Biology subjects

Meehan, S.

Publications and source records attributed to Meehan, S..

6 recordsLinked to original sources

bioRxiv2026

Alfalfa intercropping maintains intermediate wheatgrass grain yield relative to nitrogen fertilization across site conditions and stand ages

Intermediate wheatgrass (IWG; Thinopyrum intermedium) is a promising perennial grain crop, but yield instability remains a major challenge. We compared effects of nitrogen fertilization and intercropping with alfalfa (Medicago sativa L.) on IWG biomass, grain yield, and root traits across three stand ages at two nearby sites in eastern Missouri differing in soil properties (Planthaven Farms and Danforth Center Field Research Site). Four treatments (unfertilized IWG, fertilized IWG, IWG-alfalfa intercrop, and alfalfa monoculture) were established in a randomized complete block design with four replications per site. Biomass and grain yield were evaluated at per-row and field scales, while roots were measured to 1 m depth during the second stand age. Alfalfa intercropping maintained IWG grain yield without synthetic N fertilizer, although treatment responses varied by site and stand age. At Planthaven, differences became more pronounced as stands matured, with intercropped IWG producing the greatest per-row biomass and grain yield in stand age three. At the Danforth Center Field Research Site, intercropped IWG produced greater per-row biomass and grain yield than monocultures, whereas fertilized IWG tended to produce greater field-scale biomass; grain yield declined across treatments with stand age. Across sites, nitrogen fertilization increased vegetative biomass more consistently than grain yield. Despite having fewer IWG rows, intercrops maintained field-scale grain yield comparable to fertilized IWG in several site-years. Root traits responded weakly to management and were structured primarily by soil depth. These findings highlight the importance of site conditions, and stand age, when evaluating management strategies for perennial grain production.

plant biology↗

bioRxiv2026

A Human Recombinant Antibody Against DRP1 Serine 616 Phosphorylation Enables Detection of BRAFV600E-Associated Mitochondrial Division in Cancer

Mitochondria are dynamic organelles that continuously undergo balanced cycles of fusion and division to meet cellular demands. Mitochondrial division is mediated by Dynamin-Related Protein 1 (DRP1), a cytosolic large GTPase whose phosphorylation at serine 616 (DRP1-S616) promotes its translocation to the outer mitochondrial membrane and organelle division. Dysregulated, mitochondrial division disrupts cellular homeostasis and contributes to disease pathogenesis, including cancer. Our prior work demonstrated that the oncogene-induced mitogen-activated protein kinase (MAPK) pathway constitutively phosphorylates DRP1 at serine 616 (DRP1-S616), which is essential to cellular transformation and correlates with oncogene status in patient tissues. Similarly, DRP1-S616 is subject to pharmacologic control by targeted therapies against oncogenic MAPK signaling. Building upon this foundation, we developed a human recombinant monoclonal antibody with high specificity for DRP1-S616, referred to as 3G11. Using diverse biochemical platforms, we demonstrate the robust utility of 3G11 to detect DRP1-S616 in melanoma cell extracts and isolated organelles. Immunofluorescence revealed that pharmacologic inhibition of oncogenic MAPK signaling reduces DRP1-S616 levels which correlates with mitochondrial hyperfusion; while immunohistochemistry showed that elevated DRP1-S616 expression in human tissues correlates with BRAFV600E disease. Together, these findings establish 3G11 as a specific, versatile, renewable, and cost-effective tool for studying mitochondrial division, with strong potential for clinical applications.

cancer biology↗

bioRxiv2025

MUDflow: Combining Neural Networks, UMAP and DBM Clustering to Identify Cell Populations Accurately, Quickly and Easily in Mass and Fluorescence Cytometry

Identifying cell populations in flow cytometry data is mostly done via a "manual gating" method that often lacks verifiability and reproducibility, even in the hands of experienced investigators. Recently developed automatic gating methods have been shown to have good performance in cell population identification, but may require fine-tuned setup from experts or struggle to identify small populations. Here, we introduce an easily trainable multilayer perceptron neural network for automatic gating (MLPgater). Compared to the three popular automatic gating methods LDA, FlowSOM and PhenoGraph on three mass and six fluorescence cytometry datasets, MLPgater is most accurate by a substantial margin, tied with LDA as the fastest and uniquely able to replace manual gating except for training purposes. Furthermore, we show that combining MLPgater with UMAPs guided dimensionality reduction feature and DBMs clustering (MUDflow) effectively detects new populations that did not exist or were not identified in the training set.

bioinformatics↗

bioRxiv2024

Microphysiological uremia model reveals biophysical potentiators of vascular dysfunction

Cardiovascular disease is a leading cause of mortality in individuals with chronic kidney disease. Hypertension, common among patients with chronic kidney disease, is a major contributor to both kidney damage and the heightened cardiovascular risk in these patients. Advanced chronic kidney disease is associated with elevated levels of circulating uremic toxins, particularly indoxyl sulfate and p-cresyl sulfate, and are known to exacerbate cardiovascular risk by promoting inflammatory processes, including monocyte adhesion, rolling, and extravasation. However, despite the established link between chronic kidney disease and cardiovascular disease, the specific role of uremic toxins in monocyte-endothelial interactions in hypertensive settings remains largely underexplored. In this study, we developed a 3D microfluidic model to examine the effects of indoxyl sulfate on monocyte adhesion and extravasation across engineered microvessels embedded in collagen hydrogels with different densities under controlled luminal pressure. We found that elevated pressure alone significantly enhanced monocyte adhesion and extravasation, regardless of matrix density, and that the uremic environment further increased these effects. Additionally, denser hydrogels primed THP-1 monocyte cells toward a pro-inflammatory like phenotype with reduced phagocytic capacity, while softer hydrogels induced an anti-inflammatory like phenotype with enhanced phagocytosis. However, exposure to the uremic environment diminished phagocytosis and shifted cells toward a pro-inflammatory like state, irrespective of matrix density. The presented approach has the potential to experimentally dissect multiple factors that contribute to elevated cardiovascular risks in chronic kidney disease patients and improve the understanding of mechanisms involved in monocyte dynamics in chronic kidney disease- related cardiovascular disease.

bioengineering↗

bioRxiv2022

Constructed Synchronized Multimodal Signalling in Great Bowerbirds

Great bowerbird males build bowers for attracting females for mating. Bowers consist of a thatched twig tunnel (avenue) which opens onto two flat courts covered with objects. Male displays on a court are seen by a female from within the avenue. She sees and hears displays through the avenue entrance but can only see the males head and objects in his bill as it passes repeatedly across the entrance. We investigated bower acoustic properties by playing standard sounds from multiple court positions and recorded the resulting sounds at the females typical avenue head position within the avenue. Bower geometry significantly affects both his acoustic and visual display components and physically synchronizes them as he repeatedly moves in and out of the females view. Consequently, complex neural circuitry is unnecessary for linking sound to vision. Experimentally removing bower objects shows that objects significantly increase higher frequencies, hence bandwidth and loudness received inside the avenue. Great Bowerbird bowers produce a synchronized multimodal signal to females which may increase male attractiveness more than if a single sensory mode were used. This multimodal signal is unusual in that it is constructed rather than being part of the body and synchronized as a result of physics rather than neurons. Summary StatementBowerbird bower geometry jointly effects both visual and auditory signal components and synchronizes them without the need for additional neural circuitry.

animal behavior and cognition↗

bioRxiv2022

Formation of amyloid loops in brain tissues is controlled by the flexibility of protofibril chains

Neurodegenerative diseases, such as Alzheimers Disease (AD), are associated with protein misfolding and aggregation into amyloid fibrils. Increasing evidence suggests that soluble, low molecular weight aggregates play a key role in disease-associated toxicity. Within these aggregates, protofibrillar loop-like structures have been observed for a variety of amyloid systems and their presence in brain tissues is associated with high levels of neuropathology. However, their mechanism of formation and relationship with mature fibrils has largely remained challenging to elucidate. Here, we use atomic force microscopy and statistical theory of biopolymers to characterise amyloid ring structures derived from the brains of AD patients. We analyse the bending fluctuations of protofibrils and show that the process of loop formation is governed by the mechanical properties of their chains. We conclude that ex vivo protofibril chains possess greater flexibility than that imparted by hydrogen-bonded networks characteristic of mature amyloid fibrils, such that they are able to form end-to-end connections. Furthermore, we show that these findings can be extended to several amyloid systems, giving a general framework relating the mechanical properties of assemblies and the conditions in which they can form loop structures. These results explain the diversity in the structures formed from protein aggregation and sheds light on the links between early forms of flexible ring-forming aggregates and their role in disease.

molecular biology↗