Biology subjects

Ong, J. L.

Publications and source records attributed to Ong, J. L..

5 recordsLinked to original sources

bioRxiv2026

Myeloperoxidase (MPO) exacerbates dengue-associated liver injury and contributes to disease pathogenesis in mouse models

Severe dengue can damage the liver through unestablished mechanisms. We investigated the role of myeloperoxidase (MPO), a neutrophil enzyme, in dengue through patients, fatal liver samples, and mouse infection models. Observations from two independent clinical cohorts revealed elevated plasma MPO levels in dengue and, in one cohort, MPO was further linked to liver injury markers during the critical phase of disease, whereas livers from dengue fatal cases revealed MPO build-up in the vicinity of CD177+ activated neutrophils. In mice, dengue led to MPO overexpression, oxidative damage, and broad activation of innate and systemic inflammatory pathways in livers. Blocking MPO activity alleviated these and improved survival in one model and delayed disease progression without preventing death in another. These findings establish MPO as a functional mediator of severe dengue-associated liver injury and inflammation, which warrants further preclinical investigation into its hepatic pathogenic mechanism and its validity as target for therapeutic intervention.

pathology↗

bioRxiv2026

Nanoluciferase reporter preserves immunocompetent glioma model fidelity while facilitating longitudinal molecular imaging

Glioblastoma studies employ syngeneic orthotopic models to preserve tumor-immune interactions, but intracranial tumor burden is challenging to monitor longitudinally. Bioluminescence imaging enables non-invasive assessment, although reporter immunogenicity may compromise model fidelity. We engineered murine GL261 glioma cells to stably express nanoluciferase (NLuc) and compared them with parental GL261 (WT) and GL261 cells expressing red-shifted firefly luciferase (Red-FLuc). In vitro, GL261-NLuc retained growth kinetics and morphology comparable to GL261-WT and produced >100-fold stronger bioluminescence than GL261-Red-FLuc. In immunocompetent mice, GL261-NLuc formed lethal brain tumors with survival and tumor histopathology, immune profile, and response patterns to experimental oncolytic virus therapy broadly resembling GL261-WT. In contrast, GL261-Red-FLuc tumors regressed and exhibited heightened inflammation and increased infiltration of activated CD8+ T-cells. Longitudinal imaging of GL261-NLuc tumors detected treatment-associated changes in growth kinetics not captured by survival alone. These establish GL261-NLuc as a practical reporter for longitudinal immunocompetent glioblastoma studies amenable to immunotherapy evaluations.

molecular biology↗

bioRxiv2020

Splitting sleep between the night and a daytime nap reduces homeostatic sleep pressure and enhances long-term memory

Daytime naps have been linked with enhanced memory encoding and consolidation. It remains unclear how a daily napping schedule impacts learning throughout the day, and whether these effects are the same for well-rested and sleep restricted individuals. We compared memory in 112 adolescents who underwent two simulated school weeks containing 8 or 6.5 hour sleep opportunities each day. Sleep episodes were nocturnal or split between nocturnal sleep and a 90-min afternoon nap, creating four experimental groups: 8h-continuous, 8h-split, 6.5h-continuous and 6.5h-split. Declarative memory was assessed with picture encoding and an educationally realistic factual knowledge task. Splitting sleep significantly enhanced afternoon picture encoding and factual knowledge under both 6.5h and 8h durations. Splitting sleep also significantly reduced slow-wave activity during nocturnal sleep, suggesting lower homeostatic sleep pressure during the day. There was no negative impact of the split sleep schedule on morning performance, despite a reduction in nocturnal sleep duration. These findings suggest that naps could be incorporated into a daily sleep schedule that provides sufficient sleep and benefits learning.

neuroscience↗

bioRxiv2019

Cognitive vulnerability to sleep deprivation is robustly associated with two dynamic connectivity states

Robustly linking dynamic functional connectivity (DFC) states to behaviour is an important goal of the fledgling research using these methods. Previously, using a sliding window approach, we identified two dynamic connectivity states (DCS) linked to arousal. Here, in an independent dataset, 32 healthy participants underwent two sets of resting-state functional magnetic resonance imaging (fMRI) scans, once in a well-rested state and once after a single night of total sleep deprivation. Using a temporal differencing method, DFC and clustering analysis on the resting state fMRI data revealed five centroids that were highly correlated with those found in previous work, including the two states associated with high and low arousal. Individual differences in cognitive vulnerability to sleep deprivation were measured using changes in Psychomotor Vigilance Test (PVT) performance (lapses and median reaction speed), Changes in the percentage of time spent in the arousal states from the well-rested to the sleep-deprived condition specifically were correlated with declines in PVT performance. Our results provide good evidence of the validity and reproducibility of DFC measures, particularly with regard to measuring arousal and attention, and are an encouraging base from which to build a chronnectome mapping DCS to cognition.

neuroscience↗

bioRxiv2018

Optimization of Golden Gate assembly through application of ligation sequence-dependent fidelity and bias profiling

Modern synthetic biology depends on the manufacture of large DNA constructs from libraries of genes, regulatory elements or other genetic parts. Type IIS restriction enzyme-dependent DNA assembly methods (e.g., Golden Gate) enable rapid one-pot, ordered, multi-fragment DNA assembly, facilitating the generation of high-complexity constructs. The order of assembly of genetic parts is determined by the ligation of flanking Watson-Crick base-paired overhangs. The ligation of mismatched overhangs leads to erroneous assembly, and the need to avoid such pairings has typically been accomplished by using small sets of empirically vetted junction pairs, limiting the number of parts that can be joined in a single reaction. Here, we report the use of a comprehensive method for profiling end-joining ligation fidelity and bias to predict highly accurate sets of connections for ligation-based DNA assembly methods. This data set allows quantification of sequence-dependent ligation efficiency and identification of mismatch-prone pairings. The ligation profile accurately predicted junction fidelity in ten-fragment Golden Gate assembly reactions, and enabled efficient assembly of a lac cassette from up to 24-fragments in a single reaction. Application of the ligation fidelity profile to inform choice of junctions thus enables highly flexible assembly design, with >20 fragments in a single reaction.

synthetic biology↗