Biology subjects

Jeffries, A.

Publications and source records attributed to Jeffries, A..

7 recordsLinked to original sources

bioRxiv2026

Chromosome-level assembly of the Arabian killifish as a novel biomedical model species.

The Arabian killifish (Aphaniops dispar) is an excellent model for studying human diseases such as fungal infections and cancer progression. The embryos possess a transparent chorion for live imaging and display an extended period of independent feeding (13 days post-fertilisation). They also exhibit broad thermal tolerance which enables live imaging at physiologically relevant human temperatures. However, omics resources for this species remain limited and restricts its use in genomics studies. We generated a 1.45 GB high-quality reference assembly with 24 chromosome-level scaffolds and N50 score of 60.64 Mb by combining long-read, long-range, and short-read sequencing. The A. dispar genome exhibits a high level of homozygosity (95.6%) with BUSCO gene completeness scores of 99.2% and 97.5% for the Actinopterygii and Cyprinodontiformes lineages, respectively. The genome is highly repetitive (58.7%) and the majority of these are DNA transposons. The mitochondrial genome is 81.55% similar to that of Aphanius iberus (the Spanish toothcarp), with minor structural modifications. A. dispar exhibits highly conserved synteny with Fundulus heteroclitus within the Cyprinodontoidei clade. Together, these findings provide a valuable genomic resource for comparative genomics within the teleost community.

genomics↗

bioRxiv2026

Prophage and metabolic determinants of Staphylococcus aureus survival to vancomycin identified via TraDIS screening

Reduced vancomycin susceptibility phenotypes in Staphylococcus aureus contribute to treatment failure, yet the genetic determinants of survival under inhibitory vancomycin exposure remain incompletely defined. We performed transposon directed insertion-site sequencing (TraDIS) on a methicillin resistant S. aureus (MRSA) ST398 mutant library following exposure to vancomycin at its minimum inhibitory concentration, identifying 52 genes whose disruption was associated with loss of population survival at inhibitory drug concentrations. Prophage associated loci were the largest functional group, spanning predicted structural and regulatory genes as well as multiple conserved hypothetical proteins. Targeted testing of defined transposon mutants in a USA300 background confirmed that disruption of selected loci impaired growth under vancomycin exposure. Our results highlight the contribution of diverse physiological processes, including metabolism, stress responses, and a prominent role for prophage-associated functions, rather than discrete resistance pathways. Together, these findings indicate that vancomycin tolerance is shaped by the general physiological state of the bacterial cell, including metabolic capacity and stress adaptation. ImportanceTreatment failure in Staphylococcus aureus infections often occurs in the absence of known antibiotic resistance determinants, suggesting that additional survival mechanisms influence therapeutic outcomes. In this study, we identify genetic determinants required for survival during inhibitory vancomycin exposure, revealing a broad role for metabolic functions, stress adaptation, and prophage-associated loci. The prominence of these diverse processes highlights that survival reflects global physiological adaptation rather than discrete resistance pathways. This insight underscores the need to consider cellular physiology and stress responses when developing strategies to prevent antibiotic tolerance and improve treatment efficacy.

microbiology↗

bioRxiv2026

Yersinia pseudotuberculosis employs a multifaceted strategy to survive antimicrobials

Microbes have evolved a variety of strategies to survive exposure to naturally occurring and synthetic antimicrobials. These strategies have been investigated extensively in model bacterial organisms, whereas less is known about under explored pathogenic bacteria such as bacteria within the Yersinia genus. In this study we investigated the inhibitory effect and bactericidal activity of antibiotics from five different classes and of the disinfectant hydrogen peroxide against Yersinia pseudotuberculosis, the ancestral species from which Yersinia pestis and Yersinia enterocolitica have emerged. We found that Y. pseudotuberculosis is able to survive exposure to clinical antibiotics and disinfectants by employing a variety of strategies, with persisters and the Eagle effect playing a role in survival to quinolones, tolerance playing a role in survival to ceftriaxone and overexpression of catalases and peroxidases playing a role in survival to hydrogen peroxide. Our findings suggest that future research should focus on informing new, effective ways to treat infections caused by Yersinia species. IMPORTANCEAntimicrobial resistance is routinely investigated by measuring the minimum inhibitory concentration of antimicrobials needed to stop microbial growth. Here we show that the bacterial pathogen Yersinia pseudotuberculosis is not killed when antibiotics and disinfectants are used at these concentrations and that, in some cases, increasing antibiotic concentrations decreases their activity against this bacterium, therefore posing a potential risk to human and animal health.

microbiology↗

bioRxiv2024

A Framework to Identify Opportunities to Address Socioscientific Issues in the Elementary School Curricula: A Case Study from England, Italy, and Portugal

Scientific literacy is crucial to address important and complex societal problems, both current and future. Teaching using a socioscientific issues (SSI) approach is a potential strategy to develop students scientific literacy, although teachers have reported concerns about its implementation, such as the inability to add additional distinct requirements to already demanding curricula. To facilitate this task, we describe the development of a valid and reliable instrument for curricula analysis, called "Framework for Identifying Opportunities to implement an SSI approach in science school curricula" (FIOSSI), and use it to identify opportunities to implement the SSI approach in the elementary school science curriculum of three European countries (England, Italy and Portugal). The framework categorizes SSI opportunities into three areas: 1) awareness of the issue; 2) socioscientific reasoning; and 3) socioscientific identity. Our analyses of the three countries elementary curricula reveal that the current versions have significant opportunities to explore awareness of SSI (especially relating to environmental and human health issues), promote the development of socioscientific reasoning, and foster socioscientific identity. FIOSSI can be a useful tool for education research and practice, and our results can help inform future research and guide educational policies.

scientific communication and education↗

bioRxiv2023

In field use of water samples for genomic surveillance of ISKNV infecting tilapia fish in Lake Volta, Ghana

Viral outbreaks are a constant threat to aquaculture, limiting production for better global food security. A lack of diagnostic testing and monitoring in resource-limited areas hinders the capacity to respond rapidly to disease outbreaks and to prevent viral pathogens becoming endemic in fisheries productive waters. Recent developments in diagnostic testing for emerging viruses, however, offers a solution for rapid in situ monitoring of viral outbreaks. Genomic epidemiology has furthermore proven highly effective in detecting viral mutations involved in pathogenesis and assisting in resolving chains of transmission. Here, we demonstrate the application of an in-field epidemiological tool kit to track viral outbreaks in aquaculture on farms with reduced access to diagnostic labs, and with non-destructive sampling. Inspired by the "lab in a suitcase" approach used for genomic surveillance of human viral pathogens and wastewater monitoring of COVID19, we evaluated the feasibility of real-time genome sequencing surveillance of the fish pathogen, Infectious spleen and kidney necrosis virus (ISKNV) in Lake Volta. Viral fractions from water samples collected from cages holding Nile tilapia (Oreochromis niloticus) with suspected ongoing ISKNV infections were concentrated and used as a template for whole genome sequencing, using a previously developed tiled PCR method for ISKNV. Mutations in ISKNV in samples collected from the water surrounding the cages matched those collected from infected caged fish, illustrating that water samples can be used for detecting predominant ISKNV variants in an ongoing outbreak. This approach allows for the detection of ISKNV and tracking of the dynamics of variant frequencies, and may thus assist in guiding control measures for the rapid isolation and quarantine of infected farms and facilities.

genomics↗

bioRxiv2023

Phage-induced efflux down-regulation boosts antibiotic efficacy

The interactions between a virus and its host vary in space and time and are affected by the presence of molecules that alter the physiology of either the host or the virus. Determining the molecular mechanisms underpinning these interactions is paramount for predicting the fate of bacterial and phage populations and for designing rational phage-antibiotic therapies. We study the interactions between stationary phase Burkholderia thailandensis and the phage {Phi}Bp-AMP1. Although heterogeneous genetic resistance to phage rapidly emerges in B. thailandensis, the presence of phage enhances the efficacy of three major antibiotic classes, the quinolones, the beta-lactams and the tetracyclines, but antagonizes tetrahydrofolate synthesis inhibitors. We discovered that enhanced antibiotic efficacy is underpinned by reduced antibiotic efflux in the presence of phage. This new phage-antibiotic therapy allows for eradication of stationary phase bacteria, whilst requiring reduced antibiotic concentrations, which is crucial for treating infections in sites where it is difficult to achieve high antibiotic concentrations.

microbiology↗

bioRxiv2019

Transcriptional signatures of progressive neuropathology in transgenic tau and amyloid mouse models.

The onset and progression of Alzheimers disease (AD) is characterized by increasing intracellular aggregation of hyperphosphorylated tau protein and accumulation of {beta}-amyloid (A{beta}) in the neocortex. Despite recent success in identifying genetic risk factors for AD the transcriptional mechanisms involved in disease progression are not fully understood. We used transgenic mice harbouring human tau (rTg4510) and amyloid precursor protein (J20) mutations to investigate transcriptional changes associated with the development of both tau and amyloid pathology. Using highly-parallel RNA sequencing we profiled transcriptional variation in the entorhinal cortex at four time points identifying robust genotype-associated differences in entorhinal cortex gene expression in both models. We quantified neuropathological burden across multiple brain regions in the same individual mice, identifying widespread changes in gene expression paralleling the development of tau pathology in rTg4510 mice. Differentially expressed transcripts included genes associated with familial AD from genetic studies of human patients, and genes annotated to both common and rare variants identified in GWAS and exome-sequencing studies of late-onset sporadic AD. Systems-level analyses identified discrete co-expression networks associated with the progressive accumulation of tau, with these enriched for genes and pathways previously implicated in the neuro-immunological and neurodegenerative processes driving AD pathology. Finally, we report considerable overlap between tau-associated networks and AD-associated co-expression modules identified in the human cortex. Our data provide further support for an immune-response component in the accumulation of tau, and reveal novel molecular pathways associated with the progression of AD neuropathology.

genomics↗