alzheimers process. This study explores the potential of brain functional connectivity (FC) alterations associated with AD pathology as a non-invasive avenue for A{beta} detection. While current stationary FC measurements lack sensitivity at the single-subject level, our investigation focuses on dynamic FC using resting-state functional MRI (rs-fMRI) and introduces the Generalized Auto-Regressive Conditional Heteroscedastic Dynamic Conditional Correlation (DCC-GARCH) model. Our findings demonstrate the superior sensitivity of DCC-GARCH to CSF A{beta} status, and offer key insights into dynamic functional connectivity analysis in AD.

neuroscience↗

bioRxiv2023

Xanthomonas rydalmerenesis sp. nov., a novel plant bacteria isolated from Fragaria x ananassa

We describe five bacterial isolates that were isolated from Fragaria x ananassa in 1976 in Rydalmere, Australia, during routine biosecurity surveillance. Initially, biochemical characterisation identified these isolates as members of the Xanthomonas genus. To determine their species, we conducted further analysis using both phenotypic and genotypic approaches. Phenotypic analysis involved using MALDI-TOF MS and BIOLOG GEN III microplates, which confirmed that the isolates belonged to the Xanthomonas genus but could not classify species. Genome relatedness indices and extensive phylogenetic analysis confirmed that the isolates belonged to the Xanthomonas genus and represented a new species. Based on the absence of virulence factors typically found in Xanthomonas spp. genomes, we suggest that these isolates are non-pathogenic. This conclusion was supported by a pathogenicity assay. Based on these findings, we propose the name Xanthomonas rydalmerenesis, with DAR34855 = ICMP24941 as the type strain.

genetics↗

bioRxiv2021

Dairy vs. beef production - expert views on welfare

Consumers views and concerns about the welfare of farm animals may play an important role in their decision to consume dairy, meat and/or plants as their primary protein source. As animals are killed prematurely in both dairy and beef industries, it is important to quantify and compare welfare compromise in these two sectors before the point of death. Seventy world-leading bovine welfare experts based in 23 countries, were asked to evaluate the likelihood of a bovine to experience 12 states of potential welfare concern, inspired by the Welfare Quality(R) protocol. The evaluation focused on the most common beef and dairy production systems in the experts country, and was carried out separately for dairy/beef calves raised for red-meat, dairy/beef calves raised for veal, dairy/beef calves raised as replacement, and for dairy/beef cows. The results show experts rated the overall likelihood of a negative welfare state (i.e. welfare risk) to be higher in animals from dairy herds than from beef herds, for all animal categories, regardless of whether they were used to produce milk, red-meat or veal. These findings suggest that consuming food products derived from common dairy production systems (dairy or meat), may be more harmful to the welfare of animals than consuming products derived from common beef production systems (i.e. from animals solely raised for their meat). Raising awareness about the linkage between dairy and meat production, and the toll of milk production on the welfare state of animals in the dairy industry, may encourage a more sustainable and responsible food consumption.

animal behavior and cognition↗

bioRxiv2020

Non-canonical autophagy drives alternative ATG8 conjugation to phosphatidylserine

Autophagy is a fundamental catabolic process essential for development, homeostasis and proper immune function 1. During autophagy, a cascade of ATG proteins target intracellular cargoes for lysosomal degradation and recycling 2. This pathway utilises a unique post-translational modification, the conjugation of ATG8 proteins to phosphatidylethanolamine (PE) at autophagosomes, which modulates cargo selection and maturation. ATG8 lipidation also occurs during non-canonical autophagy, a parallel pathway involving Single Membrane ATG8 Conjugation (SMAC) to endolysosomal compartments, which plays a key role in phagocytosis and other processes 3. It has been widely assumed that SMAC involves the same lipidation of ATG8 to PE, but this has yet to be formally tested. Here, we show that ATG8 undergoes alternative lipidation to phosphatidylserine (PS) during non-canonical autophagy/SMAC. Using mass spectrometry, we find that activation of SMAC, by pharmacological agents 4,5, or during non-canonical autophagy processes such as LC3-associated phagocytosis 6,7 and Influenza A virus infection 8, induces the covalent conjugation of ATG8 to PS, as well as PE. This alternative lipidation event is dependent on the ATG16L1 WD40 domain, and occurs at PS enriched endolysosomal membranes. Importantly, we find that the ATG8-PS and ATG8-PE adducts are differentially delipidated by isoforms of the ATG4 family, indicating significant molecular distinctions and mechanisms between these two species. Together, these results provide an important new insight into autophagy signalling, revealing an alternative form of the hallmark ATG8-lipidation event, so widely used to define and assay autophagy. Furthermore, ATG8-PS lipidation provides a specific molecular signature for non-canonical autophagy, uncovering a novel means of detecting and monitoring this emerging pathway.

cell biology↗

bioRxiv2019

The Gag Protein PEG10 Binds to RNA and Regulates Trophoblast Stem Cell Lineage Specification.

Peg10 (paternally expressed gene 10) is an imprinted gene that is essential for placental development. It is thought to derive from a Ty3-gyspy LTR (long terminal repeat) retrotransposon and retains Gag and Pol-like domains. Here we show that the Gag domain of PEG10 can promote vesicle budding similar to the HIV p24 Gag protein. Expressed in a subset of mouse endocrine organs in addition to the placenta, PEG10 was identified as a substrate of the deubiquitinating enzyme USP9X. Consistent with PEG10 having a critical role in placental development, PEG10-deficient trophoblast stem cells (TSCs) exhibited impaired differentiation into placental lineages. PEG10 expressed in wild-type, differentiating TSCs was bound to many cellular RNAs including Hbegf (Heparin-binding EGF-like growth factor), which is known to play an important role in placentation. Expression of Hbegf was reduced in PEG10-deficient TSCs suggesting that PEG10 might bind to and stabilize RNAs that are critical for normal placental development.

molecular biology↗