Biology subjects

Park, J.-W.

Publications and source records attributed to Park, J.-W..

10 recordsLinked to original sources

bioRxiv2026

Anticipatory modulation of motor unit discharge rate before rapid isometric elbow flexion force production

Surface electromyography (EMG) studies have demonstrated anticipatory muscle activation prior to predictable voluntary actions. However, the mechanism through which this preparation is expressed, whether through motor-unit recruitment or discharge-rate modulation, remains to be elucidated. We employed surface decomposition EMG to quantify motor-unit behavior prior to self-paced rapid isometric elbow-flexion force pulses. Twelve healthy young men were instructed to generate elbow-flexion pulse force at 30%, 40%, and 50% of the maximal voluntary contraction (MVC) at a self-selected time. Motor-unit activity was decomposed from the biceps brachii and triceps brachii muscles, and the normalized active motor-unit number and mean discharge rate were analyzed prior to pulse onset. In the agonist, the pre-pulse increase mean discharge rate exhibited a higher value than the change in detected motor-unit count, particularly at the 40% and 50% MVC targets. The discharge-rate increase scaled with the target force, with a heightened response observed in high-threshold as compared to low-threshold motor units. Antagonist recordings with sufficient decomposition yield exhibited a similar discharge-rate-dominant pattern; however, these data were available from a smaller sample size. Present findings suggest that discharge-rate modulation is a primary motor-unit-level feature of anticipatory preparation for rapid isometric force production.

neuroscience↗

bioRxiv2026

Seasonal dynamics in lettuce phyllosphere microbiota and potential transmission to the human gut

The surface of fresh vegetable leaves harbors diverse microorganisms with the potential to influence human health through the microbiome-food-gut axis. We investigated the ecology of the bacterial and fungal microbiota on green and red lettuces (n=143) for a 12-month period using high-throughput amplicon sequencing, and assessed the potential transfer of these microbiota to the human gut. Lettuce-associated fungal and bacterial microbiota exhibited substantial temporal variation, converging into two distinct seasonal cycles: early-season (S1) and late-season (S2). Seasonal progression from S1 to S2 increased species richness in season-specific fungal and bacterial taxa, while inducing abundance shifts in persistent fungal taxa and compositional shifts in persistent bacterial taxa. These seasonal dynamics resulted in more complex and stable microbial networks, in which potentially pathogenic fungi were less frequently enriched. Comparative analyses with gut microbiota datasets from 2,831 (fungal) and 3,254 (bacterial) individuals revealed that lettuce-associated fungi and bacteria were widely detected in the human gut, with bacteria detected more frequently than fungi. Season-specific taxa were detected more frequently than persistent taxa, and microbial assembly in the gut was shaped by both neutral and deterministic processes. Notably, lettuce-associated bacteria predominantly co-occurred with non-plant glycan-degrading commensal bacteria in a season-dependent manner, and enrichment of these co-occurring taxa correlated positively with gut microbiota richness and composition. Our findings provide insights into the ecological linkages between fresh vegetable microbiota and the human gut microbiota through the food-gut axis.

microbiology↗

bioRxiv2026

Fructose utilization by GM-CSF-differentiated macrophages aggravates autoimmune inflammation via MG-derived AGE-RAGE signaling

Excessive fructose intake is increasingly associated with metabolic and inflammatory pathologies; however, the direct impact of fructose metabolism on immune cell function remains insufficiently understood. Here, we demonstrate that GM-CSF-differentiated macrophages markedly upregulate the fructose-specific transporter GLUT5, enabling efficient fructose utilization through two complementary metabolic pathways. Using 13C-fructose tracing, we identified distinct carbon fluxes via a hexokinase (HK)-dependent glycolytic route and a ketohexokinase (KHK)-ALDOB-mediated fructolytic route. The HK-dependent pathway sustains glycolytic activity under glucose-limiting conditions, stabilizing HIF-1 and preserving pro-inflammatory gene expression. Conversely, the KHK-ALDOB axis increases dihydroxyacetone phosphate (DHAP) production, leading to methylglyoxal-derived advanced glycation end-products (MG-AGEs) that engage receptor for AGE (RAGE) signaling. This activation enhances MMP9 expression in macrophages and drives Th17 differentiation in CD4 T cells, amplifying inflammatory and tissue-remodeling processes. In vivo, fructose intake exacerbates autoimmune arthritis in SKG mice, and elevated fructose-driven glycolysis and MG-AGE accumulation are observed in monocytes from patients with rheumatoid arthritis. These results link fructose-driven carbonyl stress to macrophage effector programs and downstream T cell polarization. Collectively, these findings uncover a dual fructose metabolic program that integrates nutrient stress with persistent inflammation via the MG-AGE-RAGE axis and underscore the immunometabolic risks of excessive fructose exposure.

immunology↗

bioRxiv2024

The food-gut axis: the phyllosphere virome of fresh vegetables is diverse, abundant, and transmitted to the human gut virome

Fresh vegetables harbor diverse microorganisms on leaf surfaces, yet their viral communities remain unexplored. We investigated the diversity and ecology of phyllosphere viromes of six leafy green vegetables using virus-like particle (VLP) enrichment and shotgun metagenome sequencing. On average, 9.2 x 107 viruses were present per gram of leaf tissue. The majority (93.1 {+/-} 6.2%) of these viruses were taxonomically unclassified. Virome compositions were distinct among vegetable types and exhibited temporal variations. Virulent phages with replication-enhancing auxiliary metabolic genes (AMGs) were more dominant than temperate phages with host fitness-benefiting AMGs. Analysis of 1,498 human fecal VLP metagenomes revealed that approximately 10% of vegetable viruses were present in the human gut virome, including viruses commonly observed in multiple studies. These gut-associated vegetable viruses were enriched with short-term vegetable intake, and depleted in individuals with metabolic and immunologic disorders. Overall, this study elucidates the ecological contribution of the fresh vegetable virome to human gut virome diversity.

microbiology↗

bioRxiv2024

Extracellular Vesicle-Mediated Delivery of HIF1a Reprograms Macrophages for resolutive response in Sepsis

In sepsis, the liver functions as a central filter organ, where hepatic macrophages form a primary antimicrobial defense layer by eliminating bacteria and regulating immune responses. Therefore, precise regulation of the immune response in hepatic macrophages is crucial for triggering effective defense mechanisms. We aim to modulate the defense immune response by delivering transcription factor HIF1, a key regulator of monocyte/macrophage reprogramming in sepsis. Transcription factors are promising candidates because they dynamically modulate gene expression across diverse conditions, though delivering them remains challenging. In this study, we suggest a novel method for loading HIF1 into extracellular vesicles (EVs) to enhance immune defense and resolve sepsis. By delivering HIF1 to macrophages during sepsis, we promoted the differentiation of Nr1h3-dependent pro-efferocytic MoMFs and C/ebp{beta}-dependent pro-survival MoMFs. Pro-efferocytic MoMFs eliminate damaged hepatocytes and immune cells and pro-survival MoMFs withstand inflammatory conditions and trigger innate memory responses. Particularly, the zonation of these macrophages in the periportal region ensures effective pathogen clearance and minimizes tissue damage. These findings suggest that EV-mediated HIF1 delivery could be a promising therapeutic option for managing sepsis.

bioengineering↗

bioRxiv2023

Antibody-based immunotherapy targeting FAM19A5 reverses synaptic loss and improves cognitive function in Alzheimer's disease.

IntroductionAlzheimers disease (AD) is characterized by the dysregulation of synaptic balance, with progressive loss of synapses outpacing formation, ultimately leading to cognitive decline. However, the lack of effective strategies for restoring lost synapses poses a major barrier to improving clinical outcomes. MethodsWe developed NS101, a monoclonal antibody targeting FAM19A5, a brain-secreted protein. Its preclinical efficacy in restoring synapses and cognition was evaluated using APP/PS1 and P301S mice. The clinical safety and target engagement of NS101 were examined in human participants. ResultsFAM19A5 binds to LRRC4B, a postsynaptic adhesion molecule, leading to synapse reduction. Blocking this interaction with NS101 normalized the rate of synapse elimination in AD mice. This synaptic rebalancing restored the number and function of synapses, resulting in improved cognition. Systemically administered NS101 facilitated the transport of brain FAM19A5 into the bloodstream. DiscussionTargeting FAM19A5 may hold clinical promise for treating AD by restoring synaptic balance.

neuroscience↗

bioRxiv2021

MEOX2 homeobox gene promotes growth of malignant gliomas

Glioblastoma (GBM) is an aggressive tumor that frequently exhibits gain of chromosome 7, loss of chromosome 10 and aberrantly activated receptor tyrosine kinase signaling pathways. Here, we identify mesenchyme homeobox 2 (MEOX2) on chromosome 7 with increased expression in GBM as a salient oncogenic transcription factor. Specifically, we show that MEOX2 overexpression leads to increased ERK phosphorylation, and we identify a phosphorylation site on MEOX2 that regulates its transcriptional activity by altering its subnuclear localization. We show that MEOX2 overexpression can lead to increased growth in GBM implantation models and cooperates with loss of p53 and PTEN in cerebral organoid models of human malignant gliomas to induce cell proliferation. Furthermore, using high-throughput genomics, we identify transcriptional target genes of MEOX2 in patient-derived GBM tumorsphere models and a fresh frozen GBM tumor. These analyses show that MEOX2 activates several oncogenic pathways involved in MAPK signaling and extracellular matrix organization. Furthermore, MEOX2 binds to oncogenic ETS factors and known glioma oncogenes such as FABP7. In total, we reveal a novel role for MEOX2 in GBM initiation and progression and demonstrate that MEOX2 can enhance ERK signaling through a feed-forward mechanism. Significance StatementGlioblastoma (GBM) harbors gain of chromosome 7 as an early driver event. In this study, we show that mesenchyme homeobox 2 (MEOX2), an aberrantly upregulated transcription factor on chromosome 7, is an oncogene in human glioblastoma. In contrast to GBM, MEOX2 expression is very low in normal brain. We show that MEOX2 cooperates with p53 and PTEN loss to promote tumor initiation in cerebral organoid models. In addition, we identify direct and indirect molecular targets of MEOX2 and demonstrate its role in activating the ERK signaling cascade. These findings identify a novel oncogene in GBM and highlight the transcriptional networks hijacked by these tumors to activate signaling pathways central to GBM biology.

cancer biology↗

bioRxiv2020

Curvature effect of PE-included membrane on the behavior of cinnamycin on the membrane

The behavior of the cinnamycin on the biomimetic membrane was studied with respect to the curvature of the phosphatidylethanolamine(PE)-included membrane with the adhesion measured by the atomic force microscope(AFM). The membrane was formed through vesicle fusion on the hydrophobic surface of the sphere spheres, which was used to define the curvature of the membrane. The hydrophobicity was generated by the reaction of alkyl-silane and analyzed with the X-ray photoelectron spectrometer. The cinnamycin, immobilized covalently to the AFM tip coated with 1-mercapto-1-undecanol that was observed inert to any adhesion to the membrane, showed that the adhesion became stronger with the increase in the curvature. The correlation between the adhesion and the curvature was linearly proportional. Previously, it was found that the cinnamycin was bound to PE headgroup and the binding was enhanced by the interaction of the hydrophobic area located at one side of the cinnamycin. Therefore, the linear proportionality seems to suggest that the interaction is related to the one dimensional orientation of the binding. Statement of SignificanceThe behavior of the cinnamycin was studied on the phosphatidylethanolamine(PE)-included membrane with respect to the curvature of the membrane. The cinnamycin, immobilized covalently to the atomic force microscope, showed that the adhesion became stronger linearly with the increase in the curvature. Previously, it was found that the specific binding between the cinnamycin and PE headgroup was enhanced by the interaction of the hydrophobic area located at one side of the cinnamycin. Therefore, the linear proportionality seems to suggest that the interaction is related to the one dimensional orientation of the binding.

biophysics↗

bioRxiv2020

Antibiotic-dependent relationships between nasal microbiome and secreted proteome in chronic rhinosinusitis and nasal polyps

BackgroundAntibiotics are commonly prescribed to treat chronic rhinosinusitis (CRS); however, the effects of antibiotics on the microbiome and secreted proteome remain unknown in regard to CRS. ObjectiveWe analyzed the effects of antibiotics on the nasal microbiome and secreted proteome in the context of CRS using multi-omic analysis. MethodsNasal secretions were collected from 29 control, 30 CRS patients without nasal polyps (CRSsNP), and 40 CRS patients with nasal polyps (CRSwNP). A total of 99 subjects were divided into two groups that included subjects who had taken antibiotics 3 months prior to sampling (ABX) and those who had not (NABX). We performed 16S rDNA sequence analyses and Orbitrap mass spectrometry-based proteomic analyses in data-independent acquisition (DIA) on the nasal secretions. Spearman correlation was used to assess the correlations between the nasal microbiome and secreted proteome. ResultsWe observed a strong association between the nasal microbiome and secreted proteome according to disease status. Antibiotic use reduced differences in the microbial community and secreted proteome according to disease status. Interestingly, in nasal polyp (NP) patients, antibiotics exhibited strong effects not only on the nasal microbiome and the secreted proteome but also on their associations. Additionally, their correlations were strengthened in subjects who had taken antibiotics. ConclusionIntegrative analyses revealed that the correlations between the microbiome and the secreted proteome could be altered and strengthened in subjects who used antibiotics. These findings provide novel insight into the effects of antibiotics on the nasal environment and the host responses in CRS.

microbiology↗

bioRxiv2017

Bacterial Community Shift in Marine Tar Balls following Low Salinity Exposure

The persistence and recurrence of tar balls causes detrimental effects on coastal wildlife, tourism, and fisheries. Previously, the human pathogen Vibrio vulnificus was detected in marine tar balls in the Gulf of Mexico. Marine tar balls also migrate to low-salt water bodies near the shore. The bacterial communities in tar balls from these environments, however, have not been fully characterized. Herein we describe our studies on the effect of reduced salinity on bacterial communities in marine tar balls. Tar balls collected from the Gulf of Mexico were incubated in deionized water for six months, and their microbial fingerprints were visualized using denaturing gradient gel electrophoresis. Our data show that the indigenous bacterial communities in marine tar balls shifted after being exposed to low-salinity condition. Dominant genera in the tar balls at low salinity were Aquisalimonas and Parvibaculum, neither of which includes known human pathogens.

ecology↗