Biology subjects

Valentine, A.

Publications and source records attributed to Valentine, A..

3 recordsLinked to original sources

bioRxiv2026

Non-viral vasculogenic reprogramming restores cognition and mitigates pathology in Alzheimer's disease

Alzheimers Disease (AD) is characterized by progressive cognitive decline associated with amyloid-beta (A{beta}) plaques, neurofibrillaiy tangles, inflammation, synaptic loss, and profuse neuronal death. Accumulating evidence demonstrates that cerebrovascular impairment precedes the emergence of neuropathological hallmarks, implicating vascular dysfunction as an early contributor to AD onset and progression. We investigated a non-viral strategy to generate pro-vasculogenic fibroblasts by transiently overexpressing Et{upsilon}2, Foxc2, and Flii (EFF) as a potential cell-based therapy for neurovascular deficits in AD. To assess therapeutic potential, FFF-primc[d] fibroblasts were injected into a mouse model of AD (3xTg-AD) and wild-type controls via the intracerebroventricular (ICV) route, followed by cognitive assessments and subsequent brain tissue analyses. Our findings demonstrate that FFF-primed fibroblasts acquire vasculogenic properties, enhance cerebral blood flow (CBF), and alleviate spatial memory deficits in 3xTg-AD mice. Moreover, transplanted FFF-primed fibroblasts exhibited long-term survival, integrated into the brain vasculature, and promoted cortical vascular remodeling in the AD brain. Notably, ICV deployment of these cells is also correlated with reduced cortical amyloid-beta load, suggesting potential therapeutic benefits in reducing AD pathology. Transcriptomic analysis identified the activation of genes involved in fatty acid oxidation, such as Ppar, known for its anti-amyloidogenic and anti-inflammatory effects. Collectively, these findings highlight non- viral, reprogramming-based vasculogenic cell therapy as a promising strategy for Alzheimers disease, capable of alleviating cognitive decline and addressing AD pathology across cellular and tissue scales.

neuroscience↗

bioRxiv2023

Functional traits shape plant-plant interactions and recruitment in a hotspot of woody plant diversity.

O_LIUnderstanding and predicting recruitment in species-rich plant communities requires identifying the functional determinants of both density-independent performance and interactions. C_LIO_LIIn a common-garden field experiment with 25 species of the woody plant genus Protea, we varied the initial spatial and taxonomic arrangement of seedlings and followed their survival and growth during recruitment. Neighbourhood models quantified how six key functional traits affect density-independent performance, interaction effects and responses. C_LIO_LITrait-based neighbourhood models accurately predicted individual survival and growth from the initial spatial and functional composition of species-rich experimental communities. Functional variation among species caused substantial variation in density-independent survival and growth that was not correlated with interaction effects and responses. Interactions were spatially-restricted but had important, predominantly competitive, effects on recruitment. Traits increasing the acquisition of limiting resources (water for survival, soil P for growth) mediated a trade-off between competitive effects and responses. Moreover, resprouting species had higher survival but reduced growth, likely reinforcing the survival-growth trade-off in adult plants. C_LIO_LIThe combination of field experiments and trait-based neighbourhood analyses holds substantial potential for community ecology. It permits the identification of traits that mediate performance trade-offs promoting coexistence in species-rich communities and contributes key knowledge to guide conservation and restoration of biodiversity hotspots. C_LI

ecology↗

bioRxiv2022

Single cell transcriptomics uncovers a non-autonomous Tbx1-dependent genetic program controlling cardiac neural crest cell deployment and progression

Disruption of cardiac neural crest cells (CNCCs) results in congenital heart disease, yet we do not understand the cell fate dynamics as these cells differentiate to vascular smooth muscle cells. Here we utilized single-cell RNA-sequencing of NCCs from the pharyngeal apparatus with heart in control mouse embryos and when Tbx1, the gene for 22q11.2 deletion syndrome, is inactivated. We uncovered three dynamic transitions of pharyngeal NCCs expressing Tbx2 and Tbx3 through differentiated CNCCs expressing cardiac transcription factors with smooth muscle genes, and that these transitions are altered non-autonomously by loss of Tbx1. Further, inactivation of Tbx2 and Tbx3 in early CNCCs resulted in aortic arch branching defects due to failed smooth muscle differentiation. Loss of Tbx1 interrupted mesoderm to CNCC cell-cell communication with upregulation of BMP signaling with reduced MAPK signaling and failed dynamic transitions of CNCCs leading to disruption of aortic arch artery formation and cardiac outflow tract septation.

developmental biology↗