Biology subjects

Grant, K.

Publications and source records attributed to Grant, K..

4 recordsLinked to original sources

bioRxiv2026

Polystyrene microplastics uptake drives Inflammatory, Epitranscriptomic, and Metabolic Reprogramming in Human aortic endothelial cells

Microplastics (MPLs) are pervasive environmental pollutants increasingly linked to adverse human health outcomes, including atherosclerosis. However, the underlying mechanisms remain poorly understood. Human aortic endothelial cells (HAECs), which line the inner surface of blood vessels, play a critical role in maintaining vascular homeostasis and in the development of atherosclerosis. This study demonstrates that polystyrene microplastics enter HAECs through clathrin-mediated endocytosis and macropinocytosis and subsequently co-localize with mitochondria and lysosomes. Exposure to MPLs induced coordinated transcriptional, epitranscriptomic, and metabolomic reprogramming in HAECs. Transcriptomic analysis revealed disruption of mitochondrial genes and activation of inflammatory pathways with the response of the NF-{kappa}B pathway being particularly prominent. Mass spectrometry analysis of RNA modification further identified significant remodeling of the epitranscriptomic landscape, highlighted by increased 1-methyladenosine (m1A) modification and reciprocal regulation of its associated enzymes (TRMT61A upregulation and ALKBH3 suppression), along with alterations in other RNA modifications such as m3C, pseudouridine ({Psi}), m5C, and m7G. Comparative analysis of transcriptomic profiles from human atherosclerotic plaques revealed shared dysregulated pathways in vascular regulation and cellular signaling. Metabolomic profiling further showed extensive remodeling of lipid metabolic networks associated with oxidative stress and inflammation. Together, these findings suggest that MPLs exposure may disrupt endothelial function and pose a potential risk to human cardiovascular health. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=141 SRC="FIGDIR/small/737624v2_ufig1.gif" ALT="Figure 1"> View larger version (34K): org.highwire.dtl.DTLVardef@2ad601org.highwire.dtl.DTLVardef@47f041org.highwire.dtl.DTLVardef@ee45cdorg.highwire.dtl.DTLVardef@128d6d5_HPS_FORMAT_FIGEXP M_FIG C_FIG

molecular biology↗

bioRxiv2020

Phylogeny of docks and sorrels (Rumex, Polygonaceae) reveals plasticity of reproductive systems

The genus Rumex is a unique member of the Polygonaceae (Buckwheat) family of plants. A source of intrigue for Rumex lies in the diversity of the reproductive systems associated with the subgenera, species, and subspecies within this genus. Four previously circumscribed subgenera, some 200 species, and a number of subspecies comprise the collective Rumex genus. These species exhibit monoecious, dioecious, synoecious (hermaphroditic), and polygamous reproductive systems. Moreover, some of the dioecious species contain sex chromosomes, a phenomenon that is very rare in angiosperms. Apart from the confirmed morphological and phytogeographical distinctions, two of the four described subgenera, Acetosa and Acetosella, are distinctive in their exhibited sex chromosome systems. For this study, we used three chloroplast markers, rbcL, trnH-psbA, trnL-F, and dense taxon sampling, to reconstruct a molecular phylogeny for Rumex.The reconstructed phylogeny for this work resolves six major clades and one large grade in Rumex. In addition, the species with known dioecious reproductive systems derived from unique sex chromosome systems are resolved in two different clades nested within "the dioecious clade". These results suggest that the species with divergent sexual systems are more closely related to each other than to other species comprising the rest of the Rumex genus. Furthermore, some species with known synoecious reproductive systems are resolved in a single clade which is also nested within "the dioecious clade". These results imply a possible reversal occurring over time which suggests the highly plastic nature of reproductive systems among Rumex species.

plant biology↗

bioRxiv2019

A real-time PCR for the differentiation of typhoidal and non-typhoidal Salmonella

Rapid and accurate differentiation of Salmonella spp. causing enteric fever from non-typhoidal Salmonella is essential for clinical management of cases, laboratory risk management and implementation of public health measures. Current methods used for confirmation of identification including biochemistry and serotyping as well as whole genome sequencing analyses, takes several days. Here we report the development and evaluation of a real-time PCR assay that can be performed directly on crude DNA extracts from bacterial colonies, for the rapid identification of typhoidal and non-typhoidal Salmonella. This novel two-hour assay identifies the genus Salmonella by detecting the ttr gene, encoding tetrathionate reductase, and defines typhoidal Salmonella by the detection of S. Typhi and Paratyphi-specific gene combinations. PCR assay performance was determined using 211 clinical cultures of Salmonella (114 non-typhoidal and 97 Typhoidal strains) and 7 clinical non-Salmonella cultures. In addition, the specificity of the assay was evaluated in silico using a diverse in-house collection of 1882 Salmonella whole genome sequences. The real-time PCR results for 218 isolates and the genomic analysis of the 1882 isolates produced 100% sensitivity and 100% specificity (based on a 7 gene profile) for identifying typhoidal Salmonella compared to the Salmonella whole genome sequening identification methods currently used at Public Health England. This paper describes a robust real-time PCR assay for the rapid, accurate identification of typhoidal and non-typhoidal Salmonella which will be invaluable for the urgent screening of isolates from symptomatic individuals, the safe processing of isolates in laboratories and for assisting the management of public health risks.

microbiology↗

bioRxiv2017

SnapperDB: A database solution for routine sequencing analysis of bacterial isolates

Real-time surveillance of infectious disease using whole genome sequencing data poses challenges in both result generation and communication. SnapperDB represents a set of tools to store bacterial variant data and facilitate reproducible and scalable analysis of bacterial populations. We also introduce the SNP address nomenclature to describe the relationship between isolates in a population to the single nucleotide resolution.\n\nSummaryWe announce the release of SnapperDB v1.0 a program for scalable routine SNP analysis and storage of microbial populations.\n\nAvailabilitySnapperDB is implemented as a python application under the open source BSD license. All code and user guides are available at https://github.com/phe-bioinformatics/snapperdb.\n\nContacttim.dallman@phe.gov.uk\n\nSupplementary informationSupplementary data are available at Bioinformatics online.

bioinformatics↗