Biology subjects

Nguyen, D. K.

Publications and source records attributed to Nguyen, D. K..

5 recordsLinked to original sources

bioRxiv2026

H2A.Z levels control the timing of major events at the maternal-zygotic transition

Across animals, early embryonic events are temporally tightly coordinated but the underlying mechanisms remain incompletely understood. In Drosophila, both global and nuclear levels of the histone variant H2Av rise progressively during the maternal-zygotic transition (MZT), but whether this increase is functionally important is unknown. We find that increased H2Av dosage expedites specific MZT events: the transition from nuclear cycle (NC) 13 to 14 occurs prematurely as does the turnover of thousands of maternal transcripts; in addition, a subset of genes is precociously expressed in the zygote. Reduced H2Av dosage has reciprocal effects. Comparable transcriptional shifts are observed in zebrafish embryos overexpressing the H2Av ortholog H2A.Z, suggesting H2Av/H2A.Z dosage as a conserved timer of early development. We also examined mutants with impaired H2Av sequestration on lipid droplets which exhibit increased nuclear H2Av levels but reduced cytoplasmic levels. Unexpectedly, nuclear H2Av abundance influences the timing of NC 13 but is not the main driver of transcriptome remodeling. In summary, we find that H2Av/H2A.Z levels are critical timers of early embryogenesis and that H2Av can act in part via a non-nuclear mechanism. Author summaryIn animals, the earliest stages of embryogenesis are initially driven by proteins and RNAs that the mother provides via the egg; later development is controlled by the embryos own genes. The switch from maternal to zygotic control is called the maternal-zygotic transition (MZT). This conserved process involves degradation of maternal mRNAs, activation of zygotic genes, cell cycle lengthening, and morphological remodeling. All these events require precise control, but how they are coordinated remains incompletely understood. Here we show that the levels of a specific histone, H2A.Z, provide a timer for the MZT. In Drosophila, H2A.Z levels - both in the embryo overall and in nuclei - increase during the MZT. When we ectopically increased H2A.Z levels, specific MZT events occurred prematurely. Reducing H2A.Z levels had the opposite effect. Using mutant flies in which H2A.Z levels are ectopically increased in the nucleus but reduced in the embryo as a whole, we uncovered both nuclear and non-nuclear roles for H2A.Z in the establishment of developmental timing. Moreover, we observed similar outcomes in genetically manipulated zebrafish embryos. Our results are consistent with an ancient mechanism in which H2A.Z abundance functions as a timer of early embryogenesis.

developmental biology↗

bioRxiv2025

The Hemodynamic Response Function Varies Across Anatomical Location and Pathology in the Epileptic Brain

The hemodynamic response function (HRF) links neuronal activity to functional magnetic resonance imaging (fMRI) signals. While most fMRI studies use a "canonical" HRF, increasing evidence from studies of healthy subjects suggests that the HRF depends on anatomical location and disease states. Here, we investigate how HRF variability relates to anatomical location and pathology in the epileptic brain, using a large simultaneous electroencephalogram and fMRI dataset. Applying HRF deconvolution and temporal decomposition, we built the first whole-brain HRF library specific to epilepsy, identifying four distinct shape groups. We mapped HRF features across parcellations of two atlases using novel Bayesian hierarchical models. In non-epileptogenic regions, HRF shape and spatial distributions align with findings from healthy subjects. Within pathological regions, they vary significantly according to pathology. Our results indicate that HRF variability is associated with pathology, in addition to its dependence on anatomical location, motivating region- and pathology-based HRF modulation in epilepsy studies.

neuroscience↗

bioRxiv2025

A high throughput assay to detect enzymatic polyethylene oxidation

Biological plastics deconstruction and upcycling have emerged as a sustainable alternative to traditional recycling technologies for plastics waste. The discovery and engineering of efficient thermostable poly(ethylene terephthalate) (PET) hydrolases has made biological PET recycling possible at scale; however, enzymes for non-PET plastics, which account for approximately 70% of all plastics produced, remain largely undiscovered. To accelerate the discovery of such enzymes, a high throughput screening (HTS) platform is needed. Here, we develop a HTS liquid-based assay to detect one of the first committed steps of polyolefin degradation, oxidation of the C-H bond to an aldehyde. We test 4-hydrazino-7-nitro-2,1,3-benxoxadiozole hydrazine (NBD-H), which reacts with generated aldehydes to form a fluorescent hydrazone, on oxidized low-density polyethylene (LDPE) films. Hydrazone generation correlated well with established carbonyl index metrics for polymer oxidation (R2 = 0.97). Moreover, we demonstrate that the probe reliably identifies LDPE-active dye decolorizing peroxidases (DyPs) that generate aldehydes on LDPE films, serving as effective screen as demonstrated by a receiver operating characteristic area under the curve of 0.95. Due to the rapid fluorescent readout and parallelization in microarray plates, this assay enables screening thousands of enzymes in 24 hours compared to time-consuming established approaches, accelerating discovery of enzymes that catalyze the first step of polyolefin biodeconstruction.

biochemistry↗

bioRxiv2023

Pain reflects the informational value of nociceptive inputs.

Pain perception and its modulation are fundamental to human learning and adaptive behavior. This study investigated the hypothesis that pain perception is tied to pains learning function. Thirty-one participants performed a threat conditioning task where certain cues were associated with a possibility of receiving a painful electric shock. The cues that signalled potential pain or safety were regularly changed, requiring participants to continually establish new associations. Using computational models, we quantified participants pain expectations and prediction errors throughout the task and assessed their relationship with pain perception and electrophysiological responses. Our findings suggest that subjective pain perception increases with prediction error, that is when pain was unexpected. Prediction errors were also related to physiological nociceptive responses, including the amplitude of the nociceptive flexion reflex and EEG markers of cortical nociceptive processing (N2-P2 evoked potential and gamma-band power). Additionally, higher pain expectations were related to increased late event-related potential responses and alpha/beta decreases in amplitude during cue presentation. These results further strengthen the idea of a crucial link between pain and learning and suggest that understanding the influence of learning mechanisms in pain modulation could help us understand when and why pain perception is modulated in health and disease.

neuroscience↗

bioRxiv2021

PRE-CLINICAL IMMUNE RESPONSE AND SAFETY EVALUATION OF THE PROTEIN SUBUNIT VACCINE NANOCOVAX FOR COVID-19

The Coronavirus disease-2019 (COVID-19) pandemic caused by the Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2), has become a dire global health concern. The development of vaccines with high immunogenicity and safety is crucial for control of the global COVID-19 pandemic and prevention of further illness and fatalities. Here, we report development of SARS-CoV-2 vaccine candidate, Nanocovax, based on recombinant protein production of the extracellular (soluble) portion of the S protein of SARS-CoV-2. The results showed that Nanocovax induced high levels of S protein-specific IgG, as well neutralizing antibody in three animal models including Balb/C mice, Syrian hamsters, and non-human primate (Macaca leonina). In addition, the viral challenge study using the hamster model showed that Nanocovax protected the upper respiratory tract from SARS-CoV-2 infection. No adverse effects were induced by Nanocovax in swiss mice (Musmusculus var. Albino), Rats (Rattus norvegicus), and New Zealand rabbits. These pre-clinical results indicated that Nanocovax is safe and effective.

immunology↗