Biology subjects

Bernal, J.

Publications and source records attributed to Bernal, J..

5 recordsLinked to original sources

bioRxiv2026

Automated quantification of white matter hyperintensity confluence: A measure of spatial organisation beyond volume and visual rating scales

White matter hyperintensities (WMH) are a highly prevalent finding on FLAIR MRI scans and a prominent feature of white matter pathology across cerebrovascular and neurodegenerative diseases. Currently, WMH are assessed with visual rating scales such as the Fazekas scale or with their volume, as calculated from automatic or manual segmentations. Both methods have limitations: Visual rating scales are rater-dependent and coarse, while WMH volume does not take the confluence of lesions into account and thus disregards their spatial organisation. As an alternative, here we propose a novel automated method for quantifying the confluence of white matter hyperintensities on a continuous standardised scale between 0 and 1. The metric is based on WMH segmentations from routine MRI and quantifies the extent to which individual WMH merge into coherent lesions, independently of total lesion volume. We apply the method to QMIN-MC, a large UK memory clinic cohort, and show associations of the confluence metric with age, cognitive performance across domains, and Fazekas ratings. Participants with vascular and mixed dementia showed higher confluence than other diagnostic groups, whereas cognitively unimpaired participants showed lower confluence. However, confluence did not explain additional cognitive variance after accounting for log-transformed WMH volume. Findings were validated in DELCODE, an independent cohort of individuals with neurodegenerative disorders, replicating our original results. In this validation cohort, periventricular WMH confluence remained associated with cognition after adjustment for WMH volume. These findings introduce WMH confluence as a reproducible, automated, and fine-grained measure of lesion spatial organisation. It provides complementary information about morphological WMH severity beyond volume and is an alternative to visual rating scales. Although related to WMH volume in memory-clinic populations, confluence captures clinically interpretable information and may complement existing WMH measures for improved lesion characterisation in studies of white matter disease, ageing, and cognitive impairment.

neuroscience↗

bioRxiv2025

Domestication Compromised Microbiome-Mediated Resistance to Western Corn Rootworm in Maize

Western corn rootworm (WCR) (Diabrotica virgifera virgifera) represents a significant threat to global maize production, with annual costs exceeding $1 billion. While modern maize is highly susceptible, wild teosinte (Zea mays ssp. parviglumis) exhibits superior resistance through poorly understood mechanisms. This study investigated rhizosphere microbiome contributions to WCR resistance across the domestication gradient. We screened 23 accessions (15 wild teosinte accessions, 6 ancestral maize accessions, 2 modern maize accessions) for WCR resistance and analyzed rhizosphere microbiomes of selected resistant and susceptible accessions using Oxford Nanopore sequencing. Resistant accessions retained >80% of root structure (85.4% {+/-} 3.2%) while supporting minimal larval survival (22.5% {+/-} 4.8%) compared to susceptible accessions (46.7% {+/-} 5.1% root retention, 78.6% {+/-} 6.3% larval survival; P < 0.001). Resistant accessions recruited significantly more diverse bacterial communities under WCR pressure, with 28-31 enriched species versus 7-19 in susceptible accessions. Key enriched taxa included Pseudomonas putida (3.0-3.2-fold), Stenotrophomonas maltophilia (2.7-2.9-fold), and Bacillus subtilis, all possessing documented insecticidal properties. Functional analysis revealed enrichment of defense-related pathways in resistant accessions, including hydrogen cyanide production and antimicrobial compound synthesis. Wild teosinte showed the strongest responses, with significant diversity increases (P < 0.0001) and 31 enriched species under WCR herbivory. Modern maize exhibited attenuated responses regardless of resistance classification, suggesting domestication compromised plant-microbiome defensive interactions. These findings demonstrate that WCR resistance involves coordinated plant-microbiome networks and identify bacterial taxa with biocontrol potential for developing sustainable management strategies. Author Summary

microbiology↗

bioRxiv2025

Microbiome differentiation between micro-sympatric maize and teosinte reveals domestication-driven functional erosion of the microbiome across plant compartments

IntroductionCrop domestication has fundamentally transformed plant phenotypes through artificial selection, yet the consequences of domestication for plant-associated microbial communities across the plant-soil continuum remain poorly understood. Gap StatementWhile recent studies suggest that domestication impacts microbiome structures, the magnitude, mechanisms, and functional implications of such impacts have not been systematically quantified using controlled experimental designs that eliminate environmental confounding factors. AimTo characterize and quantify the effects of crop domestication on microbial community structure and function by comparing maize (Zea mays subsp. mays) and its wild ancestor Balsas teosinte (Zea mays subsp. parviglumis) across multiple plant compartments in an unmanipulated field setting in Mexico, maizes domestication center. MethodologyWe applied a micro-sympatric design in a natural setting to compare microbial communities between maize and Balsas teosinte across five plant compartments: bulk soil, rhizosphere, mucilage, leaves, and seeds. Full-length 16S rRNA gene sequencing was used for taxonomic characterization, Functional Annotation of Prokaryotic Taxa (FAPROTAX) and PICRUSt 2.0 were used to predict functional profiles, and network analysis was used to assess functional connectivity. ResultsCompartment identity explained 72.2% of variation in community structure, with consistent host effects across all niches (9.0%). Teosinte maintained significantly higher microbial diversity than maize across all compartments, with pronounced differences in seeds (32.0 {+/-} 1.9 vs 9.3 {+/-} 1.8 species, P < 0.01) and rhizosphere (60.3 {+/-} 5.8 vs 33.8 {+/-} 10.4 species, P < 0.01). Eighty-nine percent of predicted metabolic functions showed significant changes associated with domestication, with teosinte exhibiting enhanced nitrogen fixation (0.89 {+/-} 0.07 vs 0.44 {+/-} 0.04 in maize mucilage), siderophore production, and pathogen suppression. Network analysis revealed functional fragmentation in maize, with reduced connections (80 to 49) and lower clustering coefficients (0.62 {+/-} 0.03 vs 0.25 {+/-} 0.02, P < 0.001). ConclusionBalsas teosinte domestication fundamentally eroded microbial diversity and functional capacity in maize leading to a "domestication gap" that encompasses taxonomic loss, functional simplification, and network fragmentation, and replaced mutualistic plant-microbe partnerships with simplified microbial assemblages that may compromise crop resilience vis-a-vis a changing climate. Impact statementUnderstanding how plants select their microbial partners is crucial for enhancing agricultural productivity yet distinguishing between environmental and host genetic effects on microbiome assemblage remains challenging. Our study provides compelling evidence for host-driven microbiome assembly by comparing ancestral Balsas teosinte with derived maize growing in a common farm field in Mexico, eliminating environmental variation and experimental manipulation as confounding factors. By characterizing bacterial communities across different plant compartments, from soil to seed, we showed that each hosts genotype shaped divergent microbiome compositions despite growing in common environmental conditions. This research represents a significant step forward in understanding plant-microbe co-evolution during crop domestication and has three key implications. First, it suggests that microbiome traits were likely selected in conjunction with plant (host) traits during domestication and post-domestication selection. Second, it identifies specific bacterial communities that could be targeted for improving crop productivity and resilience. And third, it provides a methodological framework for studying host-microbe interactions in other crop-wild ancestor pairs. Our findings are particularly relevant for developing microbiome-based agricultural technologies and conservation strategies for beneficial plant-microbe interactions for deployment in traditional and modern farming systems. Data summaryThe authors confirm all supporting data, code and protocols have been provided within the article or through supplementary data files.

microbiology↗

bioRxiv2024

SMAS: Structural MRI-Based AD Score using Bayesian VAE

This study introduces the Structural MRI-based Alzheimers Disease Score (SMAS), a novel index intended to quantify Alzheimers Disease (AD)-related morphometric patterns using a deep learning Bayesian-supervised Variational Autoencoder (Bayesian-SVAE). SMAS index was constructed using baseline structural MRI data from the DELCODE study and evaluated longitudinally in two independent cohorts: DEL-CODE (n=415) and ADNI (n=190). Our findings indicate that SMAS has strong associations with cognitive performance (DELCODE: r=-0.83; ADNI: r=-0.62), age (DEL-CODE: r=0.50; ADNI: r=0.28), hippocampal volume (DEL-CODE: r=-0.44; ADNI: r=-0.66), and total grey matter volume (DELCODE: r=-0.42; ADNI: r=-0.47), suggesting its potential as a biomarker for AD-related brain atrophy. Moreover, our longitudinal studies suggest that SMAS may be useful for early identification and tracking of AD. The model demonstrated significant predictive accuracy in distinguishing cognitively healthy individuals from those with AD (DELCODE: AUC=0.971 at baseline, 0.833 at 36 months; ADNI: AUC=0.817 at baseline, improving to 0.903 at 24 months). Notably, over a 36-month period, SMAS index outperformed existing measures such as SPARE-AD and hippocampal volume. Relevance map analysis revealed significant morphological changes in key AD-related brain regions--including the hippocampus, posterior cingulate cortex, precuneus, and lateral parietal cortex--highlighting that SMAS is a sensitive and interpretable biomarker of brain atrophy, suitable for early AD detection and longitudinal monitoring of disease progression.

neuroscience↗

bioRxiv2023

Construction and reconfiguration of dynamic DNA origami assemblies with coiled-coil patches and patterns

DNA origami nanodevices achieve programmable structure and tunable mechanical and dynamic properties by leveraging the sequence specific interactions of nucleic acids. Previous advances have also established DNA origami as a useful building block to make well-defined micron-scale structures through hierarchical self-assembly, but these efforts have largely leveraged the structural features of DNA origami. The tunable dynamic and mechanical properties also provide an opportunity to make assemblies with adaptive structure and properties. Here we report the integration of DNA origami hinge nanodevices and coiled-coil peptides into hybrid reconfigurable assemblies. With the same dynamic device and peptide interaction, we make multiple higher order assemblies by organizing clusters of peptides (i.e. patches) or arranging single peptides (i.e. patterns) on the surfaces of DNA origami to control the relative orientation of devices. We use coiled-coil interactions to construct circular and linear assemblies whose structure and mechanical properties can be modulated with DNA-based actuation. Actuation of linear assemblies leads to micron scale motions and [~]2.5-10-fold increase in bending stiffness. Our results provide a foundation for stimulus responsive hybrid assemblies that can adapt their structure and properties in response to nucleic acid, peptide, protein, or other triggers.

bioengineering↗