Biology subjects

Winn, M.

Publications and source records attributed to Winn, M..

6 recordsLinked to original sources

bioRxiv2026

Acoustic Salience Drives Pupillary Dynamics in an Interrupted, Reverberant Task

Listeners face many challenges when trying to maintain attention to a target source in everyday settings; for instance, reverberation distorts acoustic cues and interruptions capture attention. However, little is known about how these challenges affect the ability to maintain selective attention. Here, we measured syllable recall accuracy and pupil dilation during a spatial selective attention task that was sometimes disrupted. Participants heard two competing, temporally interleaved syllable streams presented in pseudo-anechoic or reverberant environments. On randomly selected trials, a sudden interruption occurred mid-sequence. Compared to anechoic trials, reverberant performance was worse overall, and the interrupter disrupted performance. In uninterrupted trials, reverberation reduced peak pupil dilation both when it was consistent across all stimuli in a block and when it was randomized trial to trial, suggesting temporal smearing reduced clarity of the scene and the salience of events in the ongoing streams. Pupil dilations in response to interruptions indicated perceptual salience was strong across reverberant and anechoic conditions. Specifically, baseline pupil size before trials did not vary across room conditions, and mixing or blocking of trials (altering stimulus expectations) had no impact on pupillary responses. Together, these findings highlight that stimulus salience drives cognitive load more strongly than does task performance.

neuroscience↗

bioRxiv2026

Stitching genomics data to protein structures: Virulence factors in non-O157 Shiga toxin-producing Escherichia coli

The genetic diversity of the Shiga toxin-producing Escherichia coli (STEC) sub-species group poses major challenges for assigning pathogenic potential, and for accurate diagnostics. Although existing risk-based frameworks work for the predominant serotypes e.g. STEC O157 or O26, they are less useful for more diverse genotypes, with variation in the genetic complement of virulence factors that is responsible for disease outcome. Moreover, genetic diversity occurs at the virulence factor allele level. We investigated the functional potential of genetic variation at a whole genome level and at an allele variant level, based on the premise that genomic variability underlies phenotypic traits including disease outcomes. We analysed 286 non-O157 STEC genomes for their virulence factor complement and determined co-occurrence patterns. Genetic variation in the well-characterized virulence factor intimin (eae) and its receptor (tir) was analyzed at a sequence level, and by modelling the three-dimensional protein-protein complex using AlphaFold3 and homology modelling. Different subtypes of Eae were shown to preserve their interaction with the receptor Tir by retaining the interactions at the protein-protein interface. The study shows that virulence factor characterisation in association with 3-D modelling of protein complexes can aid genomic analysis for risk assessment, and inform on functional mechanisms for pathogenicity.

bioinformatics↗

bioRxiv2025

Uncovering synaptic and cellular nanoarchitecture of brain tissue via seamless in situ trimming and milling for cryo-electron tomography

Cell-cell communication underlies all emergent properties of the brain, including cognition, learning and memory. The physical basis for these communications is the synapse, a multi-component structure requiring coordinated interactions between diverse cell types. However, many aspects of three-dimensional (3D) synaptic organization remain poorly understood. Here, we developed an approach, seamless in situ trimming and milling (SISTM), to reliably fabricate sufficiently thin lamellae for mapping of the 3D nanoarchitecture of synapses in mouse, monkey and human brain tissue under near-native conditions via cryo-electron tomography (cryo-ET). We validated SISTM in a mouse model of Huntingtons disease, demonstrating distinct 3D alterations to synaptic vesicles and mitochondria. By successfully applying SISTM to macaque brain, we described the 3D architecture of a tripartite synapse within the cortex. Subtomogram averaging (STA) enabled spatial mapping of astrocyte-neuron contacts within the tripartite synapse, revealing neurexin-neuroligin complexes as potential constituents that tether the two cell types. Finally, we showed that the defining features of synaptic nanoarchitecture were conserved across species and evident in human brain tissue obtained postmortem. Combining SISTM with cryo-ET and STA is a starting point for a new understanding of brain organization, disease-induced structural alterations and the development of rational, structure-guided therapeutics.

cell biology↗

bioRxiv2021

Small molecules enhance the potency of natural antimicrobial peptides

The skin-associated microbiome plays an important role in general well-being and in a variety of treatable conditions. In this regard, endogenous antimicrobial peptides have a role in controlling the microbial population. We demonstrate here that certain small molecular species can amplify the potency of naturally-occurring antimicrobial peptides. For example, Niacinamide is a vitamin B3 analogue naturally found in foods and widely used in topical skin care products, and here we have investigated its cooperativity with the human antimicrobial peptide LL37 on the bacterium Staphylococcus aureus. We have also studied two other structurally related B3 analogs. We observed a clear synergistic effect of niacinamide and, to some extent, methyl niacinamide, whereas isonicotinamide showed no significant cooperativity with LL37. Adaptively-biased molecular dynamics simulations revealed that the analogs partition into the head group region of an anionic bilayer used to mimic the bacterial membrane. The observed effects on the physical properties of the membrane are well correlated with experimental activity. In contrast, the analogs have little effect on zwitterionic bilayers which mimic a mammalian membrane. We conclude that these vitamin B3 analogues can potentiate the activity of host peptides by modulating the physical properties of the bacterial membrane, and to a lesser extent through direct interactions with the peptide. The level of cooperativity is strongly dependent on the detailed chemistry of the additive, suggesting an opportunity to fine-tune the behaviour of host peptides.

molecular biology↗

bioRxiv2020

Explainable AI reveals key changes in skin microbiome associated with menopause, smoking, aging and skin hydration

Alterations in the human microbiome have been observed in a variety of conditions such has asthma, gingivitis, dermatitis and cancer, and much remains to be learned about the links between the microbiome and human health. The fusion of artificial intelligence with rich microbiome datasets can offer an improved understanding of the microbiomes role in our health. To gain actionable insights it is essential to consider both the predictive power and the transparency of the models by providing explanations for the predictions. We combine the effort of collecting a corpus of leg skin microbiome samples of two healthy cohorts of women with the development of an explainable artificial intelligence (EAI) approach that provides accurate predictions of phenotypes and explanations. The explanations are expressed in terms of variations in the abundance of key microbes that drive the predictions. We predict skin hydration, subjects age, pre/post-menopausal status and smoking status from the leg skin microbiome. The key changes in microbial composition linked to skin hydration can accelerate the development of personalised treatments for healthy skin, while those associated with age may offer insights into the skin aging process. The leg microbiome signatures associated with smoking and menopausal status are consistent with previous findings from oral/respiratory tract microbiomes and vaginal microbiomes respectively. This suggests that easily accessible microbiome samples could be used to investigate health-related phenotypes, offering potential for non-invasive diagnosis and condition monitoring. Our EAI approach sets the stage for new work focused on understanding the complex relationships between microbial communities and phenotypes. Our approach can be applied to predict any conditions from microbiome samples and has the potential to accelerate the development of microbiome-based personalised therapeutics and non-invasive diagnostics.

bioinformatics↗

bioRxiv2017

K-mer clustering algorithm using a MapReduce framework: application to the parallelization of the Inchworm module of Trinity

BackgroundDe novo transcriptome assembly is an important technique for understanding gene expression in non-model organisms. Many de novo assemblers using the de Bruijn graph of a set of the RNA sequences rely on in-memory representation of this graph. However, current methods analyse the complete set of read-derived k-mer sequence at once, resulting in the need for computer hardware with large shared memory.\n\nResultsWe introduce a novel approach that clusters k-mers as the first step. The clusters correspond to small sets of gene products, which can be processed quickly to give candidate transcripts. We implement the clustering step using the MapReduce approach for parallelising the analysis of large datasets, which enables the use of compute clusters. The computational task is distributed across the compute system, and no specialised hardware is required. Using this approach, we have re-implemented the Inchworm module from the widely used Trinity pipeline, and tested the method in the context of the full Trinity pipeline. Validation tests on a range of real datasets show large reductions in the runtime and per-node memory requirements, when making use of a compute cluster.\n\nConclusionsOur study shows that MapReduce-based clustering has great potential for distributing challenging sequencing problems, without loss of accuracy. Although we have focussed on the Trinity package, we propose that such clustering is a useful initial step for other assembly pipelines.

bioinformatics↗