Biology subjects

Harrington, C.

Publications and source records attributed to Harrington, C..

7 recordsLinked to original sources

bioRxiv2026

Single-time-point shotgun metagenomics of four Irish Integrated Constructed Wetlands reveals microbial dynamics in wastewater treatment.

Over the past 20 years, the Integrated Constructed Wetland (ICW) concept has been applied in Ireland for wastewater treatment, offering a nature-based solution for reducing pollutants and antimicrobial resistance genes (ARGs) in effluents and receiving environments. However, wastewater microbial communities remain inadequately characterized and their dynamics across treatment largely unexplored. Here, we present a culture-independent investigation of four Irish ICWs, aiming to advance our understanding of microbial dynamics in wastewater treatment. Shotgun metagenomic sequencing was conducted on influent and effluent samples collected in biological triplicates from four ICWs treating agricultural, companion animal, industrial, and municipal wastewater, alongside eight positive and ten negative controls for filtering and sequencing. End-to-end metagenomic analysis was performed with SqueezeMeta. Taxonomic placement of high-quality metagenome-assembled-genomes (HQ-MAGs) was confirmed with GTDB-Tk. Decontamination and statistical analyses were conducted in R. Coassembled contigs were screened for ARGs, virulence- and plasmid-associated sequences. Results revealed statistically significant shifts in taxonomic and functional profiles across treatment. Effluent populations exhibited generally higher richness than corresponding influents, yet were more similar to one another across locations. Multi-log-scale increases were observed in the relative abundance of environmental genera (Legionella, Methylotenera, Thiothrix), alongside reductions in common faecal/human indicators (Bacteroides, Lactococcus, Prevotella), and up to 80% ARGs removal. Collectively, our findings provide insights into ICW efficacy, showing that they can drive marked shifts in wastewater microbiome and ARG reduction. Our culture-independent approach retrieved 34 HQ-MAGs, including 19 potentially novel taxa, uncovering previously uncharacterized microbial diversity that is potentially unique to the Irish environment and warrants further investigation.

microbiology↗

bioRxiv2026

Social Context Suppresses Food Anticipatory Activity and Associated Thermoregulation in Mice

Food anticipatory activity (FAA) is a robust behavioral output of food-entrained circadian rhythms, characterized by increased locomotor activity prior to scheduled feeding. Despite the social nature of rodents, FAA is almost exclusively studied in singly housed animals, leaving the influence of social context largely unexplored. Here, we used implanted wireless devices to measure individual locomotor activity and subcutaneous body temperature in group-housed mice and compared these measures to singly housed controls. Social housing significantly suppressed FAA in both male and female mice, with the effect being more pronounced and sustained in males. In parallel, preprandial increases in body temperature were markedly attenuated in group-housed animals. These findings demonstrate that FAA is a flexible, state-dependent behavior that reflects both circadian timing and energetic demand. Together, these results identify social context as an important and underappreciated determinant of food-entrained circadian biology.

neuroscience↗

bioRxiv2025

A proteomic analysis of the PHF-forming tau fragment (tau297-391) following uptake into differentiated human neuronal SHSY5Y cells

Tau self-assembly and intracellular deposition is associated with a group of neurodegenerative diseases called tauopathies, which include Alzheimers disease (AD) and Picks disease. Here, we measured the proteome response in human neuronal cells (differentiated SH-SY5Y) following addition of a spontaneously amyloidogenic region of tau known as dGAE (tau297-391) which forms AD-like paired helical filaments in vitro and proteomic analysis showed increased endogenous tau expression. Further interactome analysis uncovered increased association between tau and proteins associated with nuclear chromatin, the nucleolus, and the spliceosome as well as the thiol-peroxidase, PRDX6 alongside an increase in reactive oxygen species (ROS). This work highlights a method to identify proteome pathways that may play an important role in the development of tau pathology.

cell biology↗

bioRxiv2025

PEDIA-BRAIN: A single nuclei multiomic encyclopedia of the human pons provides a resource for normal development and disease vulnerability

The human pons relays information between the brain and the body. It is affected by pathological processes, including diffuse midline gliomas (DMGs) and multiple sclerosis (MS) which predominantly arise in childhood and middle age, respectively. Although multiple studies address these disease states, a comprehensive resource for normal pons development is lacking. Here we present the first installment of PEDIA-BRAIN, an encyclopedia of gene expression and chromatin accessibility from 140,771 human pons nuclei spanning the first trimester to early adulthood, as a resource for the scientific community. Exploration of the encyclopedia identified two trajectories to mature oligodendrocytes and developmental restriction of genes for neuron to oligodendrocyte progenitor cell synapses. To illustrate the utility of the resource, we compared single cell transcriptomes from DMG and MS tissues to the encyclopedia and identified perturbation of oligodendrocyte subtypes in both diseases. Data may be accessed at https://pediabrain.nchgenomics.org.

neuroscience↗

bioRxiv2025

Inhibiting disulphide bonding in truncated tau297-391 results in enhanced self-assembly of tau into seed-competent assemblies.

Tau undergoes fibrillogenesis in a group of neurodegenerative diseases termed tauopathies. Each tauopathy is characterized by tau fibrils with disease-specific conformations, highlighting the complexity of tau self-assembly. This has led to debate surrounding the precise mechanisms that govern the self-assembly of tau in disease, especially the involvement of disulphide bonding (DSB) between cysteine residues. In this study, we use a truncated form of tau, dGAE, capable of forming filaments identical to those in disease. We reveal the impact of DSB in dGAE assembly and propagation by resolving the global mechanisms that dominate its assembly. We found evidence for surface-mediated secondary nucleation and fragmentation being active in dGAE assembly. The inhibition of DSB during dGAE assembly leads to an enhanced aggregation rate through a reduced lag phase, but with no effect on the global assembly mechanisms. We suggest this is due to the formation a dominant, seed-competent species in the absence of DSB that facilitates elongation and secondary nucleation resulting in enhanced assembly. In vitro seeding assays reveal the recruitment of endogenous tau in a cell model only when using dGAE species formed under conditions that inhibit DSB. Our results further support the use of the in vitro dGAE tau aggregation model for investigating the mechanism of tau assembly, the effect of varying conditions on tau assembly and how these conditions affect the resultant species. Further studies may utilise dGAE and its aggregates to investigate tau seeding, propagation and to highlight or test potential targets for therapies that reduce the spread of pathologic tau throughout the brain.

biochemistry↗

bioRxiv2022

Dityrosine cross-links are present in Alzheimer's disease-derived tau oligomers and paired helical filaments (PHF) which promotes the stability of PHF-core tau (297-391) in vitro.

A characteristic hallmark of Alzheimers Disease (AD) is the pathological aggregation and deposition of tau into paired helical filaments (PHF) in neurofibrillary tangles (NFTs). Oxidative stress is an early event during AD pathogenesis and is associated with tau-mediated AD pathology. Oxidative environments can result in the formation of covalent dityrosine crosslinks that can increase protein stability and insolubility. Dityrosine cross-linking has been shown to occur in vivo in A{beta} plaques and -synuclein aggregates in Lewy bodies, and this modification may increase the insolubility of these aggregates and their resistance to degradation. Using the PHF-core tau fragment (residues 297 - 391) as a model, we have previously demonstrated that dityrosine formation traps tau assemblies to reduce further elongation. However, it is unknown whether dityrosine crosslinks are found in tau deposits in vivo in AD and its relevance to disease mechanism is unclear. Here, using transmission electron microscope (TEM) double immunogold-labelling, we reveal that neurofibrillary NFTs in AD are heavily decorated with dityrosine crosslinks alongside tau. Single immunogold-labelling TEM and fluorescence spectroscopy revealed the presence of dityrosine on AD brain-derived tau oligomers and fibrils. Using the tau (297-391) PHF-core fragment as a model, we further showed that prefibrillar tau species are more amenable to dityrosine crosslinking than tau fibrils. Dityrosine formation results in heat and SDS stability of oxidised prefibrillar and fibrillar tau assemblies. This finding has implications for understanding the mechanism governing the insolubility and toxicity of tau assemblies in vivo.

biochemistry↗

bioRxiv2020

Oxidative stress conditions result in trapping of PHF-core tau (297-391) intermediates.

The self-assembly of tau into paired helical filaments (PHF) in neurofibrillary tangles (NFTs) is a significant event in Alzheimers disease (AD) pathogenesis. Oxidative stress, which accompanies AD, induces multiple post-translational modifications in proteins including the formation of dityrosine (DiY) cross-links, previously observed for A{beta}. Here, metal catalysed- and ultra-violet oxidation were used to study the influence of DiY cross-linking on the self-assembly of the PHF-core tau fragment. We report that DiY cross-linking facilitates tau assembly into tau oligomers and prevents their elongation into filaments. The DiY cross-linked tau oligomers were not toxic to cells. Our findings suggest that DiY cross-linking of pre-assembled tau, promotes the formation of soluble tau oligomers that show no acute toxicity.

biochemistry↗