Biology subjects

Haigh, R.

Publications and source records attributed to Haigh, R..

3 recordsLinked to original sources

bioRxiv2026

Genomic variation and ancestry of Helicobacter pylori in the admixed population of Cabo Verde reveal host adaptation, limited host-pathogen ancestry concordance, and signatures of trans-Atlantic slave trade migrations

The genomic structure of the stomach-colonising, gastric cancer-associated bacterium Helicobacter pylori mirrors human evolutionary history, making it difficult to disentangle shared ancestry from true host-pathogen interactions driving disease risk. Recently admixed populations offer opportunities for new coevolutionary trajectories between H. pylori and its host that may disrupt parallel evolution. Here, we analyse host H. pylori IgG, blood serum biomarkers, and paired host-bacterial genomic data from the general population (independent of dyspepsia symptoms) of Cabo Verde. Seropositivity is high (82.8%), as in neighbouring African populations. Serum biomarkers indicate that this unique cohort mainly comprises hosts with limited gastric inflammation. Genomic analyses show that Cabo Verdean H. pylori derive European (hspSWeurope) and West African (hspAfrica1WAfrica) ancestry. The delineation of a reference dataset that includes new strains from Ghana and Portugal, uncovered a distinct West-Central African cluster (hspAfrica1WCAfrica). This dataset allowed inference of within-Africa and within-Europe ancestries in Cabo Verdean and American strains that reflect historical migrations linked to European colonisation and the trans-Atlantic Slave Trade. European strains in Cabo Verde show additional population structure, including two low-diversity clusters. Approximate Bayesian Computation (ABC) inference indicates that the most common cluster represents a clonal expansion, likely driven by host adaptation leading to increased transmission within Cabo Verde. Notably, these strains lack known virulence genes and show significant divergence from gastric cancer strains. Finally, host and bacterial ancestry are uncoupled, indicating disruption of ancestral parallel evolution. Cabo Verde, therefore, provides a unique natural model for studying host-pathogen interactions underlying susceptibility to H. pylori.

evolutionary biology↗

bioRxiv2022

CD98 is critical for a conserved inflammatory response to diverse injury stimuli relevant to IPF exacerbations and COVID pneumonitis

Progressive fibrosing interstitial lung diseases (PFILDs) cause substantial morbidity and mortality. Antifibrotic agents slow progression, but most of the clinical need remains unmet. The archetypal PFILD is idiopathic pulmonary fibrosis (IPF). Chronic progression is driven by transforming growth factor (TGF-){beta}1 signalling. It is punctuated by inflammatory flares known as acute exacerbations (AE-IPF), which are associated with accelerated decline and high mortality. We hypothesized that acute injury responses underlying exacerbations and the mechanisms of chronic fibrosis overlap at the molecular level, via a cell surface assembly nucleated by galectin-3 that we term the gal-3-fibrosome. We focused upon a putative pro-inflammatory galectin-3 ligand, the CD98:integrin complex. Our data indicate CD98 and {beta}1-integrin co-localise with galectin-3 within epithelial cells in IPF lung tissue, and within 40 nm in human lung tissue treated with TGF-{beta}1 compared to controls. CD98 is required for interleukin (IL-)6 and IL-8 responses to biochemical and biophysical conditions mimicking stimuli of AE-IPF in vivo, ex vivo and in cells, and for an interstitial neutrophilic response in a mouse model. We demonstrate this pathway progresses via intracellular influx of Ca2+ mediated by TRPV4, and NF-{kappa}B activation, operating in positive feedback. Lastly we show the CD98- and galectin-3-dependence of IL-6 and IL-8 responses to the SARS-CoV-2 spike protein receptor binding domain and the conservation of this response pattern between lung epithelial cells and monocyte-derived macrophages. Taken together our findings identify CD98 as a key mediator of both pro-fibrotic and acute inflammatory responses in the lung with relevance to AE- and chronic progression of IPF, and the priming of fibrotic lungs for acute inflammatory responses. They similarly implicate CD98 and galectin-3 as mediators of COVID pneumonitis and worse outcomes in ILD patients with COVID.

cell biology↗

bioRxiv2021

Trends in Pacific Canadian groundfish stock status

We assembled estimated biomass (B) time series from stock assessments for 24 Pacific Canadian groundfish stocks and modelled average and stock status through 2020 based on biomass relative to each stocks (1) Limit Reference Point (B/LRP), (2) Upper Stock Reference (B/USR), and (3) biomass at maximum sustainable yield (B/BMSY). The overall mean B/LRP in 2020 was 3.2 (95% credible interval [CI]: 2.6-3.9). The overall mean B/USR and B/BMSY in 2020 was 1.5 (95% CI: 1.3-1.9) and 1.4 (95% CI: 1.1-1.7), respectively. Average stock status declined from 1950 to around 2000 and has remained relatively stable since then. The change around 2000 followed the implementation of ITQs (individual transferable quotas) for the trawl fleet and the commencement of the synoptic trawl surveys. As of their last assessment, four stocks (Strait of Georgia Lingcod [Area 4B], coastwide Bocaccio, and inside and outside Quillback Rockfish) had a greater than 5% probability of being below their LRP (i.e., in the " critical zone"); Pacific Cod in Area 3CD had a 4.6% probability. Roughly one-third of stocks had a greater than 1 in 4 chance of being below their USR (i.e., in the " cautious zone"). Conversely, two-thirds of assessed groundfish stocks had a high (>75%) probability of being above the USR (i.e., in the " healthy zone").

ecology↗