Publications by authors named "Jeongmi Lee"

81 Publications

Reactive oxygen species-responsive dendritic cell-derived exosomes for rheumatoid arthritis.

Acta Biomater 2021 Apr 18. Epub 2021 Apr 18.

School of Chemical Engineering, College of Engineering, Sungkyunkwan University, Suwon, 16419, Republic of Korea; Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Suwon, 16419, Republic of Korea. Electronic address:

Although tolerogenic dendritic cell-derived exosomes (TolDex) have emerged as promising therapeutics for rheumatoid arthritis (RA), their clinical applications have been hampered by their poor in vivo disposition after systemic administration. Herein, we report the development of stimuli-responsive TolDex that induces lesion-specific immunoregulation in RA. Responsiveness to reactive oxygen species (ROS), a physiological stimulus in the RA microenvironment, was conferred on TolDex by introducing a thioketal (TK) linker-embedded poly(ethylene glycol) (PEG) on TolDex surface via hydrophobic insertion. The detachment of PEG following overproduction of ROS facilitates the cellular uptake of ROS-responsive TolDex (TKDex) into activated immune cells. Notably, TolDex and TKDex downregulated CD40 in mature dendritic cells (mDCs) and regulated secretion of pro-inflammatory cytokines, including tumor necrosis factor (TNF)-α and interleukin-6 (IL-6) at the cellular level. In the collagen-induced arthritis (CIA) mouse model, PEG prolonged the blood circulation of TKDex following intravenous administration and enhanced their accumulation in the joints. In addition, TKDex decreased IL-6, increased transforming growth factor-β, and induced the CD4CD25Foxp3 regulatory T cells in CIA mice. Overall, ROS-responsive TolDex might have potential as therapeutic agents for RA. STATEMENT OF SIGNIFICANCE: Tolerogenic dendritic cell-derived exosomes (TolDex) are emerging immunoregulators of autoimmune diseases, including rheumatoid arthritis (RA). However, their lack of long-term stability and low targetability are still challenging. To overcome these issues, we developed reactive oxygen species (ROS)-responsive TolDex (TKDex) by incorporating the ROS-sensitive functional group-embedded poly(ethylene glycol) linker into the exosomal membrane of TolDex. Surface-engineered TKDex were internalized in mature DCs because of high ROS-sensitivity and enhanced accumulation in the inflamed joint in vivo. Further, for the first time, we investigated the potential mechanism of action of TolDex relevant to CD40 downregulation and attenuation of tumor necrosis factor (TNF)-α secretion. Our strategy highlighted the promising nanotherapeutic effects of stimuli-sensitive TolDex, which induces immunoregulation.
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http://dx.doi.org/10.1016/j.actbio.2021.04.026DOI Listing
April 2021

-GlcNAcylation ameliorates the pathological manifestations of Alzheimer's disease by inhibiting necroptosis.

Sci Adv 2021 Jan 13;7(3). Epub 2021 Jan 13.

School of Pharmacy, Sungkyunkwan University, Suwon 16419, Korea.

-GlcNAcylation (-linked β--acetylglucosaminylation) is notably decreased in Alzheimer's disease (AD) brain. Necroptosis is activated in AD brain and is positively correlated with neuroinflammation and tau pathology. However, the links among altered -GlcNAcylation, β-amyloid (Aβ) accumulation, and necroptosis are unclear. Here, we found that -GlcNAcylation plays a protective role in AD by inhibiting necroptosis. Necroptosis was increased in AD patients and AD mouse model compared with controls; however, decreased necroptosis due to -GlcNAcylation of RIPK3 (receptor-interacting serine/threonine protein kinase 3) was observed in 5xFAD mice with insufficient -linked β--acetylglucosaminase. -GlcNAcylation of RIPK3 suppresses phosphorylation of RIPK3 and its interaction with RIPK1. Moreover, increased -GlcNAcylation ameliorated AD pathology, including Aβ burden, neuronal loss, neuroinflammation, and damaged mitochondria and recovered the M2 phenotype and phagocytic activity of microglia. Thus, our data establish the influence of -GlcNAcylation on Aβ accumulation and neurodegeneration, suggesting -GlcNAcylation-based treatments as potential interventions for AD.
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http://dx.doi.org/10.1126/sciadv.abd3207DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7806231PMC
January 2021

Preparation and characterization of various chitin-glucan complexes derived from white button mushroom using a deep eutectic solvent-based ecofriendly method.

Int J Biol Macromol 2021 Feb 14;169:122-129. Epub 2020 Dec 14.

School of Pharmacy, Sungkyunkwan University, Suwon, Gyeonggi 16419, Republic of Korea. Electronic address:

Deep eutectic solvents (DESs) have gained great interests as ecofriendly and safe solvents in diverse areas. Herein, various chitin-glucan complexes (CGCs) were prepared from white button mushroom (Agaricus bisporus) using DESs. Ultrasonication of mushroom in five DESs yielded two types of CGCs from each DES, one from the DES-insoluble residue (DES_P) and another from the DES-soluble extract (DES_S). The ten resulting CGCs with varying chitin-to-β-glucan ratios were compared with alkali-insoluble matter (AIM), chemically prepared using NaOH. BU_S and BU_P, prepared using BU comprising betaine and urea, were obtained in the highest yields with reasonably low protein and mineral contents. Despite different acetylation degrees (77.3% and 57.3%, respectively), BU_S and BU_P both degraded at 318 °C and showed remarkably low crystallinity (32.0% and 37.0% for BU_S and BU_P, respectively) compared to AIM, commercial chitin, and the reported CGCs. The surface of BU_S and BU_P was very porous and rough compared with AIM as a result of reduced H-bonds and lowered crystallinity. The DES-based method can potentially enable the preparation of advanced biomaterials from mushrooms under mild and ecofriendly conditions.
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http://dx.doi.org/10.1016/j.ijbiomac.2020.12.081DOI Listing
February 2021

Sub-Ciliary Segregation of Two Transient Receptor Potential Channels Begins at the Initial Stage of Their Pre-Ciliary Trafficking.

Mol Cells 2020 Dec;43(12):1002-1010

Department of Life Sciences, University of Seoul, Seoul 02504, Korea.

Cilia are important eukaryotic cellular compartments required for diverse biological functions. Recent studies have revealed that protein targeting into the proper ciliary subcompartments is essential for ciliary function. In chordotonal cilium, where mechano-electric transduction occurs, two transient receptor potential (TRP) superfamily ion channels, TRPV and TRPN, are restricted to the proximal and distal subcompartments, respectively. To understand the mechanisms underlying the sub-ciliary segregation of the two TRPs, we analyzed their localization under various conditions. In developing chordotonal cilia, TRPN was directly targeted to the ciliary tip from the beginning of its appearance and was retained in the distal subcompartment throughout development, whereas the ciliary localization of TRPV was considerably delayed. Lack of intraflagella transport-related proteins affected TRPV from the initial stage of its pre-ciliary trafficking, whereas it affected TRPN from the ciliary entry stage. The ectopic expression of the two TRP channels in both ciliated and nonciliated cells revealed their intrinsic properties related to their localization. Taken together, our results suggest that subciliary segregation of the two TRP channels relies on their distinct intrinsic properties, and begins at the initial stage of their pre-ciliary trafficking.
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http://dx.doi.org/10.14348/molcells.2020.0205DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7772507PMC
December 2020

Applications of deep eutectic solvents to quantitative analyses of pharmaceuticals and pesticides in various matrices: a brief review.

Arch Pharm Res 2020 Sep 12;43(9):900-919. Epub 2020 Sep 12.

Department of Chemistry, Seoul National University, Seoul, 08826, Republic of Korea.

Pharmaceuticals and pesticides are important analytes of interest in clinical, environmental, and food analyses for ensuring public health. Sample pretreatment steps are often prerequisites for the quantitative analysis of these compounds, which are generally present in low concentrations in samples with complex matrices. In compliance with the current trend towards green analytical chemistry, the replacement of conventional toxic organic solvents with ecofriendly and safe solvents has been pursued in developing sample pretreatment methods. Subsequent to several reports in 2017, deep eutectic solvents (DESs) have been increasingly applied as desirable alternative solvents in numerous types of sample pretreatment methods for the analysis of pharmaceuticals and pesticides. The present review summarizes analytical methods involving DESs as extraction solvents and as the reaction media or functional materials for preparing adsorbents to quantify pharmaceuticals and pesticides in various matrices.
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http://dx.doi.org/10.1007/s12272-020-01266-7DOI Listing
September 2020

Safe scarless cassette-free selection of genome-edited human pluripotent stem cells using temporary drug resistance.

Biomaterials 2020 12 1;262:120295. Epub 2020 Sep 1.

College of Pharmacy, Seoul National University, Seoul, South Korea. Electronic address:

An efficient gene-editing technique for use in human pluripotent stem cells (hPSCs) has great potential value in regenerative medicine, as well as in drug discovery based on isogenic human disease models. However, the extremely low efficiency of gene editing in hPSCs remains as a major technical hurdle. Previously, we demonstrated that YM155, a survivin inhibitor developed as an anti-cancer drug, induces highly selective cell death in undifferentiated hPSCs. In this study, we demonstrated that the high cytotoxicity of YM155 in hPSCs, which is mediated by selective cellular uptake of the drug, is due to the high expression of SLC35F2 in these cells. Knockout of SLC35F2 with CRISPR-Cas9, or depletion with siRNAs, made the hPSCs highly resistant to YM155. Simultaneous editing of a gene of interest and transient knockdown of SLC35F2 following YM155 treatment enabled the survival of genome-edited hPSCs as a result of temporary YM155 resistance, thereby achieving an enriched selection of clonal populations with gene knockout or knock-in. This precise and efficient genome editing approach took as little as 3 weeks and required no cell sorting or the introduction of additional genes, to be a more feasible approach for gene editing in hPSCs due to its simplicity.
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http://dx.doi.org/10.1016/j.biomaterials.2020.120295DOI Listing
December 2020

Insights into the Vastly Different Effects of Eutectic Solvents on the Stability of Phenolic Compounds.

J Phys Chem Lett 2020 Jul 18;11(13):5268-5272. Epub 2020 Jun 18.

School of Pharmacy, Sungkyunkwan University, Suwon, Gyeonggi 16419, Republic of Korea.

Eutectic solvents (ESs) have shown stabilizing effects on several molecules. Due to the potential applicability of bioactive compounds, understanding how ESs stabilize them is of great interest in pharmaceutical and related fields. Here, among various ESs, CTU, which comprise thiourea and choline chloride (ChCl), exerted remarkably high stabilizing effects on various phenolic compounds, whereas CU consisting of urea and ChCl exhibited the opposite effects. Using a potent polyphenol, (-)-epigallocatechin gallate (EGCG), as a model compound, we conducted experimental and studies to unravel the underlying mechanisms of the two very similar ESs for the contrasting effects. The results suggest that ESs can affect with great diversity the stability of EGCG by complicated interactions arising from the unique properties of both ESs and their components.
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http://dx.doi.org/10.1021/acs.jpclett.0c00610DOI Listing
July 2020

Small extracellular vesicles from human adipose-derived stem cells attenuate cartilage degeneration.

J Extracell Vesicles 2020 9;9(1):1735249. Epub 2020 Mar 9.

Department of Chemical Engineering, Hanyang University, Ansan, Korea.

Osteoarthritis (OA) is a chronic degenerative disease of articular cartilage that is the most common joint disease worldwide. Mesenchymal stem cells (MSCs) have been the most extensively explored for the treatment of OA. Recently, it has been demonstrated that MSC-derived extracellular vesicles (EVs) may contribute to the potential mechanisms of MSC-based therapies. In this study, we investigated the therapeutic potential of human adipose-derived stem cells EVs (hASC-EVs) in alleviating OA, along with the mechanism. EVs were isolated from the culture supernatants of hASCs by a multi-filtration system based on the tangential flow filtration (TFF) system. The isolated EVs were characterised using dynamic light scattering (DLS), transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA) and flow cytometry analysis. The hASC-EVs not only promoted the proliferation and migration of human OA chondrocytes, but also maintained the chondrocyte matrix by increasing type Ⅱ collagen synthesis and decreasing MMP-1, MMP-3, MMP-13 and ADAMTS-5 expression in the presence of IL-1β . Intra-articular injection of hASC-EVs significantly attenuated OA progression and protected cartilage from degeneration in both the monosodium iodoacetate (MIA) rat and the surgical destabilisation of the medial meniscus (DMM) mouse models. In addition, administration of hASC-EVs inhibited the infiltration of M1 macrophages into the synovium. Overall results suggest that the hASC-EVs should be considered as a potential therapeutic approach in the treatment of OA.
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http://dx.doi.org/10.1080/20013078.2020.1735249DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7144299PMC
March 2020

In situ formation of thymol-based hydrophobic deep eutectic solvents: Application to antibiotics analysis in surface water based on liquid-liquid microextraction followed by liquid chromatography.

J Chromatogr A 2020 Mar 22;1614:460730. Epub 2019 Nov 22.

School of Pharmacy, Sungkyunkwan University, Suwon 16419, Republic of Korea. Electronic address:

A simple and ecofriendly sample preparation method was developed for quantifying fluoroquinolone (FQ) antibiotics in surface water. Seventeen combinations of monoterpenes (menthol, thymol, and camphor), fatty acids (heptanoic, octanoic, nonanoic, and decanoic acids), and a benzoate ester (salol) were utilized for the in situ formation of hydrophobic deep eutectic solvents (hDESs) for liquid-liquid microextraction (LLME). The hDES comprising thymol and heptanoic acid (HA) exhibited the highest extraction efficiency for ofloxacin, norfloxacin, ciprofloxacin, and enrofloxacin. Optimization via the one-variable-at-a-time strategy revealed that a 2:1 ratio of thymol to HA yielded the highest efficiency for antibiotic extraction at pH 4-7. Further, response surface methodology-based optimization suggested that the optimal extraction conditions involved the use of appropriate amounts of thymol and HA to generate 100 μL of hDES in 10 mL of aqueous sample with incubation at 52 °C for 5 min, followed by automated shaking for 1 min. The collected hDES phase was diluted and subjected to liquid chromatography-ultraviolet detection analysis. The established method based on in situ formation of hDES coupled with shaker-assisted LLME (in situ hDES-SA-LLME) was validated. The method was specific and showed good linearity in the 15-3000 ng mL concentration range (r ≥ 0.9997), with a limit of detection of 3.0 ng mL, limit of quantification of 9.0 ng mL, accuracy of 84.1-113.65%, and intra-day and inter-day precision of ≤7.78% RSD and ≤7.91% RSD, respectively. The method was successfully applied to three different types of real surface water samples. Without toxic volatile organic solvents, the developed method allows for safe and rapid, yet reliable, analysis of FQ antibiotics.
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http://dx.doi.org/10.1016/j.chroma.2019.460730DOI Listing
March 2020

Flexible weighting of target features based on distractor context.

Atten Percept Psychophys 2020 Feb;82(2):739-751

Center for Mind and Brain, University of California, Davis, 267 Cousteau Pl, Davis, CA, 95618, USA.

Models of attention posit that attentional priority is established by summing the saliency and relevancy signals from feature-selective maps. The dimension-weighting account further hypothesizes that information from each feature-selective map is weighted based on expectations of how informative each dimension will be. In the current studies, we investigated the question of whether attentional biases to the features of a conjunction target (color and orientation) differ when one dimension is expected to be more diagnostic of the target. In a series of color-orientation conjunction search tasks, observers saw an exact cue for the upcoming target, while the probability of distractors sharing a target feature in each dimension was manipulated. In one context, distractors were more likely to share the target color, and in another, distractors were more likely to share the target orientation. The results indicated that despite an overall bias toward color, attentional priority to each target feature was flexibly adjusted according to distractor context: RT and accuracy performance was better when the diagnostic feature was expected than unexpected. This occurred both when the distractor context was learned implicitly and explicitly. These results suggest that feature-based enhancement can occur selectively for the dimension expected to be most informative in distinguishing the target from distractors.
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http://dx.doi.org/10.3758/s13414-019-01910-5DOI Listing
February 2020

Headspace conditions and ingredients can affect artefactual benzene formation in beverages.

Food Chem 2019 Sep 25;293:278-284. Epub 2019 Apr 25.

School of Pharmacy, Sungkyunkwan University, Suwon, Gyeonggi 16419, Republic of Korea. Electronic address:

A headspace sampling-gas chromatography/mass spectrometry (HS-GC/MS) method using mild HS conditions (40 °C, 30 min) was established, validated in terms of specificity, linearity (1.75-87.65 ng mL), precision (0.3-9.1% RSD), and accuracy (81.1-117.7%); and applied for the monitoring of 900 commercial beverage samples of six different types. These mild (low-temperature) conditions were compared with 1) optimized (high-temperature) conditions and 2) a liquid-phase microextraction method involving no heat treatment. This method was desirable because a high equilibrium temperature induced artefactual benzene formation from benzoate and ascorbic acid. In a 2 fractional factorial design, eight variables-ascorbic acid, benzoate, benzaldehyde, Cu, Fe, riboflavin, pyridoxine, and heat treatment-were tested as potential factors affecting benzene formation. All variables except Fe and pyridoxine significantly affected benzene formation, both individually and interactively. The present study suggests an accurate and reliable method for benzene analysis and provides strategies to prevent unintentional benzene formation in beverages.
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http://dx.doi.org/10.1016/j.foodchem.2019.04.089DOI Listing
September 2019

A comprehensive metabolomics investigation of hippocampus, serum, and feces affected by chronic fluoxetine treatment using the chronic unpredictable mild stress mouse model of depression.

Sci Rep 2019 05 20;9(1):7566. Epub 2019 May 20.

School of Pharmacy, Sungkyunkwan University, Suwon, 16419, Republic of Korea.

A metabolomic investigation of depression and chronic fluoxetine treatment was conducted using a chronic unpredictable mild stress model with C57BL/6N mice. Establishment of the depressive model was confirmed by body weight measurement and behavior tests including the forced swim test and the tail suspension test. Behavioral despair by depression was reversed by four week-treatment with fluoxetine. Hippocampus, serum, and feces samples collected from four groups (control + saline, control + fluoxetine, model + saline, and model + fluoxetine) were subjected to metabolomic profiling based on ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry. Alterations in the metabolic patterns were evident in all sample types. The antidepressant effects of fluoxetine appeared to involve various metabolic pathways including energy metabolism, neurotransmitter synthesis, tryptophan metabolism, fatty acid metabolism, lipid metabolism, and bile acid metabolism. Predictive marker candidates of depression were identified, including β-citryl-L-glutamic acid (BCG) and docosahexaenoic acid (DHA) in serum and chenodeoxycholic acid and oleamide in feces. This study suggests that treatment effects of fluoxetine might be differentiated by altered levels of tyramine and BCG in serum, and that DHA is a potential serum marker for depression with positive association with hippocampal DHA. Collectively, our comprehensive study provides insights into the biochemical perturbations involved in depression and the antidepressant effects of fluoxetine.
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http://dx.doi.org/10.1038/s41598-019-44052-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6527582PMC
May 2019

Assembly of a GPCR-G Protein Complex.

Cell 2019 05 9;177(5):1232-1242.e11. Epub 2019 May 9.

School of Pharmacy, Sungkyunkwan University, Suwon 16419, Republic of Korea. Electronic address:

The activation of G proteins by G protein-coupled receptors (GPCRs) underlies the majority of transmembrane signaling by hormones and neurotransmitters. Recent structures of GPCR-G protein complexes obtained by crystallography and cryoelectron microscopy (cryo-EM) reveal similar interactions between GPCRs and the alpha subunit of different G protein isoforms. While some G protein subtype-specific differences are observed, there is no clear structural explanation for G protein subtype-selectivity. All of these complexes are stabilized in the nucleotide-free state, a condition that does not exist in living cells. In an effort to better understand the structural basis of coupling specificity, we used time-resolved structural mass spectrometry techniques to investigate GPCR-G protein complex formation and G-protein activation. Our results suggest that coupling specificity is determined by one or more transient intermediate states that serve as selectivity filters and precede the formation of the stable nucleotide-free GPCR-G protein complexes observed in crystal and cryo-EM structures.
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http://dx.doi.org/10.1016/j.cell.2019.04.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6763313PMC
May 2019

Comprehensive Investigation of the Effects of Brewing Conditions in Sample Preparation of Green Tea Infusions.

Molecules 2019 May 4;24(9). Epub 2019 May 4.

School of Pharmacy, Sungkyunkwan University, Suwon 16419, Korea.

Chemical and biological investigation of green tea has been generally performed while using different infusions that are prepared without consideration of the effects of sample preparation conditions. In this study, for the first time, the effects of green tea brewing conditions on the antioxidant activity and chemical profiles of metabolome and catechin compounds were examined at 60 °C and 95 °C for a period of 5-300 min. The antioxidant capacities of the tea infusions, which were assessed as per 2,2-diphenyl-1-picryl-hydrazyl hydrate (DPPH) radical scavenging activity, depended more on temperature than time. Metabolomics study that was based on ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry (UHPLC-QTOF/MS) revealed that the metabolic profiles, including 33 differential metabolites, were significantly changed by temperature and time, with the effects of time being more evident at 95 °C starting after 30 min. Infusions that were brewed at 95 °C for greater than 30 min yielded distinct profiles in the hierarchical clustering analysis. The quantification of eight catechins by UHPLC-QqQ/MS showed that the total catechin level peaked at 95 °C brewing at 10 min, after which the levels of four epi-forms of catechins decreased and those of four non-epi-forms increased, implying the epimerization of catechins over time. These results suggest that the brewing conditions for sample preparation of green tea should be put into careful consideration in studies where green tea extracts are applied as aqueous infusions.
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http://dx.doi.org/10.3390/molecules24091735DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6539062PMC
May 2019

Cytotoxic Withanolides from the Roots of Indian Ginseng ( Withania somnifera).

J Nat Prod 2019 04 18;82(4):765-773. Epub 2019 Feb 18.

School of Pharmacy , Sungkyunkwan University , Suwon 16419 , Republic of Korea.

Withania somnifera, commonly known as "Indian ginseng" or "ashwagandha", is popular as a functional food because of its diverse purported therapeutic efficacies including invigorating, improvement of cognitive ability, and stress release activities. Chemical investigation of the MeOH extract of W. somnifera roots combined with LC/MS-based analysis resulted in the identification of six new withanolides, withasilolides A-F (1-6), as well as seven known compounds (7-13). The structures of the new compounds were established by application of spectroscopic methods, including 1D and 2D NMR, HRMS, and ECD measurements. The cytotoxicity of the isolated compounds was evaluated against four human cancer cell lines (A549, SK-OV-3, SK-MEL-2, and HCT-15). Compounds 1, 2, 4, 6, and withanone (11) each showed cytotoxicity for one or more of the four cancer cell lines used.
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http://dx.doi.org/10.1021/acs.jnatprod.8b00665DOI Listing
April 2019

Metabolomics Approach Based on Multivariate Techniques for Blood Transfusion Reactions.

Sci Rep 2019 02 11;9(1):1740. Epub 2019 Feb 11.

College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, 08826, Korea.

Blood transfusions temporarily improve the physical state of the patient but exert widespread effects on immune and non-immune systems. Perioperative allogeneic blood transfusions (ABT) are associated with various risks, including coagulopathy, incompatibility, transmission of infectious agents, and allergic reactions. Nevertheless, little is known about the global metabolic alterations that reflect the possible reactions of blood transfusions. In this study, we investigated metabolite changes generated by ABT in a rat model using metabolomics technology. To further profile the "metabolome" after blood transfusions, we used both liquid chromatography-quadrupole time-of-flight high-definition mass spectrometry and gas chromatography-mass spectrometry. ABT promoted a stimulatory microenvironment associated with a relative increase in glucose transporter 1/4 (GLUT1/GLUT4) expression. Supporting this result, glucose metabolism-related enzyme IRS1 and interleukin-6 (IL-6) were abnormally expressed, and levels of lysophosphatidylcholine (LysoPC) and its related enzyme phospholipase A2 (PLA2) were significantly altered in allogeneic groups compared to those in autologous groups. Finally, amino acid metabolism was also altered following ABT. Taken together, our results show a difference between autologous and allogeneic blood transfusions and demonstrate correlations with cancer-associated metabolic changes. Our data provide endogenous information for a better understanding of blood transfusion reactions.
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http://dx.doi.org/10.1038/s41598-018-37468-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6370787PMC
February 2019

Tirucallane Triterpenoids from the Stems and Stem Bark of that Control Adipocyte and Osteoblast Differentiations.

Molecules 2018 Oct 23;23(11). Epub 2018 Oct 23.

School of Pharmacy, Sungkyunkwan University, Suwon 16419, Korea.

Wanger (Cornaceae) has been broadly used in traditional East Asian medicine for the treatment of various disorders, including skin inflammation and diarrhea. As part of our efforts to identify structurally and/or biologically new compounds from Korean medicinal plants, we have explored potentially new bioactive constituents from . In the present study, seven triterpenoids (⁻) were isolated from stems and stem bark. Compounds ⁻ were new tirucallane triterpenoids (cornusalterins N-P) and compounds ⁻ were isolated for the first time from . The structures of the new compounds were determined based on 1D and 2D NMR spectroscopic data interpretations and HR-ESIMS, as well as a computational method coupled with a statistical procedure (DP4+). The regulatory effects of the isolated triterpenoids (⁻) on mesenchymal stem cell (MSC) differentiation to adipocytes and osteoblasts were examined in the C3H10T1/2 cell line. Although these compounds had little effect on MSC differentiation to osteoblasts, lipid droplet formation in adipocyte-differentiated MSCs decreased in the presence of the seven triterpenoids. Compounds and each had a relatively distinct correlation between dose and efficacy, showing adipogenesis suppression at higher concentrations. Our findings demonstrate that the active compounds and can exert beneficial effects in regulation of adipocyte differentiation.
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http://dx.doi.org/10.3390/molecules23112732DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6278563PMC
October 2018

Assessment of chemical equivalence in herbal materials using chromatographic fingerprints by combination of three similarity indices and three-dimensional kernel density estimation.

Anal Chim Acta 2018 Dec 13;1037:220-229. Epub 2018 Mar 13.

School of Pharmacy, Sungkyunkwan University, Suwon 16419, Republic of Korea. Electronic address:

An intuitive and practical way to control chemical equivalence of secondary metabolites in herbal materials based on chromatographic fingerprints deserves a thorough discussion, yet it is relatively unexplored. For the first time, we propose a mixture of three similarity indices, the congruence coefficient, the average of the peak area ratios, and the larger value between the maximum peak area ratio and the reciprocal of the minimum peak area ratio, to make up for the weak points of some widely used similarity indices and to evaluate the chemical equivalence of two fingerprints from various perspectives. The three similarity values are fed into a three-dimensional kernel density estimation to determine the quality of herbal materials. This estimation enables precise detection of anomalies in the absence of prior quality determination experience. Forty Atractylodes samples similar in appearance and indiscriminately used for medical purposes were used to demonstrate the effectiveness of the developed approach. After a reference sample was postulated, a quality assessment of the 40 samples was performed using the three similarity values and the estimated kernel density. The samples that were judged by the developed approach to be of good quality were compared with those chosen by the most popular approach using decision criterion of a single similarity index. The benefits of the proposed approach were evident in that the qualified samples had the composition ratio and individual concentrations of multi-components closer to those of the reference in general, and their inter-sample deviation was significantly smaller.
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http://dx.doi.org/10.1016/j.aca.2018.02.044DOI Listing
December 2018

Dynamics of Feature-based Attentional Selection during Color-Shape Conjunction Search.

J Cogn Neurosci 2018 12 31;30(12):1773-1787. Epub 2018 Jul 31.

University of California, Davis.

Feature-based attentional selection is accomplished by increasing the gain of sensory neurons encoding target-relevant features while decreasing that of other features. But how do these mechanisms work when targets and distractors share features? We investigated this in a simplified color-shape conjunction search task using ERP components (N2pc, P, and SPCN) that index lateralized attentional processing. In Experiment 1, we manipulated the presence and frequency of color distractors while holding shape distractors constant. We tested the hypothesis that the color distractor would capture attention, requiring active suppression such that processing of the target can continue. Consistent with this hypothesis, we found that color distractors consistently captured attention, as indexed by a significant N2pc, but were reactively suppressed (indexed by P). Interestingly, when the color distractor was present, target processing was sustained (indexed by SPCN), suggesting that the dynamics of attentional competition involved distractor suppression interlinked with sustained target processing. In Experiment 2, we examined the contribution of shape to the dynamics of attentional competition under similar conditions. In contrast to color distractors, shape distractors did not reliably capture attention, even when the color distractor was very frequent and attending to target shape would be beneficial. Together, these results suggest that target-colored objects are prioritized during color-shape conjunction search, and the ability to select the target is delayed while target-colored distractors are actively suppressed.
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http://dx.doi.org/10.1162/jocn_a_01318DOI Listing
December 2018

Deep eutectic solvent-based valorization of spent coffee grounds.

Food Chem 2018 Jul 19;255:357-364. Epub 2018 Feb 19.

School of Pharmacy, Sungkyunkwan University, Suwon, Gyeonggi-do 16419, Republic of Korea. Electronic address:

Spent coffee grounds (SCGs) are viewed as a valuable resource for useful bioactive compounds, such as chlorogenic acids and flavonoids, and we suggest an eco-friendly and efficient valorization method. A series of choline chloride-based deep eutectic solvents (DESs) were tested as green extraction solvents for use with ultrasound-assisted extraction. Extraction efficiency was evaluated based on total phenolic content (TPC), total flavonoid content, total chlorogenic acids, and/or anti-oxidant activity. A binary DES named HC-6, which was composed of 1,6-hexanediol:choline chloride (molar ratio 7:1) was designed to produce the highest efficiency. Experimental conditions were screened and optimized for maximized efficiency using a two-level fractional factorial design and a central composite design, respectively. As a result, the proposed method presented significantly enhanced TPC and anti-oxidant activity. In addition, phenolic compounds could be easily recovered from extracts at high recovery yields (>90%) by adsorption chromatography.
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http://dx.doi.org/10.1016/j.foodchem.2018.02.096DOI Listing
July 2018

One-step sample preparation for convenient examination of volatile monoterpenes and phenolic compounds in peppermint leaves using deep eutectic solvents.

Food Chem 2018 Jun 11;251:69-76. Epub 2018 Jan 11.

School of Pharmacy, Sungkyunkwan University, Jangan-gu, Suwon, Gyeonggi-do 16419, Republic of Korea. Electronic address:

Deep eutectic solvents (DESs) were investigated as an extraction medium for one-step sample preparation for chemical characterization of peppermint (Mentha piperita L.). Rather than applying discontinuous, time-consuming extraction methods to prepare two types of extracts, peppermint leaves were extracted efficiently into a DES, which was composed of choline chloride and d-(+)-glucose at a 5:2 molar ratio. The produced peppermint extracts contained volatile monoterpenes and phenolics at levels sufficient for direct chemical examination of peppermint leaves. The extracted monoterpenes in DES could be quantified via a newly developed method based on headspace solid-phase microextraction coupled to gas chromatography. The same extracts were also directly used to assess phenolics in terms of total phenolic content, total flavonoid content, and antioxidant activity. The proposed method allowed one-step sample preparation for extraction of volatile monoterpenes and phenolics of peppermint leaves and could be applied to various peppermint samples obtained from different origins.
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http://dx.doi.org/10.1016/j.foodchem.2018.01.079DOI Listing
June 2018

Migration of epoxidized soybean oil from polyvinyl chloride/polyvinylidene chloride food packaging wraps into food simulants.

Environ Sci Pollut Res Int 2018 Feb 23;25(5):5033-5039. Epub 2017 Dec 23.

Institute of Pharmaceutical Science and Technology and College of Pharmacy, Hanyang University, Ansan, Gyeonggi-do, 15588, South Korea.

Epoxidized soybean oil (ESBO) has been used in polyvinyl chloride (PVC)/polyvinylidene chloride (PVDC) food packaging cling film as a plasticizer and stabilizer. The aim of this study was to investigate the migration of ESBO from PVC/PVDC cling film, based on gas chromatography mass spectrometry (GC-MS). The specific migration of ESBO was evaluated using various food simulants (water, 4% acetic acid, 50% ethanol and n-heptane) for PVC and PVDC wrap products. ESBO did not migrate into water and 4% acetic acid for all the tested samples. However, it was released into 50% ethanol and n-heptane in several PVC/PVDC wraps, with maximum migration levels of 38.4 ± 0.7 and 37.4 ± 0.8 μg/mL, respectively. These results demonstrate that ESBO is capable of being released from PVC/PVDC wrap into amphiphilic/oily food and its migration should be regularly monitored.
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http://dx.doi.org/10.1007/s11356-017-0951-9DOI Listing
February 2018

Designing Tyrosinase siRNAs by Multiple Prediction Algorithms and Evaluation of Their Anti-Melanogenic Effects.

Biomol Ther (Seoul) 2018 May;26(3):282-289

Gachon Institute of Pharmaceutical Sciences, College of Pharmacy, Gachon University, Incheon 21936, Republic of Korea.

Melanin is a pigment produced from tyrosine in melanocytes. Although melanin has a protective role against UVB radiation-induced damage, it is also associated with the development of melanoma and darker skin tone. Tyrosinase is a key enzyme in melanin synthesis, which regulates the rate-limiting step during conversion of tyrosine into DOPA and dopaquinone. To develop effective RNA interference therapeutics, we designed a melanin siRNA pool by applying multiple prediction programs to reduce human tyrosinase levels. First, 272 siRNAs passed the target accessibility evaluation using the program. Then we selected 34 siRNA sequences with ΔG ≥-34.6 kcal/mol, value ≥65, and ≤30. siRNAs were designed as 19-bp RNA duplexes with an asymmetric 3' overhang at the 3' end of the antisense strand. We tested if these siRNAs effectively reduced tyrosinase gene expression using qRT-PCR and found that 17 siRNA sequences were more effective than commercially available siRNA. Three siRNAs further tested showed an effective visual color change in MNT-1 human cells without cytotoxic effects, indicating these sequences are anti-melanogenic. Our study revealed that human tyrosinase siRNAs could be efficiently designed using multiple prediction algorithms.
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http://dx.doi.org/10.4062/biomolther.2017.115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5933895PMC
May 2018

Identification of Major Flavone C-Glycosides and Their Optimized Extraction from Cymbidium kanran Using Deep Eutectic Solvents.

Molecules 2017 Nov 18;22(11). Epub 2017 Nov 18.

School of Pharmacy, Sungkyunkwan University, Jangan-gu, Suwon 16419, Gyeonggi-do, Korea.

, an orchid exclusively distributed in Northeast Asia, has been highly valued as a decorative plant and traditional herbal medicine. Here, extracts were prepared in 70% aqueous methanol using ultrasound-assisted extraction (UAE) and subjected to liquid chromatography-photodiode array detection and ultra-high performance liquid chromatography-quadrupole-time-of-flight-mass spectrometry analysis, which were used for quantitative and qualitative analysis, respectively. It was found that the extracts were rich in flavone -glycosides including vicenin-2, vicenin-3, schaftoside, vitexin, and isovitexin. Ten deep eutectic solvents (DESs) were synthesized by combining choline chloride (hydrogen bond acceptor) with various polyols and diols (hydrogen bond donors) and were tested as a medium for the efficient production of extracts enriched with potentially bioactive flavone -glycosides from . A DES named ChCl:DPG, composed of choline chloride and dipropylene glycol at a 1:4 molar ratio, exhibited the best extraction yields. Then, the effects of extraction conditions on the extraction efficiency were investigated by response surface methodology. Lower water content in the extraction solvent and longer extraction time during UAE were desirable for higher extraction yields. Under the statistically optimized conditions, in which 100 mg of powder were extracted in 0.53 mL of a mixture of ChCl:DPG and water (74:26, ) for 86 min, a total of 3.441 mg g flavone -glycosides including 1.933 mg g vicenin-2 was obtained. This total yield was 196%, 131%, and 71% more than those obtained using 100% methanol, water, and 70% methanol, respectively.
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http://dx.doi.org/10.3390/molecules22112006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6150217PMC
November 2017

Development and Validation of an Analytical Method Readily Applicable for Quality Control of (Taheebo) Ethanolic Extract.

J AOAC Int 2018 May 19;101(3):695-700. Epub 2017 Sep 19.

Nutribiotech Co., Ltd, Seoul 06248, Republic of Korea.

The dried inner bark of Tabebuia impetiginosa, known as taheebo or red lapacho, has numerous beneficial effects on human health. This study presents the first simple and reliable quantitative method that could serve for the QC of taheebo. The method uses LC-UV spectroscopy to determine the veratric acid (VA; 3,4-dimethoxybenzoic acid) content of taheebo extracts (TEs). Sample preparation entailed the dissolution of TE in methanol (MeOH), facilitated by ultrasonic radiation for 10 min. The optimized conditions included chromatographic separation on an Agilent Eclipse Plus C18 column (4.6 × 150 mm, 5 µm) at 30°C. The mobile phase consisted of 1% acetic acid in water and MeOH, which was eluted under gradient mode at a flow rate of 1.0 mL/min. The detection wavelength was 254 nm. Using these conditions, VA was selectively resolved, and the entire chromatographic analysis time was 27 min. The method was linear in the range of 50-500 μg/mL (r2 = 0.9995), precise (≤3.97% RSD), and accurate (97.10-102.72%). The validated method was applied to three batches of TE samples, yielding an estimated VA content range of 14.92-15.58 mg/g. Thus, the proposed method could serve as an easy and practical method for the QC of TEs or related products containing TEs.
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http://dx.doi.org/10.5740/jaoacint.17-0228DOI Listing
May 2018

Simple and rapid determination of zaltoprofen in human plasma by manual-shaking-assisted dispersive liquid-liquid microextraction followed by liquid chromatography with ultraviolet detection.

J Sep Sci 2017 Oct 11;40(20):4050-4059. Epub 2017 Sep 11.

School of Pharmacy, Sungkyunkwan University, Suwon, Republic of Korea.

A readily applicable method was developed to determine the concentration level of zaltoprofen, a non-steroidal antiinflammatory drug from the propionic acid family, in human plasma. This method is based on manual-shaking-assisted dispersive liquid-liquid microextraction coupled with liquid chromatography with ultraviolet detection. Factors affecting the extraction efficiency were screened and optimized by experimental design using fractional factorial and central composite designs, respectively. Optimal conditions were: 220 μL of C H Cl (extraction solvent), 5 mL of 3.75% w/v NaCl aqueous solution at pH 2.0, and manual shaking for 13 s (65 times). The resulting extraction method yielded a reasonable enrichment factor of 18.0 (±0.6, n = 3) and extraction recovery of 86.0% (±3.3%, n = 3). The established method was validated for selectivity, linearity, precision, accuracy, matrix effect, recovery, dilution integrity, and stability, and it met the acceptable criteria for all of the tested parameters. Specifically, the method was linear in the range of 0.16-50.0 mg/L, precise (< 8.8% RSD), accurate (-7.5-5.6% deviation), and showed negligible matrix effects (96.1-106.4%) with high absolute recovery (94.5-97.7%). Compared with previous methods involving labor-intensive liquid-liquid extraction or non-specific protein precipitation, our method allows the simple, rapid, and efficient determination of zaltoprofen using the most affordable analytical instrument, liquid chromatography with ultraviolet detection.
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http://dx.doi.org/10.1002/jssc.201700451DOI Listing
October 2017

Solid-phase extraction assisted dispersive liquid-liquid microextraction based on solidification of floating organic droplet to determine sildenafil and its analogues in dietary supplements.

J Sep Sci 2017 Aug 5;40(15):3120-3129. Epub 2017 Jul 5.

College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Korea.

A novel analytical method for the simultaneous determination of the concentration of sildenafil and its five analogues in dietary supplements using solid-phase extraction assisted reversed-phase dispersive liquid-liquid microextraction based on solidification of floating organic droplet combined with ion-pairing liquid chromatography with an ultraviolet detector was developed. Parameters that affect extraction efficiency were systematically investigated, including the type of solid-phase extraction cartridge, pH of the extraction environment, and the type and volume of extraction and dispersive solvent. The method linearity was in the range of 5.0-100 ng/mL for sildenafil, homosildenafil, udenafil, benzylsildenafil, and thiosildenafil and 10-100 ng/mL for acetildenafil. The coefficients of determination were ≥0.996 for all regression curves. The sensitivity values expressed as limit of detection were between 2.5 and 7.5 ng/mL. Furthermore, intraday and interday precisions expressed as relative standard deviations were less than 5.7 and 9.9%, respectively. The proposed method was successfully applied to the analysis of sildenafil and its five analogues in complex dietary supplements.
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http://dx.doi.org/10.1002/jssc.201700159DOI Listing
August 2017

Multi-platform metabolomics and a genetic approach support the authentication of agarwood produced by Aquilaria crassna and Aquilaria malaccensis.

J Pharm Biomed Anal 2017 Aug 4;142:136-144. Epub 2017 May 4.

College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 08826, Republic of Korea; Plant Genomics and Breeding Institute, Seoul National University, Seoul 08826, Republic of Korea. Electronic address:

Agarwood, the resinous heartwood produced by some Aquilaria species such as Aquilaria crassna, Aquilaria malaccensis and Aquilaria sinensis, has been traditionally and widely used in medicine, incenses and especially perfumes. However, up to now, the authentication of agarwood has been largely based on morphological characteristics, a method which is prone to errors and lacks reproducibility. Hence, in this study, we applied metabolomics and a genetic approach to the authentication of two common agarwood chips, those produced by Aquilaria crassna and Aquilaria malaccensis. Primary metabolites, secondary metabolites and DNA markers of agarwood were authenticated by H NMR metabolomics, GC-MS metabolomics and DNA-based techniques, respectively. The results indicated that agarwood chips could be classified accurately by all the methods illustrated in this study. Additionally, the pros and cons of each method are also discussed. To the best of our knowledge, our research is the first study detailing all the differences in the primary and secondary metabolites, as well as the DNA markers between the agarwood produced by these two species.
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http://dx.doi.org/10.1016/j.jpba.2017.04.047DOI Listing
August 2017

Simultaneous Determination of Volatile Organic Compounds in Commercial Alcoholic Beverages by Gas Chromatography with Flame Ionization Detection.

J AOAC Int 2017 Sep 18;100(5):1492-1499. Epub 2017 Apr 18.

Seoul National University, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul 08826, Korea.

A simple and fast method was developed for the determination of volatile organic compounds in alcoholic beverages. Eleven volatile organic compounds (acetaldehyde, methanol, 2-propanol, tert-butanol, 1-propanol, ethyl acetate, 2-butanol, isobutanol, 1-butanol, 3-methyl-1butanol, and 2-methyl-1-butanol) in alcoholic beverages were analyzed with a simple direct-injection method using GC with flame ionization detection. These compounds should be monitored in the QC of production processes because they are detrimental to human health. The method was validated with four types of alcoholic beverages (beers, fruit wines, rice wines, and spirits) to confirm the versatility of the method. Linearity showed r2 values from 0.9986 to 0.9995, with LODs ranging from 0.010 to 1.000 mg/L. Precision and accuracy showed acceptable results, proving the effectiveness of the method. The developed method was applied to 40 commercial samples representing the four types of alcoholic beverages, and principal component analysis was performed to determine profiles of the volatile organic compounds, depending on the type of alcoholic beverage.
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http://dx.doi.org/10.5740/jaoacint.17-0006DOI Listing
September 2017

Idiosyncratic Patterns of Representational Similarity in Prefrontal Cortex Predict Attentional Performance.

J Neurosci 2017 02 27;37(5):1257-1268. Epub 2016 Dec 27.

Center for Mind and Brain, University of California, Davis, Davis, California 95618.

The efficiency of finding an object in a crowded environment depends largely on the similarity of nontargets to the search target. Models of attention theorize that the similarity is determined by representations stored within an "attentional template" held in working memory. However, the degree to which the contents of the attentional template are individually unique and where those idiosyncratic representations are encoded in the brain are unknown. We investigated this problem using representational similarity analysis of human fMRI data to measure the common and idiosyncratic representations of famous face morphs during an identity categorization task; data from the categorization task were then used to predict performance on a separate identity search task. We hypothesized that the idiosyncratic categorical representations of the continuous face morphs would predict their distractability when searching for each target identity. The results identified that patterns of activation in the lateral prefrontal cortex (LPFC) as well as in face-selective areas in the ventral temporal cortex were highly correlated with the patterns of behavioral categorization of face morphs and search performance that were common across subjects. However, the individually unique components of the categorization behavior were reliably decoded only in right LPFC. Moreover, the neural pattern in right LPFC successfully predicted idiosyncratic variability in search performance, such that reaction times were longer when distractors had a higher probability of being categorized as the target identity. These results suggest that the prefrontal cortex encodes individually unique components of categorical representations that are also present in attentional templates for target search.

Significance Statement: Everyone's perception of the world is uniquely shaped by personal experiences and preferences. Using functional MRI, we show that individual differences in the categorization of face morphs between two identities could be decoded from the prefrontal cortex and the ventral temporal cortex. Moreover, the individually unique representations in prefrontal cortex predicted idiosyncratic variability in attentional performance when looking for each identity in the "crowd" of another morphed face in a separate search task. Our results reveal that the representation of task-related information in prefrontal cortex is individually unique and preserved across categorization and search performance. This demonstrates the possibility of predicting individual behaviors across tasks with patterns of brain activity.
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http://dx.doi.org/10.1523/JNEUROSCI.1407-16.2016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6596852PMC
February 2017