Biology subjects

Ellis, K.

Publications and source records attributed to Ellis, K..

7 recordsLinked to original sources

bioRxiv2025

Characterising anthelmintic resistance against benzimidazoles and macrocyclic lactones in gastrointestinal nematode populations of dairy cattle

Anthelmintic resistance in gastrointestinal nematode populations is endemic across all grazing livestock production systems, particularly in small ruminants, but also in cattle. In this study resistance in Cooperia oncophora and Ostertagia ostertagi to macrocyclic lactones and benzimidazoles (BZ) in Scotland was assessed. The faecal egg count reduction test (FECRT) remains the primary tool for assessing anthelmintic resistance in the field; however, differing methodologies and recent guideline updates complicate the interpretation of results across studies. Statistical approaches, such as Bayesian methods used by eggCounts and bayescount, produce varying confidence intervals, which further influence conclusions. The ability of the egg hatch test to detect anthelmintic resistance was evaluated under field conditions, and the EC50 values obtained enabled assessment of the BZ efficacy at both the farm and GIN species levels, without the need for treatment. Mixed amplicon sequencing was applied, and nemabiome analysis confirmed that C. oncophora and Os. ostertagi were the predominant species. Sequencing of the beta-tubulin isotype-1 gene in strongyle communities identified resistance alleles in multiple species. The high EC values and elevated frequencies of BZ-resistance alleles on some farms emphasise the importance of in vitro assays and molecular diagnostics for farm-level resistance management. The detection of resistance against both benzimidazoles and macrocyclic lactones on certain farms highlights the urgency of implementing sustainable control strategies. Although the data presented here are from Scotland, given the high rate of animal movement and similar patterns of anthelmintic usage in the UK, these findings are likely to be relevant across much of the UK. Highlights- Resistance to MLs and BZs was detected in GIN populations of cattle - Multidrug resistance found in Scottish GIN populations of cattle - Egg hatch test results suggest, and sequencing confirms high BZ-resistance allele frequencies

microbiology↗

bioRxiv2024

USP50 suppresses alternative RecQ helicase use and deleterious DNA2 activity during replication.

Mammalian DNA replication employs several RecQ DNA helicases to orchestrate the faithful duplication of genetic information. Helicase function is often coupled to the activity of specific nucleases, but how helicase and nuclease activities are co-directed is unclear. Here we identify the inactive ubiquitin-specific protease, USP50, as a ubiquitin-binding and chromatin-associated protein required for ongoing replication, fork restart, telomere maintenance and cellular survival during replicative stress. USP50 supports WRN:FEN1 at stalled replication forks, suppresses MUS81-dependent fork collapse and restricts double-strand DNA breaks at GC-rich sequences. Surprisingly we find that cells depleted for USP50 and recovering from a replication block exhibit increased DNA2 and RECQL4 foci and that the defects in ongoing replication, poor fork restart and increased fork collapse seen in these cells are mediated by DNA2, RECQL4 and RECQL5. These data define a novel ubiquitin-dependent pathway that promotes the balance of helicase: nuclease use at ongoing and stalled replication forks.

cancer biology↗

bioRxiv2022

Differential Expression Enrichment Tool (DEET): an interactive atlas of human differential gene expression

Differential gene expression analysis using RNA sequencing (RNA-seq) data is a standard approach for making biological discoveries. Ongoing large-scale efforts to process and normalize publicly available gene expression data enable rapid and systematic reanalysis. While several powerful tools systematically process RNA-seq data, enabling their reanalysis, few resources systematically recompute differentially expressed genes (DEGs) generated from individual studies. We developed a robust differential expression analysis pipeline to recompute 3162 human DEG lists from The Cancer Genome Atlas, Genotype-Tissue Expression Consortium, and 142 studies within the Sequence Read Archive. After measuring the accuracy of the recomputed DEG lists, we built the Differential Expression Enrichment Tool (DEET), which enables users to interact with the recomputed DEG lists. DEET, available through CRAN and RShiny, systematically queries which of the recomputed DEG lists share similar genes, pathways, and TF targets to their own gene lists. DEET identifies relevant studies based on shared results with the users gene lists, aiding in hypothesis generation and data-driven literature review. HighlightsBy curating metadata from uniformly processed human RNA-seq studies, we created a database of 3162 differential expression analyses. These analyses include TCGA, GTEx, and 142 unique studies in SRA, involving 985 distinct experimental conditions. The Differential Expression Enrichment Tool (DEET) allows users to systematically compare their gene lists to this database.

bioinformatics↗

bioRxiv2021

Assessing the utility of marine filter feeders for environmental DNA (eDNA) biodiversity monitoring

Aquatic environmental DNA (eDNA) surveys are transforming how we monitor marine ecosystems. The time-consuming pre-processing step of active filtration, however, remains a bottleneck. Hence, new approaches omitting active filtration are in great demand. One exciting prospect is to use the filtering power of invertebrates to collect eDNA. While proof-of-concept has been achieved, comparative studies between aquatic and filter feeder eDNA signals are lacking. Here, we investigated the differences among four eDNA sources (water; bivalves; sponges; and ethanol in which filter-feeding organisms were stored) along a vertical transect in Doubtful Sound, New Zealand using three metabarcoding primers (fish (16S); MiFish-E/U). While concurrent SCUBA diver observations validated eDNA results, laboratory trials corroborated in-field bivalve eDNA detection results. Combined, eDNA sources detected 59 vertebrates, while divers observed eight fish species. There were no significant differences in alpha and beta diversity between water and sponge eDNA and both sources were highly correlated. Vertebrate eDNA was detected in ethanol, although only a reduced number of species were detected. Bivalves failed to reliably detect eDNA in both field and mesocosm experiments. While additional research into filter feeder eDNA accumulation efficiency is essential, our results provide strong evidence for the potential of incorporating sponges into eDNA surveys.

molecular biology↗

bioRxiv2021

Microglia-specific promoter activities of human HexB gene

Adeno-associated virus (AAV)-mediated genetic targeting of microglia remains challenging. Overcoming this hurdle is essential for gene editing in the central nervous system (CNS). Here, we characterized the minimal/native promoter of the HexB gene, which is known to be specifically and stably expressed in the microglia during homeostatic and pathological conditions. Dual reporter and serial deletion assays identified the critical role of the natural 5 untranslated region (-97 bp related to the first ATG) in driving transcriptional activity of the mouse HexB gene. The native promoter region of mouse, human and monkey HexB located at -135, -134 and -170 bp to the first ATG, respectively. These promoters were highly active and specific in microglia with strong cross-species transcriptional activities, but had no activities in primary astrocytes. In addition, we identified a 135 bp promoter of CD68 gene was also highly active in microglia but not in astrocytes. Considering that HexB is specifically expressed in microglia, not in monocytes/macrophages or other neuronal cells, these data suggest that the newly characterized 134 bp microglia-specific HexB promoter can be an ideal candidate for microglia-targeting AAV gene therapy, which could be developed for HIV eradication in the brain wherein microglia harbor the main HIV reservoirs in the CNS. SummaryIt is hard to overstate the importance of gene therapy that can remove viral genes from human cells. A cure for HIV would mean a lifetime free of treatment for patients who now must maintain a strict regimen of ART indefinitely. In order to develop a cure using AAV delivery, payload DNA must meet the AAV vector size limitations, and the payload genes must be expressed appropriately. Previous studies have identified microglia-specific HexB gene that shows stable expression during neural homeostasis and pathogenesis. Our study identified the essential HexB gene promoter (134 bp) as a strong candidate for AAV gene therapy to specifically target the brain microglia, the main cellular reservoirs of HIV in the central nervous system. Our studies continue to move us closer to identifying target-specific gene therapy for NeuroAIDS.

neuroscience↗

bioRxiv2019

The making of an olfactory specialist

The evolution of animal behaviour is poorly understood. Despite numerous correlations of behavioural and nervous system divergence, demonstration of the genetic basis of interspecific behavioural differences remains rare. Here we develop a novel neurogenetic model, Drosophila sechellia, a close cousin of D. melanogaster that displays profound behavioural changes linked to its extreme host fruit specialisation. Through calcium imaging, we identify olfactory pathways detecting host volatiles. Mutational analysis indicates roles for individual receptors in long- and short-range attraction. Cross-species allele transfer demonstrates that differential tuning of one receptor is important for species-specific behaviour. We identify the molecular determinants of this functional change, and characterise their behavioural significance and evolutionary origin. Circuit tracing reveals that receptor adaptations are accompanied by increased sensory pooling onto interneurons and novel central projection patterns. This work links molecular and neuronal changes to behavioural divergence and defines a powerful model for investigating nervous system evolution and speciation.

neuroscience↗

bioRxiv2018

Perceived threat bias and reduced hippocampal volume in combat veterans

BackgroundReduced hippocampal volume is frequently observed in posttraumatic stress disorder (PTSD), but the exact psychological processes associated with these alterations remain unclear. Given the role of the hippocampus in contextual representations of threat and memory, we investigated relationships between retrospectively reported combat exposure, perceived threat, and hippocampal volume in trauma-exposed veterans.\n\nMethodsT1-weighted anatomical MRI scans were obtained from 52 male veterans with a broad range of PTSD symptoms. Hippocampal volume was estimated using automatic segmentation tools in FreeSurfer. An index of perceived threat bias was calculated, reflecting the degree of discordance between subjective perceptions of threat while deployed and self-reported combat exposure. Hippocampal volume was regressed on perceived threat bias and PTSD symptoms on the Clinician-Administered PTSD Scale (CAPS).\n\nResultsPerceived threat bias was unrelated to overall CAPS symptoms, but was positively correlated with CAPS avoidance/numbing symptoms and symptoms of depression, anxiety, and worry. The degree of perceived threat bias was inversely correlated with hippocampal volume. Hippocampal volume was also inversely related to avoidance/numbing CAPS symptoms.\n\nConclusionsThese results indicate that volume of the hippocampus, a region involved in contextual threat processing and memory, is related to recalled associations between traumatic events and accompanying subjective threat appraisals. Future research should clarify the precise temporal milieu of these effects and investigate whether individual differences in hippocampal structure and function contribute to exaggerated threat appraisal at the time of trauma, or in subsequently biased memories or appraisals of traumatic events.

neuroscience↗