Biology subjects

Evers, J.

Publications and source records attributed to Evers, J..

5 recordsLinked to original sources

bioRxiv2025

Von Willebrand Factor Deficiency Impairs Vascular Morphogenesis via Angiopoietin-2: Relevance for Gut Angiodysplasia

Management of recurrent gastrointestinal (GI) bleeding is a clinical unmet need for patients with Von Willebrand disease (VWD) and is linked to the presence of gut vascular malformations (angiodysplasia). We previously demonstrated that von Willebrand factor (VWF) regulates angiogenesis and vascular integrity, the likely mechanism underlying angiodysplasia. VWF controls the storage of the angiogenesis regulator Angiopoietin-2 (Angpt-2) in endothelial cells (EC), suggesting a candidate for the genesis of angiodysplasia; however, no direct evidence of the role of Angpt-2 in VWF-dependent angiogenesis is available. Here we use VWF-deficient HUVEC, and endothelial colony forming cells (ECFCs) from severe VWD patients and find that loss of VWF in EC results in increased Angpt-2 expression through a positive feedback loop via the Angpt-2-TIE2-AKT-FOXO1 pathway. We also show an imbalance of the Angpt/Tie2 pathway in vivo. In the gut of VWF-deficient mice, Angpt-2 expression is increased whilst Angpt-1 expression is decreased; this correlates with reduced expression of the pericyte marker NG2. These data suggest that VWF regulates the Angpt/Tie2 balance in the gut. To investigate the functional defects caused by loss of VWF, we use a fibrin bead assay and show that VWF-deficient HUVEC present increased sprouting. We develop a microfluidic model of 3D vasculogenesis/angiogenesis and find that ECFCs from VWD patients exhibit defective remodeling and abnormal lumen formation compared to healthy controls. Importantly, inhibition of Angpt-2 reduces sprouting in VWF-deficient HUVEC and normalises vascular networks in ECFCs from severe VWD, suggesting Angpt-2 inhibitors may be effective in VWD patients with GI bleeding and angiodysplasia. Key pointsO_LIEndothelial VWF regulates multiple steps of angiogenesis, including sprouting and lumen formation. C_LIO_LIVWF regulates Angpt-2 storage and expression, and Angpt-2 blockade normalises defective angiogenesis in VWD ECFCs. C_LI Visual Abstract O_FIG O_LINKSMALLFIG WIDTH=170 HEIGHT=200 SRC="FIGDIR/small/675051v1_ufig1.gif" ALT="Figure 1"> View larger version (19K): org.highwire.dtl.DTLVardef@150eb15org.highwire.dtl.DTLVardef@179e6beorg.highwire.dtl.DTLVardef@1bcadborg.highwire.dtl.DTLVardef@a30fb8_HPS_FORMAT_FIGEXP M_FIG VWF deficiency in HUVECs results in increased Angpt-2 release and expression via the Tie2-Akt-FOXO1 pathway. A. Model pathway for the regulation of Angpt-2 levels by VWF. Loss of VWF results in increased Angpt-2 release from endothelial cells; Angpt-2 binds to and inhibits the Tie2 receptor, decreasing its phosphorylation as well as the downstream phosphorylation of Akt and FOXO1; this leads to FOXO1 activation and an increase expression of Angpt-2, generating a feedback loop. B. Model for the pathogenesis of angiodysplasia in VWD. In the absence of VWF, the increase in Angpt-2 disrupts vascular morphogenesis through multiple mechanisms: increased sprouting, impaired vascular remodelling and an imbalance between Angpt-1 and Angpt-2 in the gut. Figure generated with Biorender. C_FIG

cell biology↗

bioRxiv2025

Disentangling the contribution of trait plasticity to improve the productivity of a maize-soybean intercrop system for the Midwest, USA

Crop yields in intercropping systems are the result of a combination of factors dominated by plastic responses in plant traits to the heterogeneity associated with the intercrop design and the row configuration of the intercrop. Disentangling their relative influence is infeasible in situ but crucial for cultivar selection and intercrop design. Using functional-structural plant (FSP) modelling, these effects can be separated in silico. Here, a mechanistic FSP model was developed, including three-dimensional aboveground plant architecture of maize and soybean, radiation distribution, and assimilate allocation. The model was used to explore the potential to improve yields in a simultaneous intercrop by disentangling the contribution of three plastic traits related to photosynthesis, leaf thickness and plant height. The improved phenotypes were then simulated in two intercrop configurations, single- and twin-rows of maize, for potential increases in land-use efficiency. The study revealed that for maize, photosynthesis had the greatest contribution (+78%), followed by plant height (+31%) and leaf thickness (+6%) where the total maize monoculture phenotype produced the greatest maize yield without affecting the yield of intercropped soybean. However, soybean trait plasticity had a negligible effect on soybean yield, but the soybean monoculture phenotype with a low light-saturated photosynthetic rate resulted in the greatest intercropped maize yield. These improved phenotypes may increase land-use efficiency by 1-3% relative to the standard monoculture systems of the Midwest, USA. Together, these results could aid the selection of maize and soybean germplasm that could improve the productivity of a simultaneous intercrop.

plant biology↗

bioRxiv2024

The Virtual Plant Laboratory: a modern plant modeling framework in Julia

The Virtual Plant Laboratory (VPL) is a novel software for building, simulating, and visualizing functional- structural plant (FSP) models. FSP models focus on the interactions between plant structure, internal physiological processes, and the biotic and abiotic environment. VPL is built in the Julia programming language and is designed to be a flexible and extensible platform for FSP modeling. Using Julia brings the advantage that only one programming language is required for the whole modeling cycle as Julia is as fast as compiled languages but also dynamic as interpreted languages. VPL provides a graph rewriting system for building dynamic models of plant growth and development, an interactive 3D visualization system and a Monte Carlo ray tracer for simulating radiation interception by plant canopies. In this paper, we introduce VPL, highlighting the main components, modeling paradigms, and design decisions behind it, as well as a future roadmap for further development. We also present a short case study of a model for intercropping of legumes and cereals that was built fully with VPL, as an example of what can be built with this software. VPL is fully open source and available in all common computing platforms for anyone to use. Full documentation and tutorials are available at https://virtualplantlab.com.

plant biology↗

bioRxiv2024

Identifying and quantifying the contribution of maize plant traits to nitrogen uptake and use through plant modelling

Breeding for high nitrogen use efficient crops can contribute to maintaining or even increasing yield with less nitrogen. Nitrogen use is co-determined by N uptake and physiological use efficiency (PE, biomass per unit of N taken up), to which soil processes as well as plant architectural, physiological and developmental traits contribute. The relative contribution of these crop traits to N use is not well known but relevant to identify breeding targets in important crop species like maize. To quantify the contribution of component plant traits to maize N uptake and use, we used a functional-structural plant model. We evaluated the effect of varying both shoot and root traits on crop N uptake across a range of nitrogen levels. Root architectural traits were found to play a more important role in root N uptake than physiological traits. Phyllochron determined the structure of the shoot through changes in source: sink ratio over time which, in interaction with light and temperature, resulted in a significant effect on PE and N uptake. Photosynthesis traits were more relevant to biomass accumulation rather than yield, especially under high nitrogen conditions. The traits identified in this study are potential targets in maize breeding for improved crop N uptake and use. HighlightOur research provides insight into the relevance of a range of traits for maize N uptake and N use, and identifies several potential target traits based on underlying mechanisms to assist maize breeding.

plant biology↗

bioRxiv2023

Micromotion derived fluid shear stress mediates peri-electrode gliosis through mechanosensitive ion channels

Clinical applications for neural implant technologies are steadily advancing. Yet, despite clinical successes, neuroelectrode-based therapies require invasive neurosurgery and can subject local soft-tissues to micro-motion induced mechanical shear, leading to the development of peri-implant scaring. This reactive glial tissue creates a physical barrier to electrical signal propagation, leading to loss of device function. Although peri-electrode gliosis is a well described contributor to neuroelectrode failure, the mechanistic basis behind the initiation and progression of glial scarring remains poorly understood. Here, we develop an in silico model of electrode-induced shear stress to evaluate the evolution of the peri-electrode fluid-filled void, encompassing a solid and viscoelastic liquid/solid interface. This model was subsequently used to inform an in vitro parallel-plate flow model of micromotion mediated peri-electrode fluid shear stress. Ventral mesencephalic E14 rat embryonic in vitro cultures exposed to physiologically relevant fluid shear exhibited upregulation of gliosis-associated proteins and the overexpression of two mechanosensitive ion channel receptors, PIEZO1 and TRPA1, confirmed in vivo in a neural probe induced rat glial scar model. Finally, it was shown in vitro that chemical inhibition/activation of PIEZO1 could exacerbate or attenuate astrocyte reactivity as induced by fluid shear stress and that this was mitochondrial dependant. Together, our results suggests that mechanosensitive ion channels play a major role in the development of the neuroelectrode micromotion induced glial scar and that the modulation of PIEZO1 and TRPA1 through chemical agonist/antagonist may promote chronic electrode stability in vivo. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=144 SRC="FIGDIR/small/523766v1_ufig1.gif" ALT="Figure 1"> View larger version (41K): org.highwire.dtl.DTLVardef@962f03org.highwire.dtl.DTLVardef@1e8a6adorg.highwire.dtl.DTLVardef@116cbb6org.highwire.dtl.DTLVardef@19830da_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIPeri-electrode void progression is mediated by fluid flow shear stress C_LIO_LIOscillatory fluid flow shear stress replicates neuroelectrode glial scarring in vitro C_LIO_LIAstrocyte PIEZO1 and TRPA1 are upregulated at the peri-electrode region in response to electrode micromotion C_LIO_LIPIEZO1 pharmaceutical activation diminishes shear stress-induced gliosis C_LIO_LIPIEZO1 chemical inhibition exacerbates gliosis and reduces mitochondrial functions C_LI

neuroscience↗