Biology subjects

Douglas, L.

Publications and source records attributed to Douglas, L..

4 recordsLinked to original sources

bioRxiv2025

Deletion or Targeted Blockade of FcγRIIb (CD32b) Impairs α-Syn Propagation In-Vivo

Parkinsons disease (PD), the most common neurodegenerative movement disorder, is characterised by pervasive deposition of alpha-synuclein (-Syn) aggregates and the death of dopaminergic neurons. Fc gamma receptor IIb (Fc{gamma}RIIb or CD32b), the sole inhibitory Fc{gamma}R in humans (h) and mice (m), serves as a molecular conduit for intercellular -Syn transmission in-vitro. Here, we demonstrate that Fc{gamma}RIIb facilitates -Syn propagation and neurotoxicity in-vivo using the pre-formed fibril (PFF) -Syn model in mice. Genetic ablation of mFc{gamma}RII attenuated PFF -Syn-induced Lewy pathology, dampened associated neuroinflammatory responses, and preserved nigrostriatal dopaminergic neurons. Furthermore, pharmacological blockade of hFc{gamma}RIIb using clinically-related monoclonal antibodies mitigated acute-phase -Syn pathology in hFc{gamma}RIIb-transgenic mice following PFF challenge. Collectively, our results indicate that Fc{gamma}RIIb is a mediator of -Syn propagation in-vivo and highlight it as a tractable therapeutic target against -synucleinopathies like PD.

neuroscience↗

bioRxiv2025

Constitutive NF-kB Activation is Amplified by VSV in Aggressive PC3 Prostate Cancer Cells that Resist Viral Oncolysis

Cancer cells often have defects in antiviral pathways, making them susceptible to oncolytic viruses like vesicular stomatitis virus (VSV). However, some cancer cells resist viral infection through the constitutive expression of interferon-stimulated genes. This study examined whether NF-{kappa}B activation and NF-{kappa}B-dependent antiviral signaling contributes to resistance to VSV infection in the PC3 cell line, derived from an aggressive metastatic prostate cancer (PrCa) tumor. We found that NF-{kappa}B localized to the nucleus in VSV-infected PC3 cells, but not in the VSV-susceptible LNCaP PrCa cell line. Analysis of the upstream NF-{kappa}B inhibitor I{kappa}B- revealed higher levels of both total and phosphorylated I{kappa}B- in PC3 cells compared to LNCaP cells, indicating constitutive activation of the NF-{kappa}B pathway via an I{kappa}B--dependent mechanism. Notably, VSV infection did not alter I{kappa}B- phosphorylation in PC3 cells, suggesting that VSV may amplify NF-{kappa}B signaling through an I{kappa}B--independent pathway. Furthermore, PC3 cells displayed elevated levels of the NF-{kappa}B p65 protein subunit compared to LNCaP cells, with its phosphorylated form significantly increased upon VSV infection. These results from phosphorylation assays confirm that multiple steps in the NF-{kappa}B pathway are differentially activated in PC3 and LNCaP cells. Additionally, the expression of several NF-{kappa}B-dependent cytokine and proinflammatory genes, including IL12 and IL6, were upregulated following VSV infection in PC3 cells, as compared to LNCaP cells. Blocking the NF-{kappa}B pathway using a pharmaceutical inhibitor resulted in increased PC3 cell death with VSV infection. Collectively, these findings suggest that enhanced NF-{kappa}B signaling may underlie the resistance of PC3 cells to VSV oncolysis, potentially offering new insights into therapeutic strategies targeting NF-{kappa}B in resistant prostate cancers.

cancer biology↗

bioRxiv2024

Longitudinal evidence for the emergence of multiple intelligences in assistance dog puppies

Cognitive test batteries suggest that adult dogs have different types of cognitive abilities that vary independently. In the current study, we tested puppies repeatedly over a crucial period of development to explore the timing and rate at which these different cognitive skills develop. Service dog puppies (n = 113), raised using two different socialization strategies, were either tested longitudinally (n =91) or at a single time point (n = 22). Subjects tested longitudinally participated in the battery every two weeks during and just beyond their final period of rapid brain growth (from approximately 8-20 weeks of age). Control puppies only participated in the test battery once, which allowed us to evaluate the impact of repeated testing. In support of the multiple intelligences hypothesis (MIH), cognitive skills emerged at different points across the testing period, not simultaneously. Maturational patterns also varied between cognitive skills, with puppies showing adult-like performance on some tasks only weeks after a skill emerged, while never achieving adult performance in others. Differences in rearing strategy did not lead to differences in developmental patterns while, in some cases, repeated testing did. Overall, our findings provide strong support for the MIH by demonstrating differentiated development across the cognitive abilities tested.

animal behavior and cognition↗

bioRxiv2024

Terrestrial 3D Laser Scanning for Ecosystem and Fire Effects Monitoring

Long-term terrestrial ecosystem monitoring is a critical component of documenting outcomes of land management actions, assessing progress towards management objectives, and guiding realistic long-term ecological goals, all through repeated observation and measurement. Traditional monitoring methods have evolved for specific applications in forestry, ecology, and fire and fuels management. While successful monitoring programs have clear goals, trained expertise, and rigorous sampling protocols, new advances in technology and data management can help overcome the most common pitfalls in data quality and repeatability. This paper presents Terrestrial Laser Scanning (TLS), a specific form of LiDAR (Light Detection and Ranging), as an emerging sampling method that can complement and enhance existing monitoring methods. TLS captures in high resolution the 3D structure of a terrestrial ecosystem (forest, grassland, etc.), and is increasingly efficient and affordable (<$30,000). Integrating TLS into ecosystem monitoring can standardize data collection, improve efficiency, and reduce bias and error. Streamlined data processing pipelines can rigorously analyze TLS data and incorporate constant improvements to inform management decisions and planning. The approach described in this paper utilizes portable, push-button TLS equipment that, when calibrated with initial transect sampling, captures detailed forestry, fuels, and ecological features in less than 5 minutes per plot. We also introduce an interagency automated processing pipeline and dashboard viewer for instant, user-friendly analysis, and data retrieval of hundreds of metrics. Forest metrics and inventories produced with these methods offer effective decision-support data for managers to quantify landscape-scale conditions and respond with efficient action. This protocol further supports interagency compatibility for efficient natural resource monitoring across jurisdictional boundaries with uniform data, language, methods, and data analysis. With continued improvement of scanner capabilities and affordability, these data will shape the future of terrestrial ecosystem monitoring as an important means to address the increasingly fast pace of ecological change facing natural resource managers.

ecology↗