Biology subjects

Turvey, S.

Publications and source records attributed to Turvey, S..

5 recordsLinked to original sources

bioRxiv2026

Human breast milk extracellular vesicles from mothers with asthma differentially modulate the release of inflammatory cytokines by primary human airway smooth muscle cells in a recipient-cell specific manner

Breastfeeding provides health benefits in childhood, reducing the frequency of gastrointestinal and respiratory infections. Breastmilk (BM) is a rich source of bioactive molecules including extracellular vesicles (EVs), which exert immunomodulatory signalling in recipient cells, with cargo that is affected by maternal characteristics. Here we investigated the biophysical characteristics of BM-EVs from mothers with (asthmatic BM-EVs) or without asthma (control BM-EVs) and their effect on the release of cytokines from primary human hTERT-immortalized airway smooth muscle cells (hASMs) from asthmatic or non-asthmatic (control) donors. BM-EVs were isolated using size exclusion chromatography (N=5/group), characterized biophysically and by EV-specific protein markers. In addition, BM-EV were co-cultured (48h) with primary hASM cells from both non-asthmatic (control) and asthmatic donors to determine the effect on cytokine release. All participants were Caucasian and the BM was collected 12-15 weeks postpartum. BM-EVs showed the presence of intact and small-EVs ([~]100 nm). Asthmatic BM-EVs appeared to have a smaller average EV size (135.6 nm) vs. controls (148.3 nm, p=0.0613), but [~]5-fold higher concentration of both total (p=0.0014) and small EVs (p=0.0016). The expression of EV subtype protein expression was reduced in asthmatic BM-EVs vs. control BM-EVs: CD63 by 86% (p=0.0224), flotillin-1 by 40% (p=0.0196), CD9 by 24% (p=0.0646) and HSP70 by 69% (p=0.0873). Asthmatic BM-EVs co-cultured with hASMs from control donors decreased pro-inflammatory cytokine release: MCP-1 by 55% (p=0.0286), IL-6 by 45% (p=0.0801) and IL-2 by 32% (p=0.0970) vs. control-BM-EVs. Conversely, asthmatic BM-EVs co-cultured with hASMs from asthmatic donors increased secretion of anti-inflammatory cytokine IL-10 by 32% (p=0.0660), and IL-1Ra by 75% (p=0.0875), and pro-inflammatory IL-2 by 57% (p=0.0688) vs. control-BM-EVs. Internalization of control and asthmatic BM-EVs was confirmed by labelled EV uptake experiments. No detrimental effects on cell viability with BM-EV treatment were observed. In summary, asthmatic BM-EVs are smaller and enriched in BM, and exert differential effects on cytokine release in a BM-donor and recipient-cell specific manner. Given that BM can enter infant airways, the immunomodulatory effects of BM-EVs on hASMs warrants further investigation to delineate the under underlying mechanisms.

cell biology↗

bioRxiv2025

RAMEN: Dissecting individual, additive and interactive gene-environment contributions to DNA methylome variability in cord blood

DNA methylation (DNAme) is the most commonly studied epigenetic mark in human populations. DNAme has gained attention in the Developmental Origins of Health and Disease field due to its gene expression regulation and potential long-term stability. Genetic variation and environmental exposures are amongst the main factors influencing inter-individual DNAme variability. However, the proportion and genomic distribution of their individual, additive and interactive effects on the DNA methylome remains unclear. Here, we introduce RAMEN, a Findable, Accessible, Interoperable, and Reusable (FAIR) framework tailored for DNAme microarrays. Using machine learning and statistical techniques, RAMEN models and dissects gene-environment contributions to genome-wide Variably Methylated Regions (VMRs), while controlling for spurious associations. To comprehensively test the power of RAMEN, we analyzed and characterized VMRs from cord blood samples from two independent cohorts (CHILD and PREDO; overall n=1,662). We identified genetics as a consistent key contributor to DNAme variability, usually in additive and interactive combinations with the environment, with genetic terms explaining the largest proportion of DNAme variance, compared to environmental and interaction terms. Operationalizing RAMEN as an R package to conduct scalable genome-exposome contribution analyses, our results highlighted the importance of genetic variation in sculpting DNAme patterns in early life.

bioinformatics↗

bioRxiv2023

MAGinator enables strain-level quantification of de novo MAGs

MotivationMetagenomic sequencing has provided great advantages in the characterization of microbiomes, but currently available analysis tools lack the ability to combine strain-level taxonomic resolution and abundance estimation with functional profiling of assembled genomes. In order to define the microbiome and its associations with human health, improved tools are needed to enable comprehensive understanding of the microbial composition and elucidation of the phylogenetic and functional relationships between the microbes. ResultsHere, we present MAGinator, a freely available tool, tailored for the profiling of shotgun metagenomics datasets. MAGinator provides de novo identification of subspecies-level microbes and accurate abundance estimates of metagenome-assembled genomes (MAGs). MAGinator utilises the information from both gene- and contig-based methods yielding insight into both taxonomic profiles and the origin of genes as well as genetic content, used for inference of functional content of each sample by host organism. Additionally, MAGinator facilitates the reconstruction of phylogenetic relationships between the MAGs, providing a framework to identify clade-level differences within subspecies MAGs. Availability and implementationMAGinator is available as a Python module at https://github.com/Russel88/MAGinator ContactTrine Zachariasen, trine_zachariasen@hotmail.com

bioinformatics↗

bioRxiv2020

Consumption of artificially sweetened beverages during pregnancy impacts infant gut microbiota and body mass index

Artificial sweetener consumption by pregnant women has been associated with an increased risk of infant obesity, but the underlying mechanisms are unknown. We aimed to determine if maternal consumption of artificially sweetened beverages (ASB) during pregnancy is associated with modifications of infant gut bacterial community composition during the first year of life, and whether these alterations are linked with infant body mass index (BMI) at one year of age. This research included 100 infants from the prospective Canadian CHILD Cohort Study, selected based on maternal ASB consumption during pregnancy (50 non-consumers and 50 daily consumers). We identified four microbiome clusters, of which two recapitulated the maturation trajectory of the infant gut bacterial communities from immature to mature and two deviated from this trajectory. Maternal ASB consumption was associated with the depletion of several Bacteroides sp. and higher infant BMI. As we face an unprecedented rise in childhood obesity, future studies should evaluate the causal role of gut microbiota in the association between maternal ASB consumption, infant development and metabolism, and body composition.

microbiology↗

bioRxiv2019

Silencing cryptic specialized metabolism in Streptomyces by the nucleoid-associated protein Lsr2

Lsr2 is a nucleoid-associated protein conserved throughout the actinobacteria, including the antibiotic-producing Streptomyces. Streptomyces species encode paralogous Lsr2 proteins (Lsr2 and Lsr2-like, or LsrL), and we show here that of the two, Lsr2 has greater functional significance. We found that Lsr2 binds AT-rich sequences throughout the chromosome, and broadly represses gene expression. Strikingly, specialized metabolic clusters were over-represented amongst its targets, and the cryptic nature of many of these clusters appears to stem from Lsr2-mediated repression. Manipulating Lsr2 activity in model species and uncharacterized isolates resulted in the production of new metabolites not seen in wild type strains. Our results suggest that the transcriptional silencing of biosynthetic clusters by Lsr2 may protect Streptomyces from the inappropriate expression of specialized metabolites, and provide global control over Streptomyces arsenal of signalling and antagonistic compounds.

microbiology↗