Biology subjects

Kim, K.-W.

Publications and source records attributed to Kim, K.-W..

7 recordsLinked to original sources

bioRxiv2026

Metabolic signals regulate resuscitation speed of antibiotic persister bacteria during infection

All living organisms adjust their metabolism in response to environmental changes. Under unfavorable conditions, organisms enter a state of dormancy by halting metabolism, enabling survival. Dormant bacteria become highly tolerant to antibiotics-a phenomenon called persistence. Here, we demonstrate that selective metabolic reprogramming controls the resuscitation speed of persister after antibiotic exposure. Using multi-omics and in silico modeling, we found that dormant bacteria reprogram metabolic pathways to modulate persister awakening. Accumulation of L-serine and reduction of arginine drive rapid resuscitation. L-serine promotes cysteine biosynthesis and motility while reducing energy metabolism to facilitate rapid resuscitation. In contrast, arginine slows regrowth from dormancy by enhancing ethanol-aldehyde and energy metabolism. L-serine and arginine can, respectively, promote or inhibit the regrowth of antibiotic persister cells in macrophages and mouse models, and regulate the awakening speed of Salmonella, E. coli, and methicillin-resistant Staphylococcus aureus (MRSA). These findings suggest new strategies to target chronic bacterial infections. TeaserL-serine speeds and arginine slows the awakening of antibiotic persisters, revealing targets for chronic infection.

microbiology↗

bioRxiv2025

Tolerance to Lung Infection in TWIK2 K+ Efflux Mediated Macrophage Trained Immunity

Lung macrophages such as alveolar macrophages (AM{varphi}) are essential for innate immune function in the lungs. It is now apparent that macrophages can be trained to become better at attacking infections. Although trained immunity is thought to result from metabolic and epigenetic reprogramming, the underlying mechanisms remain unclear. Here, we report that macrophages can be trained by extracellular ATP, which is ubiquitously released during inflammation. ATP ligates the canonical Purinergic Receptor 2 subtype X7 receptor (P2X7) to mediate endosomal Two-pore domain Weak Inwardly rectifying K+ channel 2 (TWIK2) translocation into the plasma membrane (PM). This enables the cells to transit to a ready state for microbial killing in two directions: first, K+ efflux via PM-TWIK2 induces NLRP3 inflammasome activation, which further activates metabolic pathways; second, upon bacterial phagocytosis, PM-TWIK2 internalizes into phagosome membrane with proper topological orientation, where TWIK2 mediates K+ influx into phagosomes to control pH and ionic strength favoring bacterial killing. Therefore, the enhanced association of TWIK2 in phagosomal and plasma membranes signaled by danger-associated molecular patterns (DAMPs), such as ATP, mediates trained immunity in macrophages and enhances microbiocidal activity.

immunology↗

bioRxiv2024

IDH-mutant gliomas arise from glial progenitor cells harboring the initial driver mutation

Discovering the cell-of-origin harboring the initial driver mutation provides a fundamental basis for understanding tumor evolution and development of new treatments. For isocitrate dehydrogenase (IDH)-mutant gliomas - the most common malignant primary brain tumors in adults under 50 - the cell-of-origin remains poorly understood. Here, using patient brain tissues and genome-edited mice, we identified glial progenitor cells (GPCs), including oligodendrocyte progenitor cells (OPCs), as the glioma-originating cell type harboring the IDH mutation as the initial driver mutation. We conducted comprehensive deep sequencing, including droplet digital PCR and deep panel and amplicon sequencing to 128 tissues from 62 patients (29 IDH-mutant gliomas and 33 IDH-negative controls) comprising tumors, normal cortex or normal subventricular zone (SVZ), and blood. Surprisingly, low-level IDH mutation was found in the normal cortex away from the tumor in 38.5% (10 of 26) of IDH-mutant glioma patients, whereas no IDH mutation was detected in the normal SVZ. Furthermore, by analyzing cell-type-specific mutations, the direction of clonal evolution, the single-cell transcriptome from patient brains and novel mouse model of IDH-mutant glioma arising from mutation-carrying OPCs, we determined that GPCs, including OPCs, harboring the initial driver mutation are responsible for the development and evolution of IDH-mutant gliomas. In summary, our results demonstrate that GPCs containing the IDH mutation are the cells-of-origin harboring the initial driver mutation in IDH-mutant gliomas.

cancer biology↗

bioRxiv2024

A Mathematical Sequence Representing Tonic Action Potential Spike Trains

This is a study outlining the regularity of action potential spikes. Through a stochastic study, we observed a series of strong correlations between the intervals of tonically firing spikes generated by injecting constant currents of varying intensities into layer V pyramidal neurons of the ferret medial prefrontal cortex. Based on this, we derived a formulaic relationship for the interspike intervals (ISIs). According to this formula, an ISI can be expressed as a product of two factors: the timing precursor and the scale factor. Those arise from a linear relationship between activities of ion channels that modulate spike frequency adaptation and spike timing. Using this rule, we successfully predicted spike timing and demonstrated that the spike timing can be determined by the linear combination of various ion channel activities, reflecting different cellular signaling pathways such as G-protein coupled receptor (GPCR) activation. These findings not only aid studies on cellular signaling but also expand our insight into neural coding, while increasing research efficacy through neural modeling. Significant StatementWhile the action potential (AP) pattern may appear simple at first glance, no rule has been discovered in the nearly 100 years since it was first recorded. Building on this finding, we have developed a method to intuitively measure the activity of various ion channels responsible for determining spike timing from the AP spikes, as well as the associated intracellular and extracellular signaling pathways.

neuroscience↗

bioRxiv2021

Stepwise evolution of a butterfly supergene via duplication and inversion

Supergenes maintain adaptive clusters of alleles in the face of genetic mixing. Although usually attributed to inversions, supergenes can be complex, and reconstructing the precise processes that led to recombination suppression and their timing is challenging. We investigated the origin of the BC supergene, which controls variation in warning colouration in the African Monarch butterfly, Danaus chrysippus. By generating chromosome-scale assemblies for all three alleles, we identified multiple structural differences. Most strikingly, we find that a region of >1 million bp underwent several segmental duplications at least 7.5 million years ago. The resulting duplicated fragments appear to have triggered four inversions in surrounding parts of the chromosome, resulting in stepwise growth of the region of suppressed recombination. Phylogenies for the inversions are incongruent with the species tree, and suggest that structural polymorphisms have persisted for at least 4.1 million years. In addition to the role of duplications in triggering inversions, our results suggest a previously undescribed mechanism of recombination suppression through independent losses of divergent duplicated tracts. Overall, our findings add support for a stepwise model of supergene evolution involving a variety of structural changes.

evolutionary biology↗

bioRxiv2019

Low handgrip strength is closely associated with anemia among adults: A cross-sectional study using Korea National Health and Nutrition Examination Survey (KNHANES)

BackgroundAnemia occurs because of insufficient hemoglobin, which provides oxygen to the body. Because of its close relationship with various illnesses, it must always be investigated clinically. Previous studies have demonstrated an association between hemoglobin concentration and handgrip strength. Thus, we aimed to analyze the association between handgrip strength and anemia in Korean adults to determine whether the handgrip strength test can be used as a tool to identify anemia.\n\nMethodsThe research subjects data were extracted from the 6th and 7th Korean National Health and Nutrition Examination Survey, between January 2013 and December 2017. Overall, data of 16,637 adults (weighted n= 9,734,598) were analyzed. Differences in sociodemographic factors (sex, age, education, income, and employment), lifestyle factors (alcohol consumption, smoking, and physical activity), and illness and health factors (body mass index, vitamin intake, iron intake, comorbid illnesses, and handgrip strength) by existence of anemia were analyzed using a chi square test. Binary logistic regression was performed to identify factors of anemia. Subgroup analysis, stratified by sex and age, was performed.\n\nResultsAmong Korean adults aged [≥] 19 years, 745,296 (7.7%) had anemia. Higher odds ratio (OR) of anemia occurred in the weak handgrip strength group compared to the strong handgrip strength group (OR=1.92, 95% CI: 1.58-2.33). The subgroup analysis showed a higher OR for anemia in the weak handgrip strength group than in the strong handgrip strength group, regardless of sex or age. However, the results showed that this association was greater for males (OR=2.13, 95% CI: 1.35-3.34) and for those aged [≥]65 years (OR=1.92, 95% CI: 1.42-2.58).\n\nConclusionThis study showed a strong association between handgrip strength and anemia, which was particularly strong for males and those aged [≥]65 years. Therefore, it is anticipated that handgrip strength can be used in anemia screening tests as a useful tool.

epidemiology↗

bioRxiv2018

Black or red: A sex-linked colour polymorphism in a songbird is maintained by balancing selection

Colour polymorphisms play a key role in sexual selection and speciation, yet the mechanisms that generate and maintain them are not fully understood. We therefore used genomic and transcriptomic tools to identify the precise genetic architecture and evolutionary history of a sex-linked colour polymorphism in the Gouldian finch Erythrura gouldiae that is also accompanied by remarkable differences in behaviour and physiology. We found that differences in colour are associated with an ~72-kbp region of the Z chromosome in a putative regulatory region for follistatin, an antagonist of the TGF-{beta} superfamily genes. The region is highly differentiated between morphs, unlike the rest of the genome, yet we found no evidence that an inversion is involved in maintaining the distinct haplotypes. Coalescent simulations confirm that that there is elevated nucleotide diversity and an excess of intermediate frequency alleles at this locus. We conclude that this pleiotropic colour polymorphism is most probably maintained by balancing selection.

evolutionary biology↗