Biology subjects

Kim, Y. K.

Publications and source records attributed to Kim, Y. K..

7 recordsLinked to original sources

bioRxiv2024

A HigB-like toxin promotes non-replicating Salmonella inside macrophages by inhibiting ribonuclease III

Many bacteria are often resistant to antibiotic treatment because they can slow down their growth rate, thereby attenuating the drugs effectiveness. A similar growth-rate control is observed in pathogens that infect and persist inside their hosts. The bacterial toxin-antitoxin (TA) system serves as a non-heritable phenotypic switch by slowing down growth through the expression of a toxin component. Here, we investigated a HigB-like type II toxin from the intracellular bacterial pathogen Salmonella Typhimurium. Unlike other HigB-like toxins that cleave ribosome-bound mRNAs, it does not exhibit endoribonuclease activity. Instead, it inhibits ribonuclease III, which mediates the initial cleavage for rRNA processing, by directly binding to the dsRNA-binding domain of RNase III, thereby decreasing ribosome assembly and bacterial growth. Given that the formation of HigB-like toxin-mediated non-replicating Salmonella within macrophages is RNase III-dependent, persister formation by inhibiting RNase III is a newly identified strategy for pathogens to survive within host cells.

microbiology↗

bioRxiv2024

Dual-mode action of scalable, high-quality engineered stem cell-derived SIRP alpha extracellular vesicles for treating acute liver failure

Acute liver failure (ALF) is a critical inflammatory condition characterized by rapid hepatocyte death, impaired liver regeneration due to the delayed removal of necroptotic cells, and high mortality rates. This study introduces a novel dual-mode action therapeutic approach using extracellular vesicles expressing Signal Regulatory Protein Alpha (SIRP-EVs) derived from genetically engineered mesenchymal stem cells (MSCs). These SIRP-EVs are designed to concurrently resolve necroptosis and promote liver regeneration. Our studies identified CD47 and SIRP as promising therapeutic targets for ALF. We developed a scalable 3D bioreactor-based process that produces high-purity SIRP-EVs, which preserve MSC properties and achieve significant production levels. SIRP-EVs target both macrophages and necroptotic hepatocytes in ALF models, enhancing macrophage phagocytic activity against necroptotic cells via CD47 blockade and promoting liver regeneration by reprogramming macrophages with MSC-derived cargo. Comprehensive in vitro and in vivo studies demonstrate that SIRP-EVs decrease CD47+ necroptotic cells and promote liver regeneration in ALF models, leading to reduced liver damage markers and enhanced survival rates. These findings highlight the potential of SIRP-EVs as a dual-mode action therapeutic for ALF, offering promising prospects for their application in other inflammatory diseases. Moreover, these results pave the way for advancing engineered EV-based therapies toward clinical implementation.

bioengineering↗

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↗

bioRxiv2022

Genetic mapping of craniofacial traits in the Mexican tetra reveals loci associated with bite differences between cave and surface fish

The Mexican tetra, Astyanax mexicanus, includes interfertile surface-dwelling and cave-dwelling morphs, enabling powerful studies aimed at uncovering genes involved in the evolution of cave-associated traits. Compared to surface fish, cavefish harbor several extreme traits within their skull, such as a protruding lower jaw, a wider gape, and an increase in tooth number. These features are highly variable between individual cavefish and even across different cavefish populations. To investigate these traits, we created a novel feeding behavior assay wherein bite impressions could be obtained. We determined that fish with an underbite leave larger bite impressions with an increase in the number of tooth marks. Capitalizing on the ability to produce hybrids from surface and cavefish crosses, we investigated genes underlying these segregating orofacial traits by performing Quantitative Trait Loci (QTL) analysis with F2 hybrids. We discovered significant QTL for bite (underbite vs. overbite) that mapped to a single region of the Astyanax genome. This work highlights cavefish as a valuable genetic model for orofacial patterning and will provide insight into the genetic regulators of jaw and tooth development.

evolutionary biology↗

bioRxiv2022

Neuroanatomical substrates in Parkinson's Disease psychosis and their association with serotonergic receptor gene expression: A coordinate-based meta-regression analysis.

BackgroundCommon neural underpinning of Parkinsons Disease (PD) psychosis across different structural magnetic resonance imaging (MRI) studies remains unclear to this day with few studies and even fewer meta-analyses available. ObjectivesOur meta-analysis aimed to identify and summarise studies using MRI approach to identify PD psychosis-specific brain regions and examine the relation between cortical volume loss and dopaminergic and serotonergic receptor density. MethodsPubMed, Web of Science and Embase were searched for MRI studies of PD psychosis (PDP) compared to PD patients without psychosis (PDnP). Seed-based d Mapping with Permutation of Subject Images was applied in the meta-analysis where coordinates were available. Multiple linear regressions to examine the relationship between grey matter volume loss in PDP and receptor gene expression density (extracted from the Allen Human Brain Atlas) were conducted in R. ResultsWe observed lower grey matter volume in parietal-temporo-occipital regions from our meta-analysis (N studies =10, PDP n=211, PDnP, n=298). These results remained significant after adjusting for PD medications and for cognitive scores. Grey matter volume loss in PDP was associated with local expression of 5-HT1a (b=0.109, p=0.012) and 5-HT2a receptors (b=-0.106, p=0.002) also after adjusting for PD medications (5-HT1a, p = 0.005; 5-HT2a, p = 0.001). ConclusionsWidespread cortical volume loss in the parieto-temporo-occipital regions involved in information processing and integration, as well as attention, could result in PD psychosis symptoms. Neurobiological mechanisms implicating serotonergic receptors may also contribute to this condition.

neuroscience↗

bioRxiv2021

Characterization of aquaporin1b (AQP1b) mRNA in mud loach (Misgurnus mizolepis) in response to heavy metal and immunostimulant stimuli

Aquaporins (AQPs) facilitate the transport of water or other small solutes into cells in the presence of osmotic gradients. However, the current understanding of piscine AQP gene with cellular stress responses has been still limitedly exemplified. In present study, we characterized the mud loach AQP1b gene at the nucleotide and amino acid levels. We identified three AQP 1b transcript variants (mmAQP1b_tv1, mmAQP1b_tv2, and mmAQP1b_tv3). Then, we examined the AQP1b promoter region and observed several transcription factor binding sites (TFBS) for nuclear factor of activated T-cells (NFAT), SRY-box, c-AMP responsive element binding protein (CREB), GATA binding factor, and hepatic nuclear factor-1. Interestingly, mmAQP1b transcription was differentially modulated by heavy metal or immunostimulant challenge. Further studies to deepen the knowledge of fish AQP-mediated adaptation response potentially relevant to molecular pathogenesis are warranted. Summary statementWe identified mud loach AQP1b transcript variants and consensus sequences involved in stress or innate immunity in promotor region. AQP1b transcription was differentially modulated by heavy metal or immunostimulant challenge.

molecular biology↗

bioRxiv2019

Chromosome-scale assembly comparison of the Korean Reference Genome KOREF from PromethION and PacBio with Hi-C mapping information

BackgroundLong DNA reads produced by single molecule and pore-based sequencers are more suitable for assembly and structural variation discovery than short read DNA fragments. For de novo assembly, PacBio and Oxford Nanopore Technologies (ONT) are favorite options. However, PacBios SMRT sequencing is expensive for a full human genome assembly and costs over 40,000 USD for 30x coverage as of 2019. ONT PromethION sequencing, on the other hand, is one-twelfth the price of PacBio for the same coverage. This study aimed to compare the cost-effectiveness of ONT PromethION and PacBios SMRT sequencing in relation to the quality.\n\nFindingsWe performed whole genome de novo assemblies and comparison to construct an improved version of KOREF, the Korean reference genome, using sequencing data produced by PromethION and PacBio. With PromethION, an assembly using sequenced reads with 64x coverage (193 Gb, 3 flowcell sequencing) resulted in 3,725 contigs with N50s of 16.7 Mbp and a total genome length of 2.8 Gbp. It was comparable to a KOREF assembly constructed using PacBio at 62x coverage (188 Gbp, 2,695 contigs and N50s of 17.9 Mbp). When we applied Hi-C-derived long-range mapping data, an even higher quality assembly for the 64x coverage was achieved, resulting in 3,179 scaffolds with an N50 of 56.4 Mbp.\n\nConclusionThe pore-based PromethION approach provides a good quality chromosome-scale human genome assembly at a low cost with long maximum contig and scaffold lengths and is more cost-effective than PacBio at comparable quality measurements.

genomics↗