Biomedical subjects

Soohyun Lee

Publications and source records attributed to Soohyun Lee.

9 recordsLinked to original sources

PubMed2026

A plasmid-associated immunoglobulin-binding protein in Acinetobacter baumannii.

BACKGROUND: Acinetobacter baumannii is a critical global health threat due to multidrug resistance and high mortality. Although antimicrobial resistance mechanisms are well characterised, the virulence determinants that drive severe infections remain poorly understood. METHODS: We screened 89 carbapenem-resistant clinical isolates of A. baumannii for virulence in animal infection models and combined comparative genomics with functional assays to identify virulence factors. An immunoglobulin-binding protein from A. baumannii (ImbA) encoded on the type D plasmid was selected and characterised. Protein-immunoglobulin interactions were analysed by pull-down and biolayer interferometry. Additional ImbA inhibition of IgG-Fcγ receptor binding by flow cytometry were tested. Protective efficacy was evaluated in mice using vaccination or anti-ImbA antibodies. FINDINGS: A type D plasmid was consistently linked to high virulence in clinical isolates. The deletion of plasmid-encoded ImbA attenuated virulence. ImbA bound murine IgA and IgG with high affinity. The binding to the Fc region of IgG disrupted IgG-Fcγ receptor interactions. Vaccination with recombinant ImbA improved survival and reduced bacterial dissemination in female mice with anti-ImbA antibodies partially protecting against lethal infection. Bacterial burdens in the blood were reduced in treated groups. INTERPRETATION: Our study demonstrates ImbA as an unrecognised plasmid-encoded virulence factor in A. baumannii. By intercepting host immunoglobulins, ImbA drives immune evasion and hypervirulence. Blocking ImbA by vaccination and antibody therapy restored host defence and improved outcomes in female mice, highlighting ImbA as a non-antibiotic therapeutic target with potential against multidrug-resistant A. baumannii. FUNDING: Bio&Medical Technology Development Program of the National Research Foundation (NRF), funded by the Korean government (MSIT) (No. RS-2023-00219213); Korea Research Institute of Bioscience and Biotechnology (KRIBB) Research Initiative Program.

Animals↗

PubMed2006

Towards pathogenomics: a web-based resource for pathogenicity islands.

Pathogenicity islands (PAIs) are genetic elements whose products are essential to the process of disease development. They have been horizontally (laterally) transferred from other microbes and are important in evolution of pathogenesis. In this study, a comprehensive database and search engines specialized for PAIs were established. The pathogenicity island database (PAIDB) is a comprehensive relational database of all the reported PAIs and potential PAI regions which were predicted by a method that combines feature-based analysis and similarity-based analysis. Also, using the PAI Finder search application, a multi-sequence query can be analyzed onsite for the presence of potential PAIs. As of April 2006, PAIDB contains 112 types of PAIs and 889 GenBank accessions containing either partial or all PAI loci previously reported in the literature, which are present in 497 strains of pathogenic bacteria. The database also offers 310 candidate PAIs predicted from 118 sequenced prokaryotic genomes. With the increasing number of prokaryotic genomes without functional inference and sequenced genetic regions of suspected involvement in diseases, this web-based, user-friendly resource has the potential to be of significant use in pathogenomics. PAIDB is freely accessible at http://www.gem.re.kr/paidb.

Bacteria↗

PubMed2006

The complete genome sequence of a dog: a perspective.

A complete, high-quality reference sequence of a dog genome was recently produced by a team of researchers led by the Broad Institute, achieving another major milestone in deciphering the genomic landscape of mammalian organisms. The genome sequence provides an indispensable resource for comparative analysis and novel insights into dog and human evolution and history. Together with the survey sequence of a poodle previously published in 2003, the two dog genome sequences allowed identification of more than 2.5 million single nucleotide polymorphisms within and between dog breeds, which can be used in evolutionary analysis, behavioral studies and disease gene mapping.(1)

Animals↗

PubMed2006

Disruption of NaS1 sulfate transport function in mice leads to enhanced acetaminophen-induced hepatotoxicity.

Sulfate is required for detoxification of xenobiotics such as acetaminophen (APAP), a leading cause of liver failure in humans. The NaS1 sulfate transporter maintains blood sulfate levels sufficiently high for sulfonation reactions to work effectively for drug detoxification. In the present study, we identified two loss-of-function polymorphisms in the human NaS1 gene and showed the Nas1-null mouse to be hypersensitive to APAP hepatotoxicity. APAP treatment led to increased liver damage and decreased hepatic glutathione levels in the hyposulfatemic Nas1-null mice compared with that in normosulfatemic wild-type mice. Analysis of urinary APAP metabolites revealed a significantly lower ratio of APAP-sulfate to APAP-glucuronide in the Nas1-null mice. These results suggest hyposulfatemia increases sensitivity to APAP-induced hepatotoxicity by decreasing the sulfonation capacity to metabolize APAP. In conclusion, the results of this study highlight the importance of plasma sulfate level as a key modulator of acetaminophen metabolism and suggest that individuals with reduced NaS1 sulfate transporter function would be more sensitive to hepatotoxic agents.

Acetaminophen↗

PubMed2006

Using perylene-doped polymer nanotubes as fluorescence sensors.

Al(2)O(3) filters (200 nm) are used as templates to form polymer nanotubes containing an energy donor (perylene). The perylene is isolated from chemical interactions but can undergo electronic energy transfer to acceptor molecules in aqueous solutions passing through the membrane. This energy transfer is analyzed quantitatively in terms of both radiative and nonradiative (Forster transfer) mechanisms and provides a way for the chemically inert filter to sense the presence of analyte molecules in the filtrate.

Energy Transfer↗

PubMed2005

Genes involved in complex adaptive processes tend to have highly conserved upstream regions in mammalian genomes.

BACKGROUND: Recent advances in genome sequencing suggest a remarkable conservation in gene content of mammalian organisms. The similarity in gene repertoire present in different organisms has increased interest in studying regulatory mechanisms of gene expression aimed at elucidating the differences in phenotypes. In particular, a proximal promoter region contains a large number of regulatory elements that control the expression of its downstream gene. Although many studies have focused on identification of these elements, a broader picture on the complexity of transcriptional regulation of different biological processes has not been addressed in mammals. The regulatory complexity may strongly correlate with gene function, as different evolutionary forces must act on the regulatory systems under different biological conditions. We investigate this hypothesis by comparing the conservation of promoters upstream of genes classified in different functional categories. RESULTS: By conducting a rank correlation analysis between functional annotation and upstream sequence alignment scores obtained by human-mouse and human-dog comparison, we found a significantly greater conservation of the upstream sequence of genes involved in development, cell communication, neural functions and signaling processes than those involved in more basic processes shared with unicellular organisms such as metabolism and ribosomal function. This observation persists after controlling for G+C content. Considering conservation as a functional signature, we hypothesize a higher density of cis-regulatory elements upstream of genes participating in complex and adaptive processes. CONCLUSION: We identified a class of functions that are associated with either high or low promoter conservation in mammals. We detected a significant tendency that points to complex and adaptive processes were associated with higher promoter conservation, despite the fact that they have emerged relatively recently during evolution. We described and contrasted several hypotheses that provide a deeper insight into how transcriptional complexity might have been emerged during evolution.

Animals↗

PubMed2005

Dependence of the two-photon absorption cross section on the conjugation of the phenylacetylene linker in dipolar donor-bridge-acceptor chromophores.

The nonlinear optical properties of four isomeric dipolar two-photon chromophores are compared. The chromophores consist of a carbazole electron donor coupled to a naphthalimide electron acceptor by a phenylacetylene bridge. By variation of the connectivity of the bridge at the phenyl groups, four compounds with 0, 1, and 2 meta linkages are synthesized. The linear and nonlinear optical properties of these compounds are measured. Despite similar linear absorption cross sections, the two-photon absorption cross section delta of the all-meta compound is almost a factor of 10 lower than the all-para compound. By taking the detailed molecular conformations into account in order to calculate accurate dipole moment changes, we find that the decrease in delta results largely from the decreased charge transfer ability with increasing number of meta linkages. We find that a two-state model can be used to predict semiquantitatively the observed trend in delta on the basis of the linear optical properties of the molecules. This work illustrates the dramatic effect the ground-state polarizability can have on the nonlinear optical response of organic compounds and also provides a way to quantify the ability of meta linkages to inhibit charge transfer in their ground-state configuration.

Acetylene↗

PubMed2005

Effects of sonication on the size and crystallinity of stable zwitterionic organic nanoparticles formed by reprecipitation in water.

Nanoparticles of a novel organic zwitterionic Meisenheimer complex, N',N' ',N' ''-tri(isopropyl)-4-oxo-6-(isopropyliminio)-2-s-(2H)triazinespiro-1'-2',4',6'-trinitrocyclohexadienylide, were synthesized by reprecipitation in water under different conditions. While reprecipitation alone resulted in a suspension of amorphous particles that fell out of solution within hours, sonication for different periods of time resulted in the formation of crystalline particles that were stable in solution over the course of weeks. The disk-shaped particles had an average diameter of 140 nm and a thickness of 70 nm. Comparison of the optical spectroscopy of these particles with the monomer indicates that they possess delocalized excitonic states and enhanced radiative decay rates. The use of zwitterionic molecules in conjunction with sonication provides a way to exert some level of control over particle size and morphology, as well as increased colloidal stability.

Journal Article↗

PubMed2004

CHOISS for selection of single nucleotide polymorphism markers on interval regularity.

We developed algorithms that find a set of single nucleotide polymorphism (SNP) markers based on interval regularity, given either the number of SNPs to choose (m) or the desired interval (I), subject to minimum variance or minimum sum of squared deviations from I. In both cases, the number of all possible sets increases exponentially with respect to the number of input SNPs (n), but our algorithms find the minima only with O(n(2)) calculations and comparisons by elimination of redundancy.

Algorithms↗