Biology subjects

Proctor, G. B.

Publications and source records attributed to Proctor, G. B..

4 recordsLinked to original sources

bioRxiv2023

Gate keeping the sebaceous gland.

Sebaceous gland (SG) secretions are pivotal to skin and eye health. At the SG-epidermis confluence is an overlooked epidermal collar we named the follicular epidermis (FE). Here, we show that the FE is similar among different SG types and contains unique Axin2+ stem cells in a niche at its basal FE-perpendicular flexure (FE-PF). Lineage tracing and ablation assays demonstrate Axin2+ cells as integral for FE homeostasis. Wnt-secretion arrest experiments resulted in FE-obstruction via hyperproliferation and inhibited differentiation inferring FE-PF Axin2+ cells are Wnt-producers maintaining FE-patency. Upon constitutive Axin2+ cell Wnt signalling, FE-PF-specific cell proliferation with early-stage signs of malignancy formed alongside a keratin-plugging FE-obstruction type. While keratin-based obstructions are recognized, inhibited differentiation obstructions are not, which suggests a one-size-fits-all therapeutic approach is not optimal. We offer a molecular identification toolkit to aid anti-obstruction advances in dermatology/ophthalmology and highlight the FE-PF as a skin tumorigenic site. SummaryThis work characterises a novel site in the skin, its stem cells and niche, a site prone to cancer. Obstructions can occur at this site by two mechanisms, one of which is novel, bringing into question current therapy and prompting a rethink of disease in dermatology and ophthalmology to account for this novel site. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=133 HEIGHT=200 SRC="FIGDIR/small/554243v1_ufig1.gif" ALT="Figure 1"> View larger version (40K): org.highwire.dtl.DTLVardef@19ebe94org.highwire.dtl.DTLVardef@f1ef95org.highwire.dtl.DTLVardef@1a846aaorg.highwire.dtl.DTLVardef@b75322_HPS_FORMAT_FIGEXP M_FIG C_FIG

molecular biology↗

bioRxiv2021

The Reactobiome Unravels a New Paradigm in Human Gut Microbiome Metabolism

Changes in microbial metabolism have been used as the main approach to assess function and elucidate environmental and host-microbiome interactions. This can be hampered by uncharacterised metagenome species and lack of metabolic annotation. To address this, we present a comprehensive computational platform for population stratification based on microbiome composition, the underlying metabolic potential and generation of metagenome species and community level metabolic models. We revisit the concepts of enterotype and microbiome richness introducing the reactobiome as a stratification method to unravel the metabolic features of the human gut microbiome. The reactobiome encapsulates resilience and microbiome dysbiosis at a functional level. We describe five reactotypes in healthy populations from 16 countries, with specific amino acid, carbohydrate and xenobiotic metabolic features. The validity of the approach was tested to unravel host-microbiome and environmental interactions by applying the reactobiome analysis on a one-year Swedish longitudinal cohort, integrating gut metagenomics, plasma metabolomics and clinical data.

systems biology↗

bioRxiv2020

Agonists of orally expressed TRP channels stimulate salivary secretion and modify the salivary proteome

Natural compounds that can stimulate salivary secretion are of interest in developing treatments for xerostomia, the perception of a dry mouth, that affects between 10 and 30% of the adult and elderly population. Chemesthetic transient receptor potential (TRP) channels are expressed in the surface of the oral mucosa. The TRPV1 agonists capsaicin and piperine have been shown to increase salivary flow when introduced into the oral cavity but the sialogogic properties of other TRP channel agonists have not been investigated. In this study we have determined the influence of different TRP channel agonists on the flow and protein composition of saliva.Mouth rinsing with the TRPV1 agonist nonivamide or menthol, a TRPM8 agonist, increased whole mouth saliva (WMS) flow and total protein secretion compared to unstimulated saliva, the vehicle control mouth rinse or cinnamaldehyde, a TRPA1 agonist. Nonivamide also increased the flow of labial minor gland saliva but parotid saliva flow rate was not increased. The influence of TRP channel agonists on the composition and function of the salivary proteome was investigated using a multi-batch quantitative mass spectrometry method novel to salivary proteomics. Inter-personal and inter-mouth rinse variation was observed in the secreted proteomes and, using a novel bioinformatics method, inter-day variation was identified with some of the mouth rinses. Significant changes in specific salivary proteins were identified after all mouth rinses. In the case of nonivamide, these changes were attributed to functional shifts in the WMS secreted, primarily the over representation of salivary and non-salivary cystatins which was confirmed by immunoassay.This study provides new evidence of the impact of TRP channel agonists on the salivary proteome and the stimulation of salivary secretion by a TRPM8 channel agonist, which suggests that TRP channel agonists are potential candidates for developing treatments for sufferers of xerostomia.AbbreviationsCARD10CAspase Recruitment Domain-containing protein 10DTTDiThioThreitolLC-MS/MSLiquid Chromatography - tandem Mass SpectrometryGOGene OntologyIEFIsoElectric FocusingLDSLithium Dodecyl SulphateMSMass SpectrometryPGPropylene GlycolPGK1PhosphoGlycerate Kinase 1TCEPTris (2-CarboxyEthyl) PhosphineTEABTriEthylAmmonium BicarbonateTMTTandem Mass TagTRPTransient Receptor PotentialTRPA1Transient Receptor Potential cation channel, subfamily A, member 1TRPM8Transient Receptor Potential cation channel subfamily M member 8TRPV1Transient Receptor Potential cation channel subfamily V member 1WMSWhole Mouth SalivaUWMSUnstimulated Whole Mouth SalivaView Full Text

physiology↗

bioRxiv2019

Abundance and diversity of resistomes differ between healthy human oral cavities and gut

The global threat of the \"antimicrobial resistance apocalypse\" that has arisen in recent years has driven the use of high-throughput sequencing techniques to monitor the profile of resistance genes, known as the \"resistome\", in microbial populations. The human oral cavity contains a poorly explored reservoir of these genes, and little is known about their abundance and diversity, or how their profile compares with antimicrobial resistance genes in the gut. Here we analyse the resistome profiles of 788 oral cavities worldwide and compare these profiles with paired stool samples from shotgun metagenomic data. We find country and body site-specific differences in the prevalence of antimicrobial resistance genes, classes and mechanisms in oral and stool samples. However, the abundance of these antimicrobial resistance classes do not correlate with antibiotic prescription rates. A greater similarity was found in interpersonal resistomes between the same body sites than intrapersonal resistomes across different body sites. Between individuals, the oral cavity contains the highest and lowest abundances of specific antimicrobial resistance genes, but a lower diversity of resistance genes compared to the gut, which is likely influenced by differences in microbial composition and exposure to antimicrobial selection pressures. Co-occurrence analysis shows contrasting ARG-species associations between saliva and stool samples. This is the first study to date that characterises the oral cavity resistome worldwide, identifying its distinctive signatures compared to the gut.Maintenance and persistence of antimicrobial resistance is likely to vary across different body sites. Thus, we highlight the importance of characterising the resistome across body sites to uncover the antimicrobial resistance potential in the human body.

microbiology↗