Biology subjects

Davies, T.

Publications and source records attributed to Davies, T..

12 recordsLinked to original sources

bioRxiv2026

The Effect of Plosive Content on the Loudness Perception of Vowel-Consonant-Vowel Syllables in Listeners with Sensorineural Hearing Loss

Objective: This study investigated whether plosive consonants carry a perceptual loudness weighting that significantly exceeds that of non-plosive consonants when judged by hearing-impaired listeners. Design: A prospective loudness matching experiment utilizing the method of adjustment. Study Sample: 19 consenting native English speakers (Mean age: 61.4, SD: 16.4) with bilateral mild to moderate high-frequency sensorineural hearing loss, indicative of presbycusis. Stimuli: 13 vowel-consonant-vowel (VCV) nonsense syllables, exclusively utilizing the flanking vowel /u/. Results: Descriptive analysis revealed a strong time-order effect influencing loudness judgments for 7 of the 13 VCV test stimuli. Statistical testing showed no significant didference (P = 0.94) between the relative amplitudes corresponding to the point of equal loudness for plosive-containing versus non-plosive-containing VCV stimuli. However, 6 individual VCV stimuli, containing consonants from 4 separate manners of articulation, produced significant loudness matching data (P < 0.01). Conclusions: The results falsify the hypothesis that plosives, analyzed collectively as a class, possess a heavier perceptual loudness weighting than non-plosive consonants. While 6 individual VCV stimuli indicated potential individual consonantal loudness weightings, these findings must be interpreted cautiously due to the restriction to a single vowel context and the presence of procedural time-order biases.

neuroscience↗

bioRxiv2026

Invertebrate species produce taxon-specific acoustic profiles under controlled conditions

Soil degradation threatens food security, climate regulation, biodiversity and human wellbeing worldwide. Up to 75% of the worlds soils are already degraded, and in response, global restoration efforts are rapidly scaling up to meet international targets. Monitoring soil biodiversity recovery remains a major barrier to tracking restoration success, particularly for invertebrates that underpin key processes including nutrient cycling and soil aggregation. Traditional sampling methods are labour-intensive, destructive and poorly suited to long-term or landscape-scale monitoring. Soil ecoacoustics is rapidly emerging as a promising non-destructive soil biodiversity monitoring tool. However, its capacity for taxonomic resolution of invertebrate groups remains untested. Here, we present a proof-of-concept study that establishes the potential for a soil invertebrate acoustic classifier. We used a low-cost, sound-attenuated recording system and quantified 19 spectral and temporal audio features from six morphologically and behaviourally distinct invertebrate species under controlled conditions. Acoustic profiles differed among taxa and generally clustered into podous and apodous groups (i.e., organisms with legs versus those without). Variation was driven primarily by taxon identity rather than body mass, suggesting that acoustic signatures capture taxon-specific traits. This work provides a foundation for developing automated acoustic classifiers that could enable scalable, non-destructive soil biodiversity monitoring.

ecology↗

bioRxiv2025

Cryptococcus neoformans employs both PP1 and PP2A phosphatases to silence the spindle checkpoint

The spindle checkpoint preserves genomic integrity by delaying anaphase onset until all kinetochores achieve bi-polar microtubule attachment. While checkpoint activation is well-characterised across eukaryotes, the mechanisms governing its silencing remain less defined and are more variable in different systems. In this study, we reveal that the fungal pathogen Cryptococcus neoformans employs a dual phosphatase-mediated mechanism to silence the spindle checkpoint. We show that PP1 is recruited to kinetochores by Spc105KNL1, via conserved SILK and RVSF motifs, while PP2A-B56 is recruited to kinetochores through direct Bub1 binding via an LxxIxE motif. Disruption of either recruitment pathway leads to prolonged checkpoint signalling and mitotic defects, underscoring the critical roles of these phosphatases in checkpoint silencing and mitotic exit. These findings further establish C. neoformans as a powerful model for studying mitotic regulation in the basidiomycete lineage and identify phosphatase recruitment interfaces as potential targets for antifungal intervention.

cell biology↗

bioRxiv2024

Comparing diploid and triploid apples from a diverse collection

Apples (Malus X. domestica Borkh.) are an economically important fruit species and the focus of continuing breeding efforts around the world. While most apple varieties are diploid, ploidy levels vary across the species, and triploids may be used in breeding despite poor fertility. The impact of ploidy on agricultural traits in apple is not well understood but is an important factor to consider when breeding new apple varieties. Here, we use mean heterozygosity values to categorize 970 apple accessions as diploid or triploid and then contrast apples of varying ploidy levels across 10 agriculturally important traits with sample sizes ranging from 427 to 928 accessions. After correction for multiple testing, we determine that triploids have significantly higher phenolic content. By examining historical release dates for apple varieties, our findings suggest that contemporary breeding programs are primarily releasing diploid varieties, and triploids tend to be older varieties. Ultimately, our results suggest that phenotypic differences between diploids and triploids are subtle and often insignificant indicating that triploids may not provide substantial benefit above diploids to apple breeding programs.

plant biology↗

bioRxiv2023

Energetic driving force for LHCII clustering in plant membranes

Plants protect themselves against photodamage from excess energy using a process known as non-photochemical quenching (NPQ). A significant fraction of NPQ is induced by a {Delta}pH across the membrane, which changes the conformation, composition, and organization of the antenna complexes. In particular, clustering of the major light-harvesting complex (LHCII) has been observed, yet the thermodynamic driving force behind this reorganization has not been determined, largely because measurements of membrane protein interaction energies have not been possible. Here, we introduce a method to quantify membrane protein interaction energies and its application to the thermodynamics of LHCII clusters. By combining single-molecule measurements of LHCII-proteoliposomes at different protein densities and a rigorous analysis of LHCII clusters and photophysics, we quantified the LHCII-LHCII interaction energy to be approximately -5 kBT at neutral pH and at least -7 kBT at acidic pH. From these values, we found the thermodynamic driving force for LHCII clustering was dominated by these enthalpic contributions. Collectively, this work captures the membrane protein-protein interactions responsible for LHCII clustering from the perspective of equilibrium statistical thermodynamics, which has a long and rich tradition in biology.

biophysics↗

bioRxiv2023

mps1 and mad mutations reduce Cryptococcus neoformans titan cell viability

Cryptococcus neoformans is an opportunistic, human fungal pathogen which undergoes fascinating switches in cell cycle control and ploidy when it encounters stressful environments such as the human lung. Here we carry out a mechanistic analysis of the spindle assembly checkpoint (SAC) which regulates the metaphase to anaphase transition, focusing on Mps1 kinase and the downstream checkpoint components Mad1 and Mad2. We demonstrate that Cryptococcus mad1{Delta} or mad2{Delta} strains are unable to respond to microtubule perturbations, continuing to re-bud and divide, and die rapidly as a consequence. Fluorescent tagging of Chromosome 3, using a lacO array and mNeonGreen-lacI fusion protein, demonstrates that mad mutants are unable to maintain sister-chromatid cohesion in the absence of microtubule polymers. Thus, the classic checkpoint functions of the SAC are conserved in Cryptococcus. In interphase, GFP-Mad1 is enriched at the nuclear periphery, and it is recruited to unattached kinetochores in mitosis. Purification of GFP-Mad1 followed by mass spectrometric analysis of associated proteins show that that it forms a complex with Mad2 and that it interacts with other checkpoint signalling components (Bub1) and effectors (Cdc20 and APC/C sub-units) in mitosis. We also demonstrate that overexpression of Mps1 kinase is sufficient to arrest Cryptococcus cells in mitosis, and show that this arrest is dependent on both Mad1 and Mad2. We find that a C-terminal fragment of Mad1 is an effective in vitro substrate for Mps1 kinase and map several Mad1 phosphorylation sites. Some sites are highly conserved within the C-terminal Mad1 structure and we demonstrate that mutation of threonine 667 (T667A) leads to loss of checkpoint signalling and abrogation of the GAL-MPS1 arrest. Thus Mps1-dependent phosphorylation of C-terminal Mad1 residues is a critical step in Cryptococcus spindle checkpoint signalling. Finally, we analyse the phenotype of mad and mps1 mutants during titan cell generation: quantitating viability of titan cells and their daughters generated during the ensuing reductive division. The mad1{Delta}, mad2{Delta} and mps{Delta} mutants show significantly reduced viability: many titans are dead and others produce slow growing colonies. We propose that these Cryptococcus neoformans checkpoint proteins have important roles in ensuring high fidelity chromosome segregation during stressful conditions, such that those heightened during its polyploid infection cycle.

cell biology↗

bioRxiv2022

Bub1 kinase acts as a signalling hub for the entire Cryptococcus neoformans spindle assembly checkpoint pathway

Cryptococcus neoformans (Cn) is an important human pathogen and a model system for basidiomycetes. Here we carry out a dissection of its spindle assembly checkpoint (SAC), focusing on Bub1 and Bub3. In many eukaryotes, including humans, Saccharomyces cerevisiae and Schizosaccharomyces pombe, Bub1 underwent gene duplication, generating paralogues referred to as Bub1 and BubR1 (or Mad3). Bub1 has upstream signalling functions at kinetochores, whilst BubR1/Mad3 is a component of the downstream mitotic checkpoint complex (MCC) that delays anaphase onset until all chromosomes are correctly attached. Here we demonstrate that the single CnBub1 protein carries out all the checkpoint roles of both Bub1 kinase and Mad3/BubR1. Proteomic analysis reveals kinetochore targeting via Spc105KNL1 and interactions with all downstream SAC components and effectors (Cdc20 and the anaphase promoting complex/cyclosome). We demonstrate that CnBub1 kinase activity is required to maintain prolonged checkpoint arrest. Thus CnBub1 acts as a SAC signalling hub and is a future target for anti-mitotic drugs.

cell biology↗

bioRxiv2022

Diet suppresses tumour initiation by maintaining quiescence of mutation-bearing neural stem cells

Glioblastoma is thought to originate from neural stem cells (NSCs) of the subventricular zone that acquire genetic alterations. In the adult brain, NSCs are largely quiescent, suggesting that deregulation of quiescence maintenance may be a pre-requisite for tumour initiation. Although inactivation of the tumour suppressor p53 is a frequent event in gliomagenesis, whether, or how, it affects quiescent NSCs (qNSCs) remains unclear. Here we show that p53 maintains quiescence by inducing fatty acid oxidation (FAO) and that acute p53 deletion in qNSCs results in their premature activation to a proliferative state. Mechanistically, this occurs through direct transcriptional induction of PPARGC1a, which in turn activates PPAR to upregulate FAO genes. Strikingly, dietary supplementation with fish oil containing omega-3 fatty acids, natural PPAR ligands, fully restores quiescence of p53-deficient NSCs and delays tumour initiation in a glioblastoma mouse model. Thus, diet can silence glioblastoma driver mutations, with important implications for cancer prevention.

cancer biology↗

bioRxiv2021

Phenotypic divergence between the cultivated apple (Malus domestica) and its primary wild progenitor (Malus sieversii)

An understanding of the relationship between the cultivated apple (Malus domestica) and its primary wild progenitor species (M. sieversii) not only provides an understanding of how apples have been improved in the past, but may be useful for apple improvement in the future. We measured 10 phenotypes in over 1000 unique apple accessions belonging to M. domestica and M. sieversii from Canadas Apple Biodiversity Collection. Using principal components analysis (PCA), we determined that M. domestica and M. sieversii differ significantly in phenotypic space and are nearly completely distinguishable as two separate groups. We found that M. domestica had a shorter juvenile phase than M. sieversii and that cultivated trees produced flowers and ripe fruit later than their wild progenitors. Cultivated apples were also 3.6 times heavier, 43% less acidic, and had 68% less phenolic content than wild apples. Using historical records, we found that apple breeding over the past 200 years has resulted in a trend towards apples that have higher soluble solids, are less bitter, and soften less during storage. Our results quantify the significant changes in phenotype that have taken place since apple domestication, and provide evidence that apple breeding has led to continued phenotypic divergence of the cultivated apple from its wild progenitor species.

plant biology↗

bioRxiv2020

FHOD-1 is the only formin in Caenorhabditis elegans that promotes striated muscle growth and Z-line organization in a cell autonomous manner

The striated body wall muscles of Caenorhabditis elegans are a simple model system with well-characterized sarcomeres that have many vertebrate protein homologs. Previously, we observed deletion mutants for two formin genes, fhod-1 and cyk-1, developed thin muscles with abnormal dense bodies/sarcomere Z-lines. However, the nature of the cyk-1 mutation necessitated maternal CYK-1 expression for viability of the examined animals. Here, we tested the effects of complete loss of CYK-1 using a fast acting temperature-sensitive cyk-1(ts) mutant. Surprisingly, neither post-embryonic loss of CYK-1 nor acute loss of CYK-1 during embryonic sarcomerogenesis caused muscle defects, suggesting CYK-1 might not play a direct role in muscle development. Consistent with this, examination of cyk-1({Delta}) mutants re-expressing CYK-1 in a mosaic pattern showed CYK-1 cannot rescue muscle defects in a muscle cell autonomous manner, suggesting muscle phenotypes caused by cyk-1 deletion are likely indirect. Conversely, mosaic re-expression of FHOD-1 in fhod-1({Delta}) mutants promoted muscle cell growth, as well as proper Z-line organization, in a muscle cell autonomous manner. As we can observe no effect of loss of any other worm formin on muscle development, we conclude that FHOD-1 is the only formin that directly promotes striated muscle development in C. elegans.

developmental biology↗

bioRxiv2017

Trends in Escherichia coli bloodstream infection, urinary tract infections and antibiotic susceptibilities in Oxfordshire, 1998-2016: an observational study

BackgroundThe incidence of Escherichia coli bloodstream infections (EC-BSIs), particularly those caused by antibiotic-resistant strains, is increasing in the UK and internationally. This is a major public health concern but the evidence base to guide interventions is limited.\n\nMethodsIncidence of EC-BSIs and E. coli urinary tract infections (EC-UTIs) in one UK region (Oxfordshire) were estimated from anonymised linked microbiological and hospital electronic health records, and modelled using negative binomial regression based on microbiological, clinical and healthcare exposure risk factors. Infection severity, 30-day allcause mortality, and community and hospital co-amoxiclav use were also investigated.\n\nFindingsFrom 1998-2016, 5706 EC-BSIs occurred in 5215 patients, and 228376 EC-UTIs in 137075 patients. 1365(24%) EC-BSIs were nosocomial (onset >48h post-admission), 1863(33%) were community (>365 days post-discharge), 1346(24%) were quasi-community (31-365 days post-discharge), and 1132(20%) were quasi-nosocomial ([≤]30 days postdischarge). 1413(20%) EC-BSIs and 36270(13%) EC-UTIs were co-amoxiclav-resistant (41% and 30%, respectively, in 2016). Increases in EC-BSIs were driven by increases in community (10%/year (95% CI:7%-13%)) and quasi-community (8%/year (95% CI:7%-10%)) cases. Changes in EC-BSI-associated 30-day mortality were at most modest (p>0{middle dot}03), and mortality was substantial (14-25% across groups). By contrast, co-amoxiclav-resistant EC-BSIs increased in all groups (by 11%-19%/year, significantly faster than susceptible EC-BSIs, pheterogeneity<0{middle dot}001), as did co-amoxiclav-resistant EC-UTIs (by 13%-29%/year, pheterogeneity*0{middle dot}001). Co-amoxiclav use in primary-care facilities was associated with subsequent co-amoxiclav-resistant EC-UTIs (p=0{middle dot}03) and all EC-UTIs (p=0{middle dot}002).\n\nInterpretationCurrent increases in EC-BSIs in Oxfordshire are primarily community-associated, with high rates of co-amoxiclav resistance, nevertheless not impacting mortality. Interventions should target primary-care facilities with high co-amoxiclav usage.\n\nFundingNational Institute for Health Research.\n\nResearch in contextO_ST_ABSEvidence before this studyC_ST_ABSWe searched PubMed for publications from inception up until October 26, 2017, with the terms \"Escherichia coli\", \"E. coli\", \"bacteraemia\", \"bloodstream infection\", restricting the search to English language articles, and also reviewed references from retrieved articles. Escherichia coli (E. coli) is the most common cause of bloodstream infection, and the incidence of E. coli bloodstream infection, and particularly antibiotic-resistant infections, is increasing in the UK and internationally. Although the UK government aims to reduce healthcare-associated E. coli bloodstream infection, there is only limited evidence to inform appropriate interventions.\n\nAdded value of this studyWe investigated potential drivers for these increases in incidence by exploiting available linked electronic health records over 19 years for ~5200 patients with E. coli bloodstream infection and ~140000 with E. coli urinary tract infection, together with community antimicrobial prescribing data for the most recent six years. Our study identified several findings with significant implications for health policy and patient care: O_LIIncreases in the incidence of E. coli bloodstream infections were driven mainly by non-hospital-associated cases; however, neither patients with previous urinary tract infections nor having previously had urine specimens sent from catheters appeared to be driving the increases\nC_LIO_LICo-amoxiclav-resistant bloodstream infections rose significantly faster than co-amoxiclav-susceptible bloodstream infections, with the greatest number of co-amoxiclav-resistant bloodstream infections in 2016 being in patients discharged more than a month previously (i.e. community-associated)\nC_LIO_LIHigher co-amoxiclav use in primary care was associated with higher rates of both co-amoxiclav-resistant E. coli urinary tract infections and E. coli urinary tract infections overall, supporting drives to reduce broad-spectrum and inappropriate antibiotic use in primary care\nC_LIO_LIDespite substantial increases in co-amoxiclav-resistant bloodstream infections there was no evidence that mortality was increasing in these cases; this does not support moving to broader empiric antibiotic prescribing in hospitals (i.e. carbapenems, piperacillin-tazobactam)\nC_LI\n\nImplications of all available adviceThis suggests that government strategies to effectively reduce E. coli bloodstream infections should target community settings, as well as healthcare-associated settings. The absence of an increased mortality signal suggests that co-amoxiclav resistant E. coli infections are either being successfully treated by dual empiric therapy in severe cases (e.g. with concomitant gentamicin), can be \"rescued\" once isolate susceptibilities become available, or currently deployed phenotypic susceptibility testing breakpoints do not adequately correlate with clinical outcome.

epidemiology↗

bioRxiv2017

Epidemiology of paediatric gastrointestinal colonisation by extended spectrum cephalosporin-resistant Escherichia coli and Klebsiella pneumoniae isolates in north-west Cambodia

Extended-spectrum cephalosporin resistance (ESC-R) in Escherichia coli and Klebsiella pneumoniae is a healthcare threat; high gastrointestinal carriage rates are reported from South-east Asia. Colonisation prevalence data in Cambodia are lacking. We determined gastrointestinal colonisation prevalence of ESC-resistant E. coli (ESC-R-EC) and K. pneumoniae (ESC-R-KP) in Cambodian children/adolescents and associated risk factors; characterised relevant resistance genes, their genetic contexts, and the genetic relatedness of ESC-R strains using whole genome sequencing (WGS). Faeces and questionnaire data were obtained from individuals <16 years in northwestern Cambodia, 2012. WGS of cultured ESC-R-EC/KP was performed (Illumina). Maximum likelihood phylogenies were used to characterise relatedness of isolates; ESC-R-associated resistance genes and their genetic contexts were identified from de novo assemblies using BLASTn and automated/manual annotation. 82/148 (55%) of children/adolescents were ESC-R-EC/KP colonised; 12/148 (8%) were co-colonised with both species. Independent risk factors for colonisation were hospitalisation (OR: 3.12, 95%, CI [1.52-6.38]) and intestinal parasites (OR: 3.11 [1.29-7.51]); school attendance conferred decreased risk (OR: 0.44 [0.21-0.92]. ESC-R strains were diverse; the commonest ESC-R mechanisms were blaCTX-M 1 and 9 sub-family variants. Structures flanking these genes were highly variable, and for blaCTX-M-15, -55 and -27, frequently involved IS26. Chromosomal blaCTX-M integration was common in E. coli. Gastrointestinal ESC-R-EC/KP colonisation is widespread in Cambodian children/adolescents; hospital admission and intestinal parasites are independent risk factors. The genetic contexts of blaCTX-M are highly mosaic, consistent with rapid horizontal exchange. Chromosomal integration of blaCTX-M may result in stable propagation in these community-associated pathogens.

microbiology↗