Biology subjects

Barnard, A.

Publications and source records attributed to Barnard, A..

5 recordsLinked to original sources

bioRxiv2026

Correlating Structure and Rheology in Ionically Crosslinked Alginate Biopolymer Hydrogels - A Case for Why "Less" can be "More"

We probe the structural and rheological properties of ionically crosslinked alginate, a model biopolymer hydrogel, using microscopy, rheology and viscosity dependent molecular probes. This combination of techniques enables the quantification and correlation of microstructure, microviscosity, bulk viscoelasticity and yielding dynamics. By adjusting the stoichiometric ratio, R, between the alginate biopolymer and its cation crosslinks, we observe a transition from a homogeneous network-like structure to a coarse bundle-like structure at high (R>0.67) stoichiometric ratio. Intriguingly, these bundle-like structures have distinct and counter-intuitive rheological properties. Using molecular probes, we observe a continuous decrease in microviscosity that is correlated with a decrease in bulk elastic modulus and an increase in energy dissipation. This is accompanied by a transition in the hydrogel yielding under strain from a sharp, well-defined yield point to a continuous ductile-like yielding. We ascribe these surprising transitions to the looser intermolecular interaction between alginate biopolymers in the bundle-like state, as previously predicted by x-ray scattering experiments. These findings reveal new and counter-intuitive structure-property relations that demonstrate high crosslink concentration does not necessarily translate to optimal mechanical performance. SignificanceAlginate is a polysaccharide biopolymer naturally found in brown seaweed cell walls. Extracted alginate forms ionically crosslinked hydrogels that are strong, flexible and increasingly valuable in the biomedical, packaging and food industries. A large part of the utility of these hydrogels stems from the ease with which their mechanics can be tuned through adjusting the stoichiometry between alginate and its ionic crosslinks. However, little is known about how the material properties of alginate hydrogels, in particular their rheology and dynamics, are affected by microscale structural transitions at high stoichiometric ratios. Here, we use a multi-modal approach to describe and correlate hydrogel material properties and to demonstrate that increased polymer crosslinking can, counterintuitively, sometimes weaken hydrogel performance.

biophysics↗

bioRxiv2026

Hyperspectral Remote Sensing for Harmful Algal Bloom Detection: Pseudo-nitzschia in the Northeast Pacific

1Diatoms are microscopic marine algae that are critical for global primary production, carbon sequestration, and fisheries productivity. However, select diatoms may form harmful algal blooms, which threaten marine ecosystems and the fisheries they sustain. Rapidly identifying harmful blooms is necessary to effectively manage marine resources, yet current identification methods are limited by expensive and labor-intensive in situ point sampling. Hyperspectral remote sensing enables scalable monitoring, but its ability to resolve taxonomic shifts within phytoplankton groups (e.g. diatoms) is largely unknown. To investigate this uncertainty, we cultured four dominant diatom genera from the California Current upwelling system, including this systems most abundant harmful algae, Pseudo-nitzschia. The hyperspectral absorption and backscatter of these taxa were measured and used to model spectral reflectances that remote sensing platforms (satellites/drones) might detect. Differences between fingerprints of these taxa were quantified using vector-based and statistical analyses. Mean spectral differences of 48% were observed between the most dominant diatom, Thalassiosira, and the most toxic diatom, Pseudo-nitzschia. Differences of approximately 30% were found between Pseudo-nitzschia and the second and third most abundant diatoms, Chaetoceros and Asterionellopsis. Successful identification of Pseudo-nitzschias reflectance fingerprint was driven by the presence of a unique feature around 560 nm. The distinct spectral fingerprint of Pseudo-nitzschia indicates that it can be distinguished from benign diatom blooms using hyperspectral remote sensing platforms.

ecology↗

bioRxiv2024

AlphaRING: Missense Variant Classification via Protein Modelling and Residue Interaction Network Analysis

BackgroundAccurate interpretation of missense variants remains a significant challenge hindering genomic diagnosis. While state-of-the-art machine learning and deep learning predictors offer high accuracy, they often lack the transparency required for clinical evidence weighting. To bridge this gap between accuracy and clinical utility, we developed AlphaRING-X. MethodsAlphaRING-X is an open-source framework that integrates local and global protein structural stability features using an efficient implementation of gradient boosting, XGBoost, to predict variant deleteriousness. Local stability is interrogated through a combination of AlphaFold-based modelling and residue interaction network analysis. Changes in global stability upon mutation ({Delta}{Delta}G) are estimated using FoldX. For each prediction, AlphaRING-X quantifies the magnitude and direction of each features contribution using Shapley additive explanations (SHAP), providing a unified yet interpretable score. We trained and evaluated the model using a gold standard ClinVar dataset of validated neutral and deleterious variants. ResultsAlphaRING-X achieved an area under the receiver operator curve of 0.94, significantly outperforming widely used predictors such as CADD. Crucially, it provided unambiguous classification for 95.5% of variants at 90% precision in both neutral and deleterious classes. We analysed each predictions SHAP values, identifying local connectivity and disorder as the strongest contributors. ConclusionsAlphaRING-X combines high-performance prediction with the interpretability necessary for clinical decision-making. Its flexible, open-source architecture makes it a powerful, transparent tool for enhancing genomic diagnostics and advancing precision medicine.

bioinformatics↗

bioRxiv2021

Plasmodium falciparum protein Pfs16 is a target for transmission-blocking antimalarial drug development

Phenotypic cell-based screens are critical to the discovery of new antimalarial lead compounds. However, identification and validation of cellular targets of lead compounds is required following discovery in a phenotypic screen. We recently discovered a Plasmodium transmission-blocking N-((4-hydroxychroman-4-yl)methyl)-sulfonamide (N-4HCS) compound, DDD01035881, in a phenotypic screen. DDD01035881 and its potent derivatives have been shown to block Plasmodium male gamete formation (microgametogenesis) with nanomolar activity. Here, we synthesised a photoactivatable N-4HCS derivative, probe 2, to identify the N-4HCS cellular target. Using probe 2 in photo-affinity labelling coupled with mass spectrometry, we identified the 16 kDa Plasmodium falciparum parasitophorous vacuole membrane protein Pfs16 as the likely cellular target of the N-4HCS series. Further validating Pfs16 as the cellular target of the N-4HCS series, the Cellular Thermal Shift Assay (CETSA) confirmed DDD01035881 stabilised Pfs16 in lysate from activated mature gametocytes. Additionally, photo-affinity labelling combined with in-gel fluorescence and immunoblot analysis confirmed the N-4HCS series interacted with Pfs16. High-resolution, widefield fluorescence and electron microscopy of N-4HCS-inhibited parasites was found to result in a cell morphology entirely consistent with targeted gene disruption of Pfs16. Taken together, these data strongly implicate Pfs16 as the target of DDD01035881 and establish the N-4HCS scaffold family as a powerful starting point from which future transmission-blocking antimalarials can be developed.

microbiology↗

bioRxiv2017

Mechanical And Tactile Incompatibilities Cause Reproductive Isolation Between Two Young Damselfly Species

External male reproductive structures have received considerable attention as an early-acting cause of reproductive isolation (RI), because the morphology of these structures often evolves rapidly between populations. This presents the potential for mechanical incompatibilities with heterospecific female structures during mating and could thus prevent interbreeding between nascent species. Although such mechanical incompatibilities have received little empirical support as a common cause of RI, the potential for mismatch of reproductive structures to cause RI due to incompatible species-specific tactile cues has not been tested. We tested the importance of mechanical and tactile incompatibilities in RI between Enallagma anna and E. carunculatum, two damselfly species that diverged within the past ~250,000 years and currently hybridize in a sympatric region. We quantified 19 prezygotic and postzygotic RI barriers using both naturally occurring and lab-reared damselflies. We found incomplete mechanical isolation between the two pure species and between hybrid males and pure species females. Interestingly, where mechanical isolation was incomplete, females showed greater resistance and refusal to mate with hybrid or heterospecific males compared to conspecific males, which suggests that tactile incompatibilities involving male reproductive structures can influence female mating decisions and form a strong barrier to gene flow in early stages of speciation.

evolutionary biology↗