Biology subjects

Thompson, A.

Publications and source records attributed to Thompson, A..

At least 19 recordsLinked to original sources

bioRxiv2026

Fallopian Tube Organoid-Integrated Microfluidic Platform for Real-Time Imaging and Outflow Analysis

The fallopian tube is a dynamic, hormonally regulated epithelial conduit whose luminal microenvironment governs oocyte transport, fertilisation, early embryo development, and the initiation of gynaecological diseases including ectopic pregnancy, hydrosalpinx, and serous tubal intraepithelial carcinoma (STIC), yet existing models such as 2D monolayers, intact organoids, and static Transwell systems fail to recapitulate a polarised epithelium lining a perfused lumen under physiological fluid shear while preserving native organoid secretory function. We present a robust and accessible workflow integrating mechanically opened fallopian tube organoids into a custom-designed polydimethylsiloxane (PDMS) microfluidic device, in which organoid fragments form epithelial sheets and re-establish luminal-like architecture under controlled perfusion. The focus of this study is organoid integration and the characterisation of the resulting organoid-derived epithelium, rather than establishing chip cultures from individual cell lines. As this epithelium is built from expandable organoid stock rather than primary tissue, which typically survives only a few days in culture, the approach removes a major bottleneck to establishing organ-on-chip models, and we maintain viable cultures for up to 10 days. Epithelial sheets reproducibly covered more than 90% of the channel area by day 6 (n = 5 devices) and formed continuous ZO-1-positive tight junctions. The platform supports longitudinal brightfield and fluorescence microscopy at subcellular resolution, continuous collection of conditioned flow-through for ELISA, and quantitative analysis of cell coverage and health using CellProfiler software. We characterise the organoid-derived epithelium by benchmarking against tissue culture (TC) formats, comparing nuclear morphology on-chip with conventional well culture, and showing that the damage-associated cytokine interleukin-1 alpha (IL1 alpha) was undetectable in chip outflow, as in intact organoid secretions, indicating that cell health on-chip is comparable to that of intact organoids. Computational flow modelling characterises perfusion through the device and predicts how factors secreted by healthy epithelium and by tumour cells are distributed along the channel. The feasibility of tumour epithelium co culture was explored using OVCAR3 ovarian cancer spheroids as a proof of concept model of early tumour interaction with the tubal epithelium. Together, these results establish the technical feasibility of the platform and support its further development as an accessible system for studying reproductive health conditions affecting the fallopian tube, including tubal damage from infection, endometriosis, STIC lesions, and occlusion.

bioengineering↗

bioRxiv2026

An open field phenomics resource for multimodal maize yield prediction across divergent environments

Temporal drone phenotyping captures crop development, but irregular flight schedules complicate comparisons across environments. We release curated imagery from 356 flights across 19 Genomes to Fields environments containing 1,180 maize (Zea mays L.) hybrids. To evaluate its utility, we integrated functional principal components of vegetation index and weather trajectories with genomic information. Combinined genomic and phenomic kernels improved yield prediction, reaching correlations up to r = 0.501 for held-out hybrids in environments represented in training and 0.408 when environments were also withheld. Accumulated growing degree days offered no consistent predictive advantage over days after planting, and weather contributed modest, task-dependent gains. A transformer neural process learned directly from irregular observations, serving as a novel application of neural process models in agriculture. Mapping vegetation index functional principal components identified recurrent quantitative trait loci on chromosomes 3 and 7. This resource and its reproducible analyses guide the use of temporal spectral data for crop prediction and genetic discovery.

plant biology↗

bioRxiv2026

Microbial communities in tropical soils are highly resilient to fluctuating redox conditions

Many wet tropical soils alternate frequently between fully oxygenated and anaerobic conditions, constraining the terminal electron acceptors available for microbial metabolism, and the mineral-organic matter interactions that regulate many aspects of soil carbon (C) cycling. However, it is still unclear how fluctuating soil redox conditions influence the microbial community composition and if microbially mediated C flux is sensitive to extended oxic or anoxic periods like those observed during drought and flooding respectively. Using a 44-day redox manipulation of tropical soils that experience daily-to-weekly oxygen (O2) fluctuations in the field, we measured how different redox regimes shape soil biogeochemistry and microbial and metabolite composition. Replicate microcosms were exposed to four treatments (static oxic, static anoxic, high frequency fluctuation (4 day oxic/4 day anoxic), or low frequency fluctuation (8 day oxic/4 day anoxic)) regimes, and harvested for microbial, metabolite, carbon dioxide (CO2) flux, and biogeochemical assays at multiple timepoints. Oxic and fluctuating redox conditions caused the microbial community to shift in a manner correlated with soil iron content and directly orthogonal to communities from anoxic soils. The identity of both iron oxidizers and iron reducers was distinct in static anoxic soils but was resilient to redox fluctuation and prolonged O2 exposure. The total amount of CO2 respired was similar across all four redox regimes. Water-extractable organic matter composition was distinct across redox treatments, with anoxic soils accumulating higher levels of carbohydrate-, proteins-, amino sugar-, and lignin-like compounds consistent with reduced enzymatic decomposition and release of mineral-associated organic matter via iron reduction, while oxic soils showed elevated lipid- and unsaturated hydrocarbon-like compounds indicative of greater microbial biomass turnover. The microbial community adapted to dynamic redox conditions and the results substantiate cycling of distinct C compounds under varying redox conditions resulting from varying bioavailability (driven by mineral-OM dynamics) and/or shifted microbial metabolism.

microbiology↗

bioRxiv2026

Deletion of GPR39 Prevents Pulmonary Arterial Hypertension by Attenuating Hypoxia-Induced Aberrant Signaling

Pulmonary arterial hypertension (PAH) is a devastating disease with poor outcome affecting relatively young subjects. The arachidonic acid (AA) metabolite, 15-hydroxyeicosatetraenoic acid (15-HETE), has been implicated in the pathogenesis of hypoxia-induced PAH. We tested the hypothesis that genetic deletion of GPR39, the target receptor for 15-HETE, will attenuate PAH. We subjected wild-type (WT) and GPR39 KO to 4 weeks of hypoxia versus normoxia, after which right ventricular and systemic hemodynamics were measured. Immunohistochemistry of lung was performed for pulmonary arteriolar thickness as well as capillary and pericyte density. Lung tissue was also analyzed for AA and 15-HETE levels as well as signaling events (mRNA and protein levels) downtream of GPR39 activation. Unlike WT mice, GPR39 KO mice did not develop PAH. They also exhibited markedly less pulmonary ateriolar remodeling and greater pulmonary capillary density. mRNA expression of genes in the Gq, Gsand G12/13 pathways were upregulated in the WT mice while GPR39 KO hypoxic showed no change in these genes. WT and not GPR39 KO hypoxic mice exhibited enhanced AKT phosphorylation. Downstream of the phosphatidylinositol 3-kinase-AKT pathway, endothelial nitric oxide synthetase was upregulated in both WT hypoxia and GPR39 KO hypoxia mice, while sonic hedgehog was upregulated only in WT hypoxia mice. We conclude that hypoxia-induced aberrant signaling is markedly attenuated with genetic deletion of GPR39, which is associated with less pulmonary arteriolar remodeling and greater capillary density, thus preventing PAH. These results suggest that pharmacological inhibition of GPR39 may offer a novel treatment for PAH.

physiology↗

bioRxiv2026

Context-dependent peptide recognition shapes tyrosine kinase substrate specificity beyond consensus motifs

Protein tyrosine kinases (PTKs) regulate cellular biochemistry by phosphorylating tyrosine residues that alter protein function; their substrate preferences define the topology of signaling cascades. Previous studies of PTKs have mapped their average preferences for amino acids surrounding phosphorylation sites, but their sensitivity to sequence variation remains poorly understood. Here, we used microbial biosensors for PTK activity to examine the influence of local sequence context on substrate specificity. Across five well-studied PTKs, we identified amino acid substitutions within consensus substrates that could confer sensitivity to substrate length or enhance selectivity for one PTK over others. Using a secondary decoy screen, we found sequence-diverse substrates with unexpectedly orthogonal PTK compatibilities. Our findings show how context-specific sequence features alter PTK substrate specificity far beyond what might be expected from classical consensus models and establish an experimental framework for defining the limits of substrate overlap between closely related kinases.

biochemistry↗

bioRxiv2026

Somatic variants activating the RAS-MAPK pathway confer susceptibility to hippocampal sclerosis in drug-resistant epilepsy

Hippocampal sclerosis is a frequent finding in pediatric epilepsy surgery and has traditionally been regarded as an acquired lesion. It commonly co-occurs with focal cortical dysplasia (FCD IIIa), yet whether hippocampal injury is secondary to seizures or reflects a shared underlying etiology remains unresolved. Here we identified somatic variants activating the RAS-MAPK pathway in 40% of patients with hippocampal sclerosis, but in none with non-sclerotic hippocampus. Gain-of-function variants in PTPN11 were the most common finding, with mutations present in both cortex and hippocampus and enriched in hippocampal neurons, consistent with a shared developmental origin. In mice, Ptpn11D61Y mutants developed profound hippocampal degeneration and gliosis following subthreshold kainic acid exposure, whereas wild-type controls were unaffected. p38-dependent stress pathways were upregulated in patients and mice, suggesting a mechanism through which ERK-p38 crosstalk lowers the threshold for seizure-induced injury. These results provide a genetic explanation for FCD IIIa, elucidate the role of somatic mutations within the RAS-MAPK pathway in driving hippocampal sclerosis, and provide a target for pathway-specific interventions for intractable seizures.

neuroscience↗

bioRxiv2026

Decoupled calcium homeostasis and signaling associated with cytoskeletal instability in YWHAG R132C induced pluripotent stem cell-derived cortical neurons

YWHAG Syndrome (Developmental and Epileptic Encephalopathy 56, DEE56) is an ultra- rare childhood epilepsy associated with neurodevelopmental delays, with no therapeutic intervention available. Multiple de novo mutations in the YWHAG gene, encoding for the 14-3-3{gamma} protein, have been identified as causative for YWHAG Syndrome. 14-3-3{gamma} interacts with various targets, including major neurodevelopmental signaling proteins such as components of the ROCK pathway. Despite substantial evidence of the essential role of 14-3-3{gamma} in neurite outgrowth, cytoskeletal rearrangements, and neuronal migration during cortical development, little is known regarding the molecular consequences of YWHAG mutations and their effect on neuronal function and survival. Here, we characterized an isogenic, pluripotent stem cell (iPSC) model of YWHAGR132C/+ cortical neurons. The YWHAGR132C/+iPSC-derived neurons exhibited early cytoskeletal phenotypes, coupled with an elevated calcium baseline, lower frequency of calcium spikes, and reduced network activity. The widespread alterations in the transcriptome of mutant neurons revealed a biphasic dysregulation in the core genes and modulators associated with the ROCK pathway that resulted in maturation-dependent changes to cytoskeletal protein stability and calcium phenotypes. Direct inhibition of ROCK with Y27632 further increased the calcium baseline compared to the isogenic control. Exposure of YWHAGR132C/+ neurons to Trypsin-EDTA revealed underlying cytoskeletal instability, which was partially reversed by lovastatin treatment. Further, lovastatin partially rescued the elevated calcium baseline, but not the frequency or amplitude of calcium spikes. Together, these results suggest decoupling of calcium homeostasis and calcium signaling associated with cytoskeletal instability in YWHAGR132C/+ neurons. These findings lay the groundwork for future mechanistic studies of YWHAG function and molecular therapeutic targets for YWHAG Syndrome and YWHAG-associated conditions.

neuroscience↗

bioRxiv2026

Validation of a molecular workflow for Cochliomyia hominivorax (New World screwworm) identification in field samples

Cochliomyia hominivorax, New world Screwworm (NWS), has become a reemerging veterinary concern in the United States due to the recent northward expansion of fly detections as far as northern Mexico. Rapid, accurate and validated detection pipelines need to be developed in the case of an incursion into the United States. Confirmatory cases are evaluated by morphological identification with no paired test to verify identifications. With the frequency of submissions of non-ideal samples, particularly from fly traps, a molecular tool would be necessary for species identification. In this manuscript, we develop and assess a pipeline including three real-time PCR assays targeting the ribosomal RNA and five sets of Sanger primers targeting the mitochondrial genome that would be used as a paired tool with morphological identification. Two of the assessed real-time PCR assays are highly specific, sensitive and repeatable requiring <1 copy per reaction for detection. Four of the five Sanger primer sets were assessed, optimized and results evaluated for potential use in preliminary geographic analysis of specimens. This workflow will expedite screening of samples, provide a method to verify results using different tools and help understand genetic variations within the mitochondria for NWS outbreaks.

molecular biology↗

bioRxiv2026

A Hidden Binding Pocket in the β- ketoacyl-ACP Synthase FabB

Assembly-line enzymes carry out multi-step synthesis of diverse metabolites by using a handful of catalytic motifs in which minor structural differences control substrate specificity and reaction order. Here we examine differences in substrate binding to FabB and FabF, the two {beta}-ketoacyl-ACP synthases (KSs) responsible for fatty acid elongation in Escherichia coli, by exploring a peculiar mutational effect. In FabB, a blocking mutation in the acyl binding pocket yields a shifted, but broad product profile, while in FabF, the same mutation disrupts the binding of acyl chains longer than eight carbons (C8). X-ray crystal structures of the FabB mutant provide an explanation: a second, previously unobserved binding pocket allows medium-to-long acyl chains ([≥] C8) to bind with an alternate conformation. Molecular simulations suggest that this pocket is more stable in FabB than in FabF, where mutations reduce the catalytic competency of longer chains instead of shifting them to the alternate pocket. Our findings indicate that homologous KSs differ not only in their primary binding sites but also in the availability of alternative binding modes that can buffer against mutational effects and enable functional diversification.

biochemistry↗

bioRxiv2025

Beyond Coral Cover: A framework for assessing the condition of coral reef habitats and informing conservation targets

The goal of ecosystem management is to maintain healthy and resilient ecosystems over time. These attributes can be summarised under a general term widely used in management plans: ecosystem condition, defined as the overall quality of an ecosystem relative to a desired or reference state. However, measuring and monitoring ecosystem condition remains a challenge. Monitoring ecosystem condition requires a suite of ecological indicators that simultaneously capture the complexity and variability of ecological processes, while being informative and usable in management and decision-making contexts. Such indicators need to be holistic, measurable, sensitive and scalable. Here we outline a resilience-based monitoring framework for coral reefs that consolidates monitoring data and research insights into a relevant, integrated format. The framework includes indicators of ecosystem state (coral cover) and key processes (represented by recovery performance, macroalgae prevalence, community composition, and coral juvenile density). Indicators are generated and scaled from monitoring data by applying explicit, reef-specific thresholds, providing a simple but comprehensive set of ecosystem condition values. Using cases from the Great Barrier Reef, we demonstrate how the framework integrates these indicators for detailed assessments of reef habitat condition and its potential role in management. Based on these case studies, we discuss important considerations for applying this framework worldwide, acknowledging current limitations related to data availability, resolution, and the length of time series.

ecology↗

bioRxiv2025

Predicting complex phenotypes using multi-omics data in maize

Understanding and predicting complex traits in plants remains a fundamental challenge due to the emergent nature of most phenotypes and their dependence on genetic, regulatory, and environmental interactions. Accurate prediction of traits and identification of underlying genetic elements has broad applications for plant breeding, systems biology, and biotechnology. Here, we tested if multi-omic datasets could improve predictive accuracy of 129 diverse maize phenotypes across nine environments using genomic markers, field based transcriptomic data from two locations, and drone-derived phenomic data of vegetative indices. We trained and compared linear (rrBLUP) and nonlinear (support vector regression) models using single- and multi-omics inputs. Multi-omics models consistently outperformed single-omics models for most traits, with genomic and transcriptomic inputs contributing distinct biological features. Phenomic features alone yielded the lowest predictive power but improved predictions for specific trait categories like root architecture. Transcriptomic datasets enabled cross-environment prediction, demonstrating that gene expression patterns from one field site could accurately predict traits measured in another. Environment-specific expression of benchmark flowering time genes highlighted the value of transcriptomics in capturing genotype-by-environment (GxE) interactions not detectable through genomic data alone. These findings demonstrate that integrating transcriptomic and phenomic data with genotypes enhances trait prediction, improves model generalizability across environments, and provides deeper insight into the genetic and regulatory architecture of agriculturally important traits in maize.

plant biology↗

bioRxiv2025

Olfactory Bulb Pinprick Induction of Cortical Spreading Depolarizations

Cortical spreading depolarization (CSD) is a wave of cellular depolarization followed by prolonged depression of neuronal activity and is associated with a broad array of neurological diseases, including migraine with aura, traumatic brain injury, and stroke. Traditional CSD induction methods for animal studies have included pinprick, concentrated potassium chloride (KCl) application, and electrical stimulation. These methods are invasive and can cause injury to the cortex. Recently, a non-invasive approach using optogenetics has become available, but requires the use of transgenic mice or transfection of an optogene, which limits its wide adoption. Here, we describe a novel approach using olfactory bulb needle insertion in rodents to induce CSD. We also included KCl-induced CSDs as a comparator in the same mice. Olfactory bulb pinprick resulted in CSDs on every attempt (n = 18/18) as confirmed with optical intrinsic signal imaging. Histological analysis revealed that needle disruption in the caudal olfactory bulb, which is continuous with the cerebral cortex, may account for the propagation of CSD from the olfactory bulb to the cortex. Olfactory bulb pinprick reliably induces CSD and is non-invasive with respect to cortex. The approach may prove to be useful in rodent studies where maintenance of cortical integrity is important.

neuroscience↗

bioRxiv2025

Origin, domestication, and diversity of the climate resilient Ethiopian cereal teff

Teff (Eragrostis tef) is a climate-resilient cereal and staple crop in the Horn of Africa, cultivated by millions of smallholder farmers. Despite its cultural and nutritional significance, teff has limited genomic tools, constraining progress in yield improvement and trait optimization. Here, we assembled and resequenced the Teff Association Panel (TAP), a diverse set of 265 landraces and cultivars, to investigate the domestication history, genetic diversity, and agronomic traits of teff. Phylogenetic and population genetic analyses confirm Eragrostis pilosa as the direct progenitor of teff, with domestication likely occurring in the Tigray region of Ethiopia. We generated a high-quality reference genome for E. pilosa and found extensive chromosomal collinearity and minimal gene loss compared to teff, with teff-specific genes enriched in functions related to domestication traits. We identified signatures of selection across the teff genome and used genome-wide association studies (GWAS) to map loci associated with seed color and panicle architecture. Integrated GWAS, expression, metabolic, and comparative genomic analyses pinpoint a major seed color locus containing orthologs of the TT7 cytochrome P450 gene involved in flavonoid hydroxylation and the TT2 MYB transcription factor regulating proanthocyanidin biosynthesis. For panicle architecture, we identified a strong association near a teff ortholog of Dense and Erect Panicle 1 (DEP1), a key regulator of inflorescence structure in rice and sorghum. This suggests convergent selection on shared genetic pathways controlling panicle morphology across cereals. Our findings confirm the evolutionary origin of teff, identify key domestication loci, and highlight untapped genetic diversity among Ethiopian breeding lines. These genomic resources provide a foundation for accelerating teff improvement through molecular breeding and genome editing to enhance yield, resilience, and nutrition.

plant biology↗

bioRxiv2025

Investigating Rat-Brain Normal Tissue and Tumor FLASH Effects with a Novel Very High Energy Electron Beam

PurposeUltra-high dose rate (FLASH) irradiation is reported to reduce normal tissue toxicity while maintaining tumor control, however mechanism(s) remain obscure. To study FLASH mechanisms in brain tissue, we developed a novel experimental platform featuring a unique high-energy electron linear accelerator (High Intensity Gamma Source, HIGS) paired with an organotypic ex vivo brain metastasis model. MethodsWe varied inter-pulse spacing to modulate the mean dose rate (MDR) of our unique 35 MeV electron beam, while maintaining extremely high instantaneous dose rate (IDR), and used film dosimetry to characterize dosimetry and targeting accuracy. We combined this HIGS-FLASH beam with an organotypic rat brain slice/breast carcinoma co-culture model of brain metastasis to assess effects on normal and neoplastic tissues. Live cell and bioluminescence imaging demonstrated cancer cell growth effects, while normal tissue responses and immune activation were assessed with live cell imaging, cytokine profiles, and confocal microscopy. We performed comparison experiments with 20 MeV electrons from a Varian clinical linear accelerator (VCLA) operating at conventional dose rate. ResultsThe highest IDR of the HIGS-FLASH beam to-date was 20.7 {+/-} 0.6 MGy/s, with maximum MDR of 20.7 MGy/s (1 s pulse of 20.7 Gy). Beam targeting was accurate to < 1 mm and reproducible. HIGS-FLASH and VCLA dose rates equivalently decreased cancer cell growth. HIGS-FLASH irradiation significantly increased TNF and fractalkine levels and confocal microscopy revealed distinct changes in microglial morphology in normal brain slices, suggesting microglia activation following HIGS-FLASH irradiation. ConclusionsOur novel experimental platform produces extremely high dose rates and rapid normal/neoplastic tissue readouts for mechanistic research into the effects of FLASH radiation on the brain. HIGS-FLASH irradiation induces comparable cancer cell growth inhibition but differential effects on cytokines and microglial morphology, suggesting that acute innate immune responses may be involved in FLASH normal tissue effects in the brain.

cancer biology↗

bioRxiv2025

Distributional Data Analysis Uncovers Hundreds of Novel and Heritable Phenomic Features from Temporal Cotton and Maize Drone Imagery

Genomic and phenomic analyses suggest additional heritable phenomic features can improve modeling of important end traits like senescence or yield. Field phenotyping generally uses trait values averaged across individual experimental units (plants or numerous plants within plots), ignoring the full distributional pattern of collected measures. Images of plants or plots, as captured by drones (unoccupied aerial vehicles / UAVs / drones), can be viewed as individual distribution functions that capture biological information. This study introduces and validates distributional data analysis in two crops and experiment types - cotton (Gossypium hirsutum L.) single plant vegetation index (VI) analysis and maize (Zea mays L.) plot-level yield predictions. In both crops, the concept of within-day variance decomposition was demonstrated. In cotton, genotypes exerted significant influences on temporal quantile functions of VIs. Maize yield prediction using distributional data with elastic-net regression indicated improvements in yield prediction between 12.7%-21.6% with quantiles outside the conventionally used median responsible for added predictive power. A novel data visualization method for per-pixel heritability allowed distributional features to be explainable and interpretable. These results have implications for future plant phenomic studies, indicating that distributional data analysis applied across temporal imagery captures novel, heritable, and interpretable biological signal that is lost when working with conventional measures of central tendency such as mean or median summary values of experimental units. SignificanceRepeated aerial imaging of agricultural experiments produces image data sets that capture plant development in high spatial and temporal resolutions. Frequently, images are summarized by measures of central tendency, such as mean or median values. Here, functional data distributional methods were applied to cotton (Gossypium hirsutum L.) and maize (Zea mays L.) image data, capturing more information than standard approaches. Cotton genotypes significantly impacted distributional spectral data while in maize, distributional data enabled more accurate predictions of grain yield versus models trained with median data alone. Distributional data were more explainable by genetics, with novel data visualization techniques able to shine light on specific parts of plant imagery with high and low genetic variance.

plant biology↗

bioRxiv2025

High-resolution imaging reveals a cascade of interconnected cellular bioeffects differentiating the long-term fates of sonoporated cells

Low-intensity ultrasound combined with microbubbles is a promising, non-invasive treatment strategy for enhancing vascular permeability and targeted intracellular drug or gene delivery. After ultrasound insonification, cells can undergo reversible sonoporation, involving adaptation and recovery, or irreversible sonoporation, marked by a loss of cell viability. To design effective sonoporation-based therapeutic delivery strategies, it is therefore critical to identify the biological responses that determine these distinct cell fates. Here, we developed a custom-built high-resolution multicolour imaging device and applied a single pulse of ultrasound (267 kHz frequency, 20 s duration, and [~]110 kPa peak-negative pressure) to trigger targeted microbubble-mediated reversible and irreversible sonoporation events within a confluent monolayer of cultured Madin-Darby canine kidney (MDCK) II cells. We found that intracellular calcium levels rose rapidly and peaked within 10 s in both types of sonoporated cells, although the levels declined differently. In reversibly sonoporated cells, these levels gradually returned to baseline, whereas in irreversibly sonoporated cells, they dropped rapidly, falling well below baseline within 7.9 {+/-} 3.0 min (mean {+/-} s.d.). Using single-vesicle imaging, we further found that vesicles containing the tight junction protein claudin-5 remained mobile with subtly reduced movement in reversibly sonoporated cells, whereas they almost stalled in irreversibly sonoporated cells. The underlying microtubule network was partially disrupted in the reversibly sonoporated cells, recovering fully within 3.2 {+/-} 2.9 min (mean {+/-} s.d.). In contrast, in irreversibly sonoporated cells, the entire microtubule network collapsed within 4.0 {+/-} 2.4 min (mean {+/-} s.d.). Whilst in reversibly sonoporated cells, the uptake of the model drug propidium iodide was mild-to-moderate, without drastic cell size changes up to about 1 h post-sonication, irreversibly sonoporated cells presented with substantially higher propidium iodide uptake and shrunk completely within 43.2 {+/-} 10.5 min (mean {+/-} s.d.). Together, our study identified distinct spatiotemporal sequences of interconnected biological responses underlying different fates of sonoporated cells, providing a framework for identifying processes that could be manipulated for safe and effective sonoporation-based drug delivery.

pharmacology and toxicology↗

bioRxiv2025

Archaeological Bolivian maize genomes suggest Inca cultural expansion augmented maize diversity in South America

Previous archaeological and anthropological studies have demonstrated the myriad of ways that cultural and political systems shape access to food and food preferences. However, few studies have conducted a biocultural analysis linking specific genotypic/phenotypic traits as evidence of cultural selection in ancient contexts. Here, we provide insight into this topic through ancient genome data from Bolivian maize dating to [~]500-600 BP, included as an offering with the mummified remains of a young girl. These data are compared to 16 previously published archaeological maize samples spanning at least 5,000 years of evolution, and 226 modern maize samples. Our phylogenetic analysis showed that the archaeological Bolivian maize (aBM) has the closest genetic distance to the archaeological maize from ancient Peru, which in turn shared the most similarities with archaeological Peruvian maize. During the period of interaction between the Inca state and local polities in the central Andes and consequent interactions with local agricultural traditions, the genetic diversity of maize increased. Ovule development in modern maize was selected and compared to those in archaeological specimens, revealing evidence of targeted breeding strategies aimed at improving seed quality and yield. While the cultural origin of the maize - either Inca or local Aymara - is uncertain, we demonstrate that the samples are most similar to Peruvian maize and potential targeted selection strategies for enhanced growth were well established by the 15th century. Significance StatementMaize has been improved through selective breeding delivering desirable horticultural, agronomic, and cultural characteristics, related to environment, nutrition, etc. Inca culture was closely associated with maize diversity, but there is little evidence to show how and why culture influenced that diversity and modern maize biogeographic patterns in South America. We show that in the 15th century CE, maize diversity in the central Andes was enhanced through selection for specific traits associated with reproduction. We hypothesize that this may have contributed to maize becoming a staple under the Inca, as happened previously with expanding Tiwanaku interactions and influence during the Middle Horizon.

plant biology↗

bioRxiv2025

Progesterone regulation of cervix ripening in preterm and term birth

The cervix functions both as gatekeeper barrier to maintain pregnancy and virtually vanish for birth at term in mammals. The period of remodeling well-before term is characterized by an inflammatory process associated with reduced cell nuclei density and cross-linked collagen, as well as increased density of resident macrophages in cervix stroma. Contemporarily, progesterone (P4) is at or near peak concentrations in maternal circulation. The functional or actual loss of response to P4 is thought to drive the process that enhances uterine contractile activity for labor and parturition at term. The objective of the present study was to determine if actual or functional loss of P4 regulated cytomorphological characteristics associated with prepartum cervix ripening at term and with preterm birth. On day 16 of pregnancy. Ovaries were removed to eliminate the main source of P4 production and a silastic capsule implanted (with vehicle or P4, Ovx or Ovx+P4, respectively). Controls received a vehicle-filled capsule, while a P4 capsule was implanted into an addition group of Intact mice to ensure sustained concentrations throughout pregnancy (Intact+P4). Pups were born in controls at term (days 19-20 postbreeding), but deliveries were preterm in Ovx mice within 24h (day 17). In the Ovx+P4 group, births were delayed to term and post-term in most Intact+P4 mice with adverse pregnancy outcomes commonplace. Characteristics of cell nuclei and degradation of cross-linked collagen were advanced with preterm birth in Ovx mice compared to controls that gave birth by at term. Treatment of Ovx mice with P4 blocked preterm birth, but parturition was complicated by dystocia. In addition, P4 given to ovary-intact mice sustained peak pregnancy concentrations, but had minimal effects on cytoarchitecture of the prepartum cervix stroma except term birth was forestalled with dystocia and fetal morbidity. Density of resident macrophages in the cervix stroma in term Ovx+P4 mice was reduced along with area of macrophage stain versus postpartum controls. Thus, analyses of cervix cellular cytoarchitecture provided useful biomarkers of local inflammation to assessment the ripening process for preterm and term parturition. Collectively, findings suggest a functional loss of prepartum cervix responses to progesterone are part of a final common mechanism for parturition across mammals. SummaryLoss of response to progesterone withdrawal is associated with cervix ripening while some cytoarchitectural characteristics of remodeling are regulated to block preterm birth and dystocia at term

physiology↗