Development of advanced radiation sources at KAERI

The KAERI Center for Quantum Beam-Based Radiation Research, was founded in 2011. The center pursues the development of advanced radiation sources and their applications in biology, material science, and nuclear physics. There are two main research topics in the development of advanced radiation sources: a system with high-power T-ray pump and an ultrashort X-ray probe system and a compact electron storage ring based on a laser-accelerated electron beam.     

Organoruthenium Antagonists of Human A3 Adenosine Receptors

Human A₃ adenosine receptor (hA₃AR) is a membrane‐bound G protein‐coupled receptor implicated in a number of severe pathological conditions, including cancer, in which it acts as a potential therapeutic target. To derive structure–activity relationships on pyrazolo–triazolo–pyrimidine (PTP)‐based A₃AR antagonists, we developed a new class of organometallic inhibitors through replacement of the triazolo moiety with an organoruthenium fragment. The objective was to introduce by design structural diversity into the PTP scaffold in order to tune their binding efficacy toward the target receptor. These novel organoruthenium antagonists displayed good aquatic stability and moderate binding affinity toward the hA₃ receptor in the low micromolar range. The assembly of these complexes through a template‐driven approach with selective ligand replacement at the metal center to control their steric and receptor‐binding properties is discussed.     

The M-CSF receptor in osteoclasts and beyond

Colony-stimulating factor 1 receptor (CSF1R, also known as c-FMS) is a receptor tyrosine kinase. Macrophage colony-stimulating factor (M-CSF) and IL-34 are ligands of CSF1R. CSF1R-mediated signaling is crucial for the survival, function, proliferation, and differentiation of myeloid lineage cells, including osteoclasts, monocytes/macrophages, microglia, Langerhans cells in the skin, and Paneth cells in the intestine. CSF1R also plays an important role in oocytes and trophoblastic cells in the female reproductive tract and in the maintenance and maturation of neural progenitor cells. Given that CSF1R is expressed in a wide range of myeloid cells, altered CSF1R signaling is implicated in inflammatory, neoplastic, and neurodegenerative diseases. Inhibiting CSF1R signaling through an inhibitory anti-CSF1R antibody or small molecule inhibitors that target the kinase activity of CSF1R has thus been a promising therapeutic strategy for those diseases. In this review, we cover the recent progress in our understanding of the various roles of CSF1R in osteoclasts and other myeloid cells, highlighting the therapeutic applications of CSF1R inhibitors in disease conditions.Subject terms: Osteoimmunology, Cell signalling, Targeted bone remodelling, Differentiation     

A proteomic approach based on multiple parallel separation for the unambiguous identification of an antibody cognate antigen

Autoantibodies obtained from cancer patients have been identified as useful tools for cancer diagnostics, prognostics, and as potential targets for immunotherapy. Serological proteome analysis in combination with 2‐DE is a classic strategy for identification of tumor‐associated antigens in the serum of cancer patients. However, serological proteome analysis cannot always indicate the true antigen out of a complex proteome identified from a single protein spot because the most abundant protein is not always the most antigenic. To address this problem, we utilized multiple parallel separation (MPS) for proteome separation. The common identities present in the fractions obtained using different separation methods were regarded as the true antigens. The merit of our MPS technique was validated using anti‐ARPC2 and anti‐PTEN antibodies. Next, we applied the MPS technique for the identification of glycyl‐tRNA synthetase as the cognate antigen for an autoantibody that was overexpressed in the plasma of breast cancer patients. These results reveal that MPS can unambiguously identify an antibody cognate antigen by reducing false‐positives. Therefore, MPS could be used for the characterization of diagnostic antibodies raised in laboratory animals as well as autoantibodies isolated from diseased patients.     

Evaluation of the effects of Mitragyna speciosa alkaloid extract on cytochrome P450 enzymes using a high throughput assay

The extract from Mitragyna speciosa has been widely used as an opium substitute, mainly due to its morphine-like pharmacological effects. This study investigated the effects of M. speciosa alkaloid extract (MSE) on human recombinant cytochrome P450 (CYP) enzyme activities using a modified Crespi method. As compared with the liquid chromatography-mass spectrometry method, this method has shown to be a fast and cost-effective way to perform CYP inhibition studies. The results indicated that MSE has the most potent inhibitory effect on CYP3A4 and CYP2D6, with apparent half-maximal inhibitory concentration (IC(50)) values of 0.78 μg/mL and 0.636 μg/mL, respectively. In addition, moderate inhibition was observed for CYP1A2, with an IC(50) of 39 μg/mL, and weak inhibition was detected for CYP2C19. The IC(50) of CYP2C19 could not be determined, however, because inhibition was <50%. Competitive inhibition was found for the MSE-treated CYP2D6 inhibition assay, whereas non-competitive inhibition was shown in inhibition assays using CYP3A4, CYP1A2 and CYP2C19. Quinidine (CYP2D6), ketoconazole (CYP3A4), tranylcypromine (CYP2C19) and furafylline (CYP1A2) were ACCESSused as positive controls throughout the experiments. This study shows that MSE may contribute to an herb-drug interaction if administered concomitantly with drugs that are substrates for CYP3A4, CYP2D6 and CYP1A2.     

Collapse of Poly(methacrylic acid) Hydrogels in Response to Simultaneous Stimulation by an Electric Field and Complex Formation

Complex formation of poly(methacrylic acid) hydrogels with linear poly(ethylene glycol) has been studied at different pH values and in the presence of an electric field. The fastest contraction of the gel samples was observed under simultaneous action of electric field and complex formation.

Dependence of the volume ratio V/V₀ of PMAA sample on time: Sample in the absence of an electric field immersed in 0.1 M PEG solution at (1) pH 8.2, (2) at pH 5.1, and in the presence of an electric field (3) in water and (4) 0.1 M PEG solution at pH 5.1.     

Assessment of <Superscript>210</Superscript>Po in foodstuffs consumed in Korea

²¹⁰Po in the daily diet in Korea was analyzed and the ingestion dose from an intake of ²¹⁰Po was estimated by considering the dietary habit of a Korean person. The ²¹⁰Po concentrations of a leafy vegetable (0.36 Bq·kg⁻¹ for lettuce) in the terrestrial food were higher than those of grain, whereas Chinese cabbage had a lesser ²¹⁰Po concentration (0.019 Bq·kg⁻¹). The ²¹⁰Po concentration of the animal product was similar to those detected in the grain and vegetable. The ²¹⁰Po concentrations in the shell and crustaceous were high from 19.1 to 33.0 Bq·kg⁻¹, however, its value fell in the overall range of the reported values. The effective dose from ²¹⁰Po for an adult from the Korean population was about 269.4 μSv·y⁻¹. Nearly 80% of the ingestion dose from the intake of ²¹⁰Po was attributed to the consumption of seafood. It suggests that the marine food ingestion is a critical pathway for natural ²¹⁰Po to the Korean population.     

Cooperative perfunctionalization and partial labeling of 6-azido-6-deoxy-α-cyclodextrin through copper(I)-catalyzed azide-alkyne cycloaddition

In a microwave and ligand-assisted cyclodextrin click cluster synthesis, we observed the cooperative perfunctionalization in the click reaction of 6-azido-6-deoxy-α-cyclodextrin under our optimized reaction conditions. MALDI-MS data and partial fluorescein labeling via the one-pot/stepwise methods confirmed the occurrence of cooperative perfunctionalization: the fully triazole-functionalized cyclodextrin click cluster became the major product with limited alkyne equivalents. To the best of our knowledge, this work constitutes the first example of a ‘cooperative’ click reaction of an azido-cyclodextrin. This cooperative perfunctionalization of cyclodextrin click clusters offers useful synthetic insights into the partial reporter labeling strategy using azido-cyclodextrin.     

Temperature-responsive swelling and deswelling of the copolymers from vinyl ether of ethylene glycol and butyl vinyl ether

Linear and crosslinked copolymers of a vinyl ether of ethylene glycol (2-hydroxyethyl vinyl ether, ( 1 )) and butyl vinyl ether ( 2 ) are synthesized by α-irradiation polymerization. It is shown that the linear copolymers exhibit a phase separation phenomenon in dependence of the temperature due to the destruction of hydrogen bonds and the enhancement of hydrophobic interaction in aqueous solution. The processes of reversible swelling or shrinking upon temperature change are demonstrated for polymer networks.