Lee Y

References (44)

Title : Changes in dementia treatment patterns associated with changes in the National Policy in South Korea among patients with newly diagnosed Alzheimer's disease between 2011 and 2017: results from the multicenter, retrospective CAPTAIN study - Kim_2024_BMC.Public.Health_24_168
Author(s) : Kim YJ , So KY , Lee HM , Hahn C , Song SH , Lee YS , Kim SW , Park HC , Ryu J , Lee JS , Kang MJ , Kim J , Lee Y , Lee JH
Ref : BMC Public Health , 24 :168 , 2024
Abstract : BACKGROUND: The South Korean government has been actively involved in plans to combat dementia, implementing a series of national strategies and plans since 2008. In July 2014, eligibility for mandatory long-term care insurance (LTCI) was extended to people with dementia enabling access to appropriate long-term care including the cognitive function training program and home nursing service. This study aimed to investigate changes in treatment patterns for Alzheimer's disease (AD) between July 2011 and June 2017 which spanned the 2014 revision. METHODS: This multicenter, retrospective, observational study of patients with newly diagnosed AD analyzed electronic medical records from 17 general hospitals across South Korea. Based on their time of AD diagnosis, subjects were categorized into Cohort 1 (1 July 2011 to 30 June 2014) and Cohort 2 (1 July 2014 to 30 June 2017). RESULTS: Subjects (N=3,997) divided into Cohorts 1 (n=1,998) and 2 (n=1,999), were mostly female (66.4%) with a mean age of 84.4 years. Cohort 1 subjects were significantly older (P<0.0001) and had a lower number of comorbidities (P=0.002) compared with Cohort 2. Mean Mini-Mental State Examination (MMSE) scores in Cohorts 1 and 2 at the time of AD diagnosis or start of initial treatment were 16.9 and 17.1, respectively (P=0.2790). At 1 year, mean MMSE scores in Cohorts 1 and 2 increased to 17.9 and 17.4, respectively (P=0.1524). Donepezil was the most frequently administered medication overall (75.0%), with comparable rates between cohorts. Rates of medication persistence were <=98% for acetylcholinesterase inhibitor or memantine therapy. Discontinuation and switch treatment rates were significantly lower (49.7% vs. 58.0%; P<0.0001), and mean duration of initial treatment significantly longer, in Cohort 2 vs. 1 (349.3 vs. 300.2 days; P<0.0001). CONCLUSIONS: Comparison of cohorts before and after revision of the national LTCI system for dementia patients found no significant difference in mean MMSE scores at the time of AD diagnosis or start of initial treatment. The reduction in the proportion of patients who discontinued or changed their initial treatment, and the significant increase in mean duration of treatment, were observed following revision of the LTCI policy which enabled increased patient access to long-term care.
ESTHER : Kim_2024_BMC.Public.Health_24_168
PubMedSearch : Kim_2024_BMC.Public.Health_24_168
PubMedID: 38216922

Title : Genome-wide association study of metabolic dysfunction-associated fatty liver disease in a Korean population - Lee_2024_Sci.Rep_14_9753
Author(s) : Lee Y , Cho EJ , Choe EK , Kwak MS , Yang JI , Oh SW , Yim JY , Chung GE
Ref : Sci Rep , 14 :9753 , 2024
Abstract : Genome-wide association studies have identified several genetic variants associated with nonalcoholic fatty liver disease. To emphasize metabolic abnormalities in fatty liver, metabolic (dysfunction)-associated fatty liver disease (MAFLD) has been introduced; thus, we aimed to investigate single-nucleotide polymorphisms related to MAFLD and its subtypes. A genome-wide association study was performed to identify genetic factors related to MAFLD. We used a Korean population-based sample of 2282 subjects with MAFLD and a control group of 4669. We replicated the results in a validation sample which included 639 patients with MAFLD and 1578 controls. Additionally, we categorized participants into three groups, no MAFLD, metabolic dysfunction (MD)-MAFLD, and overweight/obese-MAFLD. After adjusting for age, sex, and principal component scores, rs738409 [risk allele G] and rs3810622 [risk allele T], located in the PNPLA3 gene, showed significant associations with MAFLD (P-values, discovery set=1.60x10(-15) and 4.84x10(-10); odds ratios, 1.365 and 1.284, validation set=1.39x10(-4), and 7.15x10(-4), odds ratios, 1.299 and 1.264, respectively). An additional SNP rs59148799 [risk allele G] located in the GATAD2A gene showed a significant association with MAFLD (P-values, discovery set=2.08x10(-8) and validation set=0.034, odds ratios, 1.387 and 1.250). rs738409 was significantly associated with MAFLD subtypes ([overweight/obese-MAFLD; odds ratio (95% confidence interval), P-values, 1.515 (1.351-1.700), 1.43x10(-12) and MD-MAFLD: 1.300 (1.191-1.416), 2.90x10(-9)]. There was a significant relationship between rs3810622 and overweight/obese-MAFLD and MD-MAFLD [odds ratios (95% confidence interval), P-values, 1.418 (1.258, 1.600), 1.21x10(-8) and 1.225 (1.122, 1.340), 7.06x10(-6), respectively]; the statistical significance remained in the validation set. PNPLA3 was significantly associated with MAFLD and MAFLD subtypes in the Korean population. These results indicate that genetic factors play an important role in the pathogenesis of MAFLD.
ESTHER : Lee_2024_Sci.Rep_14_9753
PubMedSearch : Lee_2024_Sci.Rep_14_9753
PubMedID: 38679617

Title : GABAergic-like dopamine synapses in the brain - Kim_2023_Cell.Rep_42_113239
Author(s) : Kim HJ , Hwang B , Reva M , Lee J , Lee BE , Lee Y , Cho EJ , Jeong M , Lee SE , Myung K , Baik JH , Park JH , Kim JI
Ref : Cell Rep , 42 :113239 , 2023
Abstract : Dopamine synapses play a crucial role in volitional movement and reward-related behaviors, while dysfunction of dopamine synapses causes various psychiatric and neurological disorders. Despite this significance, the true biological nature of dopamine synapses remains poorly understood. Here, we show that dopamine transmission is strongly correlated with GABA co-transmission across the brain and dopamine synapses are structured and function like GABAergic synapses with marked regional heterogeneity. In addition, GABAergic-like dopamine synapses are clustered on the dendrites, and GABA transmission at dopamine synapses has distinct physiological properties. Interestingly, the knockdown of neuroligin-2, a key postsynaptic protein at GABAergic synapses, unexpectedly does not weaken GABA co-transmission but instead facilitates it at dopamine synapses in the striatal neurons. More importantly, the attenuation of GABA co-transmission precedes deficits in dopaminergic transmission in animal models of Parkinson's disease. Our findings reveal the spatial and functional nature of GABAergic-like dopamine synapses in health and disease.
ESTHER : Kim_2023_Cell.Rep_42_113239
PubMedSearch : Kim_2023_Cell.Rep_42_113239
PubMedID: 37819757

Title : Gemigliptin, a DPP4 inhibitor, ameliorates nonalcoholic steatohepatitis through AMP-activated protein kinase-independent and ULK1-mediated autophagy - Song_2023_Mol.Metab__101806
Author(s) : Song Y , Yang H , Kim J , Lee Y , Kim SH , Do IG , Park CY
Ref : Mol Metab , :101806 , 2023
Abstract : OBJECTIVE: Abnormal autophagic function and activated inflammasomes are typical features in the liver of patients with non-alcoholic steatohepatitis (NASH). Here, we explored whether gemigliptin, a dipeptidyl peptidase 4 (DPP4) inhibitor for treatment of type 2 diabetes, can induce autophagy and regulate inflammasome activation as a potential NASH treatment independent of its anti-diabetic effect. METHODS: Expression analysis was performed using human liver samples obtained from 18 subjects who underwent hepatectomy. We explored the function and mechanism of gemigliptin using a methionine- and choline-deficient diet (MCD)-induced NASH mouse model and HepG2 cells cultured in MCD-mimicking medium. RESULTS: Autophagy was suppressed by marked decreases in the expression of ULK1 and LC3II/LC3I ratio in human NAFLD/NASH patients, a NASH mouse model, and HepG2 cells cultured with MCD-mimicking media. Surprisingly, we found that the expression of p-AMPK decreased in liver tissues from patients with steatosis but was restored in NASH patients. The expression of p-AMPK in the NASH mouse model was similar to that of the control group. Hence, these results indicate that autophagy was reduced in NASH via an AMPK-independent pathway. However, gemigliptin treatment attenuated lipid accumulation, inflammation, and fibrosis in the liver of MCD diet-fed mice with restoration of ULK1 expression and autophagy induction. In vitro, gemigliptin alleviated inflammasome activation through induction of ULK1-dependent autophagy. Furthermore, gemigliptin treatment upregulated ULK1 expression and activated AMPK even after siRNA-mediated knockdown of AMPKalpha1/2 and ULK1, respectively. CONCLUSIONS: Collectively, these results suggest that gemigliptin ameliorated NASH via AMPK-independent, ULK1-mediated effects on autophagy.
ESTHER : Song_2023_Mol.Metab__101806
PubMedSearch : Song_2023_Mol.Metab__101806
PubMedID: 37739179

Title : Solvent-free enzymatic synthesis and evaluation of vanillyl propionate as an effective and biocompatible preservative - Lee_2023_Bioprocess.Biosyst.Eng__
Author(s) : Lee Y , Lee S , Kim S , Lee D , Won K
Ref : Bioprocess Biosyst Eng , : , 2023
Abstract : Preservatives are chemicals added to protect products against microbial spoilage, and thus are indispensable for pharmaceuticals, cosmetics, and foods. Due to growing concerns about human health and environments in conventional chemical preservatives, many companies have been seeking safe and effective alternatives that can be produced through environment-friendly processes. In this work, in order to develop effective and safe preservatives from plants, we attempt solvent-free lipase-catalyzed transesterification of vanillyl alcohol with ethyl propionate for the first time. The reaction product, vanillyl propionate was efficiently obtained in a high yield. Unlike vanillyl alcohol and ethyl propionate, vanillyl propionate showed antimicrobial activity. The minimal inhibitory concentration test showed that it exhibited high and broad antimicrobial activity against all the tested microorganisms (Gram-negative and Gram-positive bacteria, yeasts, and molds), which was overall comparable to that of propyl paraben, which is one of the most effective preservatives. It was also found to have even higher antioxidant capacity and biocompatibility with human cells than propyl paraben. Vanillyl propionate, which is a plant-based preservative produced through a green bioprocess, is expected to be successfully applied to various industries thanks to its high antimicrobial and antioxidant effect, and high biocompatibility.
ESTHER : Lee_2023_Bioprocess.Biosyst.Eng__
PubMedSearch : Lee_2023_Bioprocess.Biosyst.Eng__
PubMedID: 37682355

Title : Tsaokoic Acid: A New Bicyclic Nonene from the Fruits of Amomum tsao-ko with Acetylcholinesterase Inhibitory Activity - Kim_2023_Molecules_28_
Author(s) : Kim H , Lee H , Jung HJ , Noh SG , Youn I , Kwak H , Lee Y , Nam SJ , Kang S , Chung HY , Seo EK
Ref : Molecules , 28 : , 2023
Abstract : A new bicyclic nonene, tsaokoic acid (1), was isolated from the fruits of Amomum tsao-ko, together with three known compounds (2-4). The structure of 1 was elucidated by analyzing spectroscopic data including 1D and 2D NMR spectra and compounds 2-4 were identified as tsaokoin, vanillin, and tsaokoarylone, respectively, by comparing their NMR spectra with previously reported data. Compounds 1-4 showed possible inhibitory activity against acetylcholinesterase (AChE) in silico molecular docking simulations. They were submitted to in vitro assay system and exhibited moderate inhibitory activity with IC(50) values of 32.78, 41.70, 39.25, and 31.13 microM, respectively.
ESTHER : Kim_2023_Molecules_28_
PubMedSearch : Kim_2023_Molecules_28_
PubMedID: 36985573

Title : Elucidating the biodegradation pathway and catabolic genes of benzophenone-3 in Rhodococcus sp. S2-17 - Baek_2022_Environ.Pollut_299_118890
Author(s) : Baek JH , Kim KH , Lee Y , Jeong SE , Jin HM , Jia B , Jeon CO
Ref : Environ Pollut , 299 :118890 , 2022
Abstract : A new bacterium, Rhodococcus sp. S2-17, which could completely degrade an emerging organic pollutant, benzophenone-3 (BP-3), was isolated from contaminated sediment through an enrichment procedure, and its BP-3 catabolic pathway and genes were identified through metabolic intermediate and transcriptomic analyses and biochemical and genetic studies. Metabolic intermediate analysis suggested that strain S2-17 may degrade BP-3 using a catabolic pathway progressing via the intermediates BP-1, 2,4,5-trihydroxy-benzophenone, 3-hydroxy-4-benzoyl-2,4-hexadienedioic acid, 4-benzoyl-3-oxoadipic acid, 3-oxoadipic acid, and benzoic acid. A putative BP-3 catabolic gene cluster including cytochrome P450, flavin-dependent oxidoreductase, hydroxyquinol 1,2-dioxygenase, maleylacetate reductase, and alpha/beta hydrolase genes was identified through genomic and transcriptomic analyses. Genes encoding the cytochrome P450 complex that demethylates BP-3 to BP-1 were functionally verified through protein expression, and the functions of the other genes were also verified through knockout mutant construction and intermediate analysis. This study suggested that strain S2-17 might have acquired the ability to catabolize BP-3 by recruiting the cytochrome P450 complex and alpha/beta hydrolase, which hydrolyzes 4-benzoyl-3-oxoadipic acid to benzoic acid and 3-oxoadipic acid, genes, providing insights into the recruitment of genes of for the catabolism of emerging organic pollutants.
ESTHER : Baek_2022_Environ.Pollut_299_118890
PubMedSearch : Baek_2022_Environ.Pollut_299_118890
PubMedID: 35085657
Gene_locus related to this paper: 9noca-a0a2s2bnz9

Title : Sugammadex in Colorectal Surgery: A Systematic Review and Meta-analysis - Chen_2021_J.Surg.Res_270_221
Author(s) : Chen AT , Patel A , McKechnie T , Lee Y , Doumouras AG , Hong D , Eskicioglu C
Ref : J Surg Res , 270 :221 , 2021
Abstract : BACKGROUND: Traditionally, reversal of neuromuscular blocking agents following the completion of surgery was achieved with cholinesterase inhibitors. Recently, sugammadex has been increasingly relied upon. Sugammadex is a gamma-cyclodextrin molecule that rapidly reverses steroidal neuromuscular blocking drugs. Its use following colorectal surgery has become more common, and while the rapidity of reversal is undoubtedly improved, whether sugammadex impacts clinical postoperative outcomes is unknown. This systematic review and meta-analysis aims to compare postoperative outcomes in patients receiving sugammadex to those receiving a control during colorectal surgery. METHODS: Medline, Embase, and CENTRAL were systematically searched. Articles were included if they compared sugammadex with a control (e.g., neostigmine, pyridostigmine, placebo) in patients undergoing colorectal surgery in terms of total hospital length of stay and frequency of postoperative adverse respiratory events. Pairwise meta-analyses using inverse variance random effects was performed. RESULTS: From 269 citations, five studies with 535 patients receiving sugammadex (45.8% female; mean age: 64.4) and 569 patients receiving a control (45.0% female; mean age: 64.3) were included. There was no significant difference in length of stay between the two groups (MD -0.01, 95% CI -0.27 to 0.25, P = 0.95). The risk of adverse respiratory events postoperatively was similar between the two groups (RR 1.33, 95% CI 0.81-2.19, P = 0.25). CONCLUSION: There are no current data to suggest an improvement in postoperative outcomes with the use of sugammadex in patients undergoing colorectal surgery. This study is limited by the number of included studies. Further prospective studies comparing sugammadex and a control in colorectal surgery is required.
ESTHER : Chen_2021_J.Surg.Res_270_221
PubMedSearch : Chen_2021_J.Surg.Res_270_221
PubMedID: 34710702

Title : The disassembly of lipid droplets in Chlamydomonas - Li-Beisson_2021_New.Phytol__
Author(s) : Li-Beisson Y , Kong F , Wang P , Lee Y , Kang BH
Ref : New Phytol , : , 2021
Abstract : Lipid droplets (LDs) are ubiquitous and specialized organelle in eukaryotic cells. Consisting of a triacylglycerol core surrounded by a monolayer of membrane lipids, LDs are decorated with proteins and have myriad functions, from carbon/energy storage to membrane lipid remodeling and signal transduction. The biogenesis and turnover of LDs are therefore tightly coordinated with cellular metabolic needs in a fluctuating environment. LD turnover requires remodeling of the protein coat, lipolysis, autophagy and fatty acid beta-oxidation. Several key components of these processes have been identified in Chlamydomonas (Chlamydomonas reinhardtii), including the major lipid droplet protein, a CXC-domain containing regulatory protein, the phosphatidylethanolamine-binding DTH1 (DELAYED IN TAG HYDROLYSIS1), two lipases, and two enzymes involved in fatty acid beta-oxidation. Here, we review LD turnover and discuss its physiological significance in Chlamydomonas, a major model green microalga in research on algal oil.
ESTHER : Li-Beisson_2021_New.Phytol__
PubMedSearch : Li-Beisson_2021_New.Phytol__
PubMedID: 34028037

Title : Clinical Application of Whole Exome Sequencing to Identify Rare but Remediable Neurologic Disorders - Kim_2020_J.Clin.Med_9_3724
Author(s) : Kim MJ , Yum MS , Seo GH , Lee Y , Jang HN , Ko TS , Lee BH
Ref : J Clin Med , 9 : , 2020
Abstract : BACKGROUND: The aim of this study was to describe the application of whole exome sequencing (WES) in the accurate genetic diagnosis and personalized treatment of extremely rare neurogenetic disorders. METHODS: From 2017 to 2019, children with neurodevelopmental symptoms were evaluated using WES in the pediatric neurology clinic and medical genetics center. The clinical presentation, laboratory findings including the genetic results from WES, and diagnosis-based treatment and outcomes of the four patients are discussed. RESULTS: A total of 376 children with neurodevelopmental symptom were evaluated by WES, and four patients (1.1%) were diagnosed with treatable neurologic disorders. Patient 1 (Pt 1) showed global muscle hypotonia, dysmorphic facial features, and multiple anomalies beginning in the perinatal period. Pt 1 was diagnosed with congenital myasthenic syndrome 22 of PREPL deficiency. Pt 2 presented with hypotonia and developmental arrest and was diagnosed with autosomal recessive dopa-responsive dystonia due to TH deficiency. Pt 3, who suffered from intractable epilepsy and progressive cognitive decline, was diagnosed with epileptic encephalopathy 47 with a heterozygous FGF12 mutation. Pt 4 presented with motor delay and episodic ataxia and was diagnosed with episodic ataxia type II (heterozygous CACNA1A mutation). The patients' major neurologic symptoms were remarkably relieved with pyridostigmine (Pt 1), levodopa (Pt 2), sodium channel blocker (Pt 3), and acetazolamide (Pt 4), and most patients regained developmental milestones in the follow-up period (0.4 to 3 years). CONCLUSIONS: The early application of WES helps in the identification of extremely rare genetic diseases, for which effective treatment modalities exist. Ultimately, WES resulted in optimal clinical outcomes of affected patients.
ESTHER : Kim_2020_J.Clin.Med_9_3724
PubMedSearch : Kim_2020_J.Clin.Med_9_3724
PubMedID: 33233562
Gene_locus related to this paper: human-PREPL

Title : Dual-Purpose Inoculants and Their Effects on Corn Silage - Paradhipta_2020_Microorganisms_8_
Author(s) : Paradhipta DHV , Lee SS , Kang B , Joo YH , Lee HJ , Lee Y , Kim J , Kim SC
Ref : Microorganisms , 8 : , 2020
Abstract : This study was conducted to screen dual-purpose lactic acid bacteria (LAB) from uncontrolled farm-scale silage, and then we confirmed their effects on corn silage. The LAB were isolated from eight farm-scale corn silages, and then we screened the antifungal activity against Fusarium graminearum and the carboxylesterase activity using spectrophotometer with p-nitrophenyl octanoate as substrate and McIlvane solution as buffer. From a total of 25 isolates, 5M2 and 6M1 isolates were selected as silage inoculants because presented both activities of antifungal and carboxylesterase. According 16S rRNA gene sequencing method, 5M2 isolate had 100.0% similarity with Lactobacillus brevis, and 6M1 isolate had 99.7% similarity with L. buchneri. Corn forage was ensiled in bale silo (500 kg) for 72 d without inoculant (CON) or with mixture of selected isolates at 1:1 ratio (INO). The INO silage had higher nutrient digestibility in the rumen than CON silage. Acetate was higher and yeasts were lower in INO silage than in CON silage on the day of silo opening. In all days of aerobic exposure, yeasts were lower in INO silage than CON silage. The present study concluded that Lactobacillus brevis 5M2 and L. buchneri 6M1 confirmed antifungal and carboxylesterase activities on farm-scale corn silage.
ESTHER : Paradhipta_2020_Microorganisms_8_
PubMedSearch : Paradhipta_2020_Microorganisms_8_
PubMedID: 32443787

Title : Lipase mimetic cyclodextrins - Lee_2020_Chem.Sci_12_1090
Author(s) : Lee Y , Devaraj NK
Ref : Chem Sci , 12 :1090 , 2020
Abstract : Glycerophospholipids (GPLs) perform numerous essential functions in biology, including forming key structural components of cellular membranes and acting as secondary messengers in signaling pathways. Developing biomimetic molecular devices that can detect specific GPLs would enable modulation of GPL-related processes. However, the compositional diversity of GPLs, combined with their hydrophobic nature, has made it challenging to develop synthetic scaffolds that can react with specific lipid species. By taking advantage of the host-guest chemistry of cyclodextrins, we have engineered a molecular device that can selectively hydrolyze GPLs under physiologically relevant conditions. A chemically modified alpha-cyclodextrin bearing amine functional groups was shown to hydrolyze lyso-GPLs, generating free fatty acids. Lyso-GPLs are preferentially hydrolyzed when part of a mixture of GPL lipid species, and reaction efficiency was dependent on lyso-GPL chemical structure. These findings lay the groundwork for the development of molecular devices capable of specifically manipulating lipid-related processes in living systems.
ESTHER : Lee_2020_Chem.Sci_12_1090
PubMedSearch : Lee_2020_Chem.Sci_12_1090
PubMedID: 34163875

Title : Characterization of an acetyl xylan esterase from the marine bacterium Ochrovirga pacifica and its synergism with xylanase on beechwood xylan - Hettiarachchi_2019_Microb.Cell.Fact_18_122
Author(s) : Hettiarachchi SA , Kwon YK , Lee Y , Jo E , Eom TY , Kang YH , Kang DH , De Zoysa M , Marasinghe SD , Oh C
Ref : Microb Cell Fact , 18 :122 , 2019
Abstract : BACKGROUND: Acetyl xylan esterase plays an important role in the complete enzymatic hydrolysis of lignocellulosic materials. It hydrolyzes the ester linkages of acetic acid in xylan and supports and enhances the activity of xylanase. This study was conducted to identify and overexpress the acetyl xylan esterase (AXE) gene revealed by the genomic sequencing of the marine bacterium Ochrovirga pacifica. RESULTS: The AXE gene has an 864-bp open reading frame that encodes 287 aa and consists of an AXE domain from aa 60 to 274. Gene was cloned to pET-16b vector and expressed the recombinant AXE (rAXE) in Escherichia coli BL21 (DE3). The predicted molecular mass was 31.75 kDa. The maximum specific activity (40.08 U/mg) was recorded at the optimal temperature and pH which were 50 degrees C and pH 8.0, respectively. The thermal stability assay showed that AXE maintains its residual activity almost constantly throughout and after incubation at 45 degrees C for 120 min. The synergism of AXE with xylanase on beechwood xylan, increased the relative activity 1.41-fold. CONCLUSION: Resulted higher relative activity of rAXE with commercially available xylanase on beechwood xylan showed its potential for the use of rAXE in industrial purposes as a de-esterification enzyme to hydrolyze xylan and hemicellulose-like complex substrates.
ESTHER : Hettiarachchi_2019_Microb.Cell.Fact_18_122
PubMedSearch : Hettiarachchi_2019_Microb.Cell.Fact_18_122
PubMedID: 31286972
Gene_locus related to this paper: 9flao-a0a481pb18

Title : Pediatric reference intervals of liver and renal function tests from birth to adolescence in Chinese children as performed on the Olympus AU5400 - Liu_2019_Clin.Chim.Acta_490_142
Author(s) : Liu J , Dai Y , Lee Y , Yuan E , Wang Q , Wang L , Su Y
Ref : Clinica Chimica Acta , 490 :142 , 2019
Abstract : BACKGROUND: The growth and development of children and adolescents influence values of liver and renal function tests. The purpose of this study was to determine age- and gender-specific reference intervals for liver and renal function tests in apparently healthy Chinese children and adolescents. METHODS: A total of 63,086 apparently healthy children and adolescents (0-15 y) were chosen as reference individuals in this study. The 15 biochemical analytes relating to liver and renal function were measured using an Olympus AU5400 analyzer. Reference intervals were partitioned according to age and/or gender subgroups using the Harris and Boyd's method and established using non-parametric methods. RESULTS: Our results showed that all analytes except for cholinesterase (ChE) and alpha1-microglobulin (alpha1-MG) required partitioning by age. Gender partitions were also required for alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), creatinine (Cre), and uric acid (UA). Age- and gender-appropriate reference intervals for liver and renal function tests were established for apparently healthy Chinese children and adolescents. CONCLUSIONS: When establishing pediatric reference intervals, partitioning by age and/or gender is essential. Those reference intervals can be adopted in other clinical laboratories after appropriate validation.
ESTHER : Liu_2019_Clin.Chim.Acta_490_142
PubMedSearch : Liu_2019_Clin.Chim.Acta_490_142
PubMedID: 30611730

Title : Makes caterpillars floppy-like effector-containing MARTX toxins require host ADP-ribosylation factor (ARF) proteins for systemic pathogenicity - Lee_2019_Proc.Natl.Acad.Sci.U.S.A_116_18031
Author(s) : Lee Y , Kim BS , Choi S , Lee EY , Park S , Hwang J , Kwon Y , Hyun J , Lee C , Kim JF , Eom SH , Kim MH
Ref : Proc Natl Acad Sci U S A , 116 :18031 , 2019
Abstract : Upon invading target cells, multifunctional autoprocessing repeats-in-toxin (MARTX) toxins secreted by bacterial pathogens release their disease-related modularly structured effector domains. However, it is unclear how a diverse repertoire of effector domains within these toxins are processed and activated. Here, we report that Makes caterpillars floppy-like effector (MCF)-containing MARTX toxins require ubiquitous ADP-ribosylation factor (ARF) proteins for processing and activation of intermediate effector modules, which localize in different subcellular compartments following limited processing of holo effector modules by the internal cysteine protease. Effector domains structured tandemly with MCF in intermediate modules become disengaged and fully activated by MCF, which aggressively interacts with ARF proteins present at the same location as intermediate modules and is converted allosterically into a catalytically competent protease. MCF-mediated effector processing leads ultimately to severe virulence in mice via an MCF-mediated ARF switching mechanism across subcellular compartments. This work provides insight into how bacteria take advantage of host systems to induce systemic pathogenicity.
ESTHER : Lee_2019_Proc.Natl.Acad.Sci.U.S.A_116_18031
PubMedSearch : Lee_2019_Proc.Natl.Acad.Sci.U.S.A_116_18031
PubMedID: 31427506
Gene_locus related to this paper: vibvy-q7mdk6

Title : Hypoxia-Induced Neuroinflammation and Learning-Memory Impairments in Adult Zebrafish Are Suppressed by Glucosamine - Lee_2018_Mol.Neurobiol_55_8738
Author(s) : Lee Y , Lee S , Park JW , Hwang JS , Kim SM , Lyoo IK , Lee CJ , Han IO
Ref : Molecular Neurobiology , 55 :8738 , 2018
Abstract : This study investigated changes in neuroinflammation and cognitive function in adult zebrafish exposed to acute hypoxia and protective effects of glucosamine (GlcN) against hypoxia-induced brain damage. The survival rate of zebrafish following exposure to hypoxia was improved by GlcN pretreatment. Moreover, hypoxia-induced upregulation of neuroglobin, NOS2alpha, glial fibrillary acidic protein, and S100beta in zebrafish was suppressed by GlcN. Hypoxia stimulated cell proliferation in the telencephalic ventral domain and in cerebellum subregions. GlcN decreased the number of bromodeoxyuridine (BrdU)-positive cells in the telencephalon region, but not in cerebellum regions. Transient motor neuron defects, assessed by measuring the locomotor and exploratory activity of zebrafish exposed to hypoxia recovered quickly. GlcN did not affect hypoxia-induced motor activity changes. In passive avoidance tests, hypoxia impaired learning and memory ability, deficits that were rescued by GlcN. A learning stimulus increased the nuclear translocation of phosphorylated cAMP response element binding protein (p-CREB), an effect that was greatly inhibited by hypoxia. GlcN restored nuclear p-CREB after a learning trial in hypoxia-exposed zebrafish. The neurotransmitters, gamma-aminobutyric acid and glutamate, were increased after hypoxia in the zebrafish brain, and GlcN further increased their levels. In contrast, acetylcholine levels were reduced by hypoxia and restored by GlcN. Acetylcholinesterase inhibitor physostigmine partially reversed the impaired learning and memory of hypoxic zebrafish. This study represents the first examination of the molecular mechanisms underlying hypoxia-induced memory and learning defects in a zebrafish model. Our results further suggest that GlcN-associated hexosamine metabolic pathway could be an important therapeutic target for hypoxic brain damage.
ESTHER : Lee_2018_Mol.Neurobiol_55_8738
PubMedSearch : Lee_2018_Mol.Neurobiol_55_8738
PubMedID: 29589284
Gene_locus related to this paper: mouse-hyes

Title : Usefulness of serum lactate as a predictor of successful discontinuation of continuous atropine infusion in patients with severe acute organophosphate poisoning - Kwon_2018_Clin.Exp.Emerg.Med_5_177
Author(s) : Kwon HC , Cha YS , An GJ , Lee Y , Kim H
Ref : Clin Exp Emerg Med , 5 :177 , 2018
Abstract : OBJECTIVE: In severe organophosphate (OP) poisoning, administration of atropine via continuous intravenous infusion is typically considered. To date, there have been no studies on predicting successful atropine discontinuation through plasma cholinesterase (PChE) and serum lactate levels, which are monitored during critical care in severe acute OP poisoning. Therefore, we retrospectively evaluated the usefulness of serum lactate and PChE as predictors of successful discontinuation of atropine infusion. METHODS: This retrospective observational study was performed on consecutive adult patients treated for severe acute OP poisoning between March 2011 and December 2016. We sequentially evaluated serum lactate and PChE levels on emergency department arrival and before a discontinuation trial of atropine infusion. Discontinuation of atropine intravenous infusion was attempted in patients after clearance of respiratory secretions and cessation of bronchoconstriction. Discontinuation of atropine infusion attempts were divided into successful and failed trials. RESULTS: A total of 95 trials were conducted in 62 patients. Serum lactate levels before trials were significantly different between patients with successful and failed trials. The area under the curve for prediction of successful atropine discontinuation using serum lactate levels before trial discontinuation were 0.742 (95% confidence interval, 0.638 to 0.846). PChE level was not significantly different between two groups. CONCLUSION: Serum lactate levels before the discontinuation trial of atropine infusion served to predict successful discontinuation in severe acute OP poisoning.
ESTHER : Kwon_2018_Clin.Exp.Emerg.Med_5_177
PubMedSearch : Kwon_2018_Clin.Exp.Emerg.Med_5_177
PubMedID: 30269453

Title : Relative Risk and Clinical Severity Assessment in Patients with Non-Oral Route Organophosphate Poisoning Compared with Oral Route Poisoning - Jung_2018_Yonsei.Med.J_59_982
Author(s) : Jung WJ , Yu MH , Lee Y , Kim H , Cha YS , Park KH
Ref : Yonsei Med J , 59 :982 , 2018
Abstract : PURPOSE: Organophosphates, commonly used in agricultural pesticides, pose high risks and incidences of poisoning. In the present study, we investigated the relative risk and clinical severity, including laboratory results, of non-oral route poisoning (NORP) patients, compared to oral route poisoning (ORP) patients. MATERIALS AND METHODS: A single institutional toxicology database registry was utilized to gain information on clinical laboratory results on organophosphate poisoning patients who visited the emergency department (ED) between January 2000 and October 2016. Clinical outcomes, such as mortality and complication rates, were compared using 1:2 propensity score matching in the total cohort. RESULTS: Among a total of 273 patients in our study, 34 experienced NORP. After 1:2 propensity score matching, rates of respiratory complications and mortality were higher in the ORP group than in the NORP group. However, there was no difference in hospitalization time and time spent in the intensive care unit between the two groups. Compared with ORP patients after matching, the relative risk of mortality in NORP patients was 0.34, and the risk of respiratory distress was 0.47. The mean level of pseudocholinesterase was significantly higher in the NORP group than in the ORP group, while recovery rates were similar between the two groups. CONCLUSION: Although the majority of NORP patients were admitted to the ED with unintentional poisoning and the relative risk of NORP was lower than that for ORP, we concluded that NORP is as critical as ORP. Considerable medical observation and intensive therapeutic approaches are also needed for NORP patients.
ESTHER : Jung_2018_Yonsei.Med.J_59_982
PubMedSearch : Jung_2018_Yonsei.Med.J_59_982
PubMedID: 30187706

Title : ANNALS EXPRESS: Gestational age-specific reference intervals for 15 biochemical measurands during normal pregnancy in China - Dai_2017_Ann.Clin.Biochem__4563217738801
Author(s) : Dai Y , Liu J , Yuan E , Lee Y , Wang Q , Jia L , Wang L , Su Y
Ref : Annals of Clinical Biochemistry , :4563217738801 , 2017
Abstract : AIMS: Physiological changes that occur during pregnancy can influence biochemical parameters. Therefore, using reference intervals based on specimens from non-pregnant women to interpret laboratory results during pregnancy may be inappropriate. This study aimed to establish essential to establish reference intervals for a range of analytes during pregnancy.
METHODS: The cross-sectional study was performed in 13656 healthy pregnant and 2634 non-pregnant women. Fifteen biochemical measurands relating to renal and hepatic function were analyzed using an Olympus AU5400 analyzer (Olympus, Tokyo, Japan). All the laboratory results were checked for outliers using Dixon's test. Reference intervals were established using a non-parametric method.
RESULTS: Alanine aminotransferase, aspartate aminotransferase, albumin, cholinesterase, creatinine, direct bilirubin, gamma-glutamyl transpeptidase, total bilirubin, total bile acid, and total protein showed a decrease during the whole gestational period, while alkaline phosphatase and uric acid increased. Urea nitrogen, beta2-microglobulin, and cystatin-C fell significantly during the first trimestersand then remained relatively stable until third trimester. Reference intervals of all the measurands during normal pregnancy have been established.
CONCLUSIONS: The reference intervals established here can be adopted in other clinical laboratories after appropriate validation. We verified the importance, for some measurands, of partitioning by gestational age when establishing reference intervals during pregnancy.
ESTHER : Dai_2017_Ann.Clin.Biochem__4563217738801
PubMedSearch : Dai_2017_Ann.Clin.Biochem__4563217738801
PubMedID: 29153025

Title : Reversible Pisa Syndrome Induced by Rivastigmine in a Patient With Early-Onset Alzheimer Disease - Hsu_2017_Clin.Neuropharmacol_40_147
Author(s) : Hsu CW , Lee Y , Lee CY , Lin PY
Ref : Clinical Neuropharmacology , 40 :147 , 2017
Abstract : Pisa syndrome (PS) is a state of dystonic muscle contraction with a marked truncal deviation to one side. It is an uncommon adverse effect of antipsychotic drugs, but is rarely reported in patients receiving acetylcholinesterase inhibitors, especially rivastigmine. We present a 57-year-old female patient with Alzheimer disease who began to develop symptoms of dementia at the age of 51 years. She was observed to have symptoms of PS after continuous use of rivastigmine (9 mg/d) for nearly 2 years. The PS symptoms improved after the dose of rivastigmine was reduced but recurred when the dose was added back to 9 mg/d. Finally, after we decreased the dose to 4.5 mg/d, her PS symptoms were remitted. This report reminds us that clinicians need to be cautious about the risk of PS when prescribing rivastigmine in a patient with early-onset Alzheimer disease.
ESTHER : Hsu_2017_Clin.Neuropharmacol_40_147
PubMedSearch : Hsu_2017_Clin.Neuropharmacol_40_147
PubMedID: 28452906

Title : New reference genome sequences of hot pepper reveal the massive evolution of plant disease-resistance genes by retroduplication - Kim_2017_Genome.Biol_18_210
Author(s) : Kim S , Park J , Yeom SI , Kim YM , Seo E , Kim KT , Kim MS , Lee JM , Cheong K , Shin HS , Kim SB , Han K , Lee J , Park M , Lee HA , Lee HY , Lee Y , Oh S , Lee JH , Choi E , Lee SE , Jeon J , Kim H , Choi G , Song H , Lee SC , Kwon JK , Koo N , Hong Y , Kim RW , Kang WH , Huh JH , Kang BC , Yang TJ , Lee YH , Bennetzen JL , Choi D
Ref : Genome Biol , 18 :210 , 2017
Abstract : BACKGROUND: Transposable elements are major evolutionary forces which can cause new genome structure and species diversification. The role of transposable elements in the expansion of nucleotide-binding and leucine-rich-repeat proteins (NLRs), the major disease-resistance gene families, has been unexplored in plants. RESULTS: We report two high-quality de novo genomes (Capsicum baccatum and C. chinense) and an improved reference genome (C. annuum) for peppers. Dynamic genome rearrangements involving translocations among chromosomes 3, 5, and 9 were detected in comparison between C. baccatum and the two other peppers. The amplification of athila LTR-retrotransposons, members of the gypsy superfamily, led to genome expansion in C. baccatum. In-depth genome-wide comparison of genes and repeats unveiled that the copy numbers of NLRs were greatly increased by LTR-retrotransposon-mediated retroduplication. Moreover, retroduplicated NLRs are abundant across the angiosperms and, in most cases, are lineage-specific. CONCLUSIONS: Our study reveals that retroduplication has played key roles for the massive emergence of NLR genes including functional disease-resistance genes in pepper plants.
ESTHER : Kim_2017_Genome.Biol_18_210
PubMedSearch : Kim_2017_Genome.Biol_18_210
PubMedID: 29089032
Gene_locus related to this paper: capch-q75qh4 , capan-a0a1u8fuf5 , capan-a0a1u8gmz3 , capch-a0a2g3bqp0 , capba-a0a2g2vcw4 , capan-a0a1u8flz5 , capch-a0a2g3bau3 , capch-a0a2g3b6c0 , capan-a0a2g2y016 , capch-a0a2g3cje8 , capba-a0a2g2xr67 , capan-a0a1u8fpc9 , capan-a0a1u8fqs3 , capan-a0a1u8ft99 , capan-a0a2g2xtt0 , capan-a0a1u8eu02 , capan-a0a1u8hd13 , capan-a0a2g2y0b6

Title : Increased cell proliferation and neural activity by physostigmine in the telencephalon of adult zebrafish - Lee_2016_Neurosci.Lett_629_189
Author(s) : Lee Y , Lee B , Jeong S , Park JW , Han IO , Lee CJ
Ref : Neuroscience Letters , 629 :189 , 2016
Abstract : Physostigmine, an acetylcholinesterase inhibitor, is known to affect the brain function in various aspects. This study was conducted to test whether physostigmine affects cell proliferation in the telencephalon of zebrafish. BrdU-labeled cells was prominently observed in the ventral zone of the ventral telencephalon of zebrafish. The increased number of BrdU- and proliferating cell nuclear antigen-labeled cells were shown in zebrafish treated with 200muM physostigmine, which was inhibited by pretreatment with 200muM scopolamine. iNOS mRNA expression was increased in the brain of zebrafish treated with 200muM physostigmine. Consistently, aminoguanidine, an iNOS inhibitor, attenuated the increase in the number of BrdU-labeled cells by physostigmine treatment. Zebrafish also showed seizure-like locomotor activity characterized by a rapid and abrupt movement during a 30min treatment with 200muM physostigmine. Neural activity in response to an electrical stimulus was increased in the isolated telencephalon of zebrafish continuously perfused with 200muM physostigmine. None of the number of BrdU-labeled cells, neural activity, or locomotor activity was affected by treatment with 20muM physostigmine. These results suggest that 200muM physostigmine increased neural activity and induced cell proliferation via nitric oxide production in zebrafish.
ESTHER : Lee_2016_Neurosci.Lett_629_189
PubMedSearch : Lee_2016_Neurosci.Lett_629_189
PubMedID: 27378362

Title : Synthesis and antitumor activity of (-)-bassianolide in MDA-MB 231 breast cancer cells through cell cycle arrest - Mun_2016_Bioorg.Chem_69_64
Author(s) : Mun B , Park YJ , Sung GH , Lee Y , Kim KH
Ref : Bioorg Chem , 69 :64 , 2016
Abstract : The high level of interest in the cyclodepsipeptides family in the natural products stems from their diverse range of biological activities. One of the cyclodepsipeptides, (-)-bassianolide, represents rich pharmacophores with diverse biological activities including potential cytotoxicity to various cancer cells. Efficient total synthesis of (-)-bassianolide was designed and achieved in nine steps, with significant improvements in the overall yield of 46.8% (vs. 7.2% yield in previous synthesis) using Ghosez's chloroenamine reagent under mild conditions. The cytotoxicity of the (-)-bassianolide was evaluated against five human tumor cells, and the results showed that the (-)-bassianolide displayed significant cytotoxicity against A549, SK-OV-3, HepG2, HCT-15, MCF-7 and MDA-MB 231 cell lines with IC(50) values of 7.24, 8.44, 15.39, 6.40, 11.42 and 3.98 microg/mL respectively. Specifically, (-)-bassianolide induced G0/G1 arrest associated with a decrease of cyclin A, D1 and an increase of p53, MDM2, and p21 expression in MDA-MB 231 cells. These results demonstrate that (-)-bassianolide possesses antitumor activities via arresting of the cell cycle and the synthetic approach features an efficient and mild method for the formation of amide bonds through three inter- and intramolecular coupling reactions.
ESTHER : Mun_2016_Bioorg.Chem_69_64
PubMedSearch : Mun_2016_Bioorg.Chem_69_64
PubMedID: 27676608

Title : Clinical Predictors for Mild Cognitive Impairment Progression in a Korean Cohort - Shim_2016_Dement.Neurocogn.Disord_15_68
Author(s) : Shim YS , Yang DW , Yoon B , Lee Y , Hong CH , Seo SW , Yoon SJ , Jeong JH , Park MH , Choi SH , Kim SY
Ref : Dement Neurocogn Disord , 15 :68 , 2016
Abstract : Background and Purpose: Patients with mild cognitive impairment (MCI) and their caregivers are concerned with the likelihood and time course of progression to dementia. This study was performed to identify the clinical predictors of the MCI progression in a Korean registry, and investigated the effects of medications without evidence, frequently prescribed in clinical practice. Methods: Using a Korean cohort that included older adults with MCI who completed at least one follow-up visit, clinical characteristics and total medical expenses including prescribed medications were compared between two groups: progressed to dementia or not. Cox proportional hazards regression analysis was conducted. Results: During the mean 1.42+/-0.72 years, 215 (27.63%) of 778 participants progressed to dementia. The best predictors were age [hazard ratio (HR), 1.036; 95% confidence interval (CI), 1.006-1.067; p=0.018], apolipoprotein epsilon4 allele (HR, 2.247; 95% CI, 1.512-3.337; p<0.001), Clinical Dementia Rating scale-sum of boxes scores (HR, 1.367; 95% CI, 1.143-1.636; p=0.001), Instrumental Activities of Daily Living scores (HR, 1.035; 95% CI, 1.003-1.067; p=0.029), and lower Mini-Mental State Examination scores (HR, 0.892; 95% CI, 0.839-0.949; p<0.001). Total medical expenses were not different. Conclusions: Our data are in accordance with previous reports about clinical predictors for the progression from MCI to dementia. Total medical expenses were not different between groups with and without progression.
ESTHER : Shim_2016_Dement.Neurocogn.Disord_15_68
PubMedSearch : Shim_2016_Dement.Neurocogn.Disord_15_68
PubMedID: 30906345

Title : Hepatic role in an early glucose-lowering effect by a novel dipeptidyl peptidase 4 inhibitor, evogliptin, in a rodent model of type 2 diabetes - Kim_2016_Eur.J.Pharmacol_771_65
Author(s) : Kim TH , Kim MK , Cheong YH , Chae YN , Lee Y , Ka SO , Jung IH , Shin CY , Bae EJ , Son MH
Ref : European Journal of Pharmacology , 771 :65 , 2016
Abstract : Although multiple dipeptidyl peptidase 4 (DPP4) inhibitors have shown glucose-lowering effects by preserving pancreatic cells in high-fat diet (HFD)/streptozotocin (STZ)-induced diabetic mice, the hepatic role in regulation of glucose homeostasis by DPP4 inhibitors in HFD/STZ mice remains elusive. In herein study, parallel comparison of effects on the liver (expression of gluconeogenic genes and the linked signaling molecules) and pancreas (islet morphology and relative area of alpha or beta cells) in combination with glucose-lowering effects were made at the end of 2- and 10-week of evogliptin treatment in HFD/STZ mice. Significant control of hyperglycemia was observed from the second week and persisted during 10-week treatment of 0.3% evogliptin in HFD/STZ mice. This effect was accompanied by increased level of plasma glucagon-like peptide-1 and preserved pancreas islet structure. Furthermore, the hepatic increases in gluconeogenic gene expression in HFD/STZ mice was significantly reduced by evogliptin treatment, which was accompanied by the suppression of cAMP response element-binding protein (CREB) phosphorylation and expression of transducer of regulated CREB protein 2. This hepatic effect of evogliptin treatment was reproduced in 2-week study, however, pancreatic beta-cell area was not altered yet although the expression of pancreatic and duodenal homeobox protein 1 was increased. We conclude that the suppression of hepatic gluconeogenesis by evogliptin is followed by preservation of pancreatic islet, leading to remarkable and persistent glucose-lowering effect in HFD/STZ mice. Our findings provide further insight for the hepatic role in DPP4 inhibitor-mediated glucose control in diabetes.
ESTHER : Kim_2016_Eur.J.Pharmacol_771_65
PubMedSearch : Kim_2016_Eur.J.Pharmacol_771_65
PubMedID: 26621343

Title : Genome information of Methylobacterium oryzae, a plant-probiotic methylotroph in the phyllosphere - Kwak_2014_PLoS.One_9_e106704
Author(s) : Kwak MJ , Jeong H , Madhaiyan M , Lee Y , Sa TM , Oh TK , Kim JF
Ref : PLoS ONE , 9 :e106704 , 2014
Abstract : Pink-pigmented facultative methylotrophs in the Rhizobiales are widespread in the environment, and many Methylobacterium species associated with plants produce plant growth-promoting substances. To gain insights into the life style at the phyllosphere and the genetic bases of plant growth promotion, we determined and analyzed the complete genome sequence of Methylobacterium oryzae CBMB20T, a strain isolated from rice stem. The genome consists of a 6.29-Mb chromosome and four plasmids, designated as pMOC1 to pMOC4. Among the 6,274 coding sequences in the chromosome, the bacterium has, besides most of the genes for the central metabolism, all of the essential genes for the assimilation and dissimilation of methanol that are either located in methylotrophy islands or dispersed. M. oryzae is equipped with several kinds of genes for adaptation to plant surfaces such as defense against UV radiation, oxidative stress, desiccation, or nutrient deficiency, as well as high proportion of genes related to motility and signaling. Moreover, it has an array of genes involved in metabolic pathways that may contribute to promotion of plant growth; they include auxin biosynthesis, cytokine biosynthesis, vitamin B12 biosynthesis, urea metabolism, biosorption of heavy metals or decrease of metal toxicity, pyrroloquinoline quinone biosynthesis, 1-aminocyclopropane-1-carboxylate deamination, phosphate solubilization, and thiosulfate oxidation. Through the genome analysis of M. oryzae, we provide information on the full gene complement of M. oryzae that resides in the aerial parts of plants and enhances plant growth. The plant-associated lifestyle of M. oryzae pertaining to methylotrophy and plant growth promotion, and its potential as a candidate for a bioinoculant targeted to the phyllosphere and focused on phytostimulation are illuminated.
ESTHER : Kwak_2014_PLoS.One_9_e106704
PubMedSearch : Kwak_2014_PLoS.One_9_e106704
PubMedID: 25211235
Gene_locus related to this paper: metrj-b1lyj4 , 9rhiz-a0a089nx06 , 9rhiz-a0a089ntx8 , 9rhiz-a0a089nl64

Title : Amyrin attenuates scopolamine-induced cognitive impairment in mice - Park_2014_Biol.Pharm.Bull_37_1207
Author(s) : Park SJ , Ahn YJ , Oh SR , Lee Y , Kwon G , Woo H , Lee HE , Jang DS , Jung JW , Ryu JH
Ref : Biol Pharm Bull , 37 :1207 , 2014
Abstract : Alzheimer's disease, a neurodegenerative disorder, is characterized by progressive cognitive impairment associated with the disruption of cholinergic neurotransmission. The aim of the present study was to evaluate the effect of alpha- or beta-amyrin, a type of pentacyclic triterpene, on the cognitive impairment induced by scopolamine, a muscarinic acetylcholine receptor antagonist. To measure the abilities of various types of learning and memory, we conducted step-through passive avoidance task. Scopolamine induced deficits in learning and memory processes in mice, which were antagonized by a single administration of alpha-amyrin (2 or 4 mg/kg) or beta-amyrin (4 mg/kg), respectively. Additionally, in vitro analysis revealed that acetylcholinesterase activity was inhibited by beta-amyrin, but not by alpha-amyrin. Furthermore, Western blot analysis revealed that the expression levels of phosphorylated extracellular signal-regulated kinase 1/2 (pERK) and phosphorylated glycogen synthase kinase-3beta (pGSK-3beta) were significantly enhanced by a single administration of alpha- and beta-amyrin in the hippocampus. Finally, the memory ameliorating effects of alpha- or beta-amyrin on the scopolamine-induced cognitive impairments were significantly blocked by ERK inhibitor U0126. The present study suggests that alpha- and beta-amyrin may ameliorate the cognitive impairment induced by hypocholinergic neurotransmission via the activation of ERK as well as GSK-3beta signaling.
ESTHER : Park_2014_Biol.Pharm.Bull_37_1207
PubMedSearch : Park_2014_Biol.Pharm.Bull_37_1207
PubMedID: 24989012

Title : The adhesion protein IgSF9b is coupled to neuroligin 2 via S-SCAM to promote inhibitory synapse development - Woo_2013_J.Cell.Biol_201_929
Author(s) : Woo J , Kwon SK , Nam J , Choi S , Takahashi H , Krueger D , Park J , Lee Y , Bae JY , Lee D , Ko J , Kim H , Kim MH , Bae YC , Chang S , Craig AM , Kim E
Ref : Journal of Cell Biology , 201 :929 , 2013
Abstract : Synaptic adhesion molecules regulate diverse aspects of synapse formation and maintenance. Many known synaptic adhesion molecules localize at excitatory synapses, whereas relatively little is known about inhibitory synaptic adhesion molecules. Here we report that IgSF9b is a novel, brain-specific, homophilic adhesion molecule that is strongly expressed in GABAergic interneurons. IgSF9b was preferentially localized at inhibitory synapses in cultured rat hippocampal and cortical interneurons and was required for the development of inhibitory synapses onto interneurons. IgSF9b formed a subsynaptic domain distinct from the GABAA receptor- and gephyrin-containing domain, as indicated by super-resolution imaging. IgSF9b was linked to neuroligin 2, an inhibitory synaptic adhesion molecule coupled to gephyrin, via the multi-PDZ protein S-SCAM. IgSF9b and neuroligin 2 could reciprocally cluster each other. These results suggest a novel mode of inhibitory synaptic organization in which two subsynaptic domains, one containing IgSF9b for synaptic adhesion and the other containing gephyrin and GABAA receptors for synaptic transmission, are interconnected through S-SCAM and neuroligin 2.
ESTHER : Woo_2013_J.Cell.Biol_201_929
PubMedSearch : Woo_2013_J.Cell.Biol_201_929
PubMedID: 23751499

Title : Terminal Schwann cells participate in the competition underlying neuromuscular synapse elimination - Smith_2013_J.Neurosci_33_17724
Author(s) : Smith IW , Mikesh M , Lee Y , Thompson WJ
Ref : Journal of Neuroscience , 33 :17724 , 2013
Abstract : The competitive processes that result in elimination/pruning of developing synapses are incompletely understood. Serial electron microscopy was used to image postnatal mouse neuromuscular junctions where elimination is well studied and events at every synaptic contact can be examined. Glial or Schwann cells (SCs) are shown to have two activities during elimination: their processes separate nerve terminals from each other and from the muscle fiber; they contact the plaque of acetylcholine receptors, apposing this surface as closely as the nerve, limiting the area where synaptic transmission occurs. SCs phagocytose nerve terminals contacting the muscle fiber. This phagocytosis involves all axons; SCs are not selecting the winner but rather driving turnover. Previous modeling of stochastic turnover and reoccupation of nerve contacts shows that single innervation of synaptic sites can result. Thus, our study shows roles of SCs in neuromuscular development beyond the previous demonstration of consumption of synaptic inputs after their elimination.
ESTHER : Smith_2013_J.Neurosci_33_17724
PubMedSearch : Smith_2013_J.Neurosci_33_17724
PubMedID: 24198364

Title : Inhibitory Activities of Cudrania tricuspidata Leaves on Pancreatic Lipase In Vitro and Lipolysis In Vivo - Kim_2012_Evid.Based.Complement.Alternat.Med_2012_878365
Author(s) : Kim YS , Lee Y , Kim J , Sohn E , Kim CS , Lee YM , Jo K , Shin S , Song Y , Kim JH , Kim JS
Ref : Evid Based Complement Alternat Med , 2012 :878365 , 2012
Abstract : To identify effective herb to treat obesity, we screened 115 herbal extracts for inhibition of porcine pancreatic lipase (triacylg-ycerol acylhydrolase, EC activity in vitro. Of the extracts tested, Cudrania tricuspidata leaves exhibited the most pronounced inhibitory effect on lipase activity with an IC(50) value of 9.91 mug/mL. Antilipid absorption effects of C. tricuspidata leaves were examined in rats after oral administration of lipid emulsions containing 50 or 250 mg C. tricuspidata/kg body weight. Plasma triacylglycerol levels 2 h after the oral administration of emulsions containing C. tricuspidata were significantly reduced compared to the untreated group (P < 0.05). These results suggest that C. tricuspidata leaves may be useful for the treatment of obesity.
ESTHER : Kim_2012_Evid.Based.Complement.Alternat.Med_2012_878365
PubMedSearch : Kim_2012_Evid.Based.Complement.Alternat.Med_2012_878365
PubMedID: 23365603

Title : Binding conformation prediction between human acetylcholinesterase and cytochrome c using molecular modeling methods - Kim_2011_J.Mol.Graph.Model_29_996
Author(s) : Kim S , Lee Y , Lazar P , Son M , Baek A , Thangapandian S , Jeong NY , Yoo YH , Lee KW
Ref : J Mol Graph Model , 29 :996 , 2011
Abstract : The acetylcholinesterase (AChE) is important to terminate acetylcholine-mediated neurotransmission at cholinergic synapses. The pivotal role of AChE in apoptosome formation through the interactions with cytochrome c (Cyt c) was demonstrated in recent study. In order to investigate the proper binding conformation between the human AChE (hAChE) and human Cyt c (hCyt c), macro-molecular docking simulation was performed using DOT 2.0 program. The hCyt c was bound to peripheral anionic site (PAS) on hAChE and binding mode of the docked conformation was very similar to the reported crystal structure of the AChE and fasciculin-II (Fas-II) complex. Two 10ns molecular dynamics (MD) simulations were carried out to refine the binding mode of docked structure and to observe the differences of the binding conformations between the absent (Apo) and presence (Holo) of heme group. The key hydrogen bonding residues between hAChE and hCyt c proteins were found in Apo and Holo systems, as well as each Tyr341 and Trp286 residue of hAChE was participated in cation-pi (pi) interactions with Lys79 of hCyt c in Apo and Holo systems, respectively. From the present study, although the final structures of the Apo and Holo systems have similar binding pattern, several differences were investigated in flexibilities, interface interactions, and interface accessible surface areas. Based on these results, we were able to predict the reasonable binding conformation which is indispensable for apoptosome formation.
ESTHER : Kim_2011_J.Mol.Graph.Model_29_996
PubMedSearch : Kim_2011_J.Mol.Graph.Model_29_996
PubMedID: 21570330

Title : Changes in aging mouse neuromuscular junctions are explained by degeneration and regeneration of muscle fiber segments at the synapse - Li_2011_J.Neurosci_31_14910
Author(s) : Li Y , Lee Y , Thompson WJ
Ref : Journal of Neuroscience , 31 :14910 , 2011
Abstract : Vertebrate neuromuscular junctions are highly stable synapses, retaining the morphology they achieve in early postnatal development throughout most of life. However, these synapses undergo dramatic change during aging. The acetylcholine receptors (AChRs) change from smooth gutters into fragmented islands, and the nerve terminals change similarly to be varicosities apposed to these islands. These changes have been attributed to a slow deterioration in mechanisms maintaining the synapse. We have used repeated, vital imaging to investigate how these changes occur in the sternomastoid muscle of aging mice. We have found, contrary to expectation, that individual junctions change infrequently, but change, when it occurs, is sudden and dramatic. The change mimics that reported previously for cases in which muscle fibers are deliberately damaged: most of the AChRs present disappear rapidly and are replaced by a new set of receptors that become fragmented. The fiber segment underneath the synapse has centrally located nuclei, showing that this segment has undergone necrosis, quickly regenerated, and been reinnervated with an altered synapse. We show that necrotic events are common in aged muscle and have likely been missed previously as a cause of the alterations in aging because central nuclei are a transient phenomenon and the necrotic events at the junction infrequent. However, the changes are permanent and accumulate over time. Interventions to reduce the neuromuscular changes during aging should likely focus on making muscle fibers resistant to injury.
ESTHER : Li_2011_J.Neurosci_31_14910
PubMedSearch : Li_2011_J.Neurosci_31_14910
PubMedID: 22016524

Title : Identification and characterization of full-length cDNAs in channel catfish (Ictalurus punctatus) and blue catfish (Ictalurus furcatus) - Chen_2010_PLoS.One_5_e11546
Author(s) : Chen F , Lee Y , Jiang Y , Wang S , Peatman E , Abernathy J , Liu H , Liu S , Kucuktas H , Ke C , Liu Z
Ref : PLoS ONE , 5 :e11546 , 2010
Abstract : BACKGROUND: Genome annotation projects, gene functional studies, and phylogenetic analyses for a given organism all greatly benefit from access to a validated full-length cDNA resource. While increasingly common in model species, full-length cDNA resources in aquaculture species are scarce. METHODOLOGY AND PRINCIPAL FINDINGS: Through in silico analysis of catfish (Ictalurus spp.) ESTs, a total of 10,037 channel catfish and 7,382 blue catfish cDNA clones were identified as potentially encoding full-length cDNAs. Of this set, a total of 1,169 channel catfish and 933 blue catfish full-length cDNA clones were selected for re-sequencing to provide additional coverage and ensure sequence accuracy. A total of 1,745 unique gene transcripts were identified from the full-length cDNA set, including 1,064 gene transcripts from channel catfish and 681 gene transcripts from blue catfish, with 416 transcripts shared between the two closely related species. Full-length sequence characteristics (ortholog conservation, UTR length, Kozak sequence, and conserved motifs) of the channel and blue catfish were examined in detail. Comparison of gene ontology composition between full-length cDNAs and all catfish ESTs revealed that the full-length cDNA set is representative of the gene diversity encoded in the catfish transcriptome.
CONCLUSIONS: This study describes the first catfish full-length cDNA set constructed from several cDNA libraries. The catfish full-length cDNA sequences, and data gleaned from sequence characteristics analysis, will be a valuable resource for ongoing catfish whole-genome sequencing and future gene-based studies of function and evolution in teleost fishes.
ESTHER : Chen_2010_PLoS.One_5_e11546
PubMedSearch : Chen_2010_PLoS.One_5_e11546
PubMedID: 20634964
Gene_locus related to this paper: ictpu-e3teh0 , ictpu-e3tfr7 , ictpu-a0a2d0pnc6

Title : Scopolamine-induced learning impairment reversed by physostigmine in zebrafish - Kim_2010_Neurosci.Res_67_156
Author(s) : Kim YH , Lee Y , Kim D , Jung MW , Lee CJ
Ref : Neurosci Res , 67 :156 , 2010
Abstract : In this study, the effects of scopolamine, an acetylcholine muscarinic receptor antagonist, and physostigmine, an acetylcholinesterase inhibitor, on the learning ability and memory of zebrafish were evaluated using a passive avoidance response test. The zebrafish were trained to stay in a dark compartment to avoid a weight dropping into an acryl shuttle chamber with a central sliding door. The crossing time was increased significantly, from 30.7+/-40.8s to 179.3+/-27.3s in the training session and 179.9+/-28.0s in the test session carried out 2h later in the controls. When treatment with 200 microM scopolamine was administered for 1h prior to the training session, the crossing time did not increase. The scopolamine-induced learning deficit was ameliorated by pretreatment with 20 microM physostigmine for 1h prior to scopolamine treatment; the crossing time was similarly increased, as shown with the controls (60.9+/-11.5s, 130.9+/-27.5s, and 183.4+/-26.6s in the training session and 108.1+/-23.9s in the test session). When scopolamine treatment was administered after the training session, the crossing time in the test session was reduced significantly as compared to that noted in the third trial of the training session, which was also ameliorated by physostigmine pretreatment. These results show that scopolamine impairs both the acquisition of passive avoidance response and retention of the learned response, and that physostigmine rescues the amnesic effects of scopolamine in zebrafish.
ESTHER : Kim_2010_Neurosci.Res_67_156
PubMedSearch : Kim_2010_Neurosci.Res_67_156
PubMedID: 20298728

Title : Reduced neuronal proliferation by proconvulsant drugs in the developing zebrafish brain - Kim_2010_Neurotoxicol.Teratol_32_551
Author(s) : Kim YH , Lee Y , Lee K , Lee T , Kim YJ , Lee CJ
Ref : Neurotoxicology & Teratology , 32 :551 , 2010
Abstract : Seizures have been reported to modify neural development in the immature brain. In this study, we attempted to determine whether pentylenetetrazol (a GABAergic receptor antagonist, PTZ)-induced seizures influence cell proliferation in zebrafish larvae (5 and 15 days of post-fertilization), using bromodeoxyuridine (BrdU) to label dividing cells. In the brains of 5 dpf larvae, PTZ treatment significantly reduced the number of BrdU-labeled cells in the telencephalic area (pallium and subpallium), diencephalic area (thalamus and preoptic area), medial tectal proliferation zone, and medial cerebellar proliferation zone to 52.4%, 62.9%, 47.2%, and 54.0% of the controls, respectively. In contrast, we noted no reductions in the number of BrdU-labeled cells in the brains of the 15 dpf larvae. The double-label of BrdU and Hu, a neuronal marker, demonstrated that the majority of newborn cells showed the neuronal phenotype. Similarly, kainic acid (200 microM), a glutamatergic receptor agonist, significantly reduced the number of BrdU-labeled cells in the telencephalic area, diencephalic area, and medial tectal proliferation zone to 51.4%, 61.9%, and 40.4% of the controls, respectively. Physostigmine (500 microM), an acetylcholinesterase inhibitor, also reduced the number of BrdU-labeled cells in the telencephalic area, diencephalic area, medial tectal proliferation zone, and medial cerebellar proliferation zone to 52.8%, 35.9%, 30.5%, and 39.8% of the controls, respectively. All of these drugs resulted in electrographic seizures in the larval brain when perfused directly through artificial cerebrospinal fluid. These results indicated that seizures result in a massive reduction in cell proliferation in wide-ranging areas of the developing brain.
ESTHER : Kim_2010_Neurotoxicol.Teratol_32_551
PubMedSearch : Kim_2010_Neurotoxicol.Teratol_32_551
PubMedID: 20420900

Title : Poster: nAChR agonists reduce l-dopa-induced dyskinesias in parkinsonian rats -
Author(s) : Quik M , Huang LZ , Lee Y , Carroll IF , Parameswaran N
Ref : Biochemical Pharmacology , 78 :922 , 2009

Title : Adenoviral vector-mediated glucagon-like peptide 1 gene therapy improves glucose homeostasis in Zucker diabetic fatty rats - Lee_2008_J.Gene.Med_10_260
Author(s) : Lee Y , Kwon MK , Kang ES , Park YM , Choi SH , Ahn CW , Kim KS , Park CW , Cha BS , Kim SW , Sung JK , Lee EJ , Lee HC
Ref : J Gene Med , 10 :260 , 2008
Abstract : BACKGROUND: Glucagon-like peptide-1 (GLP-1) is a gut-derived incretin hormone that plays an important role in glucose homeostasis. Its functions include glucose-stimulated insulin secretion, suppression of glucagon secretion, deceleration of gastric emptying, and reduction in appetite and food intake. Despite the numerous antidiabetic properties of GLP-1, its therapeutic potential is limited by its short biological half-life due to rapid enzymatic degradation by dipeptidyl peptidase IV. The present study aimed to demonstrate the therapeutic effects of constitutively expressed GLP-1 in an overt type 2 diabetic animal model using an adenoviral vector system.
METHODS: A novel plasmid (pAAV-ILGLP-1) and recombinant adenoviral vector (Ad-ILGLP-1) were constructed with the cytomegalovirus promoter and insulin leader sequence followed by GLP-1(7-37) cDNA.
RESULTS: The results of an enzyme-linked immunosorbent assay showed significantly elevated levels of GLP-1(7-37) secreted by human embryonic kidney cells transfected with the construct containing the leader sequence. A single intravenous administration of Ad-ILGLP-1 into 12-week-old Zucker diabetic fatty (ZDF) rats, which have overt type 2 diabetes mellitus (T2DM), achieved near normoglycemia for 3 weeks and improved utilization of blood glucose in glucose tolerance tests. Circulating plasma levels of GLP-1 increased in GLP-1-treated ZDF rats, but diminished 21 days after treatment. When compared with controls, Ad-ILGLP-1-treated ZDF rats had a lower homeostasis model assessment for insulin resistance score indicating amelioration in insulin resistance. Immunohistochemical staining showed that cells expressing GLP-1 were found in the livers of GLP-1-treated ZDF rats.
CONCLUSIONS: These data suggest that GLP-1 gene therapy can improve glucose homeostasis in fully developed diabetic animal models and may be a promising treatment modality for T2DM in humans.
ESTHER : Lee_2008_J.Gene.Med_10_260
PubMedSearch : Lee_2008_J.Gene.Med_10_260
PubMedID: 18085721

Title : The medaka draft genome and insights into vertebrate genome evolution - Kasahara_2007_Nature_447_714
Author(s) : Kasahara M , Naruse K , Sasaki S , Nakatani Y , Qu W , Ahsan B , Yamada T , Nagayasu Y , Doi K , Kasai Y , Jindo T , Kobayashi D , Shimada A , Toyoda A , Kuroki Y , Fujiyama A , Sasaki T , Shimizu A , Asakawa S , Shimizu N , Hashimoto S , Yang J , Lee Y , Matsushima K , Sugano S , Sakaizumi M , Narita T , Ohishi K , Haga S , Ohta F , Nomoto H , Nogata K , Morishita T , Endo T , Shin IT , Takeda H , Morishita S , Kohara Y
Ref : Nature , 447 :714 , 2007
Abstract : Teleosts comprise more than half of all vertebrate species and have adapted to a variety of marine and freshwater habitats. Their genome evolution and diversification are important subjects for the understanding of vertebrate evolution. Although draft genome sequences of two pufferfishes have been published, analysis of more fish genomes is desirable. Here we report a high-quality draft genome sequence of a small egg-laying freshwater teleost, medaka (Oryzias latipes). Medaka is native to East Asia and an excellent model system for a wide range of biology, including ecotoxicology, carcinogenesis, sex determination and developmental genetics. In the assembled medaka genome (700 megabases), which is less than half of the zebrafish genome, we predicted 20,141 genes, including approximately 2,900 new genes, using 5'-end serial analysis of gene expression tag information. We found single nucleotide polymorphisms (SNPs) at an average rate of 3.42% between the two inbred strains derived from two regional populations; this is the highest SNP rate seen in any vertebrate species. Analyses based on the dense SNP information show a strict genetic separation of 4 million years (Myr) between the two populations, and suggest that differential selective pressures acted on specific gene categories. Four-way comparisons with the human, pufferfish (Tetraodon), zebrafish and medaka genomes revealed that eight major interchromosomal rearrangements took place in a remarkably short period of approximately 50 Myr after the whole-genome duplication event in the teleost ancestor and afterwards, intriguingly, the medaka genome preserved its ancestral karyotype for more than 300 Myr.
ESTHER : Kasahara_2007_Nature_447_714
PubMedSearch : Kasahara_2007_Nature_447_714
PubMedID: 17554307
Gene_locus related to this paper: fugru-3cxest , fugru-4cxest , fugru-4neur , fugru-ACHE , fugru-ACHEE , fugru-balip , fugru-BCHE , fugru-BCHEB , fugru-cxest , oryla-ACHE , oryla-BCHE , oryla-d2x2i4 , oryla-h2m6h1 , oryla-h2m7w4 , oryla-h2m361 , oryla-h2mbn6 , oryla-h2mfw1 , oryla-h2mhi0 , oryla-h2mhl7 , oryla-h2mpb5 , oryla-h2mqz5 , oryla-h2mvs7 , oryla-h2mz49 , oryla-h2n1l9 , oryla-nlgn2 , takru-1neur , takru-2bneur , takru-3bneur , takru-h2rke7 , takru-h2rmg3 , takru-h2rsj9 , takru-h2rw77 , takru-h2ryq0 , takru-h2sci9 , takru-h2se90 , takru-h2spg7 , takru-h2sxi1 , takru-h2ts55 , takru-h2ts56 , takru-h2uxa9 , takru-h2vaf1 , takru-nlgn2a , takru-nlgn3a , takru-nlgn4a , oryla-h2mff8 , oryla-h2m2f0 , oryla-h2ler5 , takru-h2tsm6 , takru-h2tq49 , takru-h2tq47 , takru-h2s286 , takru-h2tng4 , takru-h2tq50 , takru-h2tng3 , takru-h2tng2 , oryla-h2lj38 , oryla-h2mxe6 , takru-h2tq48 , oryla-h2lf11 , takru-h2u5j0 , takru-h2rpm8 , oryla-h2n273 , oryla-h2n271 , oryla-h2lum7 , takru-h2tpz2 , takru-h2u3j1 , oryla-h2mdv3 , takru-h2tzm9 , takru-h2u8u6 , oryla-h2lcw8 , oryla-h2lc35 , oryla-h2ln66 , oryla-h2m8k0 , oryla-h2mdj7 , oryla-h2lw61 , oryla-h2lxe3 , oryla-h2l8y7 , oryla-h2mr84 , oryla-h2mr95 , oryla-h2mcz6 , oryla-h2lxr5 , oryla-h2ly57 , oryla-a0a3p9kz03 , oryla-a0a3p9hfu1 , oryla-h2m307 , oryla-h2lch5 , oryla-h2ldw9 , oryla-a0a3b3ic40 , oryla-h2ldi5 , oryla-h2mun1 , oryla-a0a3p9jla3

Title : Quantitative structure-activity relationship (QSAR) of tacrine derivatives against acetylcholinesterase (AChE) activity using variable selections - Jung_2007_Bioorg.Med.Chem.Lett_17_1082
Author(s) : Jung M , Tak J , Lee Y , Jung Y
Ref : Bioorganic & Medicinal Chemistry Lett , 17 :1082 , 2007
Abstract : A diverse approach to the quantitative structure-activity relationship (QSAR) of tacrine derivatives against acetylcholinesterase (AChE) activity was studied using variable selections of stepwise multiple linear regression (MLR), genetic algorithm (GA)-MLR, and simulated annealing (SA)-MLR. AChE activity (logRA) of tacrine derivatives was expressed with acceptable explanation (95.5-95.9%) and good predictive power (94.5-95.2%), respectively, in the models. The best equation was obtained from simulated annealing (SA) MLR with greater explanatory capability and better prediction, with a smaller standard error than other methods. The resulting models with the given descriptors illustrate the significant roles of hydrophobic and electrostatic interaction on increasing AChE activity, but hydrophilic and topological feature of molecules were shown to decrease AChE activity.
ESTHER : Jung_2007_Bioorg.Med.Chem.Lett_17_1082
PubMedSearch : Jung_2007_Bioorg.Med.Chem.Lett_17_1082
PubMedID: 17158047

Title : Effective killing of the human pathogen Candida albicans by a specific inhibitor of non-essential mitotic kinesin Kip1p - Chua_2007_Mol.Microbiol_65_347
Author(s) : Chua PR , Roof DM , Lee Y , Sakowicz R , Clarke D , Pierce D , Stephens T , Hamilton M , Morgan B , Morgans D , Nakai T , Tomasi A , Maxon ME
Ref : Molecular Microbiology , 65 :347 , 2007
Abstract : Kinesins from the bipolar (Kinesin-5) family are conserved in eukaryotic organisms and play critical roles during the earliest stages of mitosis to mediate spindle pole body separation and formation of a bipolar mitotic spindle. To date, genes encoding bipolar kinesins have been reported to be essential in all organisms studied. We report the characterization of CaKip1p, the sole member of this family in the human pathogenic yeast Candida albicans. C. albicans Kip1p appears to localize to the mitotic spindle and loss of CaKip1p function interferes with normal progression through mitosis. Inducible excision of CaKIP1 revealed phenotypes unique to C. albicans, including viable homozygous Cakip1 mutants and an aberrant spindle morphology in which multiple spindle poles accumulate in close proximity to each other. Expression of the C. albicans Kip1 motor domain in Escherichia coli produced a protein with microtubule-stimulated ATPase activity that was inhibited by an aminobenzothiazole (ABT) compound in an ATP-competitive fashion. This inhibition results in 'rigor-like', tight association with microtubules in vitro. Upon treatment of C. albicans cells with the ABT compound, cells were killed, and terminal phenotype analysis revealed an aberrant spindle morphology similar to that induced by loss of the CaKIP1 gene. The ABT compound discovered is the first example of a fungal spindle inhibitor targeted to a mitotic kinesin. Our results also show that the non-essential nature and implementation of the bipolar motor in C. albicans differs from that seen in other organisms, and suggest that inhibitors of a non-essential mitotic kinesin may offer promise as cidal agents for antifungal drug discovery.
ESTHER : Chua_2007_Mol.Microbiol_65_347
PubMedSearch : Chua_2007_Mol.Microbiol_65_347
PubMedID: 17573815

Title : PKA-activated ApAF-ApC\/EBP heterodimer is a key downstream effector of ApCREB and is necessary and sufficient for the consolidation of long-term facilitation - Lee_2006_J.Cell.Biol_174_827
Author(s) : Lee JA , Lee SH , Lee C , Chang DJ , Lee Y , Kim H , Cheang YH , Ko HG , Lee YS , Jun H , Bartsch D , Kandel ER , Kaang BK
Ref : Journal of Cell Biology , 174 :827 , 2006
Abstract : Long-term memory requires transcriptional regulation by a combination of positive and negative transcription factors. Aplysia activating factor (ApAF) is known to be a positive transcription factor that forms heterodimers with ApC/EBP and ApCREB2. How these heterodimers are regulated and how they participate in the consolidation of long-term facilitation (LTF) has not, however, been characterized. We found that the functional activation of ApAF required phosphorylation of ApAF by PKA on Ser-266. In addition, ApAF lowered the threshold of LTF by forming a heterodimer with ApCREB2. Moreover, once activated by PKA, the ApAF-ApC/EBP heterodimer transactivates enhancer response element-containing genes and can induce LTF in the absence of CRE- and CREB-mediated gene expression. Collectively, these results suggest that PKA-activated ApAF-ApC/EBP heterodimer is a core downstream effector of ApCREB in the consolidation of LTF.
ESTHER : Lee_2006_J.Cell.Biol_174_827
PubMedSearch : Lee_2006_J.Cell.Biol_174_827
PubMedID: 16966424

Title : A case with cholinesterase inhibitor responsive asymmetric posterior cortical atrophy - Kim_2005_Clin.Neurol.Neurosurg_108_97
Author(s) : Kim E , Lee Y , Lee J , Han SH
Ref : Clin Neurol Neurosurg , 108 :97 , 2005
Abstract : A 55-year-old right-handed woman presented initially with mild amnestic and depressive episodes but slowly developed progressive neurobehavioral symptoms, indicative of posterior cortical atrophy in ensuing years. A more detailed neurobehavioral test suggested predominant right temporo-parietal dysfunction with executive functional deficits. SPECT and MRI findings revealed right unilateral temporo-parietal involvement. Cholinesterase inhibitor administration led to amelioration of symptoms. We suggest that cases of posterior cortical atrophy or visual variant of Alzheimer's disease may be responsive to cholinesterase inhibitor therapy; however, the observation in a single case should be confirmed on larger populations in a clinical trial design with placebo control.
ESTHER : Kim_2005_Clin.Neurol.Neurosurg_108_97
PubMedSearch : Kim_2005_Clin.Neurol.Neurosurg_108_97
PubMedID: 16311158

Title : BmiGI: a database of cDNAs expressed in Boophilus microplus, the tropical\/southern cattle tick - Guerrero_2005_Insect.Biochem.Mol.Biol_35_585
Author(s) : Guerrero FD , Miller RJ , Rousseau ME , Sunkara S , Quackenbush J , Lee Y , Nene V
Ref : Insect Biochemistry & Molecular Biology , 35 :585 , 2005
Abstract : We used an expressed sequence tag approach to initiate a study of the genome of the southern cattle tick, Boophilus microplus. A normalized cDNA library was synthesized from pooled RNA purified from tick larvae which had been subjected to different treatments, including acaricide exposure, heat shock, cold shock, host odor, and infection with Babesia bovis. For the acaricide exposure experiments, we used several strains of ticks, which varied in their levels of susceptibility to pyrethroid, organophosphate and amitraz. We also included RNA purified from samples of eggs, nymphs and adult ticks and dissected tick organs. Plasmid DNA was prepared from 11,520 cDNA clones and both 5' and 3' sequencing performed on each clone. The sequence data was used to search public protein databases and a B. microplus gene index was constructed, consisting of 8270 unique sequences whose associated putative functional assignments, when available, can be viewed at the TIGR website (http://www.tigr.org/tdb/tgi). A number of novel sequences were identified which possessed significant sequence similarity to genes, which might be involved in resistance to acaricides.
ESTHER : Guerrero_2005_Insect.Biochem.Mol.Biol_35_585
PubMedSearch : Guerrero_2005_Insect.Biochem.Mol.Biol_35_585
PubMedID: 15857764

Title : Analysis of the mouse transcriptome based on functional annotation of 60,770 full-length cDNAs - Okazaki_2002_Nature_420_563
Author(s) : Okazaki Y , Furuno M , Kasukawa T , Adachi J , Bono H , Kondo S , Nikaido I , Osato N , Saito R , Suzuki H , Yamanaka I , Kiyosawa H , Yagi K , Tomaru Y , Hasegawa Y , Nogami A , Schonbach C , Gojobori T , Baldarelli R , Hill DP , Bult C , Hume DA , Quackenbush J , Schriml LM , Kanapin A , Matsuda H , Batalov S , Beisel KW , Blake JA , Bradt D , Brusic V , Chothia C , Corbani LE , Cousins S , Dalla E , Dragani TA , Fletcher CF , Forrest A , Frazer KS , Gaasterland T , Gariboldi M , Gissi C , Godzik A , Gough J , Grimmond S , Gustincich S , Hirokawa N , Jackson IJ , Jarvis ED , Kanai A , Kawaji H , Kawasawa Y , Kedzierski RM , King BL , Konagaya A , Kurochkin IV , Lee Y , Lenhard B , Lyons PA , Maglott DR , Maltais L , Marchionni L , McKenzie L , Miki H , Nagashima T , Numata K , Okido T , Pavan WJ , Pertea G , Pesole G , Petrovsky N , Pillai R , Pontius JU , Qi D , Ramachandran S , Ravasi T , Reed JC , Reed DJ , Reid J , Ring BZ , Ringwald M , Sandelin A , Schneider C , Semple CA , Setou M , Shimada K , Sultana R , Takenaka Y , Taylor MS , Teasdale RD , Tomita M , Verardo R , Wagner L , Wahlestedt C , Wang Y , Watanabe Y , Wells C , Wilming LG , Wynshaw-Boris A , Yanagisawa M , Yang I , Yang L , Yuan Z , Zavolan M , Zhu Y , Zimmer A , Carninci P , Hayatsu N , Hirozane-Kishikawa T , Konno H , Nakamura M , Sakazume N , Sato K , Shiraki T , Waki K , Kawai J , Aizawa K , Arakawa T , Fukuda S , Hara A , Hashizume W , Imotani K , Ishii Y , Itoh M , Kagawa I , Miyazaki A , Sakai K , Sasaki D , Shibata K , Shinagawa A , Yasunishi A , Yoshino M , Waterston R , Lander ES , Rogers J , Birney E , Hayashizaki Y
Ref : Nature , 420 :563 , 2002
Abstract : Only a small proportion of the mouse genome is transcribed into mature messenger RNA transcripts. There is an international collaborative effort to identify all full-length mRNA transcripts from the mouse, and to ensure that each is represented in a physical collection of clones. Here we report the manual annotation of 60,770 full-length mouse complementary DNA sequences. These are clustered into 33,409 'transcriptional units', contributing 90.1% of a newly established mouse transcriptome database. Of these transcriptional units, 4,258 are new protein-coding and 11,665 are new non-coding messages, indicating that non-coding RNA is a major component of the transcriptome. 41% of all transcriptional units showed evidence of alternative splicing. In protein-coding transcripts, 79% of splice variations altered the protein product. Whole-transcriptome analyses resulted in the identification of 2,431 sense-antisense pairs. The present work, completely supported by physical clones, provides the most comprehensive survey of a mammalian transcriptome so far, and is a valuable resource for functional genomics.
ESTHER : Okazaki_2002_Nature_420_563
PubMedSearch : Okazaki_2002_Nature_420_563
PubMedID: 12466851
Gene_locus related to this paper: mouse-1lipg , mouse-1llip , mouse-1plrp , mouse-3neur , mouse-ABH15 , mouse-abhd4 , mouse-abhd5 , mouse-Abhd8 , mouse-Abhd11 , mouse-abhda , mouse-acot4 , mouse-adcl4 , mouse-AI607300 , mouse-BAAT , mouse-bphl , mouse-C87498 , mouse-Ldah , mouse-Ces1d , mouse-Ces2e , mouse-CMBL , mouse-DGLB , mouse-dpp9 , mouse-ES10 , mouse-F135A , mouse-FASN , mouse-hslip , mouse-hyes , mouse-Kansl3 , mouse-LIPH , mouse-LIPK , mouse-lipli , mouse-LIPM , mouse-lypla1 , mouse-lypla2 , mouse-MEST , mouse-MGLL , mouse-ndr4 , mouse-OVCA2 , mouse-pafa , mouse-pcp , mouse-ppce , mouse-Ppgb , mouse-PPME1 , mouse-q3uuq7 , mouse-Q8BLF1 , mouse-ACOT6 , mouse-Q8C1A9 , mouse-Q9DAI6 , mouse-Q80UX8 , mouse-Q8BGG9 , mouse-Q8C167 , mouse-rbbp9 , mouse-SERHL , mouse-tssp