Biology subjects

Jeong, J. H.

Publications and source records attributed to Jeong, J. H..

7 recordsLinked to original sources

bioRxiv2026

Hypersensitive Detection of Neurotransmitters in Biological Media by Optically Enhanced Benchtop NMR Spectroscopy

Liquid-state Nuclear Magnetic Resonance (NMR) is an invaluable tool to gain atomic-resolution insights onto molecular structure and dynamics. The impact of NMR spectroscopy, however, is curtailed by high costs and hard-to-maintain high-field magnets. While low-field benchtop NMR spectrometers may address the challenge, severe trade-offs in sensitivity and resolution limit the appeal of this avenue. Here, we introduce a set of novel optically enhanced NMR pulse sequences and procedures (hyperpolarization toolkit) to readily generate 13C and 1H nuclear-spin hyperpolarization in situ on benchtop spectrometers. This approach leads to unprecedented sensitivity gains, enabling atomic-resolution conformation-dependent detection of a broad range of aromatic compounds, including clinically relevant metabolites and biomarkers. Neurotransmitters including epinephrine, serotonin and melatonin are detected at nanomolar/micromolar levels by 1D/2D photochemically-enhanced benchtop NMR in buffer and physiological media including human serum. This advance propels benchtop NMR from a predominantly pedagogical tool to a powerful bioanalytical resource for efficient neurotransmitter identification.

biophysics↗

bioRxiv2026

Efficient Through-Bond Propagation of Nuclear-Spin Hyperpolarization via TOCSY-Enhanced LC-Photo-CIDNP

Nuclear magnetic resonance (NMR) spectroscopy provides atomic-resolution insights into biomolecular structure, dynamics and interactions under non-perturbative conditions. However, the widespread applicability of this technique continues to be limited by its intrinsically low sensitivity. This drawback is particularly severe in the case of concentration-limited samples. Low-concentration photochemically induced dynamic nuclear polarization (LC-photo-CIDNP) is an optically enhanced NMR hyperpolarization strategy capable of boosting NMR sensitivity in situ by several orders of magnitude under physiologically relevant environments. Yet, the inherent nature of the LC-photo-CIDNP phenomenon confines the achievable enhancements to only a subset of nuclei, thus limiting the extent of attainable residue-specific information. Here, we overcome this shortcoming by integrating LC-photo-CIDNP with Total Correlation Spectroscopy (TOCSY) to propagate initial hyperpolarization to other nuclei via scalar-coupled spin networks. First, we demonstrate efficient through-bond transfer of LC-photo-CIDNP enhanced signals throughout entire intramolecular atomic frameworks via 1D 1H- and 13C-detected experiments. Second, we extend the approach to a model protein and demonstrate efficient polarization transfer via 1D and 2D 1H-detected 13C-TOCSY LC-photo-CIDNP. Intrinsically photo-CIDNP-inactive nuclei can thus be visualized via 13C-1H correlations within minutes down to 10 M concentration. In all, this work establishes a general strategy to achieve through-bond propagation of LC-photo-CIDNP hyperpolarization. This technology enables gaining residue-specific structural insights on amino acids and proteins at previously unattainable low concentrations.

biophysics↗

bioRxiv2026

Predation risk reweights reward preference through coordinated amygdala-prelimbic dynamics

A fundamental challenge for animals and humans is resolving competing survival demands under naturalistic threat, yet circuit-level mechanisms remain poorly understood. We developed a paradigm recapitulating a predator-prey encounter: Long-Evans rats emerged from a nest to forage in an open arena, choosing between preferred and standard reward locations while facing a robotic predator. We simultaneously recorded single-unit activity from the basolateral amygdala (BLA) and the prelimbic cortex (PL). Rats shifted to the safer option under threat. BLA neurons responded predominantly to the predator, whereas PL neurons encoded reward value, threat context, and behavioral state. Population decoding revealed threat encoding in BLA and multiplexed representations in PL. Threat-responsive BLA neurons were preferentially recruited into BLA-PL synchrony before safe choices, and information flow became biased from BLA to PL following predator attack. These findings identify coordinated corticolimbic dynamics as a candidate mechanism through which threat reweights reward-guided action selection under ecological risk.

neuroscience↗

bioRxiv2024

Mosaic display of stable hemagglutinin monomers induces broad immune responses

The nature of the interplay between immunity and viral variation is infinitely adaptive. Infection frequently induces immune responses against variation-prone epitopes, rather than against spatially hidden conserved epitopes. It thus remains a substantial challenge to elicit the immune responses to the conserved epitopes providing broad-spectrum immunity. We developed an approach of scaffold-mediated mosaic display to present monomeric influenza virus hemagglutinins (HAs), which exposes highly conserved stem and interface epitopes. Stable monomers were rationally engineered from H1 and H3 subtypes and B type HA trimers, with amino acid mutations at the monomer-monomer interface and for disulfide bond formation, and fused to a self-assembling scaffold, to generate a mosaic HA monomer-displaying nanoparticle, 3HA-np. Immunization with 3HA-np induced broadly neutralizing antibodies (bnAbs) in mice and ferrets and protected against challenges with H1N1 and H3N2 viruses. Competitive immunoassays revealed that 3HA-np induced high interface- and stem-binding Ab titers as compared to head Ab titers, indicating that the monomeric and mosaic nature of 3HA-np elicit cross-reactive Abs. Our results suggest that exposure of the hidden conserved epitope by monomer-displaying nanoparticles is a promising approach to generate a universal influenza vaccine.

bioengineering↗

bioRxiv2023

Population analyses reveal heterogenous encoding in the medial prefrontal cortex during naturalistic foraging

Foraging in the wild requires coordinated switching of critical functions, including goal-oriented navigation and context-appropriate action selection. Nevertheless, few studies have examined how different functions are represented in the brain during naturalistic foraging. To address this question, we recorded multiple single-unit activities from the medial prefrontal cortex (mPFC) of rats seeking a sucrose reward in the presence of an unpredictable attack posed by a robotic predator (Lobsterbot). Simultaneously recorded ensemble activities from neurons were analyzed in reference to various behavioral indices as the animal moved freely across the foraging area (F) between the nest (N) and the goal (E) area. An artificial neural network, trained with simultaneously recorded neural activity, estimated the rats current distance from the Lobsterbot. The accuracy of distance estimation was the highest in the middle F-zone in which the dominant behavior was active navigation. The spatial encoding persisted in the N-zone when non-navigational behaviors such as grooming, rearing, and sniffing were excluded. In contrast, the accuracy decreased as the animal approached the E-zone, when the activity of the same neuronal ensembles was more correlated with events related to dynamic decision-making between food procurement and Lobsterbot evasion. A population-wide analysis confirmed highly heterogeneous encoding by the region. To further assess the decision-related activity in the E-zone, a naive Bayesian classifier was trained to predict the success and failure of avoidance behavior. The classifier predicted the avoidance outcome as much as 6 s before the head withdrawal. In addition, two sub-populations of recorded units with distinct temporal dynamics contributed differently to the prediction. These findings suggest that an overlapping population of mPFC neurons may switch between two heterogenous modes, encoding relevant locations for goal-directed navigation or an imminent situational challenge.

neuroscience↗

bioRxiv2022

Combination therapy with nirmatrelvir and molnupiravir improves the survival of SARS-CoV-2 infected mice

As the SARS-CoV-2 pandemic remains uncontrolled owing to the continuous emergence of variants of concern, there is an immediate need to implement the most effective antiviral treatment strategies, especially for risk groups. Here, we evaluated the therapeutic potency of nirmatrelvir, remdesivir, and molnupiravir and their combinations in SARS-CoV-2-infected K18-hACE2 transgenic mice. Systemic treatment of mice with each drug (20 mg/kg) resulted in slightly enhanced antiviral efficacy and yielded an increased life expectancy of only about 20-40% survival. However, combination therapy with nirmatrelvir (20 mg/kg) and molnupiravir (20 mg/kg) in lethally infected mice showed profound inhibition of SARS-CoV-2 replication in both the lung and brain and synergistically improved survival times up to 80% compared to those with nirmatrelvir (P= 0.0001) and molnupiravir (P= 0.0001) administered alone. This combination therapy effectively reduced clinical severity score, virus-induced tissue damage, and viral distribution compared to those in animals treated with these monotherapies. Furthermore, all these assessments associated with this combination were also significantly higher than that of mice receiving remdesivir monotherapy (P= 0.0001) and the nirmatrelvir (20 mg/kg) and remdesivir (20 mg/kg) combination (P= 0.0001), underscored the clinical significance of this combination. By contrast, the nirmatrelvir and remdesivir combination showed less antiviral efficacy, with lower survival compared to nirmatrelvir monotherapy, demonstrating the inefficient therapeutic effect of this combination. The combination therapy with nirmatrelvir and molnupiravir contributes to alleviated morbidity and mortality, which can serve as a basis for the design of clinical studies of this combination in the treatment of COVID-19 patients. IMPORTANCESince SARS-CoV-2 spread rapidly with the emergence of new variants of concerns, it is necessary to develop effective treatment strategies to treat elderly individuals and those with comorbidities. Antiviral therapy using a combination of drugs is more effective in eradicating viruses and will undoubtedly improve the clinical outcome and survival probability of hospitalized SARS-CoV-2 patients. In the current study, we observed three FDA-approved antivirals nirmatrelvir, remdesivir, and molnupiravir have therapeutic significance with moderate survival for their monotherapies against SARS-CoV-2 infected K18-hACE2 mouse model. The combination of nirmatrelvir and molnupiravir showed significant antiviral activity and a higher survival rate of approximately 80%, providing in vivo evidence of the potential utility of this combination. In contrast, nirmatrelvir and remdesivir combination showed less antiviral potency and emphasized the ineffective significance with less survival. The current study suggests that the nirmatrelvir and molnupiravir combination is an effective drug regimen strategy in treating SARS-CoV-2 patients.

microbiology↗

bioRxiv2022

Mosaic receptor-binding domain nanoparticles induce protective immunity against SARS-CoV-2 challenges

Recurrent spillovers of - and {beta}-coronaviruses (CoV) such as acute respiratory syndrome (SARS)-CoV, Middle East respiratory syndrome (MERS)-CoV, SARS-CoV-2, and possibly human CoV (NL63, 229E, OC43, and HKU1) have caused serious morbidity and mortality worldwide. Six receptor binding domains (RBDs) derived from - and {beta}-CoV that are considered to have originated from animals and cross-infected humans were linked to proliferating cell nuclear antigen (PCNA) heterotrimeric subunits, PCNA1, PCNA2, and PCNA3. These were used to form a scaffold-based mosaic multivalent antigen, 6RBD-np. Electron microscopic and atomic force microscopic images show a ring-shaped disk with six protruding RBDs, like jewels in a crown, with a size of 40 nm. Prime-boost immunizations with 6RBD-np in BALB/c mice elicited strong, dose-dependent antibody responses. In human angiotensin converting enzyme 2-transgenic mice, the same immunization induced full-protection against SARS-CoV-2 wild type and Delta challenges, resulting in a 100% survival rate. The mosaic 6RBD-np provides a potential platform for developing a pan-CoV vaccine against newly emerging SARS-CoV-2 variants and future CoV spillovers. SignificanceDespite the arsenal of COVID-19 vaccines, hospitalization and mortality associated with SARS-CoV-2 (acute respiratory syndrome coronavirus 2) variants remain high. There is an urgent need to develop next-generation COVID vaccines that provide broad protection against diseases by current and newly emerging SARS-CoV-2 variants. In this study, six receptor binding domains (RBDs) derived from - and {beta}-CoV were linked to proliferating cell nuclear antigen (PCNA) heterotrimeric scaffolds. They assemble to create a stable mosaic multivalent nanoparticle, 6RBD-np, displaying a ring-shaped disk with six protruding antigens. The prime-boost immunization in BALB/c and human angiotensin converting enzyme 2-transgenic mice with the 6RBD-np elicited strong, dose-dependent antibody responses and induced full-protection against both the SARS-CoV-2 wild type (WT) and Delta challenges. This study provides proof-of-concept that the mosaic 6RBD-np induces 100% protection against SARS-CoV-2 WT and Delta. It provides the potential of co-displaying heterologous antigens for novel vaccine designs, which can be deployed countering future pandemics.

bioengineering↗