Biology subjects

Summers, R.

Publications and source records attributed to Summers, R..

6 recordsLinked to original sources

bioRxiv2026

High-content imaging of live microglia-containing Alzheimer's disease brain organoids

Alzheimer's disease (AD) is the most common progressive neurodegenerative disease for which there is currently no safe and effective treatment. AD is characterized by the pathological aggregation of amyloid-{beta} (A{beta}) in the brain resulting in neuronal dysfunction/death and cognitive decline. Modeling these processes in vitro remains challenging due to the lack of an immune-competent 3D in vitro human model of AD amenable to high-throughput analyses. Conventional cerebral organoids (COs) lack microglia and are optically dense which precludes real-time longitudinal analyses. Here, we employ the fluorescent amyloid probe PyrPeg to selectively monitor A{beta} aggregation, and calcein AM and propidium iodide to assess cellular viability within microglia-containing COs (MCOs). We identify age-dependent DS-AD-associated phenotypes within T21 MCOs including A{beta} neuropathology, neurodegeneration, and glial cell dysregulation. Our platform supports real-time, multiplexed tracking of disease progression and provides a scalable platform for longitudinal analyses studying disease mechanisms and targeted approaches to treatment.

neuroscience↗

bioRxiv2026

An open imaging and AI resource enabling unbiased quantification of extrachromosomal DNA at scale

Quantitative imaging of extrachromosomal DNA (ecDNA) is increasingly important for studying cancer heterogeneity and adaptation, yet automated analysis has been limited by the absence of accessible imaging data, gold standard annotations and adaptable computational tools. Here we establish an open resource for computational ecDNA imaging, integrating 2,986 native-resolution metaphase FISH image sets with manual annotations, standardized benchmarks and open-source quantification frameworks. We use this resource to systematically compare existing and newly developed approaches spanning rule-based computer vision, deep-learning-based segmentation and probabilistic localization. This comparison reveals count-dependent underestimation that distorts ecDNA copy-number distributions and motivates ecCount, a probabilistic localization method developed here to preserve individual ecDNA signals and quantitative burden. ecCount achieves an object-level F1 score of 0.939 on held-out images with minimal count bias. Together, the images, annotations, retrainable models, evaluation tools and guided workflows provide community infrastructure for applying, adapting and improving automated ecDNA quantification across experimental systems.

genetics↗

bioRxiv2026

Trisomy 21 cerebral organoids exhibit Alzheimer's disease amyloid and apolipoprotein E co-pathologies

Adults with Down syndrome (DS) develop Alzheimers disease (AD) brain pathology by age 40 due to triplication of the Amyloid Precursor Protein (APP) gene on chromosome 21. Inheritance of the apolipoprotein E-e4 (APOE4) allele of the APOE gene on chromosome 19 remains the greatest genetic risk factor for AD in the typical population, yet its role in DS-associated AD (DS-AD) neuropathogenesis in people with DS is unclear. We generated human induced pluripotent stem cell (hiPSC)-derived neurons, astrocytes, and cerebral organoids (COs) using cells from people with DS and from euploid individuals. Aged DS COs were smaller than aged euploid COs and showed robust amyloid-{beta} neuropathology that was positively correlated with the levels of apoE expression. We then captured extracellular vesicles (EVs) from the conditioned media of COs and observed a decrease in the levels of secreted AD-related proteins, including amyloid, contained within the EVs and in the media from which the EVs were isolated. We also identified distinct neuronal and astrocytic gene expression signatures in DS COs relative to euploid COs, including a set of genes known to interact with both APOE and APP at the gene and/or protein levels. Lastly, we determined that, despite differences in the expression levels of the specific genes involved, several common pathways were upregulated in T21 hiPSC-derived neurons, astrocytes, and COs, including apoptosis, the endolysosome, and structural stabilization pathways. Taken together, our findings provide novel insights into molecular mechanisms that may contribute to DS-AD and indicate that apoE plays an important role in the disease process.

neuroscience↗

bioRxiv2025

Regenerative agriculture effects on biomass, drought resilience and 14C-photosynthate allocation in wheat drilled into ley compared to disc or ploughed arable soil

Regenerative agriculture practices including leys and no-tillage facilitate biological reassembly of soil aggregates, increasing water, carbon and nutrient storage, but how this effects crop biomass, photosynthate partitioning, and drought resilience is unclear. To address this, we took monoliths growing semi-dwarf and taller wheat genotypes from 3-year plots that were ploughed or disc cultivated, or direct-drilled into a grass-clover ley and applied 35 kg N ha-1. Half the monoliths received a spring drought, then all were watered and the wheat 14CO2 pulse-labelled at stem elongation. The ley soil had lower bulk density, stored more water, and the taller wheat genotype maintained 8-fold higher proportion of water-stable macroaggregates despite unexpectedly having the smaller root biomass. Yields on the ley soil (3.74 t ha-1) were 77% -123% higher than on ploughed and disc cultivated soils, and unaffected by genotype or drought, despite its >70% reduction in root biomass. Of the 14C initially retained in wheat, 72% was in shoots, with root allocation decreasing by 75-90% in droughted ley soil, and at harvest soil retained <1% of the 14C, with significantly lower values for taller wheat, and ley. We conclude that soil health regeneration in the ley enhanced wheat yields, but reduced photosynthate allocation to root biomass under drought. Although taller wheat maintained better macroaggregation in ley soil, this was not explained by root biomass or photosynthate allocation and unexpectedly failed to increase soil 14C sequestration. We find no evidence that ley regeneration of macroaggregation enhances soil C sequestration under wheat, despite higher yields.

plant biology↗

bioRxiv2025

The cellular architecture of wheat leaves supports a conservation of spatial patterning of the mesophyll in grasses

Classical botany identifies a clear adaxial/abaxial (palisade/spongy) patterning of the mesophyll in leaves of eudicots but suggest that there is no comparable overt pattern within the mesophyll of most grasses. In this paper, we report on an analysis of leaves from across ploidy levels of Triticum species which reveals a patterning of mesophyll cellular architecture that has been maintained during the evolution/selection of wheat. Taking a quantitative approach to the analysis of 2D and 3D images, we show that upper and lower mesophyll cells are larger than the middle mesophyll cells, which are themselves more lobed than the mesophyll cells adjoining the upper and lower epidermis. This mesophyll patterning is superimposed on a gradual increase of cell size with ploidy, suggesting that it is evolutionarily ancient. Taken in the context of data revealing patterning of the rice mesophyll, our data support the hypothesis that grass leaves do display distinct cellular patterning across the adaxial/abaxial axis, the functional significance of which awaits full elucidation.

plant biology↗

bioRxiv2019

Incidence, predictors and reasons for initial regimen modifications in patients on antiretroviral therapy in Witbank, South Africa, 2003-2017

BackgroundAntiretroviral therapy (ART) is associated with unpleasant adverse effects that may require modification of regimens. ART modifications may lead to poor treatment outcomes. We determined the incidence, reasons and predictors for modification of initial ART regimens.\n\nMethodsWe retrospectively analysed data from Witbank pharmacovigilance sentinel site, South Africa. Censoring targeted the first incident of ART modification from the initial regimen. We included human immunodeficiency virus (HIV)-infected patients on ART, aged more than 18 years. We used the Cox-proportional hazard model to identify predictors for changing initial ART regimens.\n\nResultsAmong 2, 045 eligible patients, 38% (n=783) had their initial ART regimens changed. The overall incidence rate of ART modification was 10.0 per 100 person-years within a follow-up period of 7 794.6 person-years (PYs). Reasons for changing were adverse drug reactions (ADRs) (60%), prescribers decisions (37%), drug toxicity (26%) and treatment failure (12%). The most commonly changed regimens were stavudine (68%) and zidovudine (44%) based regimens. Stavudine-based regimen had the highest changing rate of 13.6 per 100 PYs compared to zidovudine (8.0 per 100 PYs) and tenofovir (6.5 per 100 PYs). Using tenofovir as reference, stavudine (aHR 2.3; 95% CI 1.8-2.9; p<0.001) and zidovudine (aHR 1.5; 95% CI 1.2-3.2; p<0.001) based regimens were significantly associated with regimen modifications. The predictors for changing ART regimens included drug toxicity (aHR 2.6; 95% CI 2.1-3.1), ADRs (aHR 2.1; 95% CI 1.3-3.2), treatment failure (aHR 2.0; 95% CI 1.5-2.4), baseline cd4 count of [≥]200 (aHR 1.7; 95% CI 1.3-2.1) and initiation regimens (stavudine and zidovudine).\n\nConclusionThe findings were suggestive of a moderate incidence of initial ART regimen changing. Patients on stavudine and zidovudine based regimens changed primarily due to ADRs and drug toxicity. We recommended that clinicians should consider changing patients who are still on stavudine-containing regimens, however, changing should be individualized.

epidemiology↗