Kim Y

References (54)

Title : Insect immune resolution with EpOME\/DiHOME and its dysregulation by their analogs leading to pathogen hypersensitivity - Hossain_2024_Insect.Biochem.Mol.Biol__104104
Author(s) : Hossain Hrithik MT , Shahmohammadi N , Jin G , Lee DH , Singh N , Vik A , Hammock BD , Kim Y
Ref : Insect Biochemistry & Molecular Biology , :104104 , 2024
Abstract : Upon immune challenge, recognition signals trigger insect immunity to remove the pathogens through cellular and humoral responses. Various immune mediators propagate the immune signals to nearby tissues, in which polyunsaturated fatty acid (PUFA) derivatives play crucial roles. However, little was known on how the insects terminate the activated immune responses after pathogen neutralization. Interestingly, C20 PUFA was detected at the early infection stage and later C18 PUFAs were induced in a lepidopteran insect, Spodoptera exigua. This study showed the role of epoxyoctadecamonoenoic acids (EpOMEs) in the immune resolution at the late infection stage to quench the excessive and unnecessary immune responses. In contrast, dihydroxy-octadecamonoenoates (DiHOMEs) were the hydrolyzed and inactive forms of EpOMEs. The hydrolysis is catalyzed by soluble epoxide hydrolase (sEH). Inhibitors specific to sEH mimicked the immunosuppression induced by EpOMEs. Furthermore, the inhibitor treatments significantly enhanced the bacterial virulence of Bacillus thuringiensis against S. exigua. This study proposes a negative control of the immune responses using EpOME/DiHOME in insects.
ESTHER : Hossain_2024_Insect.Biochem.Mol.Biol__104104
PubMedSearch : Hossain_2024_Insect.Biochem.Mol.Biol__104104
PubMedID: 38494144

Title : Enhanced baculoviral virulence by suppressing the degradation of an insect immune resolvin, epoxyoctadecamonoenoic acid, in three lepidopteran insects - Shahmohammadi_2024_J.Invertebr.Pathol__108095
Author(s) : Shahmohammadi N , Esmaeily M , Abdisa E , Mandal E , Kim Y
Ref : J Invertebr Pathol , :108095 , 2024
Abstract : Epoxyoctadecamonoenoic acids (EpOMEs) are produced from linoleic acid by a cytochrome P450 monooxygenase (CYP) and play a crucial role in terminating excessive and unnecessary immune responses during the late infection stage in insects. This suggests that an increase in the EpOME level may enhance the virulence of insect pathogens against pests. This study tested this hypothesis using a specific inhibitor against soluble epoxide hydrolase (sEH) to degrade EpOMEs, which leads to elevated endogenous EpOME levels. A baculovirus, Autographa californica multiple nucleopolyhedrovirus (AcMNPV), was used to infect three different lepidopteran insects (Spodoptera exigua, Maruca vitrata, and Plutella xylostella) by oral feeding or hemocoelic injection treatments. Within one hour, the viral infection induced the expression of three different phospholipase A(2) (PLA(2)) genes and, after 12 h, up-regulated the expressions of CYP and sEH genes in Spodopera exigua. As expected, AcMNPV virulence was suppressed by the addition of arachidonic acid (a catalytic product of PLA(2)) but was enhanced by the addition of either of the EpOME regioisomers. In addition, treatment with a specific sEH inhibitor (AUDA) increased AcMNPV virulence against three different lepidopteran insects, presumably by increasing endogenous EpOME levels. This enhanced effect of EpOMEs on virulence was further supported by specific RNA interference (RNAi), in which RNAi specific to CYP expression decreased AcMNPV virulence while a specific RNAi against sEH expression significantly enhanced virulence. In response to AcMNPV infection, TUNEL assay results showed that S. exigua larvae exhibited apoptosis in the midgut, fat body, and epidermis. Inhibition of apoptosis by a pan-caspase inhibitor, Z-VAD-FMK, significantly increased virulence. Similarly, the addition of AUDA to the viral treatment suppressed the gene expression of five inducible caspases and cytochrome C to suppress apoptosis, which led to a significant increase in the tissue viral titers. These results indicate that EpOMEs play a role in terminating excessive and unnecessary immune responses against viral infection during the late stage by down-regulating antiviral apoptosis in lepidopteran insects.
ESTHER : Shahmohammadi_2024_J.Invertebr.Pathol__108095
PubMedSearch : Shahmohammadi_2024_J.Invertebr.Pathol__108095
PubMedID: 38499284

Title : Four phospholipase A(2) genes encoded in the western flower thrips genome and their functional differentiation in mediating development and immunity - Esmaeily_2024_Sci.Rep_14_9766
Author(s) : Esmaeily M , Kim Y
Ref : Sci Rep , 14 :9766 , 2024
Abstract : Eicosanoids are synthesized from phospholipids by the catalytic activity of phospholipase A(2) (PLA(2)). Even though several PLA(2)s are encoded in the genome of different insect species, their physiological functions are not clearly discriminated. This study identified four PLA(2) genes encoded in the western flower thrips, Frankliniella occidentalis. Two PLA(2)s (Fo-PLA(2)C and Fo-PLA(2)D) are predicted to be secretory while the other two PLA(2)s (Fo-PLA(2)A and Fo-PLA(2)B) are intracellular. All four PLA(2) genes were expressed in all developmental stages, of which Fo-PLA(2)B and Fo-PLA(2)C were highly expressed in larvae while Fo-PLA(2)A and Fo-PLA(2)D were highly expressed in adults. Their expressions in different tissues were also detected by fluorescence in situ hybridization. All four PLA(2)s were detected in the larval and adult intestines and the ovary. Feeding double-stranded RNAs specific to the PLA(2) genes specifically suppressed the target transcript levels. Individual RNA interference (RNAi) treatments led to significant developmental retardation, especially in the treatments specific to Fo-PLA(2)B and Fo-PLA(2)D. The RNAi treatments also showed that Fo-PLA(2)B and Fo-PLA(2)C expressions were required for the induction of immune-associated genes, while Fo-PLA(2)A and Fo-PLA(2)D expressions were required for ovary development. These results suggest that four PLA(2)s are associated with different physiological processes by their unique catalytic activities and expression patterns.
ESTHER : Esmaeily_2024_Sci.Rep_14_9766
PubMedSearch : Esmaeily_2024_Sci.Rep_14_9766
PubMedID: 38684777

Title : Identification of four secretory phospholipase A(2)s in a lepidopteran insect, Acrolepiopsis sapporensis, and their functional association with cellular immune responses - Hrithik_2023_Front.Endocrinol.(Lausanne)_14_1190834
Author(s) : Hrithik MTH , Hong J , Kim Y
Ref : Front Endocrinol (Lausanne) , 14 :1190834 , 2023
Abstract : BACKGROUND: Eicosanoids are a group of the oxygenated C20 polyunsaturated fatty acids and play crucial roles in mediating various insect physiological processes. Catalytic activity of phospholipase A(2) (PLA(2)) provides an initial substrate, arachidonic acid (AA), for subsequent eicosanoid biosynthesis. RESULTS: This study identified four different secretory PLA(2) (As-PLA(2)A-As-PLA(2)D) genes encoded in the Asian onion moth, Acrolepiopsis sapporensis. A phylogenetic analysis indicated that As-PLA(2)A and As-PLA(2)D are clustered with Group III PLA(2)s while As-PLA(2)B and As-PLA(2)C are clustered with Group XII and Group X PLA(2)s, respectively. Expression levels of these PLA(2) genes increased along with larval development, especially in the fat body. A bacterial immune challenge upregulated the basal expression levels of the four PLA(2) genes, which resulted in significant increases of the PLA(2) enzyme activity. The enzyme activity was susceptible to a calcium chelator or reducing agent, suggesting Ca(2+) dependency and disulfide linkage required for the catalytic activities of the secretory type of PLA(2)s. In addition, the PLA(2) activity was also susceptible to bromophenacyl bromide (BPB), a specific inhibitor to sPLA(2), but not to intracellular PLA(2) inhibitors. An addition of BPB to the immune challenge significantly prevented hemocyte-spreading behavior of A. sapporensis. BPB treatment also suppressed a cellular immune response measured by hemocyte nodule formation. However, the immunosuppression was significantly rescued by the AA addition. To determine the PLA(2)(s) responsible for the immunity, individual RNA interference (RNAi) treatments specific to each of the four PLA(2)s were performed. Injection of gene-specific double-stranded RNAs caused significant reductions in the transcript level in all four PLA(2)s. In all four PLA(2)s, the RNAi treatments prevented the cellular immune response even after the immune challenge. CONCLUSION: This study reports four secretory PLA(2)s encoded in A. sapporensis and their function in mediating cellular immunity.
ESTHER : Hrithik_2023_Front.Endocrinol.(Lausanne)_14_1190834
PubMedSearch : Hrithik_2023_Front.Endocrinol.(Lausanne)_14_1190834
PubMedID: 37424852

Title : Pretreatment of rhesus monkeys with transdermal patches containing physostigmine and procyclidine: implications of the delivery system for the potential application against VX nerve agent intoxication in humans - Nam_2023_Arch.Toxicol__
Author(s) : Nam JH , Kim MS , Song YJ , Kim CH , Kim WS , Yu CH , Joe HE , Hur GH , Seo MR , Kim Y , Park KE , Choi JY , Chung SJ , Shin YK
Ref : Archives of Toxicology , : , 2023
Abstract : Physostigmine (Phs) is a reversible inhibitor of acetylcholinesterase (AChE) that penetrates the blood-brain barrier (BBB) and could be used to protect the central nervous system (CNS) against the effects of nerve agents. For prophylactic effectiveness, long, steady, and adequate inhibition of AChE activity by Phs is needed to broadly protect against the CNS effects of nerve agents. Here, we evaluated the efficacy of transdermal patches containing Phs and procyclidine (PC) as prophylactic agents. Patches (25 cm(2)) containing 4.4smg Phs and 17.8smg PC had a protective ratio of approximately 78.6-fold in rhesus monkeys challenged with VX nerve agent and given an antidote. Physiologically based pharmacokinetic model in conjunction with an indirect pharmacodynamic (PBPK/PD) was developed for Phs and scaled to rhesus monkeys. The model was able to reproduce the concentration profile and inhibitory effect on AChE of Phs in monkeys, as evidenced by correlation coefficients of 0.994 and 0.992 for 25 cm(2) and 49 cm(2) patches, respectively (i.e., kinetic data), and 0.989 and 0.968 for 25 cm(2) and 49 cm(2) patches, respectively (i.e., dynamic data). By extending the monkey PBPK/ PD model to humans, the effective human dose was predicted to be five applications of a 25 cm(2) patch (i.e., 22smg Phs), and two applications of a 49scm(2) patch (i.e., 17.4smg Phs). Therefore, given that patch application of Phs in rhesus monkeys has a prolonged effect (namely, AChE inhibition of 19.6% for the 25 cm(2) patch and 23.0% for the 49 cm(2) patch) for up to 216sh, patch formulation of Phs may provide similar protection against nerve agent intoxication in humans.
ESTHER : Nam_2023_Arch.Toxicol__
PubMedSearch : Nam_2023_Arch.Toxicol__
PubMedID: 36633609

Title : Using Artificial Intelligence to Learn Optimal Regimen Plan for Alzheimer's Disease - Bhattarai_2023_medRxiv__
Author(s) : Bhattarai K , Das T , Kim Y , Chen Y , Dai Q , Li X , Jiang X , Zong N
Ref : Medrxiv , : , 2023
Abstract : BACKGROUND: Alzheimer's Disease (AD) is a progressive neurological disorder with no specific curative medications. While only a few medications are approved by FDA (i.e., donepezil, galantamine, rivastigmine, and memantine) to relieve symptoms (e.g., cognitive decline), sophisticated clinical skills are crucial to optimize the appropriate regimens given the multiple coexisting comorbidities in this patient population. OBJECTIVE: Here, we propose a study to leverage reinforcement learning (RL) to learn the clinicians' decisions for AD patients based on the longitude records from Electronic Health Records (EHR). METHODS: In this study, we withdraw 1,736 patients fulfilling our criteria, from the Alzheimer's Disease Neuroimaging Initiative(ADNI) database. We focused on the two most frequent concomitant diseases, depression, and hypertension, thus resulting in five main cohorts, 1) whole data, 2) AD-only, 3) AD-hypertension, 4) AD-depression, and 5) AD-hypertension-depression. We modeled the treatment learning into an RL problem by defining the three factors (i.e., states, action, and reward) in RL in multiple strategies, where a regression model and a decision tree are developed to generate states, six main medications extracted (i.e., no drugs, cholinesterase inhibitors, memantine, hypertension drugs, a combination of cholinesterase inhibitors and memantine, and supplements or other drugs) are for action, and Mini-Mental State Exam (MMSE) scores are for reward. RESULTS: Given the proper dataset, the RL model can generate an optimal policy (regimen plan) that outperforms the clinician's treatment regimen. With the smallest data samples, the optimal-policy (i.e., policy iteration and Q-learning) gained a lesser reward than the clinician's policy (mean -2.68 and -2.76 vs . -2.66, respectively), but it gained more reward once the data size increased (mean -3.56 and -2.48 vs . -3.57, respectively). CONCLUSIONS: Our results highlight the potential of using RL to generate the optimal treatment based on the patients' longitude records. Our work can lead the path toward the development of RL-based decision support systems which could facilitate the daily practice to manage Alzheimer's disease with comorbidities.
ESTHER : Bhattarai_2023_medRxiv__
PubMedSearch : Bhattarai_2023_medRxiv__
PubMedID: 36747733

Title : Chrysanthemum coronarium L. Extract Attenuates Homocysteine-Induced Vascular Inflammation in Vascular Smooth Muscle Cells - Lee_2023_J.Med.Food__
Author(s) : Lee AS , Kim Y , Hur HJ , Lee SH , Sung MJ
Ref : J Med Food , : , 2023
Abstract : Hyperhomocysteinemia is a main risk factor for phenotypic modulation of vascular smooth muscle cells (VSMCs) and atherosclerosis. Phenotypic switching and proliferation of VSMCs are related to the progression of vascular inflammation. Chrysanthemum coronarium L. is a leafy vegetable with various biological functions, such as antioxidative, anti-inflammatory, and antiproliferative effects. In this study, we aimed to identify the mechanisms underlying the therapeutic and preventive effects of C. coronarium L. extract (CC) in regulating homocysteine (Hcy)-induced vascular inflammation in human aortic VSMCs. CC did not exhibit cytotoxicity and inhibited Hcy-stimulated VSMC proliferation and migration. In addition, CC promoted Hcy-induced expression of VSMC contractile phenotype proteins, including alpha-smooth muscle actin, calponin, and smooth muscle 22alpha. CC also decreased Hcy-induced accumulation of reactive oxygen species and expression of inflammatory markers nicotinamide adenine dinucleotide phosphate oxidase-4 and soluble epoxide hydrolase. These results showed that CC attenuates Hcy-induced inflammatory responses, highlighting its potential as a therapeutic or preventive target for Hcy-induced vascular inflammation.
ESTHER : Lee_2023_J.Med.Food__
PubMedSearch : Lee_2023_J.Med.Food__
PubMedID: 38010869

Title : Using artificial intelligence to learn optimal regimen plan for Alzheimer's disease - Bhattarai_2023_J.Am.Med.Inform.Assoc__
Author(s) : Bhattarai K , Rajaganapathy S , Das T , Kim Y , Chen Y , Dai Q , Li X , Jiang X , Zong N
Ref : J Am Med Inform Assoc , : , 2023
Abstract : BACKGROUND: Alzheimer's disease (AD) is a progressive neurological disorder with no specific curative medications. Sophisticated clinical skills are crucial to optimize treatment regimens given the multiple coexisting comorbidities in the patient population. OBJECTIVE: Here, we propose a study to leverage reinforcement learning (RL) to learn the clinicians' decisions for AD patients based on the longitude data from electronic health records. METHODS: In this study, we selected 1736 patients from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. We focused on the two most frequent concomitant diseases-depression, and hypertension, thus creating 5 data cohorts (ie, Whole Data, AD, AD-Hypertension, AD-Depression, and AD-Depression-Hypertension). We modeled the treatment learning into an RL problem by defining states, actions, and rewards. We built a regression model and decision tree to generate multiple states, used six combinations of medications (ie, cholinesterase inhibitors, memantine, memantine-cholinesterase inhibitors, hypertension drugs, supplements, or no drugs) as actions, and Mini-Mental State Exam (MMSE) scores as rewards. RESULTS: Given the proper dataset, the RL model can generate an optimal policy (regimen plan) that outperforms the clinician's treatment regimen. Optimal policies (ie, policy iteration and Q-learning) had lower rewards than the clinician's policy (mean -3.03 and -2.93 vs. -2.93, respectively) for smaller datasets but had higher rewards for larger datasets (mean -4.68 and -2.82 vs. -4.57, respectively). CONCLUSIONS: Our results highlight the potential of using RL to generate the optimal treatment based on the patients' longitude records. Our work can lead the path towards developing RL-based decision support systems that could help manage AD with comorbidities.
ESTHER : Bhattarai_2023_J.Am.Med.Inform.Assoc__
PubMedSearch : Bhattarai_2023_J.Am.Med.Inform.Assoc__
PubMedID: 37463858

Title : Insect immune resolution with EpOME\/DiHOME and its dysregulation by their analogs leading to pathogen hypersensitivity - Hrithrik_2023_bioRxiv__
Author(s) : Hrithrik MTH , Lee DH , Singh N , Vik A , Hammock BD , Kim Y
Ref : Biorxiv , : , 2023
Abstract : Epoxyoctadecamonoenoic acids (EpOMEs) are epoxide derivatives of linoleic acid (9,12-octadecadienoic acid: LA). They are metabolized into dihydroxyoctadecamonoenoic acids (DiHOMEs) in mammals. Unlike in mammals where they act as adipokines or lipokines, EpOMEs act as immunosuppressants in insects. However, the functional link between EpOMEs and pro-immune mediators such as PGE (2) is not known. In addition, the physiological significance of DiHOMEs is not clear in insects. This study analyzed the physiological role of these C18 oxylipins using a lepidopteran insect pest, Spodoptera exigua . Immune challenge of S. exigua rapidly upregulated the expression of the phospholipase A (2) gene to trigger C20 oxylipin biosynthesis, followed by the upregulation of genes encoding EpOME synthase ( SE51385 ) and a soluble epoxide hydrolase ( Se-sEH ). The sequential gene expression resulted in the upregulations of the corresponding gene products such as PGE (2) , EpOMEs, and DiHOMEs. Interestingly, only PGE (2) injection without the immune challenge significantly upregulated the gene expression of SE51825 and Se-sEH . The elevated levels of EpOMEs acted as immunosuppressants by inhibiting cellular and humoral immune responses induced by the bacterial challenge, in which 12,13-EpOME was more potent than 9,10-EpOME. However, DiHOMEs did not inhibit the cellular immune responses but upregulated the expression of antimicrobial peptides selectively suppressed by EpOMEs. The negative regulation of insect immunity by EpOMEs and their inactive DiHOMEs were further validated by synthetic analogs of the linoleate epoxide and corresponding diol. Furthermore, inhibitors specific to Se-sEH used to prevent EpOME degradation significantly suppressed the immune responses. The data suggest a physiological role of C18 oxylipins in resolving insect immune response. Any immune dysregulation induced by EpOME analogs or sEH inhibitors significantly enhanced insect susceptibility to the entomopathogen, Bacillus thuringiensis . AUTHOR SUMMARY: Upon immune challenge, recognition signal triggers insect immunity to remove the pathogens by cellular and humoral responses. Various immune mediators propagate the immune signals to nearby tissues, in which polyunsaturated fatty acid (PUFA) derivatives play crucial roles. However, little was known on how the insects terminate the activated immune responses after pathogen neutralization. Interestingly, C20 PUFA was detected at the early infection stage and later C18 PUFAs were induced in a lepidopteran insect, Spodoptera exigua . This study showed the role of epoxyoctadecamonoenoic acids (EpOMEs) in the immune resolution at the late infection stage to quench the excessive and unnecessary immune responses. In contrast, dihydroxy-octadecamonoenoates (DiHOMEs) were the hydrolyzed and inactive forms of EpOMEs. The hydrolysis is catalyzed by soluble epoxide hydrolase (sEH). Inhibitors specific to sEH mimicked the immunosuppression induced by EpOMEs. Furthermore, the inhibitor treatments significantly enhanced the bacterial virulence of Bacillus thuringiensis against S. exigua . This study proposes a negative control of the immune responses using EpOME/DiHOME in insects.
ESTHER : Hrithrik_2023_bioRxiv__
PubMedSearch : Hrithrik_2023_bioRxiv__
PubMedID: 37461499

Title : Analysis of treatment pattern of anti-dementia medications in newly diagnosed Alzheimer's dementia using OMOP CDM - Byun_2022_Sci.Rep_12_4451
Author(s) : Byun J , Lee DY , Jeong CW , Kim Y , Rhee HY , Moon KW , Heo J , Hong Y , Kim WJ , Nam SJ , Choi HS , Park JI , Chun IK , Bak SH , Lee K , Byeon GH , Kim KL , Kim JA , Park YJ , Kim JH , Lee EJ , Lee SA , Kwon SO , Park SW , Kasani PH , Kim JK , Kim S , Jang JW
Ref : Sci Rep , 12 :4451 , 2022
Abstract : Anti-dementia medications are widely prescribed to patients with Alzheimer's dementia (AD) in South Korea. This study investigated the pattern of medical management in newly diagnosed patients with AD using a standardized data format-the Observational Medical Outcome Partnership Common Data Model from five hospitals. We examined the anti-dementia treatment patterns from datasets that comprise > 5 million patients during 2009-2019. The medication utility information was analyzed with respect to treatment trends and persistence across 11 years. Among the 8653 patients with newly diagnosed AD, donepezil was the most commonly prescribed anti-dementia medication (4218; 48.75%), followed by memantine (1565; 18.09%), rivastigmine (1777; 8.98%), and galantamine (494; 5.71%). The rising prescription trend during observation period was found only with donepezil. The treatment pathways for the three cholinesterase inhibitors combined with N-methyl-D-aspartate receptor antagonist were different according to the drugs (19.6%; donepezil; 28.1%; rivastigmine, and 17.2%; galantamine). A 12-month persistence analysis showed values of approximately 50% for donepezil and memantine and approximately 40% for rivastigmine and galantamine. There were differences in the prescribing pattern and persistence among anti-dementia medications from database using the Observational Medical Outcome Partnership Common Data Model on the Federated E-health Big Data for Evidence Renovation Network platform in Korea.
ESTHER : Byun_2022_Sci.Rep_12_4451
PubMedSearch : Byun_2022_Sci.Rep_12_4451
PubMedID: 35292697

Title : Data collection from crystals grown in microfluidic droplets - Babnigg_2022_Acta.Crystallogr.D.Struct.Biol_78_997
Author(s) : Babnigg G , Sherrell D , Kim Y , Johnson JL , Nocek B , Tan K , Axford D , Li H , Bigelow L , Welk L , Endres M , Owen RL , Joachimiak A
Ref : Acta Crystallographica D Struct Biol , 78 :997 , 2022
Abstract : Protein crystals grown in microfluidic droplets have been shown to be an effective and robust platform for storage, transport and serial crystallography data collection with a minimal impact on diffraction quality. Single macromolecular microcrystals grown in nanolitre-sized droplets allow the very efficient use of protein samples and can produce large quantities of high-quality samples for data collection. However, there are challenges not only in growing crystals in microfluidic droplets, but also in delivering the droplets into X-ray beams, including the physical arrangement, beamline and timing constraints and ease of use. Here, the crystallization of two human gut microbial hydrolases in microfluidic droplets is described: a sample-transport and data-collection approach that is inexpensive, is convenient, requires small amounts of protein and is forgiving. It is shown that crystals can be grown in 50-500pl droplets when the crystallization conditions are compatible with the droplet environment. Local and remote data-collection methods are described and it is shown that crystals grown in microfluidics droplets and housed as an emulsion in an Eppendorf tube can be shipped from the US to the UK using a FedEx envelope, and data can be collected successfully. Details of how crystals were delivered to the X-ray beam by depositing an emulsion of droplets onto a silicon fixed-target serial device are provided. After three months of storage at 4 degreesC, the crystals endured and diffracted well, showing only a slight decrease in diffracting power, demonstrating a suitable way to grow crystals, and to store and collect the droplets with crystals for data collection. This sample-delivery and data-collection strategy allows crystal droplets to be shipped and set aside until beamtime is available.
ESTHER : Babnigg_2022_Acta.Crystallogr.D.Struct.Biol_78_997
PubMedSearch : Babnigg_2022_Acta.Crystallogr.D.Struct.Biol_78_997
PubMedID: 35916224

Title : Estimation of kinetic constants in high-density polyethylene bead degradation using hydrolytic enzymes - Elsayed_2022_Environ.Pollut__118821
Author(s) : Elsayed A , Kim Y
Ref : Environ Pollut , :118821 , 2022
Abstract : Microplastic beads are an emerging contaminant that can cause serious environmental and public health problems. Potential bypass of microplastic beads from wastewater to sludge treatment systems is a key challenge in the conventional wastewater treatment process. Moreover, there are no systematic studies on microplastic bead degradation by hydrolytic enzymes that are rich in concentration within wastewater and sludge treatment processes (e.g., anaerobic digestion (AD)). In this study, lab-scale experiments were conducted to investigate the degradation of high-density polyethylene beads by hydrolytic enzymes (e.g., lipase) under various experimental conditions (e.g., temperature). In a 3-day batch experiment, protease was most effective in polyethylene bead degradation as 4.0% of the initial bead mass was removed at an enzyme concentration of 88 mg/L under thermophilic temperature (55 degreesC). It was also found that the increasing enzyme concentration and high temperature enhanced the polyethylene bead degradation. In a separate 7-day experiment with repeated doses of protease, 23.3% of the initial mass of beads was removed at thermophilic temperature, indicating that AD with a long retention time (e.g., 20 days) and heated temperature has a significant potential for polyethylene bead degradation. A mathematical model was developed and calibrated using the experimental results to estimate the kinetic constant of the high-density polyethylene beads reduction by an enzyme (k(1,i)) and enzyme self-decay constant (k(2,ii)). The calibrated k(1,i) ranged from 5.0 to 8.1 x 10(-4) L/mg/hr while k(2,ii) was 0.44-1.10 L/mg/hr. Using the calibrated model, degradation of polyethylene beads using a mixture of cellulase and protease was simulated, considering an interactive-decay reaction between the two enzymes. The calibrated model was used to simulate the polyethylene bead degradation in AD where 70-95% of the initial bead mass was removed at typical retention time under mesophilic digestion (37.5 degreesC). Based on the experimental and simulation results, it can be concluded that hydrolytic enzymes can be an efficient technology for large-scale high-density polyethylene bead removal applications.
ESTHER : Elsayed_2022_Environ.Pollut__118821
PubMedSearch : Elsayed_2022_Environ.Pollut__118821
PubMedID: 35016978

Title : Simultaneous Quantification of Four Marker Compounds in Bauhinia coccinea Extract and Their Potential Inhibitory Effects on Alzheimer's Disease Biomarkers - Kim_2021_Plants.(Basel)_10_
Author(s) : Kim YJ , Sohn E , Lim HS , Kim Y , Kim JH , Jeong SJ
Ref : Plants (Basel) , 10 : , 2021
Abstract : Bauhinia coccinea is a tropical woody plant widely distributed in Vietnam and Unnan in southern China. Although many studies have shown the biological activities of extracts from various other species in the genus, no studies have investigated the effects of B. coccinea extracts on biological systems. In the present study, a quantitative analysis of four marker compounds of ethanol extracts of B. coccinea branches (EEBC) was performed using the high performance liquid chromatography (HPLC)-photodiode array (PDA) method. Among gallic acid, (+)-catechin, ellagic acid, and quercitrin contained in EEBC, the most abundant compound was (+)-catechin (18.736 mg/g). In addition, we investigated the EEBC on neuroprotection, antioxidation, and Alzheimer's disease (AD) marker molecules, acetylcholinesterase (AChE), and amyloid-beta (Abeta). EEBC significantly inhibited hydrogen peroxide (H(2)O(2))-induced cell death in a HT22 neuronal cell line and increased 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) and 2,2-diphenyl-1-picrylhydrazyl scavenging activity markedly. EEBC also inhibited AChE and Abeta aggregation. Among the four compounds, gallic acid exhibited strong inhibitory effects against AChE activation. In the Abeta aggregation assay, the four marker compounds exhibited inhibitory effects lower than 30%. According to the results, EEBC could exert anti-AChE activation and Abeta aggregation activities based on the interactive effects of the marker compounds. Our findings suggest that EEBC are sources of therapeutic candidates for application in the development of AD medication based on AChE and Abeta dual targeting.
ESTHER : Kim_2021_Plants.(Basel)_10_
PubMedSearch : Kim_2021_Plants.(Basel)_10_
PubMedID: 33917273

Title : Target highlights in CASP14: Analysis of models by structure providers - Alexander_2021_Proteins__
Author(s) : Alexander LT , Lepore R , Kryshtafovych A , Adamopoulos A , Alahuhta M , Arvin AM , Bomble YJ , Bottcher B , Breyton C , Chiarini V , Chinnam NB , Chiu W , Fidelis K , Grinter R , Gupta GD , Hartmann MD , Hayes CS , Heidebrecht T , Ilari A , Joachimiak A , Kim Y , Linares R , Lovering AL , Lunin VV , Lupas AN , Makbul C , Michalska K , Moult J , Mukherjee PK , Nutt WS , Oliver SL , Perrakis A , Stols L , Tainer JA , Topf M , Tsutakawa SE , Valdivia-Delgado M , Schwede T
Ref : Proteins , : , 2021
Abstract : The biological and functional significance of selected Critical Assessment of Techniques for Protein Structure Prediction 14 (CASP14) targets are described by the authors of the structures. The authors highlight the most relevant features of the target proteins and discuss how well these features were reproduced in the respective submitted predictions. The overall ability to predict three-dimensional structures of proteins has improved remarkably in CASP14, and many difficult targets were modeled with impressive accuracy. For the first time in the history of CASP, the experimentalists not only highlighted that computational models can accurately reproduce the most critical structural features observed in their targets, but also envisaged that models could serve as a guidance for further studies of biologically-relevant properties of proteins.
ESTHER : Alexander_2021_Proteins__
PubMedSearch : Alexander_2021_Proteins__
PubMedID: 34561912

Title : Cognitive decline according to amyloid uptake in patients with poststroke cognitive impairment - Yoon_2021_Medicine.(Baltimore)_100_e27252
Author(s) : Yoon B , Yang DW , Hong YJ , Kim T , Na S , Noh SM , Park HL , Ku BD , Yang YS , Choi H , Jang JW , Kim S , Kim Y , Shim Y
Ref : Medicine (Baltimore) , 100 :e27252 , 2021
Abstract : BACKGROUND AND PURPOSE: Poststroke cognitive impairment (PSCI) is common, but the impact of beta-amyloid (Abeta) on PSCI is uncertain. The proposed study will investigate amyloid pathology in participants with PSCI and how differently their cognition progress according to the amyloid pathology. METHODS: This multicenter study was designed to be prospective and observational based on a projected cohort size of 196 participants with either newly developed cognitive impairment, or rapidly aggravated CI, within 3 months after acute cerebral infarction. They will undergo 18F-flutemetamol positron emission tomography at baseline and will be categorized as either amyloid-positive (A+) or amyloid-negative (A-) by visual rating. The primary outcome measures will be based on Korean Mini-Mental State Examination changes (baseline to 12months) between the A+ and A- groups. The secondary outcome measures will be the dementia-conversion rate and changes in the Korean version of the Montreal Cognitive Assessment (baseline to 12months) between the A+ and A- groups. CONCLUSIONS: This study will provide a broadened perspective on the impact of Abeta on the cause and outcomes of PSCI in clinical practice. Identifying amyloid pathology in patients with PSCI will help select patients who need more focused treatments such as acetylcholinesterase inhibitors. TRIAL REGISTRATION: Clinical Research Information Service identifier: KCT0005086.
ESTHER : Yoon_2021_Medicine.(Baltimore)_100_e27252
PubMedSearch : Yoon_2021_Medicine.(Baltimore)_100_e27252
PubMedID: 34559128

Title : Contribution of dipeptidyl peptidase 4 to non-typeable Haemophilus influenzae-induced lung inflammation in COPD - Kotnala_2021_Clin.Sci.(Lond)_135_2067
Author(s) : Kotnala S , Kim Y , Rajput C , Reddyvari H , Bolla S , Marchetti NT , Kosmider B , Bahmed K , Sajjan US
Ref : Clinical Science (Lond) , 135 :2067 , 2021
Abstract : Dipeptidyl peptidase 4 (DPP4) expression is increased in the lungs of chronic obstructive pulmonary disease (COPD). DPP4 is known to be associated with inflammation in various organs, including LPS-induced acute lung inflammation. Since non-typeable Haemophilus influenzae (NTHi) causes acute exacerbations in COPD patients, we examined the contribution of DPP4 in NTHi-induced lung inflammation in COPD. Pulmonary macrophages isolated from COPD patients showed higher expression of DPP4 than the macrophages isolated from normal subjects. In response to NTHi infection, COPD, but not normal macrophages show a further increase in the expression of DPP4. COPD macrophages also showed higher expression of IL-1beta, and CCL3 responses to NTHi than normal, and treatment with DPP4 inhibitor, diprotin A attenuated this response. To examine the contribution of DPP4 in NTHi-induced lung inflammation, COPD mice were infected with NTHi, treated with diprotin A or PBS intraperitoneally, and examined for DPP4 expression, lung inflammation, and cytokine expression. Mice with COPD phenotype showed increased expression of DPP4, which increased further following NTHi infection. DPP4 expression was primarily observed in the infiltrated inflammatory cells. NTHi-infected COPD mice also showed sustained neutrophilic lung inflammation and expression of CCL3, and this was inhibited by DPP4 inhibitor. These observations indicate that enhanced expression of DPP4 in pulmonary macrophages may contribute to sustained lung inflammation in COPD following NTHi infection. Therefore, inhibition of DPP4 may reduce the severity of NTHi-induced lung inflammation in COPD.
ESTHER : Kotnala_2021_Clin.Sci.(Lond)_135_2067
PubMedSearch : Kotnala_2021_Clin.Sci.(Lond)_135_2067
PubMedID: 34405230

Title : Selective Butyrate Esterase Probe for the Rapid Colorimetric and Fluorogenic Identification of Moraxella catarrhalis - Lee_2020_Anal.Chem_92_16051
Author(s) : Lee U , Kim YH , Yoon KS , Kim Y
Ref : Analytical Chemistry , 92 :16051 , 2020
Abstract : Clinical identification of the pathogenic bacterium Moraxella catarrhalis in cultures relies on the detection of bacterial butyrate esterase (C4-esterase) using a coumarin-based fluorogenic substrate, 4-methylumbelliferyl butyrate. However, this classical probe may give false-positive responses because of its poor stability and lack of specificity. Here, we report a new colorimetric and fluorogenic probe design employing a meso-ester-substituted boron dipyrromethene (BODIPY) dye for the specific detection of C4-esterase activity expressed by M. catarrhalis. This new probe has resistance to nonspecific hydrolysis that is far superior to the classical probe and also selectively responds to esterase with rapid colorimetric and fluorescence signal changes and large "turn-on" ratios. The probe was successfully applied to the specific detection of M. catarrhalis with high sensitivity.
ESTHER : Lee_2020_Anal.Chem_92_16051
PubMedSearch : Lee_2020_Anal.Chem_92_16051
PubMedID: 33211958

Title : Vaccinium bracteatum Improves Spatial Learning and Memory by Regulating N-methyl-D-aspartate Receptors and Tau Phosphorylation in Chronic Restraint Stress-Induced Memory Impaired Mice - Oh_2020_Am.J.Chin.Med__1
Author(s) : Oh DR , Kim Y , Im S , Oh KN , Shin J , Jeong C , Choi EJ , Choi C
Ref : Am J Chin Med , :1 , 2020
Abstract : Vaccinium bracteatum Thunb. Leaves (VBL) are a component of traditional herbal medicines. However, molecular mechanisms of VBL in stress-related memory impairment are still unclear. This study aimed to investigate the spatial memory improvement effects of VBL in an animal model of chronic restraint stress (CRS) by using Y maze test and identified possible protective mechanisms against oxidative stress inducers (e.g., corticosterone and hydrogen peroxide [H(2)O(2)]) in SH-SY5Y neuronal cells. VBL showed neuroprotective effects via reduced release of lactate dehydrogenase (LDH) in corticosterone or H(2)O(2)-induced cell death that was mediated through the regulation of cleaved caspase-3 and Nrf2 pathways. Furthermore, CRS-exposed mice were orally administered VBL (10, 50, 100, and 200 mg/kg) daily for 21 days. CRS-exposed mice treated with VBL showed significantly increased spontaneous alternation in short-term memory (STM) and long-term memory (LTM) trials, and number of total arm entries in LTM trials as measured by the Y maze test. Moreover, VBL (50, 100, and 200 mg/kg) decreased acetylcholinesterase (AChE) activity in the hippocampus (HC, [Formula: see text] < 0.01 and [Formula: see text] < 0.001, respectively) and prefrontal cortex (PFC). CRS-exposed mice treated with VBL had dramatically decreased total Tau and Tau phosphorylation in the synapse of the HC and PFC which might be mediated by the regulation of CaMKII and GSK3[Formula: see text] phosphorylation. Additionally, VBL reduced CRS-induced upregulation of N-methyl-D-aspartate (NMDA) receptor subunits (NMDAR1, 2A, and 2B). Thus, VBL exerts spatial memory improvement by regulating CRS-induced NMDA receptor neurotoxicity and Tau hyperphosphorylation.
ESTHER : Oh_2020_Am.J.Chin.Med__1
PubMedSearch : Oh_2020_Am.J.Chin.Med__1
PubMedID: 33371815

Title : Sequential Emergence and Wide Spread of Neutralization Escape Middle East Respiratory Syndrome Coronavirus Mutants, South Korea, 2015 - Kim_2019_Emerg.Infect.Dis_25_1161
Author(s) : Kim YS , Aigerim A , Park U , Kim Y , Rhee JY , Choi JP , Park WB , Park SW , Lim DG , Inn KS , Hwang ES , Choi MS , Shin HS , Cho NH
Ref : Emerg Infect Dis , 25 :1161 , 2019
Abstract : The unexpectedly large outbreak of Middle East respiratory syndrome in South Korea in 2015 was initiated by an infected traveler and amplified by several "superspreading" events. Previously, we reported the emergence and spread of mutant Middle East respiratory syndrome coronavirus bearing spike mutations (I529T or D510G) with reduced affinity to human receptor CD26 during the outbreak. To assess the potential association of spike mutations with superspreading events, we collected virus genetic information reported during the outbreak and systemically analyzed the relationship of spike sequences and epidemiology. We found sequential emergence of the spike mutations in 2 superspreaders. In vivo virulence of the mutant viruses seems to decline in human patients, as assessed by fever duration in affected persons. In addition, neutralizing activity against these 2 mutant viruses in serum samples from mice immunized with wild-type spike antigen were gradually reduced, suggesting emergence and wide spread of neutralization escapers during the outbreak.
ESTHER : Kim_2019_Emerg.Infect.Dis_25_1161
PubMedSearch : Kim_2019_Emerg.Infect.Dis_25_1161
PubMedID: 30900977

Title : Production of stearidonic acid-rich triacylglycerol via a two-step enzymatic esterification - Kim_2019_Food.Chem_270_332
Author(s) : Kim NH , Kim H , Choi N , Kim Y , Kim BH , Kim IH
Ref : Food Chem , 270 :332 , 2019
Abstract : The aim of this study was to synthesize stearidonic acid (SDA)-rich triacylglycerol (TAG) via a two-step lipase-catalyzed esterification under vacuum. SDA-rich fatty acid, which was prepared from echium oil via Candida rugosa lipase-catalyzed selective esterification, was used as the substrate. Two different immobilized lipases, Novozym 435 from Candida antarctica and Lipozyme TL IM from Thermomyces lanuginosus, were employed for the synthesis of SDA-rich TAG. In the first step, Novozym 435-catalyzed esterification of the SDA-rich fatty acid with glycerol was carried out for 2 h. In the second step, Lipozyme TL IM-catalyzed esterification of the reaction mixture from the first step was performed for an additional 10 h. The optimal reaction conditions for the second step were a temperature of 65 degreeC, an enzyme loading of 20%, and a vacuum of 0.7 kPa. Consequently, the maximum TAG conversion of ca. 86.4 wt% was obtained after 12 h via a two-step lipase-catalyzed esterification.
ESTHER : Kim_2019_Food.Chem_270_332
PubMedSearch : Kim_2019_Food.Chem_270_332
PubMedID: 30174055

Title : A missense allele of KARRIKIN-INSENSITIVE2 impairs ligand-binding and downstream signaling in Arabidopsis thaliana - Lee_2018_J.Exp.Bot_69_3609
Author(s) : Lee I , Kim K , Lee S , Hwang E , Shin K , Kim D , Choi J , Choi H , Cha JS , Kim H , Lee RA , Jeong S , Kim J , Kim Y , Nam HG , Park SK , Cho HS , Soh MS
Ref : J Exp Bot , 69 :3609 , 2018
Abstract : A smoke-derived compound, karrikin (KAR), and an endogenous but as yet unidentified KARRIKIN INSENSITIVE2 (KAI2) ligand (KL) have been identified as chemical cues in higher plants that impact on multiple aspects of growth and development. Genetic screening of light-signaling mutants in Arabidopsis thaliana has identified a mutant designated as ply2 (pleiotropic long hypocotyl2) that has pleiotropic light-response defects. In this study, we used positional cloning to identify the molecular lesion of ply2 as a missense mutation of KAI2/HYPOSENSITIVE TO LIGHT, which causes a single amino acid substitution, Ala219Val. Physiological analysis and genetic epistasis analysis with the KL-signaling components MORE AXILLARY GROWTH2 (MAX2) and SUPPRESSOR OF MAX2 1 suggested that the pleiotropic phenotypes of the ply2 mutant can be ascribed to a defect in KL-signaling. Molecular and biochemical analyses revealed that the mutant KAI2ply2 protein is impaired in its ligand-binding activity. In support of this conclusion, X-ray crystallography studies suggested that the KAI2ply2 mutation not only results in a narrowed entrance gate for the ligand but also alters the structural flexibility of the helical lid domains. We discuss the structural implications of the Ala219 residue with regard to ligand-specific binding and signaling of KAI2, together with potential functions of KL-signaling in the context of the light-regulatory network in Arabidopsis thaliana.
ESTHER : Lee_2018_J.Exp.Bot_69_3609
PubMedSearch : Lee_2018_J.Exp.Bot_69_3609
PubMedID: 29722815
Gene_locus related to this paper: arath-KAI2.D14L

Title : Reduction of soluble dipeptidyl peptidase 4 levels in plasma of patients infected with Middle East respiratory syndrome coronavirus - Inn_2018_Virology_518_324
Author(s) : Inn KS , Kim Y , Aigerim A , Park U , Hwang ES , Choi MS , Kim YS , Cho NH
Ref : Virology , 518 :324 , 2018
Abstract : Dipeptidyl peptidase 4 (DPP4) is a receptor for MERS-CoV. The soluble form of DPP4 (sDPP4) circulates systematically and can competitively inhibit MERS-CoV entry into host cells. Here, we measured the concentration of sDPP4 in the plasma and sputa of 14 MERS-CoV-infected patients of various degrees of disease severity. The concentration of sDPP4 in the plasma of MERS patients (474.76+/-108.06ng/ml) was significantly lower than those of healthy controls (703.42+/-169.96ng/ml), but there were no significant differences among the patient groups. Interestingly, plasma levels of IL-10 and EGF were negatively and positively correlated with sDPP4 concentrations, respectively. The sDPP4 levels in sputa were less than 300ng/ml. Viral infection was inhibited by 50% in the presence of more than 8000ng/ml of sDPP4. Therefore, sDPP4 levels in the plasma of MERS patients are significantly reduced below the threshold needed to exert an antiviral effect against MERS-CoV infection.
ESTHER : Inn_2018_Virology_518_324
PubMedSearch : Inn_2018_Virology_518_324
PubMedID: 29587190

Title : GABA-enriched fermented Laminaria japonica improves cognitive impairment and neuroplasticity in scopolamine- and ethanol-induced dementia model mice - Reid_2018_Nutr.Res.Pract_12_199
Author(s) : Reid SNS , Ryu JK , Kim Y , Jeon BH
Ref : Nutr Res Pract , 12 :199 , 2018
Abstract : BACKGROUND/OBJECTIVES: Fermented Laminaria japonica (FL), a type sea tangle used as a functional food ingredient, has been reported to possess cognitive improving properties that may aid in the treatment of common neurodegenerative disorders, such as dementia. MATERIALS/METHODS: We examined the effects of FL on scopolamine (Sco)- and ethanol (EtOH)-induced hippocampus-dependent memory impairment, using the Passive avoidance (PA) and Morris water maze (MWM) tests. To examine the underlying mechanisms associated with neuroprotective effects, we analyzed acetylcholine (ACh) and acetylcholinesterase (AChE) activity, brain tissue expression of muscarinic acetylcholine receptor (mAChR), cAMP response element binding protein (CREB) and extracellular signal-regulated kinases 1/2 (ERK1/2), and immunohistochemical analysis, in the hippocampus of mice, compared to current drug therapy intervention. Biochemical blood analysis was carried out to determine the effects of FL on alanine transaminase (ALT), aspartate transaminase (AST), and triglyceride (TG) and total cholesterol (TC) levels. 7 groups (n = 10) consisted of a control (CON), 3 Sco-induced dementia and 3 EtOH-induced dementia groups, with both dementia group types containing an untreated group (Sco and EtOH); a positive control, orally administered donepezil (Dpz) (4mg/kg) (Sco + Dpz and EtOH + Dpz); and an FL (50 mg/kg) treatment group (Sco + FL50 and EtOH + FL50), orally administered over the 4-week experimental period. RESULTS: FL50 significantly reduced EtOH-induced increase in AST and ALT levels. FL50 treatment reduced EtOH-impaired step-through latency time in the PA test, and Sco- and EtOH-induced dementia escape latency times in the MWM test. Moreover, anticholinergic effects of Sco and EtOH on the brain were reversed by FL50, through the attenuation of AChE activity and elevation of ACh concentration. FL50 elevated ERK1/2 protein expression and increased p-CREB (ser133) in hippocampus brain tissue, according to Western blot and immunohistochemistry analysis, respectively. CONCLUSION: Overall, these results suggest that FL may be considered an efficacious intervention for Sco- and EtOH-induced dementia, in terms of reversing cognitive impairment and neuroplastic dysfunction.
ESTHER : Reid_2018_Nutr.Res.Pract_12_199
PubMedSearch : Reid_2018_Nutr.Res.Pract_12_199
PubMedID: 29854325

Title : Observational Study of Clinical and Functional Progression Based on Initial Brain MRI Characteristics in Patients with Alzheimer's Disease - Choi_2018_J.Alzheimers.Dis_66_1721
Author(s) : Choi H , Yang Y , Han HJ , Jeong JH , Park MY , Kim YB , Jo KD , Choi JY , Kang KH , Kang H , Kwon DY , Yoo BG , Lee HJ , Shin BS , Jeon SM , Kwon OD , Kim JS , Lee SJ , Kim Y , Park TH , Kim YJ , Yang HJ , Park HY , Shin HE , Lee JS , Jung YH , Lee AY , Shin DI , Shin KJ , Park KH
Ref : J Alzheimers Dis , 66 :1721 , 2018
Abstract : BACKGROUND: Magnetic resonance imaging (MRI) is a useful tool to predict the diagnosis and progression of Alzheimer's disease (AD), especially for primary physicians. However, the correlation between baseline MRI findings and AD progression has not been fully established. OBJECTIVE: To investigate the correlation between hippocampal atrophy (HA) and white matter hyperintensities (WMH) on initial brain MRI images and the degree of cognitive decline and functional changes over 1 year. METHODS: In this prospective, 12-month observational study, dementia outpatients were recruited from 29 centers across South Korea. Baseline assessments of HA and WMH on baseline brain MRI were derived as well as cognitive function, dementia severity, activities of daily living, and acetylcholinesterase inhibitor (AChEI) use. Follow-up assessments were conducted at 6 and 12 months. RESULTS: Among 899 enrolled dementia patients, 748 were diagnosed with AD of whom 654 (87%) were taking AChEIs. Baseline WMH showed significant correlations with age, current alcohol consumption, and Clinical Dementia Rating score; baseline HA was correlated with age, family history, physical exercise, and the results of cognitive assessments. Among the AChEI group, changes in the Korean version of the Instrumental Activities of Daily Living (K-IADL) were correlated with the severity of HA on baseline brain MRI, but not with the baseline severity of WMH. In the no AChEI group, changes in K-IADL were correlated with the severity of WMH and HA at baseline. CONCLUSION: Baseline MRI findings could be a useful tool for predicting future clinical outcomes by primary physicians, especially in relation to patients' functional status.
ESTHER : Choi_2018_J.Alzheimers.Dis_66_1721
PubMedSearch : Choi_2018_J.Alzheimers.Dis_66_1721
PubMedID: 30452413

Title : Synthesis of alpha-linolenic acid-rich triacylglycerol using a newly prepared immobilized lipase - Kim_2017_Food.Chem_237_654
Author(s) : Kim H , Choi N , Oh SW , Kim Y , Hee Kim B , Kim IH
Ref : Food Chem , 237 :654 , 2017
Abstract : An alpha-linolenic acid (ALA)-rich triacylglycerol (TAG) was synthesized from an ALA-rich fatty acid (FA) from perilla oil and glycerol, using a newly prepared immobilized lipase under vacuum. The ALA-rich FA (purity >90wt%) used as the substrate was prepared by urea complexation from perilla oil FAs. Liquid Lipozyme TL 100L lipase from Thermomyces lanuginosus was used for immobilization. Nine different hydrophilic and hydrophobic carriers for immobilization were tested, and Duolite A568, which is a hydrophilic resin, was selected as the best carrier. This immobilized lipase was used to synthesize TAG by direct esterification under vacuum. The parameters investigated were temperature, enzyme loading, and vacuum level. The optimum reaction conditions were a temperature of 60 degC, an enzyme loading of 15% (based on the total weight of the substrate), and a vacuum of 0.7kPa, respectively. The maximum conversion to TAG of ca. 88wt% was obtained in 12h under the optimum conditions.
ESTHER : Kim_2017_Food.Chem_237_654
PubMedSearch : Kim_2017_Food.Chem_237_654
PubMedID: 28764049

Title : Phytochemical Quantification and the In Vitro Acetylcholinesterase Inhibitory Activity of Phellodendron chinense and Its Components - Kim_2017_Molecules_22_
Author(s) : Kim YJ , Lim HS , Kim Y , Lee J , Kim BY , Jeong SJ
Ref : Molecules , 22 : , 2017
Abstract : The dried bark of Phellodendron chinense has been used as a traditional herbal medicine to remove damp heat, relieve consumptive fever, and cure dysentery and diarrhea. In the present study, we performed quantitative analyses of the two components of P. chinense, phellodendrine and berberine, using high-performance liquid chromatography. A 70% ethanol extract of P. chinense was prepared and the two components were separated on a C-18 analytical column using a gradient solvent system of acetonitrile and 0.1% (v/v) aqueous trifluoroacetic acid. The ultraviolet wavelength used for detection was 200 nm for phellodendrine and 226 nm for berberine. The analytical method established here showed high linearity (correlation coefficient, >/=0.9991). The amount of phellodendrine and berberine used was 22.255 +/- 0.123 mg/g and 269.651 +/- 1.257 mg/g, respectively. Moreover, we performed an in vitro acetylcholinesterase (AChE) activity assay and an amyloid-beta aggregation test to examine the biological properties of phellodendrine and berberine as therapeutic drugs for Alzheimer's disease. Phellodendrine and berberine inhibited AChE activity in a dose-dependent manner (IC50 = 36.51 and 0.44 muM, respectively). In contrast, neither phellodendrine nor berberine had an effect on amyloid-beta aggregation. The P. chinense extract and phellodendrine, but not berberine, exhibited antioxidant activity by increasing radical scavenging activity. Moreover, P. chinense demonstrated a neuroprotective effect in hydrogen peroxide-treated HT22 hippocampal cells. Overall, our findings suggest that P. chinense has potential as an anti-Alzheimer's agent via the suppression of the enzymatic activity of acetylcholinesterase and the stimulation of antioxidant activity.
ESTHER : Kim_2017_Molecules_22_
PubMedSearch : Kim_2017_Molecules_22_
PubMedID: 28574473

Title : Neuroprotective Effect of Corydalis ternata Extract and Its Phytochemical Quantitative Analysis - Kim_2017_Chem.Pharm.Bull.(Tokyo)_65_826
Author(s) : Kim YJ , Lim HS , Kim Y , Lee J , Kim BY , Jeong SJ
Ref : Chem Pharm Bull (Tokyo) , 65 :826 , 2017
Abstract : The tubers of Corydalis ternata have been used to treat cardiovascular diseases such as hypertension and cardiac arrhythmia. Its active components have anticholinesterase, antiamnesic, and anti-inflammatory activities, and analgesic effects. In the present study, we performed quantitative analyses of the two components of C. ternata, coptisine and berberine, using HPLC. A 70% ethanol extract of C. ternata was prepared and the two components were separated using a C-18 analytical column on a gradient solvent system of acetonitrile and 0.1% (v/v) aqueous trifluoroacetic acid. Recordings were performed at a UV wavelength of 265 nm for two standard components. The established analytical method showed high linearity (correlation coefficient (r)=1.0000) and proper precision (0.49-3.88%), accuracy (97.88-102.7%), and recovery (95.12-103.79%) for two standard components. The amount of the coptisine and berberine was 4.968+/-0.089 mg/g and 3.73+/-0.075 mg/g, respectively. In addition, we investigated the effects of coptisine and berberine on acetylcholinesterase activity and amyloid-beta aggregation, which are major biomarkers of dementia. Coptisine and berberine decreased acetylcholinesterase activity in a dose-dependent manner (IC50=0.74 and 0.48 microM, respectively). The C. ternata extract exerted an antioxidant activity by stimulating the radical scavenging activity of 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS), but not 2,2-diphenyl-1-picrylhydrazyl (DPPH). Furthermore, the C. ternata extract reversed the hydrogen peroxide-induced death of HT22 hippocampal cells, indicating its neuroprotective effect. Our results suggest the potential of C. ternata as a therapeutic agent against dementia via the inhibition of acetylcholinesterase activity and neuronal cell death.
ESTHER : Kim_2017_Chem.Pharm.Bull.(Tokyo)_65_826
PubMedSearch : Kim_2017_Chem.Pharm.Bull.(Tokyo)_65_826
PubMedID: 28867709

Title : Chlorpyrifos-induced biomarkers in Japanese medaka (Oryzias latipes) - Jeon_2016_Environ.Sci.Pollut.Res.Int_23_1071
Author(s) : Jeon HJ , Lee YH , Mo HH , Kim MJ , Al-Wabel MI , Kim Y , Cho K , Kim TW , Ok YS , Lee SE
Ref : Environ Sci Pollut Res Int , 23 :1071 , 2016
Abstract : Chlorpyrifos (CHL) is an organophosphate compound that is widely used as an insecticide. Due to its repeated use and high environmental residual property, CHL is frequently passed into aquatic environments by runoff. Consequently, there may be an adverse effect on aquatic vertebrate animals, including fish. Therefore, in this study, we assessed how CHL affected Japanese medaka (Oryzias latipes). The acute toxicity of CHL in adult fish after 96 h of exposure was determined to be 212.50, 266.79, and 412.28 mug L(-1) (LC25, LC50, and LC95, respectively). Acetylcholinesterase (AChE), glutathione S-transferase (GST), and carboxylesterase (CE) activities were obtained from the livers of dead or surviving fish, and the results showed 4.8-fold lower, 4.5-fold higher, and 18.6-fold lower activities for the AChE, GST, and CE, respectively, for 64-h exposure at a concentration of 400 mug L(-1) of CHL. In the embryo toxicity test, curved spines were observed in embryos that were exposed to CHL for 48 h in a concentration-dependent manner. With identification of biomarkers for CHL in the fish, two protein peaks, 5550.86 and 5639.79 m/z, were found to be upregulated. These two proteins can be used as protein biomarkers for CHL contamination in aquatic systems. A phosphatidyl choline with an m/z ratio of 556.32 dramatically decreased after CHL exposure in the fish; thus, it may be considered as a lipid biomarker for CHL. It is assumed as the first report to identify a phospholipid biomarker using a lipidomics approach in fish toxicology. Taken together, these results demonstrated the adverse effects of CHL on Japanese medaka and reveal several candidate biomarkers that can be used as diagnostic tools for determining CHL.
ESTHER : Jeon_2016_Environ.Sci.Pollut.Res.Int_23_1071
PubMedSearch : Jeon_2016_Environ.Sci.Pollut.Res.Int_23_1071
PubMedID: 25966881

Title : Molecular Rotors for the Detection of Chemical Warfare Agent Simulants - Kim_2016_Anal.Chem_88_9259
Author(s) : Kim TI , Maity SB , Bouffard J , Kim Y
Ref : Analytical Chemistry , 88 :9259 , 2016
Abstract : The fluorogenic probe o-OH is able to detect and quantify organophosphorus nerve agent mimics in solution and in the vapor phase following immobilization on a solid substrate, making the system a suitable candidate for the field detection of chemical warfare agents. Detection is achieved by the suppression of internal rotation upon phosphorylation of a reactive phenolate, resulting in a large fluorescence "turn-on" response.
ESTHER : Kim_2016_Anal.Chem_88_9259
PubMedSearch : Kim_2016_Anal.Chem_88_9259
PubMedID: 27536955

Title : Spread of Mutant Middle East Respiratory Syndrome Coronavirus with Reduced Affinity to Human CD26 during the South Korean Outbreak - Kim_2016_mBio_7_e00019
Author(s) : Kim Y , Cheon S , Min CK , Sohn KM , Kang YJ , Cha YJ , Kang JI , Han SK , Ha NY , Kim G , Aigerim A , Shin HM , Choi MS , Kim S , Cho HS , Kim YS , Cho NH
Ref : MBio , 7 :e00019 , 2016
Abstract : UNLABELLED: The newly emerging Middle East respiratory syndrome coronavirus (MERS-CoV) causes a severe respiratory infection with a high mortality rate (~35%). MERS-CoV has been a global threat due to continuous outbreaks in the Arabian peninsula and international spread by infected travelers since 2012. From May to July 2015, a large outbreak initiated by an infected traveler from the Arabian peninsula swept South Korea and resulted in 186 confirmed cases with 38 deaths (case fatality rate, 20.4%). Here, we show the rapid emergence and spread of a mutant MERS-CoV with reduced affinity to the human CD26 receptor during the South Korean outbreak. We isolated 13 new viral genomes from 14 infected patients treated at a hospital and found that 12 of these genomes possess a point mutation in the receptor-binding domain (RBD) of viral spike (S) protein. Specifically, 11 of these genomes have an I529T mutation in RBD, and 1 has a D510G mutation. Strikingly, both mutations result in reduced affinity of RBD to human CD26 compared to wild-type RBD, as measured by surface plasmon resonance analysis and cellular binding assay. Additionally, pseudotyped virus bearing an I529T mutation in S protein showed reduced entry into host cells compared to virus with wild-type S protein. These unexpected findings suggest that MERS-CoV adaptation during human-to-human spread may be driven by host immunological pressure such as neutralizing antibodies, resulting in reduced affinity to host receptor, and thereby impairs viral fitness and virulence, rather than positive selection for a better affinity to CD26. IMPORTANCE: Recently, a large outbreak initiated by an MERS-CoV-infected traveler from the Middle East swept South Korea and resulted in 186 confirmed cases with 38 deaths. This is the largest outbreak outside the Middle East, and it raised strong concerns about the possible emergence of MERS-CoV mutations. Here, we isolated 13 new viral genomes and found that 12 of them possess a point mutation in the receptor-binding domain of viral spike protein, resulting in reduced affinity to the human cognate receptor, CD26, compared to the wild-type virus. These unexpected findings suggest that MERS-CoV adaptation in humans may be driven by host immunological pressure.
ESTHER : Kim_2016_mBio_7_e00019
PubMedSearch : Kim_2016_mBio_7_e00019
PubMedID: 26933050

Title : Using proteomics to probe neurons - Kim_2015_Elife_4_
Author(s) : Kim Y , Kislinger T
Ref : Elife , 4 : , 2015
Abstract : Advances in mass spectrometry-based proteomics have allowed researchers to quantify the abundances of the different forms of three closely related proteins in the neurons of mice.
ESTHER : Kim_2015_Elife_4_
PubMedSearch : Kim_2015_Elife_4_
PubMedID: 26135027

Title : Ramlibacter solisilvae sp. nov., isolated from forest soil, and emended description of the genus Ramlibacter - Lee_2014_Int.J.Syst.Evol.Microbiol_64_1317
Author(s) : Lee HJ , Lee SH , Lee SS , Lee JS , Kim Y , Kim SC , Jeon CO
Ref : Int J Syst Evol Microbiol , 64 :1317 , 2014
Abstract : A Gram-staining-negative, strictly aerobic, white-colony-forming bacterium, designated strain 5-10(T), was isolated from forest soil of Bac Kan Province in Vietnam. Cells were non-motile rods or coccoids, showing oxidase- and catalase-positive reactions. Growth was observed at 10-37 degrees C (optimum, 30 degrees C), at pH 5.0-9.0 (optimum, pH 7.0) and in the presence of 0-1.0 % (w/v) NaCl (optimum, 0-0.5 %). The major cellular fatty acids were summed feature 3 (comprising C16 : 1omega6c and/or C16 : 1omega7c), C16 : 0, C10 : 0 3-OH and summed feature 8 (comprising C18 : 1omega6c and/or C18 : 1omega7c). The G+C content of the genomic DNA was 69.9 mol% and the only respiratory quinone detected was ubiquinone 8 (Q-8). Phylogenetic analysis based on 16S rRNA gene sequences showed that strain 5-10(T) formed a tight phyletic lineage with members of the genus Ramlibacter. Strain 5-10(T) was most closely related to Ramlibacter tataouinensis TTB310(T) (97.3 %), but the DNA-DNA relatedness level between the two strains was 38.2+/-1.8 %. Based on phenotypic, chemotaxonomic and molecular features, strain 5-10(T) was shown to represent a novel species of the genus Ramlibacter, for which the name Ramlibacter solisilvae sp. nov. is proposed. The type strain is 5-10(T) ( = KACC 17567(T) = JCM 19319(T)). An emended description of the genus Ramlibacter is also proposed.
ESTHER : Lee_2014_Int.J.Syst.Evol.Microbiol_64_1317
PubMedSearch : Lee_2014_Int.J.Syst.Evol.Microbiol_64_1317
PubMedID: 24425747
Gene_locus related to this paper: 9burk-a0a127juv8

Title : Familial LCAT deficiency in a child with nephrotic syndrome - Rajpal_2014_Clin.Nephrol_82_211
Author(s) : Rajpal JS , Mapel-Lentz J , Mancera AD , Reed RC , Kim Y , Chavers BM
Ref : Clin Nephrol , 82 :211 , 2014
Abstract : BACKGROUND: Lecitin cholesterol acyltransferase (LCAT) deficiency comprises a group of rare disorders related to HDL metabolism. These disorders are characterized by ophthalmologic, hematologic, and renal findings. Case diagnosis/treatment: A 15-year-old female who presented with nephrotic syndrome and hypertension was diagnosed with LCAT deficiency by renal biopsy and LCAT enzyme activity. Her edema and hypertension improved with diuretic and antihypertensive therapies. Continued care of her LCAT deficiency is ongoing. CONCLUSION: Although rare, LCAT deficiency should be in the differential diagnosis of nephrotic syndrome in the setting of abnormally low HDL cholesterol levels.
ESTHER : Rajpal_2014_Clin.Nephrol_82_211
PubMedSearch : Rajpal_2014_Clin.Nephrol_82_211
PubMedID: 23391322

Title : N-myc downstream-regulated gene 1 is involved in the regulation of cystogenesis in transgenic mice overexpressing human PKD2 gene - Kim_2013_Proteomics_13_134
Author(s) : Kim BH , Park EY , Yoo KH , Choi KM , Kim Y , Seong JK , Park JH
Ref : Proteomics , 13 :134 , 2013
Abstract : Autosomal dominant polycystic kidney disease (ADPKD) is an inheritable and progressive kidney disease featured by the formation of fluid-filled cysts. In a previous study, transgenic mice overexpressing human PKD2 gene were produced as an ADPKD animal model. To select genes controlled by PKD2, 2DE was performed using kidney tissues of 12- and 18-month-old transgenic mice. The protein localization was detected by immunohistochemistry, and 3D culture was utilized to observe in vitro cystogenesis. As a result, N-myc downstream-regulated gene 1 (NDRG1) was chosen as a candidate regulator gene of cystogenesis. NDRG1 is an intracellular protein involved in cellular proliferation and differentiation. This gene was expressed much higher in the kidney of hPKD2 TG mice. Also, the high level of NDRG1 protein was detected in the cyst lining epithelial cells. The hypothesis that PKD2 gene regulates NDRG1 expression was supported, and NDRG1 knockdown resulted in attenuation of cyst growth in vitro. Furthermore, NDRG1 knockdown suppressed cellular growth in mouse inner medullary collecting duct-3 cells. We found that early growth response 1, a transcription factor that binds to the NDRG1 promoter, was mediated in the NDRG1 expression regulation by PKD2. In this study, we found the novel gene that was involved in cystogenesis, which will provide the new insight in ADPKD.
ESTHER : Kim_2013_Proteomics_13_134
PubMedSearch : Kim_2013_Proteomics_13_134
PubMedID: 23212942

Title : Genome sequence and functional genomic analysis of the oil-degrading bacterium Oleispira antarctica - Kube_2013_Nat.Commun_4_2156
Author(s) : Kube M , Chernikova TN , Al-Ramahi Y , Beloqui A , Lopez-Cortez N , Guazzaroni ME , Heipieper HJ , Klages S , Kotsyurbenko OR , Langer I , Nechitaylo TY , Lunsdorf H , Fernandez M , Juarez S , Ciordia S , Singer A , Kagan O , Egorova O , Petit PA , Stogios P , Kim Y , Tchigvintsev A , Flick R , Denaro R , Genovese M , Albar JP , Reva ON , Martinez-Gomariz M , Tran H , Ferrer M , Savchenko A , Yakunin AF , Yakimov MM , Golyshina OV , Reinhardt R , Golyshin PN
Ref : Nat Commun , 4 :2156 , 2013
Abstract : Ubiquitous bacteria from the genus Oleispira drive oil degradation in the largest environment on Earth, the cold and deep sea. Here we report the genome sequence of Oleispira antarctica and show that compared with Alcanivorax borkumensis--the paradigm of mesophilic hydrocarbonoclastic bacteria--O. antarctica has a larger genome that has witnessed massive gene-transfer events. We identify an array of alkane monooxygenases, osmoprotectants, siderophores and micronutrient-scavenging pathways. We also show that at low temperatures, the main protein-folding machine Cpn60 functions as a single heptameric barrel that uses larger proteins as substrates compared with the classical double-barrel structure observed at higher temperatures. With 11 protein crystal structures, we further report the largest set of structures from one psychrotolerant organism. The most common structural feature is an increased content of surface-exposed negatively charged residues compared to their mesophilic counterparts. Our findings are relevant in the context of microbial cold-adaptation mechanisms and the development of strategies for oil-spill mitigation in cold environments.
ESTHER : Kube_2013_Nat.Commun_4_2156
PubMedSearch : Kube_2013_Nat.Commun_4_2156
PubMedID: 23877221
Gene_locus related to this paper: olean-olei00960 , olean-r4ym14 , olean-r4yv64 , olean-r4ys13

Title : MDGAs interact selectively with neuroligin-2 but not other neuroligins to regulate inhibitory synapse development - Lee_2013_Proc.Natl.Acad.Sci.U.S.A_110_336
Author(s) : Lee K , Kim Y , Lee SJ , Qiang Y , Lee D , Lee HW , Kim H , Je HS , Sudhof TC , Ko J
Ref : Proc Natl Acad Sci U S A , 110 :336 , 2013
Abstract : The MAM domain-containing GPI anchor proteins MDGA1 and MDGA2 are Ig superfamily adhesion molecules composed of six IG domains, a fibronectin III domain, a MAM domain, and a GPI anchor. MDGAs contribute to the radial migration and positioning of a subset of cortical neurons during early neural development. However, MDGAs continue to be expressed in postnatal brain, and their functions during postnatal neural development remain unknown. Here, we demonstrate that MDGAs specifically and with a nanomolar affinity bind to neuroligin-2, a cell-adhesion molecule of inhibitory synapses, but do not bind detectably to neuroligin-1 or neuroligin-3. We observed no cell adhesion between cells expressing neuroligin-2 and MDGA1, suggesting a cis interaction. Importantly, RNAi-mediated knockdown of MDGAs increased the abundance of inhibitory but not excitatory synapses in a neuroligin-2-dependent manner. Conversely, overexpression of MDGA1 decreased the numbers of functional inhibitory synapses. Likewise, coexpression of both MDGA1 and neuroligin-2 reduced the synaptogenic capacity of neuroligin-2 in an artificial synapse-formation assay by abolishing the ability of neuroligin-2 to form an adhesion complex with neurexins. Taken together, our data suggest that MDGAs inhibit the activity of neuroligin-2 in controlling the function of inhibitory synapses and that MDGAs do so by binding to neuroligin-2.
ESTHER : Lee_2013_Proc.Natl.Acad.Sci.U.S.A_110_336
PubMedSearch : Lee_2013_Proc.Natl.Acad.Sci.U.S.A_110_336
PubMedID: 23248271

Title : Lipase-catalysed production of triacylglycerols enriched in pinolenic acid at the sn-2 position from pine nut oil - Choi_2012_J.Sci.Food.Agric_92_870
Author(s) : Choi JH , Kim BH , Hong SI , Kim CT , Kim CJ , Kim Y , Kim IH
Ref : J Sci Food Agric , 92 :870 , 2012
Abstract : BACKGROUND: The purpose of this study was to produce triacylglycerols (TAGs) enriched in pinolenic acid (PLA) at the sn-2 position using the principle of acyl migration, from the pine nut oil containing PLA esterified exclusively at the sn-3 position. RESULTS: Two types of lipase-catalysed reactions, i.e. redistribution and reesterification of fatty acids, were successively performed using seven commercially available lipases as biocatalysts. Of the lipases tested, Novozym 435 and Lipozyme TL IM were effective biocatalysts for positioning PLA at the sn-2 location. These biocatalysts were selected for further evaluation of the effects of reaction parameters, such as temperature and water content on the migration of PLA residues to the sn-2 position and TAG content. For both lipases, a significant decrease in TAG content was observed after the lipase-catalysed redistribution of fatty acids for both lipases. The reduced TAG content could be enhanced up to approx. 92%, through lipase-catalysed re-esterification of the hydrolysed fatty acids under vacuum. CONCLUSION: TAG enriched in PLA at the sn-2 position was synthesised from pine nut oil via lipase-catalysed redistribution and re-esterification of fatty acid residues using Lipozyme TL IM and Novozym 435 as biocatalysts.
ESTHER : Choi_2012_J.Sci.Food.Agric_92_870
PubMedSearch : Choi_2012_J.Sci.Food.Agric_92_870
PubMedID: 21953622

Title : Lipase-catalyzed interesterification in packed bed reactor using 2 different temperatures - Chae_2011_J.Food.Sci_76_C555
Author(s) : Chae MH , Park HK , Kwon KI , Kim JW , Hong SI , Kim Y , Kim BH , Kim IH
Ref : J Food Sci , 76 :C555 , 2011
Abstract : Lipase-catalyzed interesterification of high oleic sunflower oil and fully hydrogenated soybean oil (70 : 30, wt/ wt) was carried out in a packed bed reactor using an immobilized lipase from Thermomyces lanuginosus (Lipozyme TL IM) and the effect of a stepwise temperature protocol involving the 2 different temperatures, 60 and 70 degreeC, was investigated. The melting point of a fat that was incubated at 70 degreeC for 9 min was 57 degreeC, which suggested that it should be to employ a lower reaction temperature of 60 degreeC, after the first 9 min of the reaction. There were no significant differences (P < 0.05) in the conversion degree, triacylglycerol profile, and solid fat content between a constant temperature protocol (70 degreeC) and a stepwise temperature protocol (a combination of 70 and 60 degreeC). After 50 cycles, the overall residual activities of enzymes employed in stepwise temperature protocol were significantly (P < 0.05) higher than those of enzymes employed in constant temperature protocol.
ESTHER : Chae_2011_J.Food.Sci_76_C555
PubMedSearch : Chae_2011_J.Food.Sci_76_C555
PubMedID: 22417335

Title : Crystal structure of the human N-Myc downstream-regulated gene 2 protein provides insight into its role as a tumor suppressor - Hwang_2011_J.Biol.Chem_286_12450
Author(s) : Hwang J , Kim Y , Kang HB , Jaroszewski L , Deacon AM , Lee H , Choi WC , Kim KJ , Kim CH , Kang BS , Lee JO , Oh TK , Kim JW , Wilson IA , Kim MH
Ref : Journal of Biological Chemistry , 286 :12450 , 2011
Abstract : Considerable attention has recently been paid to the N-Myc downstream-regulated gene (NDRG) family because of its potential as a tumor suppressor in many human cancers. Primary amino acid sequence information suggests that the NDRG family proteins may belong to the alpha/beta-hydrolase (ABH) superfamily; however, their functional role has not yet been determined. Here, we present the crystal structures of the human and mouse NDRG2 proteins determined at 2.0 and 1.7 A resolution, respectively. Both NDRG2 proteins show remarkable structural similarity to the ABH superfamily, despite limited sequence similarity. Structural analysis suggests that NDRG2 is a nonenzymatic member of the ABH superfamily, because it lacks the catalytic signature residues and has an occluded substrate-binding site. Several conserved structural features suggest NDRG may be involved in molecular interactions. Mutagenesis data based on the structural analysis support a crucial role for helix alpha6 in the suppression of TCF/beta-catenin signaling in the tumorigenesis of human colorectal cancer, via a molecular interaction.
ESTHER : Hwang_2011_J.Biol.Chem_286_12450
PubMedSearch : Hwang_2011_J.Biol.Chem_286_12450
PubMedID: 21247902
Gene_locus related to this paper: human-NDRG2

Title : Neuroprotective effects of donepezil through inhibition of GSK-3 activity in amyloid-beta-induced neuronal cell death - Noh_2009_J.Neurochem_108_1116
Author(s) : Noh MY , Koh SH , Kim Y , Kim HY , Cho GW , Kim SH
Ref : Journal of Neurochemistry , 108 :1116 , 2009
Abstract : Acetylcholinesterase inhibitors (AChE-inhibitors) are used for the treatment of Alzheimer's disease. Recently, the AChE-inhibitor donepezil was found to have neuroprotective effects. However, the protective mechanisms of donepezil have not yet been clearly identified. We investigated the neuroprotective effects of donepezil and other AChE-inhibitors against amyloid-beta1-42 (Abeta42)-induced neurotoxicity in rat cortical neurons. To evaluate the neuroprotective effects of AChE-inhibitors, primary cultured cortical neurons were pre-treated with several concentrations of AChE-inhibitors for 24 h and then treated with 20 microM Abeta42 for 6 h. In addition to donepezil, other AChE-inhibitors (galantamine and huperizine A) also showed increased neuronal cell viability against Abeta42 toxicity in a concentration-dependent manner. However, we demonstrated that donepezil has a more potent effect in inhibiting glycogen synthase kinase-3 (GSK-3) activity compared with other AChE-inhibitors. The neuroprotective effects of donepezil were blocked by LY294002 (10 microM), a phosphoinositide 3 kinase inhibitor, but only partially by mecamylamine (10 microM), a blocker of nicotinic acetylcholine receptors. Additionally, donepezil's neuroprotective mechanism was related to the enhanced phosphorylation of Akt and GSK-3beta and reduced phosphorylation of tau and glycogen synthase. These results suggest that donepezil prevents Abeta42-induced neurotoxicity through the activation of phosphoinositide 3 kinase/Akt and inhibition of GSK-3, as well as through the activation of nicotinic acetylcholine receptors.
ESTHER : Noh_2009_J.Neurochem_108_1116
PubMedSearch : Noh_2009_J.Neurochem_108_1116
PubMedID: 19077054

Title : The cmaR gene of Corynebacterium ammoniagenes performs a novel regulatory role in the metabolism of sulfur-containing amino acids - Lee_2009_Microbiology_155_1878
Author(s) : Lee SM , Hwang BJ , Kim Y , Lee HS
Ref : Microbiology , 155 :1878 , 2009
Abstract : A novel regulatory gene, which performs an essential function in sulfur metabolism, has been identified in Corynebacterium ammoniagenes and was designated cmaR (cysteine and methionine regulator in C. ammoniagenes). The cmaR-disrupted strain (DeltacmaR) lost the ability to grow on minimal medium, and was identified as a methionine and cysteine double auxotroph. The mutant strain proved unable to convert cysteine to methionine (and vice versa), and lost the ability to assimilate and reduce sulfate to sulfide. In the DeltacmaR strain, the mRNAs of the methionine biosynthetic genes metYX, metB and metFE were significantly reduced, and the activities of the methionine biosynthetic enzymes cystathionine gamma-synthase, O-acetylhomoserine sulfhydrylase, and cystathionine beta-lyase were relatively low, thereby suggesting that the cmaR gene exerts a positive regulatory effect on methionine biosynthetic genes. In addition, with the exception of cysK, reduced transcription levels of the sulfur-assimilatory genes cysIXYZ and cysHDN were noted in the cmaR-disrupted strain, which suggests that sulfur assimilation is also under the positive control of the cmaR gene. Furthermore, the expression of the cmaR gene itself was strongly induced via the addition of cysteine or methionine alone, but not the introduction of both amino acids together to the growth medium. In addition, the expression of the cmaR gene was enhanced in an mcbR-disrupted strain, which suggests that cmaR is under the negative control of McbR, which has been identified as a global regulator of sulfur metabolism. DNA binding of the purified CmaR protein to the promoter region of its target genes could be demonstrated in vitro. No metabolite effector was required for the protein to bind DNA. These results demonstrated that the cmaR gene of C. ammoniagenes plays a role similar to but distinct from that of the functional homologue cysR of Corynebacterium glutamicum.
ESTHER : Lee_2009_Microbiology_155_1878
PubMedSearch : Lee_2009_Microbiology_155_1878
PubMedID: 19383689

Title : Identification of proteins binding to decursinol by chemical proteomics - Kang_2008_J.Microbiol.Biotechnol_18_1427
Author(s) : Kang HJ , Yoon TS , Jeong DG , Kim Y , Chung JW , Ha JS , Park SS , Ryu SE , Kim S , Bae KH , Chung SJ
Ref : J Microbiol Biotechnol , 18 :1427 , 2008
Abstract : Decursinol, found in the roots of Angelica gigas Nakai, has been traditionally used to treat anemia and other various diseases. Recently, numerous biological activities such as cytotoxic effect on leukemia cells, and antitumor, neuroprotection, and antibacterial activities have been reported for this compound. Although a number of proteins including protein kinase C, androgen receptor, and acetylcholinesterase were proposed as molecular targets responsible for the activities of decursinol, they are not enough to explain such a diverse biological activity mentioned above. In this study, we employed a chemical proteomic approach, leading to identification of seven proteins as potential proteins interacting with decursinol. Most of the proteins contain a defined ATP or nucleic acid binding domain and have been implied to be involved in the pathogenesis and progression of various human diseases including cancer, autoimmune disorders, or neurodegenerative diseases. The present results may provide clues to understand the molecular mechanism of the biological activities shown by decursinol, an anticancer natural product.
ESTHER : Kang_2008_J.Microbiol.Biotechnol_18_1427
PubMedSearch : Kang_2008_J.Microbiol.Biotechnol_18_1427
PubMedID: 18756104

Title : Functional and structural characterization of four glutaminases from Escherichia coli and Bacillus subtilis - Brown_2008_Biochemistry_47_5724
Author(s) : Brown G , Singer A , Proudfoot M , Skarina T , Kim Y , Chang C , Dementieva I , Kuznetsova E , Gonzalez CF , Joachimiak A , Savchenko A , Yakunin AF
Ref : Biochemistry , 47 :5724 , 2008
Abstract : Glutaminases belong to the large superfamily of serine-dependent beta-lactamases and penicillin-binding proteins, and they catalyze the hydrolytic deamidation of L-glutamine to L-glutamate. In this work, we purified and biochemically characterized four predicted glutaminases from Escherichia coli (YbaS and YneH) and Bacillus subtilis (YlaM and YbgJ). The proteins demonstrated strict specificity to L-glutamine and did not hydrolyze D-glutamine or L-asparagine. In each organism, one glutaminase showed higher affinity to glutamine ( E. coli YbaS and B. subtilis YlaM; K m 7.3 and 7.6 mM, respectively) than the second glutaminase ( E. coli YneH and B. subtilis YbgJ; K m 27.6 and 30.6 mM, respectively). The crystal structures of the E. coli YbaS and the B. subtilis YbgJ revealed the presence of a classical beta-lactamase-like fold and conservation of several key catalytic residues of beta-lactamases (Ser74, Lys77, Asn126, Lys268, and Ser269 in YbgJ). Alanine replacement mutagenesis demonstrated that most of the conserved residues located in the putative glutaminase catalytic site are essential for activity. The crystal structure of the YbgJ complex with the glutaminase inhibitor 6-diazo-5-oxo- l-norleucine revealed the presence of a covalent bond between the inhibitor and the hydroxyl oxygen of Ser74, providing evidence that Ser74 is the primary catalytic nucleophile and that the glutaminase reaction proceeds through formation of an enzyme-glutamyl intermediate. Growth experiments with the E. coli glutaminase deletion strains revealed that YneH is involved in the assimilation of l-glutamine as a sole source of carbon and nitrogen and suggested that both glutaminases (YbaS and YneH) also contribute to acid resistance in E. coli.
ESTHER : Brown_2008_Biochemistry_47_5724
PubMedSearch : Brown_2008_Biochemistry_47_5724
PubMedID: 18459799

Title : Evolution and expansion of the Mycobacterium tuberculosis PE and PPE multigene families and their association with the duplication of the ESAT-6 (esx) gene cluster regions - Gey van Pittius_2006_BMC.Evol.Biol_6_95
Author(s) : Gey van Pittius NC , Sampson SL , Lee H , Kim Y , van Helden PD , Warren RM
Ref : BMC Evol Biol , 6 :95 , 2006
Abstract : BACKGROUND: The PE and PPE multigene families of Mycobacterium tuberculosis comprise about 10% of the coding potential of the genome. The function of the proteins encoded by these large gene families remains unknown, although they have been proposed to be involved in antigenic variation and disease pathogenesis. Interestingly, some members of the PE and PPE families are associated with the ESAT-6 (esx) gene cluster regions, which are regions of immunopathogenic importance, and encode a system dedicated to the secretion of members of the potent T-cell antigen ESAT-6 family. This study investigates the duplication characteristics of the PE and PPE gene families and their association with the ESAT-6 gene clusters, using a combination of phylogenetic analyses, DNA hybridization, and comparative genomics, in order to gain insight into their evolutionary history and distribution in the genus Mycobacterium. RESULTS: The results showed that the expansion of the PE and PPE gene families is linked to the duplications of the ESAT-6 gene clusters, and that members situated in and associated with the clusters represent the most ancestral copies of the two gene families. Furthermore, the emergence of the repeat protein PGRS and MPTR subfamilies is a recent evolutionary event, occurring at defined branching points in the evolution of the genus Mycobacterium. These gene subfamilies are thus present in multiple copies only in the members of the M. tuberculosis complex and close relatives. The study provides a complete analysis of all the PE and PPE genes found in the sequenced genomes of members of the genus Mycobacterium such as M. smegmatis, M. avium paratuberculosis, M. leprae, M. ulcerans, and M. tuberculosis. CONCLUSION: This work provides insight into the evolutionary history for the PE and PPE gene families of the mycobacteria, linking the expansion of these families to the duplications of the ESAT-6 (esx) gene cluster regions, and showing that they are composed of subgroups with distinct evolutionary (and possibly functional) differences.
ESTHER : Gey van Pittius_2006_BMC.Evol.Biol_6_95
PubMedSearch : Gey van Pittius_2006_BMC.Evol.Biol_6_95
PubMedID: 17105670

Title : Detection of maternal uniparental disomy at the two imprinted genes on chromosome 7, GRB10 and PEG1\/MEST, in a Silver-Russell syndrome patient using methylation-specific PCR assays -
Author(s) : Kim Y , Kim SS , Kim G , Park S , Park IS , Yoo HW
Ref : Clin Genet , 67 :267 , 2005
PubMedID: 15691366

Title : Purification and Characterization of Vitellin and Vitellogenin of the Beet Armyworm, Spodoptera exigua (Noctuidae: Lepidoptera) - Moon_2003_J.Asia.Pac.Entomol_6_37
Author(s) : Moon J , Kim Y
Ref : Journal of Asia-Pacific Entomology , 6 :37 , 2003
Abstract : Vitellin (Vn) and vitellogenin (Vg) of the beet armyworm, Spodoptera exigua, were identified and characterized. Both were similar in molecular size (180 kDa) and showed cross-immune reactivity. Vn was purified by ammonium sulfate (25-50%), size-exclusion chromatography (G-100), ion-exchange chromatography (DEAE), and affinity chromatography (concanavalin-A). The purified Vn was used for raising its antibody. The raised Vn-antiserum reacted specifically with Vn and Vg proteins in S. exigua, but had a slight cross-reactivity with P220, probably lipophorin large subunit. The Vn-antiserum did not react to Vns of Bombyx mori, Plutella xylostella, and Drosophila melanogaster. Using this antiserum, Vg biosynthesis could be assessed with adult development of S. exiua. Vg could be detected in the hemolymph and the fat body as early as 5h before adult emergence. Fenoxycarb, a juvenile hormone analog, could induce Vg biosynthesis.
ESTHER : Moon_2003_J.Asia.Pac.Entomol_6_37
PubMedSearch : Moon_2003_J.Asia.Pac.Entomol_6_37
PubMedID:

Title : A Pathogenic Bacterium, Enterococcus faecalis, to the Beet Armyworm, Spodoptera exigua - Youngjin_2002_J.Asia.Pac.Entomol_5_221
Author(s) : Youngjin P , Kim K , Kim Y
Ref : Journal of Asia-Pacific Entomology , 5 :221 , 2002
Abstract : A bacterial disease was found in the beet armyworm, Spodoptera exigua (Hubner). Blackened body of the infected larvae was a typical symptom of the epizootic disease especially at the intersegmental areas. We isolated the bacteria from the hemolymph of the infected 5th instar larvae and identified the isolate as a gram-positive bacterium, Enterococcus faecalis. When the 4th instar larvae were injected with the bacteria, half lethal dose of the bacteria was estimated as 22,593 colony-forming units (cfu) per larva and half lethal time of the bacteria was estimated as 2 days at 107 cfu injection and 6 days at 108 cfu injection. The bacteria were strongly resistant to each 1,000 ppm of ampicillin, kanamycin, and streptomycin. They were, however, relatively susceptible to mixture (1,000 ppm) of different combinations of the three antibiotics.
ESTHER : Youngjin_2002_J.Asia.Pac.Entomol_5_221
PubMedSearch : Youngjin_2002_J.Asia.Pac.Entomol_5_221
PubMedID:

Title : Synthesis and cytotoxicity of some rigid derivatives of methyl 2,5-dihydroxycinnamate - Nam_2002_Arch.Pharm.Res_25_590
Author(s) : Nam NH , Kim Y , You YJ , Hong DH , Kim HM , Ahn BZ
Ref : Arch Pharm Res , 25 :590 , 2002
Abstract : Eight rigid compounds designed as esterase-stable analogues of methyl 2,5-dihydroxycinnamate (1) were synthesized. These derivatives include 2-(2',5'-dihydroxybenzylidene)cyclopentenone (3a), 2-(2',5'-dihydroxybenzylidene)cyclohexanone (3b), 2,6-bis(2',5'-dihydroxybenzylidene)cyclohexanone (4b), 2,6-bis(2',5'-dihydroxybenzylidene)cyclopentenone (4a), (E)-3-(2',5'-dihydroxybenzylidene)pyrrolidin-2-one (5), (E)-5-(2',5'-dihydroxybenzylidene)-1,2-isothiazolidine-1,1-dioxide (6), 4-(2',5'-dihydroxyphenyl)-5H-furan-2-one (7), and 3-(2',5'-dihydroxyphenyl)cyclopent-2-ene-1-one (8). Among the eight compounds, the furanone 7 and cyclopentenone 8 showed the most potent cytotoxicity with IC50 values of 0.39-0.98 microg/mL. Compound 8 was further brominated, phenylated and methylated at the alpha position to give three corresponding analogues, including 2-bromo-3-(2',5'-dihydroxyphenyl)cyclopent-2-ene-1-one (24), 3-(2',5'-dihydroxyphenyl)-2-phenylcyclopent-2-ene-1-one (27), and 3-(2',5'-dihydroxyphenyl)-2-methylcyclopent-2-ene-1-one (28). Among the three, the most enhanced activity was observed with the phenylated compound 27.
ESTHER : Nam_2002_Arch.Pharm.Res_25_590
PubMedSearch : Nam_2002_Arch.Pharm.Res_25_590
PubMedID: 12433188

Title : Cloning and Sequence Analysis of the xylL Gene Responsible for 4CBA-Dihydrodiol Dehydrogenase from Pseudomonas sp. S-47. -
Author(s) : Park DW , Kim Y , Lee SM , Ka JO , Kim CK
Ref : J Microbiol , 38 :275 , 2000
PubMedID:
Gene_locus related to this paper: psepu-nahN , psepu-XYLF

Title : Age Variation in Insecticide Susceptibility and Biochemical Changes of Beet Armyworm, Spodoptera exigua (Hubner) - Kim_1998_J.Asia.Pac.Entomol_1_109
Author(s) : Kim Y , Lee J , Kang S , Han S
Ref : Journal of Asia-Pacific Entomology , 1 :109 , 1998
Abstract : The susceptibility of Spodoptera exigua (Hubner) to bifenthrin and chlorpyrifosmethyl in relation to larval development was investigated. Increased tolerances to these insecticides were associated with increasing larval instars. The insecticide tolerance increased linealy with larval body weights in bifenthrin but did exponentially in chlorpyrifos-methyl. Esterase (EST), acetylcholinesterase (AChE), and glutathione S-transferase(GST) of different larval ages were analyzed to elucidate variation of insecticide susceptibilities according to larval development within a population. Total EST activity increased linearly with body weights though the specific activities were not varied among ages. Both total and specific activity changes of GST, however, surpassed the rates of body weight gains as the larvae developed. AChE activities decreased significantly with larval development. This change of AChE activities was due to the developmental change of its catalytic function. The fifth instar larvae had the lowest catalytic capacity: the highest Km(187.39muM) and the lowest Vmax (0.58 nM/min/mug). Therefore, different insecticide tolerance of S. exigua according to larval ages can be explained by both enhanced detoxification enzymes and altered AchE.
ESTHER : Kim_1998_J.Asia.Pac.Entomol_1_109
PubMedSearch : Kim_1998_J.Asia.Pac.Entomol_1_109
PubMedID:

Title : Isolation and analysis of metA, a methionine biosynthetic gene encoding homoserine acetyltransferase in corynebacterium glutamicum - Park_1998_Mol.Cells_8_286
Author(s) : Park SD , Lee JY , Kim Y , Kim JH , Lee HS
Ref : Mol Cells , 8 :286 , 1998
Abstract : The metA gene encoding homoserine acetyltransferase, the first enzyme of the methionine biosynthetic pathway, was isolated from a pMT1-based corynebacterium glutamicum gene library via complementation of an Escherichia coli metA mutant. A DNA-sequence analysis of the cloned DNA is identified an open-reading frame of 1,137 bp which encodes a protein with the molecular weight of 41,380 comprising 379 amino acids. The putative protein product showed good amino acid-sequence homology to its counterpart in other organisms. The internal fragment of the cloned DNA was successfully used to disrupt chromosomal metA, demonstrating the identity of the cloned gene. The C. glutamicum metA mutant lost the ability to grow on glucose minimal medium supplemented with homoserine. However, the mutant could grow on a minimal medium supplemented with cystathionine, demonstrating that C. glutamicum uses the cystathionine route to synthesize methionine. Introduction of a plasmid carrying cloned metA into C. glutamicum resulted in a 10-fold increase in enzyme activities and expression of a protein product of M(r) 41,000, which agrees with the sequence data and is similar in size to those of other homoserine acetyltransferases. Unlike E. coli whose metA product uses succinyl coenzyme A as a substrate, the cloned metA gene produced homoserine acetyltransferase which uses only acetyl coenzyme A as the acyl donor.
ESTHER : Park_1998_Mol.Cells_8_286
PubMedSearch : Park_1998_Mol.Cells_8_286
PubMedID: 9666465
Gene_locus related to this paper: corgl-metx

Title : Genetic structures of the genes encoding 2,3-dihydroxybiphenyl 1,2-dioxygenase and 2-hydroxy-6-oxo-6-phenylhexa-2,4-dienoic acid hydrolase from biphenyl- and 4-chlorobiphenyl-degrading Pseudomonas sp. strain DJ-12 - Kim_1996_Appl.Environ.Microbiol_62_262
Author(s) : Kim E , Kim Y , Kim CK
Ref : Applied Environmental Microbiology , 62 :262 , 1996
Abstract : The pcbC and pcbD genes of Pseudomonas sp. strain DJ-12, a natural isolate degrading biphenyl and 4-chlorobiphenyl, encode the 2,3-dihydroxybiphenyl 1,2-dioxygenase and 2-hydroxy-6-oxo-6-phenylhexa-2,4-dienoic acid hydrolase, respectively. The two genes were sequenced and appear to be present in the order pcbD-pcbC as an operon.
ESTHER : Kim_1996_Appl.Environ.Microbiol_62_262
PubMedSearch : Kim_1996_Appl.Environ.Microbiol_62_262
PubMedID: 8572703
Gene_locus related to this paper: psesp-pcbD

Title : Combined pyridostigmine-thyrotrophin-releasing hormone test for the evaluation of hypothalamic somatostatinergic activity in healthy normal men - Yang_1995_Eur.J.Endocrinol_133_457
Author(s) : Yang I , Woo J , Kim S , Kim J , Kim Y , Choi Y
Ref : European Journal of Endocrinology , 133 :457 , 1995
Abstract : Pyridostigmine (PST), a cholinesterase inhibitor, induces a clear growth hormone (GH) release in man by suppression of hypothalamic somatostatin (SRIH). Somatostatin suppresses thyrotrophin (TSH) release in rats and men. Earlier studies showed that the thryotrophin-releasing hormone (TRH)-induced TSH response was not altered by 60-120 mg of PST. We studied whether a larger dose (180 mg) of PST can increase the TSH response to TRH. Six healthy young men were studied with the following six tests: (Test 1) 200 micrograms of TRH i.v.; (Test 2) 180 mg of PST po; (Test 3) three different doses of PST (60, 120, 180 mg) + TRH; (Test 4) 100 micrograms of octreotide (SMS) i.v.; (Test 5) SMS + TRH; (Test 6) PST + SMS + TRH. A large dose of PST (180 mg) significantly augmented GH, TSH and prolactin responses to TRH, while smaller doses of PST (60 and 120 mg) did not significantly increase the responses of GH and TSH. While the increased TRH-induced prolactin response by PST was not suppressed by SMS, the increased responses of GH and TSH were suppressed remarkably by SMS. Most of the subjects noticed a mild to moderate abdominal pain, nausea and muscular fasciculation after the administration of a large dose of PST administration. These data suggest that suppression of hypothalamic SRIH secretion by 180 mg of PST can augment the TSH response to TRH. However, the considerable side effects should be minimized before clinical application of the combined PST-TRH test.
ESTHER : Yang_1995_Eur.J.Endocrinol_133_457
PubMedSearch : Yang_1995_Eur.J.Endocrinol_133_457
PubMedID: 7581970

Title : Role of elevated alpha-fetoprotein in prenatal diagnosis of junctional epidermolysis bullosa and pyloric atresia - Nesin_1994_Am.J.Perinatol_11_286
Author(s) : Nesin M , Seymour C , Kim Y
Ref : American Journal of Perinatology , 11 :286 , 1994
Abstract : A case of junctional epidermolysis bullosa, Herlitz variant, and pyloric atresia in a 33 weeks' gestation male infant is reported. The second trimester amniotic fluid exhibited elevated concentrations of alpha-fetoprotein and presence of acetylcholinesterase; however, the fetus appeared anatomically normal by multiple high-resolution ultrasound examinations. This case, as well as others previously reported, shows that serious fetal skin disease should be considered as part of the differential diagnosis whenever persistent elevation of alpha-fetoprotein and presence of acetylcholinesterase are found in the amniotic fluid of a fetus that appears anatomically normal by ultrasound. Prenatal diagnosis may be established by fetal skin biopsy and extensive prenatal counseling should be offered to families on the basis of the prognosis and severity of this disease.
ESTHER : Nesin_1994_Am.J.Perinatol_11_286
PubMedSearch : Nesin_1994_Am.J.Perinatol_11_286
PubMedID: 7524513