Kim M

References (45)

Title : Recent advances in microbial and enzymatic engineering for the biodegradation of micro- and nanoplastics - Choi_2024_RSC.Adv_14_9943
Author(s) : Choi J , Kim H , Ahn YR , Kim M , Yu S , Kim N , Lim SY , Park JA , Ha SJ , Lim KS , Kim HO
Ref : RSC Adv , 14 :9943 , 2024
Abstract : This review examines the escalating issue of plastic pollution, specifically highlighting the detrimental effects on the environment and human health caused by microplastics and nanoplastics. The extensive use of synthetic polymers such as polyethylene (PE), polyethylene terephthalate (PET), and polystyrene (PS) has raised significant environmental concerns because of their long-lasting and non-degradable characteristics. This review delves into the role of enzymatic and microbial strategies in breaking down these polymers, showcasing recent advancements in the field. The intricacies of enzymatic degradation are thoroughly examined, including the effectiveness of enzymes such as PETase and MHETase, as well as the contribution of microbial pathways in breaking down resilient polymers into more benign substances. The paper also discusses the impact of chemical composition on plastic degradation kinetics and emphasizes the need for an approach to managing the environmental impact of synthetic polymers. The review highlights the significance of comprehending the physical characteristics and long-term impacts of micro- and nanoplastics in different ecosystems. Furthermore, it points out the environmental and health consequences of these contaminants, such as their ability to cause cancer and interfere with the endocrine system. The paper emphasizes the need for advanced analytical methods and effective strategies for enzymatic degradation, as well as continued research and development in this area. This review highlights the crucial role of enzymatic and microbial strategies in addressing plastic pollution and proposes methods to create effective and environmentally friendly solutions.
ESTHER : Choi_2024_RSC.Adv_14_9943
PubMedSearch : Choi_2024_RSC.Adv_14_9943
PubMedID: 38528920

Title : Gemigliptin, a potent selective dipeptidyl peptidase 4 inhibitor, protects endothelial progenitor cells by oxidative stress via caspase-3 dependent pathway - Lee_2024_Biochem.Biophys.Rep_38_101673
Author(s) : Lee M , Tariq AR , Kim M
Ref : Biochem Biophys Rep , 38 :101673 , 2024
Abstract : Endothelial progenitor cells (EPCs) are exclusive players in vasculogenesis and endothelial regeneration. EPCs are of two types and their differentiation is mediated by different growth factors. A decrease in EPC number and function causes cardiovascular abnormalities and reduced angiogenesis. Various studies has documented a role of EPCs in diabetes. EPCs treatment with different drugs improve insulin secretion but causes other abnormalities. In vivo and in vitro studies have reported anti glycation effect of gemigliptin but no data is available on in vitro effect of gemigliptin on EPC number and functional credibility. The current study was aimed to find an in vitro effect of gemigliptin on EPC number and function along with an effective treatment dose of gemigliptin. EPCs were isolated, cultured and phenotypically characterized using Dil- AcLDL and ulex-lectin fluorescence staining. EPCs were then treated with different doses of Zemiglo and their viability analyzed with viability assay using water-soluble tetrazolium salt (WST-1), by Annexin V and Propidium Iodide (PI) staining, senescence-associated beta-galactosidase (SA-beta-gal) staining, western blot and Flow cytometric analysis of apoptotic signals. The results demonstrated that the isolated EPCs has typical endothelial phenotypes. And these EPCs were of two types based on morphology i.e., early and late EPCs. Gemigliptin dose dependently improved the EPCs morphology and increased EPCs viability, the most effective dose being the 20 microM. Gemigliptin at 10 microM, 20 microM and 50 microM significantly increased the BCL-2 levels and at 20 microM significantly decreased the Caspase-3 levels in EPCs. In conclusion, gemigliptin dose dependently effects the EPCs viability and morphology through Caspase-3 signaling. Our results are the first report of gemigliptin effect on EPC viability and morphology.
ESTHER : Lee_2024_Biochem.Biophys.Rep_38_101673
PubMedSearch : Lee_2024_Biochem.Biophys.Rep_38_101673
PubMedID: 38444735

Title : Mathematical model of intestinal lipolysis of a long-chain triglyceride - Rezhdo_2024_bioRxiv__
Author(s) : Rezhdo O , West R , Kim M , Ng B , Saphier S , Carrier RL
Ref : Biorxiv , : , 2024
Abstract : Lipids are an important component of food and oral drug formulations. Upon release into gastrointestinal fluids, triglycerides, common components of foods and drug delivery systems, form emulsions and are digested into simpler amphiphilic lipids (e.g., fatty acids) that can associate with intestinal bile micelles and impact their drug solubilization capacity. Digestion of triglycerides is dynamic and dependent on lipid quantity and type, and quantities of other components in the intestinal environment (e.g., bile salts, lipases). The ability to predict lipid digestion kinetics in the intestine could enhance understanding of lipid impact on the fate of co-administered compounds (e.g., drugs, nutrients). In this study, we present a kinetic model that can predict the lipolysis of emulsions of triolein, a model long-chain triglyceride, as a function of triglyceride amount, droplet size, and quantity of pancreatic lipase in an intestinal environment containing bile micelles. The model is based on a Ping Pong Bi Bi mechanism coupled with quantitative analysis of partitioning of lipolysis products in colloids, including bile micelles, in solution. The agreement of lipolysis model predictions with experimental data suggests that the mechanism and proposed assumptions adequately represent triglyceride digestion in a simulated intestinal environment. In addition, we demonstrate the value of such a model over simpler, semi-mechanistic models reported in the literature. This lipolysis framework can serve as a basis for modeling digestion kinetics of different classes of triglycerides and other complex lipids as relevant in food and drug delivery systems.
ESTHER : Rezhdo_2024_bioRxiv__
PubMedSearch : Rezhdo_2024_bioRxiv__
PubMedID: 38746383

Title : Rational design, synthesis, biological evaluation, and molecular modeling of novel naphthamide derivatives possessing potent, reversible, and competitive inhibitory mode of action over human monoamine oxidase - Elkamhawy_2024_Mol.Divers__
Author(s) : Elkamhawy A , Oh JM , Kim M , El-Halaby LO , Abdellattif MH , Al-Karmalawy AA , Kim H , Lee K
Ref : Mol Divers , : , 2024
Abstract : Herein, a novel series of naphthamide derivatives has been rationally developed, synthesized, and evaluated for their inhibitory activity against monoamine oxidase (MAO) and cholinesterase (ChE) enzymes. Compared to the reported naphthalene-based hit IV, the new naphthamide hybrids 2a, 2c, 2g and 2h exhibited promising MAO inhibitory activities; with an IC(50) value of 0.294 microM, compound 2c most potently inhibited MAO-A, while compound 2g exhibited most potent MAO-B inhibitory activity with an IC(50) value of 0.519 microM. Compounds 2c and 2g showed selectivity index (SI) values of 6.02 for MAO-A and 2.94 for MAO-B, respectively. On the other hand, most compounds showed weak inhibitory activity against ChEs except 2a and 2h over butyrylcholinesterase (BChE). The most potent compounds 2c and 2g were found to be competitive and reversible MAO inhibitors based on kinetic and reversibility studies. Plausible interpretations of the observed biological effects were provided through molecular docking simulations. The drug-likeness predicted by SwissADME and Osiris property explorer showed that the most potent compounds (2a, 2c, 2g, and 2h) obey Lipinski's rule of five. Accordingly, in the context of neurological disorders, hybrids 2c and 2g may contribute to the identification of safe and potent therapeutic approaches in the near future.
ESTHER : Elkamhawy_2024_Mol.Divers__
PubMedSearch : Elkamhawy_2024_Mol.Divers__
PubMedID: 38727994

Title : Fermented Protaetia brevitarsis Larvae Improves Neurotoxicity in Chronic Ethanol-Induced-Dementia Mice via Suppressing AKT and NF-B Signaling Pathway - Lee_2024_Int.J.Mol.Sci_25_
Author(s) : Lee S , Shin H , Bae J , Lee T , Kim M , Jeon HB , Lee KH , Yoo HY , Park C , Lee HL , Kim JM , Go MJ , Lee HS , Kim JH , Heo HJ
Ref : Int J Mol Sci , 25 : , 2024
Abstract : This study was investigated to examine the neuroprotective effect of fermented Protaetia brevitarsis larvae (FPB) in ethanol-induced-dementia mice. Consumption of FPB by mice resulted in improved memory dysfunction in the Y-maze, passive avoidance, and Morris water maze tests. FPB significantly decreased oxidative stress by regulating levels of malondialdehyde (MDA), superoxide dismutase (SOD), and reduced glutathione (GSH) in brain tissues. In addition, FPB restored cerebral mitochondrial dysfunction by modulating levels of reactive oxygen species (ROS), mitochondrial membrane potential (MMP), and ATP. In addition, FPB enhanced the cholinergic system via the regulation of acetylcholine (ACh) content, acetylcholinesterase (AChE) activity, and expressions of AChE and choline acetyltransferase (ChAT) in brain tissues. FPB ameliorated neuronal apoptosis through modulation of the protein kinase B (AKT)/B-cell lymphoma (BCL)-2 signaling pathway. Also, FPB improved inflammation response by down-regulating the toll-like receptor (TLR)-4/nuclear factor (NF)-kappaB pathway. Additionally, FPB ameliorated synaptic plasticity via the increase of the expressions of synaptophysin (SYP), postsynaptic density protein (PSD)-95, and growth-associated protein (GAP)-43. Treatment with FPB also reinforced the blood-brain barrier by increasing tight junctions including zonula occludens (ZO)-1, occludin, and claudin-1. In conclusion, these results show that FPB can improve cognitive impairment via AKT/NF-kappaB pathways in ethanol-induced-dementia mice.
ESTHER : Lee_2024_Int.J.Mol.Sci_25_
PubMedSearch : Lee_2024_Int.J.Mol.Sci_25_
PubMedID: 38255784 || 38473876

Title : Balance-directed protein engineering of IsPETase enhances both PET hydrolysis activity and thermostability - Lee_2023_bioRxiv__
Author(s) : Lee SH , Seo H , Hong H , Park J , Ki D , Kim M , Kim HJ , Kim KJ
Ref : Biorxiv , : , 2023
Abstract : A mesophilic PETase from Ideonella sakaiensis (IsPETase) has been shown to exhibit high PET hydrolysis activity, but its low thermostability limits its industrial applications. We herein developed an engineering strategy for IsPETase to enhance PET hydrolysis activity, thermostability, and protein folding of the enzyme. Balance-directed Z1-PETase variant outperforms the stability-directed Z2-PETase variant under both mesophilic and thermophilic conditions, although Z2-PETase exhibits higher thermostability than Z1-PETase. The Z1-PETase is also superior to Fast-PETase, Dura-PETase, and LC-CICCG in terms of depolymerization rate regardless of temperature conditions we tested. Thus, maintaining a balance between PET hydrolysis activity and thermostability is essential for the developmentof high-performance PET hydrolases. In a pH-stat bioreactor, Z1-PETase depolymerized >90% of both transparent and colored post-consumer PET powders within 24 and 8 hours at 40C and 55C, respectively, demonstrating that the balance-directed IsPETase variant produced herein may be applicable in the bio-recycling of PET.
ESTHER : Lee_2023_bioRxiv__
PubMedSearch : Lee_2023_bioRxiv__
Gene_locus related to this paper: idesa-peth

Title : Three-directional engineering of IsPETase with enhanced protein yield, activity, and durability - Lee_2023_J.Hazard.Mater_459_132297
Author(s) : Lee SH , Seo H , Hong H , Park J , Ki D , Kim M , Kim HJ , Kim KJ
Ref : J Hazard Mater , 459 :132297 , 2023
Abstract : The mesophilic PETase from Ideonella sakaiensis (IsPETase) has been shown to exhibit high PET hydrolysis activity, but its low stability limits its industrial applications. Here, we developed a variant, Z1-PETase, with enhanced soluble protein yield and durability while maintaining or improving activity at lower temperatures. The selected Z1-PETase not only exhibited a 20-fold improvement in soluble protein yield compared to the previously engineered IsPETase(S121E/D186H/S242T/N246D) (4p) variant, but also demonstrated a 30% increase in low-temperature activity at 40 degreesC, along with an 11 degreesC increase in its Tm(D) value. The PET depolymerization test across a temperature range low to high (30-70 degreesC) confirmed that Z1-PETase exhibits high accessibility of mesophilic PET hydrolase and rapid depolymerizing rate at higher temperature in accordance with the thermal behaviors of polymer and enzyme. Additionally, structural interpretation indicated that the stabilization of specific active site loops in Z1-PETase contributes to enhanced thermostability without adversely impacting enzymatic activity. In a pH-stat bioreactor, Z1-PETase depolymerized > 90% of both transparent and colored post-consumer PET powders within 24 and 8 h at 40 degreesC and 55 degreesC, respectively, demonstrating that the utility of this IsPETase variant in the bio-recycling of PET.
ESTHER : Lee_2023_J.Hazard.Mater_459_132297
PubMedSearch : Lee_2023_J.Hazard.Mater_459_132297
PubMedID: 37595467
Gene_locus related to this paper: idesa-peth

Title : Molecular mechanism underlying high-affinity terephthalate binding and conformational change of TBP from Ideonella sakaiensis - Lee_2023_Int.J.Biol.Macromol_243_125252
Author(s) : Lee SH , Seo H , Hong H , Kim M , Kim KJ
Ref : Int J Biol Macromol , 243 :125252 , 2023
Abstract : Ideonella sakaiensis is the bacterium that can survive by degrading polyethylene terephthalate (PET) plastic, and terephthalic acid (TPA) binding protein (IsTBP) is an essential periplasmic protein for uptake of TPA into the cytosol for complete degradation of PET. Here, we demonstrated that IsTBP has remarkably high specificity for TPA among 33 monophenolic compounds and two 1,6-dicarboxylic acids tested. Structural comparisons with 6-carboxylic acid binding protein (RpAdpC) and TBP from Comamonas sp. E6 (CsTphC) revealed the key structural features that contribute to high TPA specificity and affinity of IsTBP. We also elucidated the molecular mechanism underlying the conformational change upon TPA binding. In addition, we developed the IsTBP variant with enhanced TPA sensitivity, which can be expanded for the use of TBP as a biosensor for PET degradation.
ESTHER : Lee_2023_Int.J.Biol.Macromol_243_125252
PubMedSearch : Lee_2023_Int.J.Biol.Macromol_243_125252
PubMedID: 37295700

Title : Designing multi-target-directed flavonoids: a strategic approach to Alzheimer's disease - Park_2023_Chem.Sci_14_9293
Author(s) : Park S , Kim M , Lin Y , Hong M , Nam G , Mieczkowski A , Kardos J , Lee YH , Lim MH
Ref : Chem Sci , 14 :9293 , 2023
Abstract : The underlying causes of Alzheimer's disease (AD) remain a mystery, with multiple pathological components, including oxidative stress, acetylcholinesterase, amyloid-beta, and metal ions, all playing a role. Here we report a strategic approach to designing flavonoids that can effectively tackle multiple pathological elements involved in AD. Our systematic investigations revealed key structural features for flavonoids to simultaneously target and regulate pathogenic targets. Our findings led to the development of a highly promising flavonoid that exhibits a range of functions, based on a complete structure-activity relationship analysis. Furthermore, our mechanistic studies confirmed that this flavonoid's versatile reactivities are driven by its redox potential and direct interactions with pathogenic factors. This work highlights the potential of multi-target-directed flavonoids as a novel solution in the fight against AD.
ESTHER : Park_2023_Chem.Sci_14_9293
PubMedSearch : Park_2023_Chem.Sci_14_9293
PubMedID: 37712013

Title : A physiologically-based pharmacokinetic\/pharmacodynamic (PBPK\/PD) model for the insecticide dimethoate - Reiss_2023_Xenobiotica__1
Author(s) : Reiss R , Loccisano A , Deines A , Kim M , Nallani G , Chandrasekaran A , Whatling P
Ref : Xenobiotica , :1 , 2023
Abstract : Dimethoate is an organophosphate insecticide that is converted in vivo to omethoate, the active toxic moiety. Omethoate inhibits acetylcholinesterase (AChE) in the brain and red blood cells (RBCs). This paper describes the development of rat and human physiologically-based pharmacokinetic/pharmacodynamic (PBPK/PD) models for dimethoate. The model simulates the absorption and distribution of dimethoate and omethoate, the conversion of dimethoate to omethoate and to other metabolites, the metabolism and excretion of omethoate, and the inhibition of RBC and brain AChE. An extensive data collection program to estimate metabolism and inhibition parameters is described. The suite of models includes an adult rat, post-natal rat, and human model. The rat models were evaluated by comparing model predictions of dimethoate and omethoate to measured blood time course data, and with RBC and brain AChE inhibition estimates from an extensive database of in vivo AChE measurements. After the demonstration of adequately fitted rat models that were robust to sensitivity analysis, the human model was applied for estimation of points-of-departure (PODs) for risk assessment using the human-specific parameters in the human PBPK/PD model. Thus, the standard interspecies uncertainty factor can be reduced from 10X to 1X.
ESTHER : Reiss_2023_Xenobiotica__1
PubMedSearch : Reiss_2023_Xenobiotica__1
PubMedID: 37706283

Title : Physiological roles and regulation of hepatic angiopoietin-like protein 3 in Japanese Black cattle (Bos taurus) during the fattening period - Shikida_2023_J.Anim.Sci__
Author(s) : Shikida R , Kim M , Futohashi M , Nishihara K , Lee H , Suzuki Y , Baek Y , Masaki T , Ikuta K , Iwamoto E , Uemoto Y , Haga S , Terada F , Roh S
Ref : J Anim Sci , : , 2023
Abstract : Angiopoietin-like protein 3 (ANGPTL3) is expressed predominantly in the liver and plays a major role in regulating the circulating triglyceride and lipoprotein fraction concentrations by inhibiting lipoprotein lipase (LPL) activity. Given these physiological roles, ANGPTL3 may play an important role in metabolic changes related to fat accumulation during the fattening period in Japanese Black. This study aimed to reveal the physiological roles of hepatic ANGPTL3 in Japanese Black steers (Bos taurus) during the fattening period and investigate the regulatory effects of hepatic ANGPTL3. To investigate the gene expression and protein localization of ANGPTL3, 18 tissue samples were collected from tree male Holstein bull calves aged 7 weeks. Biopsied liver tissues and blood samples were collected from 21 Japanese Black steers during the early (T1; 13 months of age), middle (T2; 20 months), and late fattening phases (T3; 28 months). Relative mRNA expression, blood metabolite concentrations, hormone concentrations, growth, and carcass traits were analyzed. To identify the regulatory factors of hepatic ANGPTL3, primary bovine hepatocytes collected by 2 Holstein calves aged 7 weeks were incubated with insulin, palmitate, oleate, propionate, acetate, or beta-hydroxybutyric acid (BHBA). The ANGPTL3 gene was most highly expressed in the liver, with minor expression in the renal cortex, lungs, reticulum, and jejunum in Holstein bull calves. In Japanese Black steers, relative ANGPTL3 mRNA expressions were less as fattening progressed, and blood triglyceride, total cholesterol, and non-esterified fatty acid (NEFA) concentrations increased. Relative ANGPTL8 and Liver X receptor alpha (LXRalpha) mRNA expressions decreased in late and middle fattening phases, respectively. Furthermore, relative ANGTPL3 mRNA expression was positively correlated with ANGPTL8 (r = 0.650; P < 0.01) and ANGPTL4 (r = 0.540; P < 0.05) in T3 and T1, respectively, and LXRalpha showed no correlation with ANGPTL3. Relative ANGTPL3 mRNA expression was negatively correlated with total cholesterol (r = -0.434; P < 0.05) and triglyceride (r = -0.645; P < 0.01) concentrations in T3 and T1, respectively; There was no significant correlation between ANGTPL3 and carcass traits. Relative ANGTPL3 mRNA expression in cultured bovine hepatocytes was downregulated in oleate treatment. Together, these findings suggest that ANGPTL3 downregulation in late fattening phases is associated with the changes in lipid metabolism.
ESTHER : Shikida_2023_J.Anim.Sci__
PubMedSearch : Shikida_2023_J.Anim.Sci__
PubMedID: 37317898

Title : Structural and biochemical insights into PsEst3, a new GHSR-type esterase obtained from Paenibacillus sp. R4 - Son_2023_IUCrJ_10_220
Author(s) : Son J , Choi W , Kim H , Kim M , Lee JH , Shin SC , Kim HW
Ref : IUCrJ , 10 :220 , 2023
Abstract : PsEst3, a psychrophilic esterase obtained from Paenibacillus sp. R4, which was isolated from the permafrost of Alaska, exhibits relatively high activity at low temperatures. Here, crystal structures of PsEst3 complexed with various ligands were generated and studied at atomic resolution, and biochemical studies were performed to analyze the structure-function relationship of PsEst3. Certain unique characteristics of PsEst3 distinct from those of other classes of lipases/esterases were identified. Firstly, PsEst3 contains a conserved GHSRA/G pentapeptide sequence in the GxSxG motif around the nucleophilic serine. Additionally, it contains a conserved HGFR/K consensus sequence in the oxyanion hole, which is distinct from that in other lipase/esterase families, as well as a specific domain composition (for example a helix-turn-helix motif) and a degenerative lid domain that exposes the active site to the solvent. Secondly, the electrostatic potential of the active site in PsEst3 is positive, which may cause unintended binding of negatively charged chemicals in the active site. Thirdly, the last residue of the oxyanion hole-forming sequence, Arg44, separates the active site from the solvent by sealing the acyl-binding pocket, suggesting that PsEst3 is an enzyme that is customized to sense an unidentified substrate that is distinct from those of classical lipases/esterases. Collectively, this evidence strongly suggests that PsEst3 belongs to a distinct family of esterases.
ESTHER : Son_2023_IUCrJ_10_220
PubMedSearch : Son_2023_IUCrJ_10_220
PubMedID: 36862488
Gene_locus related to this paper: 9mico-PsEst3

Title : Analysis of Non-Amyloidogenic Mutations in APP Supports Loss of Function Hypothesis of Alzheimer's Disease - Kim_2023_Int.J.Mol.Sci_24_2092
Author(s) : Kim M , Bezprozvanny I
Ref : Int J Mol Sci , 24 :2092 , 2023
Abstract : Proteolytic processing of amyloid precursor protein (APP) plays a critical role in pathogenesis of Azheimer's disease (AD). Sequential cleavage of APP by beta- and gamma-secretases leads to generation of Abeta40 (non-amyloidogenic) and Abeta42 (amyloidogenic) peptides. Presenilin-1 (PS1) or presenilin-2 (PS2) act as catalytic subunits of gamma-secretase. Multiple familial AD (FAD) mutations in APP, PS1, or PS2 affect APP proteolysis by gamma-secretase and influence levels of generated Abeta40 and Abeta42 peptides. The predominant idea in the field is the "amyloid hypothesis" that states that the resulting increase in Abeta42:Abeta40 ratio leads to "toxic gain of function" due to the accumulation of toxic Abeta42 plaques and oligomers. An alternative hypothesis based on analysis of PS1 conditional knockout mice is that "loss of function" of gamma-secretase plays an important role in AD pathogenesis. In the present paper, we propose a mechanistic hypothesis that may potentially reconcile these divergent ideas and observations. We propose that the presence of soluble Abeta peptides in endosomal lumen (and secreted to the extracellular space) is essential for synaptic and neuronal function. Based on structural modeling of Abeta peptides, we concluded that Abeta42 peptides and Abeta40 peptides containing non-amyloidogenic FAD mutations in APP have increased the energy of association with the membranes, resulting in reduced levels of soluble Abeta in endosomal compartments. Analysis of PS1-FAD mutations also revealed that all of these mutations lead to significant reduction in both total levels of Abeta produced and in the Abeta40/Abeta42 ratio, suggesting that the concentration of soluble Abeta in the endosomal compartments is reduced as a result of these mutations. We further reasoned that similar changes in Abeta production may also occur as a result of age-related accumulation of cholesterol and lipid oxidation products in postsynaptic spines. Our analysis more easily reconciled with the "loss of gamma-secretase function" hypothesis than with the "toxic gain of Abeta42 function" idea. These results may also explain why inhibitors of beta- and gamma- secretase failed in clinical trials, as these compounds are also expected to significantly reduce soluble Abeta levels in the endosomal compartments.
ESTHER : Kim_2023_Int.J.Mol.Sci_24_2092
PubMedSearch : Kim_2023_Int.J.Mol.Sci_24_2092
PubMedID: 36768421

Title : Free Linoleic Acid and Oleic Acid Reduce Fat Digestion and Absorption In Vivo as Potent Pancreatic Lipase Inhibitors Derived from Sesame Meal - Li_2022_Molecules_27_4910
Author(s) : Li X , Morita S , Yamada H , Koga K , Ota W , Furuta T , Yamatsu A , Kim M
Ref : Molecules , 27 :4910 , 2022
Abstract : Pancreatic lipase catalyzes the cleavage of triacylglycerols at the oil-water interface, and is known as the dominant determiner of dietary fat digestion. Reducing dietary fat digestion and absorption by modulating the activity of pancreatic lipase has become a favorable strategy to tackle obesity. Orlistat is, at present, the only pancreatic lipase inhibitor approved for the treatment of obesity; however, an array of gastrointestinal adverse effects associated with orlistat limits its tolerability. As a safe alternative to orlistat, a number of natural product-derived compounds with varying degrees of pancreatic lipase inhibitory activity have been reported. We herein reported that bioactivity-guided fractionation of sesame meal led to the identification of free linoleic acid and oleic acid as potent inhibitors of porcine pancreatic lipase in vitro with an IC50 of 23.1 microg/mL (82.4 microM) and 11.7 microg/mL (41.4 microM), respectively. In rats, a single oral dose of the mixture of these fatty acids significantly suppressed the elevation of blood triacylglycerol level following fat intake. These results substantiate the role of free linoleic acid and oleic acid as a novel class of natural product-derived functional molecules that act as pancreatic lipase inhibitors, and their potential for healthy, routine-based weight management.
ESTHER : Li_2022_Molecules_27_4910
PubMedSearch : Li_2022_Molecules_27_4910
PubMedID: 35956860

Title : Need for an Update for the Guideline for the Management of Mild Cognitive Impairment - Kim_2022_Dement.Neurocogn.Disord_21_107
Author(s) : Kim M , Moon SY
Ref : Dement Neurocogn Disord , 21 :107 , 2022
Abstract : Attention is being paid to diagnosis and treatment of mild cognitive impairment (MCI) because early diagnosis and preventive management can slow down the progression of Alzheimer's disease. In particular, in the present era, the use of biomarkers for predicting conversion into dementia is permitted in medical practice. Therefore, authors aimed to propose additional considerations when updating guidelines for the management of MCI, including predictable biomarkers, revising treatment option after additional clinical trials for cholinesterase inhibitors, and detailed regimes for lifestyle interventions. After reviewing 3 patients with MCI by detailed evaluation, we realized that cholinesterase inhibitors were not recommended. In addition, regular exercise and cognitive training were only possible recommendations for patients according to current guidelines, although all 3 patients had evidence of beta-amyloid accumulation and related neurodegeneration. Furthermore, caregivers for all 3 patients were worried whether patients could keep doing regular exercise and cognitive training by themselves and asked about the economic training system which monitors patients so that they can keep training. Therefore, we propose that guidelines for managing MCI need to be updated in the present era when the use of biomarkers for predicting conversion into dementia is permitted in medical practice.
ESTHER : Kim_2022_Dement.Neurocogn.Disord_21_107
PubMedSearch : Kim_2022_Dement.Neurocogn.Disord_21_107
PubMedID: 36407292

Title : Optimization of Fermentation Conditions of Artemisia capillaris for Enhanced Acetylcholinesterase and Butyrylcholinesterase - Choi_2022_Foods_11_
Author(s) : Choi J , Yoon J , Kim M
Ref : Foods , 11 : , 2022
Abstract : In this study, the fermentation of Artemisia capillaris by probiotic Leuconostoc mesenteroides MKJW (MKJW) was optimized to increase the acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitory and antioxidant activities using the response surface method (RSM). The independent variables were the contents of A. capillaris, Gryllus bimaculatus, and yeast extract, while the dependent variables were AChE inhibitory activity, BuChE inhibitory activity, and antioxidant activities such as FRAP, reducing power, and DPPH radical scavenging ability. Seventeen experimental runs were designed with RSM and analyzed after fermentation with MKJW. Quadratic models were used to analyze the inhibition of AChE and BuChE, and a linear model was used to analyze the FRAP. The three models were significantly appropriate (p < 0.0001). The highest optimal condition of the AChE inhibitory activity was derived by a multiple regression equation. When the optimum fermentation conditions were A. capillaris 6.75%, G. bimaculatus 0.18%, and yeast extract 1.27%, 91.1% was reached for AChE inhibitory, 74.0% for BuChE inhibitory, and 34.1 mM FeSO4 for FRAP. The predicted dependent variables were not significantly different from the experimental values (p > 0.05). In conclusion, the A. capillaris fermented by MKJW might be used as a natural antidementia improving agent with AChE inhibitory, BuChE inhibitory, and antioxidant activities.
ESTHER : Choi_2022_Foods_11_
PubMedSearch : Choi_2022_Foods_11_
PubMedID: 35954035

Title : No prominent toxicity of polyethylene microplastics observed in neonatal mice following intratracheal instillation to dams during gestational and neonatal period - Han_2021_Toxicol.Res_37_443
Author(s) : Han Y , Song Y , Kim GW , Ha C , Lee J , Kim M , Son H , Lee G , Gautam R , Heo Y
Ref : Toxicol Res , 37 :443 , 2021
Abstract : Microplastics (MPs) have been recently recognized as a global environmental threat and its exposure as a risk factor to human health. Health effects through MPs exposure have been recently reported, especially through oral route of exposure. Since MPs could be exposed to humans through routes other than oral, this study was designed to evaluate whether MPs exposed through the inhalation route could be delivered to fetal mice and exhibit systemic toxicity. Polyethylene (PE) with 10-45 microm diameter were administered at 0 (distilled water, vehicle control), 6 (low administration), and 60 (high administration) microg/mouse/day to 3 pregnant dams per group from gestational day 9 to postnatal day (PND) 7 through intratracheal instillation. Dams and neonates were sacrificed at PND 7 and blood was collected. Various neonatal organs including brain, lung, heart, stomach, intestine, kidneys, and ovaries were collected for histopathological observation and weight measurement. No influence of PE-MPs administration was observed on the number of offsprings born, but the body and organs' weight were heavier overall in the high administration group of dams and neonates than the other groups with statistical significance achieved in the heart and spleen weight. Level of serum acetylcholinesterase and glutathione peroxidase activity was decreased in the high administration group of dams and neonates compared with the other groups. Lung was the organ with highest number of PE-MPs present in the both administration groups of dams, and PE-MPs were also detected in liver and intestine of the high administration dams. Whereas, PND7 neonates showed accountable numbers of PE-MPs only in kidneys of the high administration group. Overall, the present study indicates that PE-MPs instilled intratracheally could be delivered to neonates from dams. Even though adverse effects from PE-MPs exposure during pregnant and lactational period are less prominent on both dam and neonate, potential of second-generation toxicity could be considered for further investigation.
ESTHER : Han_2021_Toxicol.Res_37_443
PubMedSearch : Han_2021_Toxicol.Res_37_443
PubMedID: 34631501

Title : Neuroprotective Effect of Cudrania tricuspidata Fruit Extracts on Scopolamine-Induced Learning and Memory Impairment - Jee_2020_Int.J.Mol.Sci_21_
Author(s) : Jee SC , Lee KM , Kim M , Lee YJ , Kim S , Park JO , Sung JS
Ref : Int J Mol Sci , 21 : , 2020
Abstract : Cudrania tricuspidata has diverse biological activities, such as antioxidant, anti-inflammatory, anticancer, and neuroprotective effects. This study investigated the protective effects of C. tricuspidata fruit extracts (CTFE) against scopolamine (SCO)-induced neuron impairment. The neuroprotective effects of CTFE on SCO-induced memory dysfunction were confirmed in mice using the Barnes maze test. The results showed that co-treatment of SCO and CTFE increased the stay time in the target zone compared with SCO treatment alone. Similarly, the results obtained by the fear conditioning test revealed that SCO-CTFE co-treatment induced the freezing action time under both the contextual fear condition and the cued fear condition compared with SCO treatment alone. Moreover, we showed that CTFE reduced the SCO-induced acetylcholinesterase (AChE) activity, thereby increasing the acetylcholine concentration in mice hippocampal tissues. Consistent with the improvement of memory and recognition function in vivo, our in vitro results showed that CTFE induced cAMP response element binding protein (CREB) and extracellular regulated kinase 1/2 (ERK1/2) activity in PC12 cells and reduced SCO-induced AChE activity. In addition, the microarray results of the hippocampal tissue support our data showing that CTFE affects gene expressions associated with neurogenesis and neuronal cell differentiation markers such as spp1 and klk6. Overall, CTFE exerts a neuroprotective effect via regulation of the CREB and ERK1/2 signaling pathways and could be a therapeutic candidate for neurodegenerative diseases.
ESTHER : Jee_2020_Int.J.Mol.Sci_21_
PubMedSearch : Jee_2020_Int.J.Mol.Sci_21_
PubMedID: 33276674

Title : Potential Regulatory Role of Human-Carboxylesterase-1 Glycosylation in Liver Cancer Cell Growth - Na_2020_J.Proteome.Res_19_4867
Author(s) : Na K , Kim M , Kim CY , Lim JS , Cho JY , Shin H , Lee HJ , Kang BJ , Han DH , Kim H , Baik JH , Swiatek-de Lange M , Karl J , Paik YK
Ref : J Proteome Res , 19 :4867 , 2020
Abstract : We previously reported that human carboxylesterase 1 (CES1), a serine esterase containing a unique N-linked glycosyl group at Asn79 (N79 CES1), is a candidate serological marker of hepatocellular carcinoma (HCC). CES1 is normally present at low-to-undetectable levels in normal human plasma, HCC tumors, and major liver cancer cell lines. To investigate the potential mechanism underlying the suppression of CES1 expression in liver cancer cells, we took advantage of the low detectability of this marker in tumors by overexpressing CES1 in multiple HCC cell lines, including stable Hep3B cells. We found that the population of CES1-overexpressing (OE) cells decreased and that their doubling time was longer compared with mock control liver cancer cells. Using interactive transcriptome, proteome, and subsequent Gene Ontology enrichment analysis of CES1-OE cells, we found substantial decreases in the expression levels of genes involved in cell cycle regulation and proliferation. This antiproliferative function of the N79 glycan of CES1 was further supported by quantitative real-time polymerase chain reaction, flow cytometry, and an apoptosis protein array assay. An analysis of the levels of key signaling target proteins via Western blotting suggested that CES1 overexpression exerted an antiproliferative effect via the PKD1/PKCmicro signaling pathway. Similar results were also seen in another HCC cell line (PLC/RFP/5) after transient transfection with CES1 but not in similarly treated non-HCC cell lines (e.g., HeLa and Tera-1 cells), suggesting that CES1 likely exerts a liver cell-type-specific suppressive effect. Given that the N-linked glycosyl group at Asn79 (N79 glycan) of CES1 is known to influence CES1 enzyme activity, we hypothesized that the post-translational modification of CES1 at N79 may be linked to its antiproliferative activity. To investigate the regulatory effect of the N79 glycan on cellular growth, we mutated the single N-glycosylation site in CES1 from Asn to Gln (CES1-N79Q) via site-directed mutagenesis. Fluorescence 2-D difference gel electrophoresis protein expression analysis of cell lysates revealed an increase in cell growth and a decrease in doubling time in cells carrying the N79Q mutation. Thus our results suggest that CES1 exerts an antiproliferative effect in liver cancer cells and that the single N-linked glycosylation at Asn79 plays a potential regulatory role. These functions may underlie the undetectability of CES1 in human HCC tumors and liver cancer cell lines. Mass spectrometry data are available via ProteomeXchange under the identifier PXD021573.
ESTHER : Na_2020_J.Proteome.Res_19_4867
PubMedSearch : Na_2020_J.Proteome.Res_19_4867
PubMedID: 33206527
Gene_locus related to this paper: human-CES1

Title : Evaluating the Memory Enhancing Effects of Angelica gigas in Mouse Models of Mild Cognitive Impairments - Kim_2019_Nutrients_12_
Author(s) : Kim M , Song M , Oh HJ , Hui J , Bae W , Shin J , Ji SD , Koh YH , Suh JW , Park H , Maeng S
Ref : Nutrients , 12 : , 2019
Abstract : (1) Background: By 2050, it is estimated that 130 million people will be diagnosed with dementia, and currently approved medicines only slow the progression. So preventive intervention is important to treat dementia. Mild cognitive impairment is a condition characterized by some deterioration in cognitive function and increased risk of progressing to dementia. Therefore, the treatment of mild cognitive impairment (MCI) is a possible way to prevent dementia. Angelica gigas reduces neuroinflammation, improves circulation, and inhibits cholinesterase, which can be effective in the prevention of Alzheimer's disease and vascular dementia and the progression of mild cognitive impairment. (2) Methods: Angelica gigas (AG) extract 1 mg/kg was administered to mildly cognitive impaired mice, models based on mild traumatic brain injury and chronic mild stress. Then, spatial, working, and object recognition and fear memory were measured. (3) Result: Angelica gigas improved spatial learning, working memory, and suppressed fear memory in the mild traumatic brain injury model. It also improved spatial learning and suppressed cued fear memory in the chronic mild stress model animals. (4) Conclusions: Angelica gigas can improve cognitive symptoms in mild cognitive impairment model mice.
ESTHER : Kim_2019_Nutrients_12_
PubMedSearch : Kim_2019_Nutrients_12_
PubMedID: 31905851

Title : Orobol: An Isoflavone Exhibiting Regulatory Multifunctionality against Four Pathological Features of Alzheimer's Disease - Nam_2019_ACS.Chem.Neurosci_10_3386
Author(s) : Nam G , Ji Y , Lee HJ , Kang J , Yi Y , Kim M , Lin Y , Lee YH , Lim MH
Ref : ACS Chem Neurosci , 10 :3386 , 2019
Abstract : We report orobol as a multifunctional isoflavone with the ability to (i) modulate the aggregation pathways of both metal-free and metal-bound amyloid-beta, (ii) interact with metal ions, (iii) scavenge free radicals, and (iv) inhibit the activity of acetylcholinesterase. Such a framework with multifunctionality could be useful for developing chemical reagents to advance our understanding of multifaceted pathologies of neurodegenerative disorders, including Alzheimer's disease.
ESTHER : Nam_2019_ACS.Chem.Neurosci_10_3386
PubMedSearch : Nam_2019_ACS.Chem.Neurosci_10_3386
PubMedID: 31199606

Title : Aspergillus terreus (Trichocomaceae): A Natural, Eco-Friendly Mycoinsecticide for Control of Malaria, Filariasis, Dengue Vectors and Its Toxicity Assessment Against an Aquatic Model Organism Artemia nauplii - Ragavendran_2018_Front.Pharmacol_9_1355
Author(s) : Ragavendran C , Srinivasan R , Kim M , Natarajan D
Ref : Front Pharmacol , 9 :1355 , 2018
Abstract : Vector-borne diseases like malaria, filariasis, and dengue are transmitted by mosquitoes and they cause global mortality and morbidity due to an increased resistance against commercial insecticides. The present study was aimed to evaluate the neurobehavioral toxicity, knock-down effect, histopathology, ovicidal, adulticidal, and smoke toxicity effect of Aspergillus terreus extract against three mosquito species, namely Anopheles stephensi, Culex quinquefasciatus, and Aedes aegypti (Diptera: Culicidae). The isolated fungal strain was identified as A. terreus (GenBank accession no: KX694148.1) through morphological and molecular (phylogenetic) analysis. The morphological changes in the treated fourth instar larvae shown the demelanization of cuticle and shrinkage of the internal cuticle of anal papillae. The time duration of extract exposure against the larvae determines the level of toxicity. The extract treated larvae were displayed excitation, violent vertical and horizontal movements with aggressive anal biting behavior as the toxic effect on the neuromuscular system. The results of the biochemical analysis indicated that a decrease in the level of acetylcholinesterase, alpha-carboxylesterase, and beta-carboxylesterase in extract treated fourth instar larvae of all tested mosquito species. The findings of histopathological investigation shown the disorganization of the abdominal region, mainly in mid, hindgut, and gastric caeca, loss of antenna, lateral hair, caudal hair, upper and lower head hairs in the mycelium extract treated An. stephensi, Cx. quinquefasciatus, and Ae. aegypti. The ovicidal bioassay test results showed the mosquito hatchability percentage was directly related to the concentrations of mycelium extract. Nil hatchability of mosquito eggs was noticed at 500 mug/ml concentration. The adulticidal activity of fungal mycelia ethyl acetate extract resulted in a dose-dependent activity (15 and 30 min recovery periods). The higher concentration of extract (1000 mg/L) acted as a repellent, the adult mosquitoes showed restless movement, uncontrolled/anesthetic flight at last died. The better adulticidal activity was observed in the ethyl acetate extract against An. stephensi, Cx. quinquefasciatus followed by Ae. aegypti with the best score of LD50 and LD90 values and nil mortality was found in the control. The results of smoke toxicity assay of the mycelia extract exhibited significant mortality rate against Ae. aegypti (91%), Cx. quinquefasciatus (89%), and An. stephensi (84%). In addition, the present investigation reported the stability and toxic effects of A. terreus mycelium ethyl acetate extract on Artemia nauplii. The swimming speed (0.88 mm s(-1)) of A. terreus was reduced with ethyl extract 24 h treatment whereas, the control A. nauplii showed the normal speed of 2.96 mm s(-1). Altered behavior and swimming movement were observed in the 8 h A. terreus mycelium extract treated A. nauplii. A pale yellow color substance (metabolites) was found in the mid-gut region of the mycelial extract exposed A. nauplii. The outcome of the present study, suggest that the A. terreus metabolites might serve as an alternative, cost-effective, eco-friendly, and target specific mosquitocidal agent in the future.
ESTHER : Ragavendran_2018_Front.Pharmacol_9_1355
PubMedSearch : Ragavendran_2018_Front.Pharmacol_9_1355
PubMedID: 30534070

Title : Panax ginseng as an adjuvant treatment for Alzheimer's disease - Kim_2018_J.Ginseng.Res_42_401
Author(s) : Kim HJ , Jung SW , Kim SY , Cho IH , Kim HC , Rhim H , Kim M , Nah SY
Ref : J Ginseng Res , 42 :401 , 2018
Abstract : Longevity in medicine can be defined as a long life without mental or physical deficits. This can be prevented by Alzheimer's disease (AD). Current conventional AD treatments only alleviate the symptoms without reversing AD progression. Recent studies demonstrated that Panax ginseng extract improves AD symptoms in patients with AD, and the two main components of ginseng might contribute to AD amelioration. Ginsenosides show various AD-related neuroprotective effects. Gintonin is a newly identified ginseng constituent that contains lysophosphatidic acids and attenuates AD-related brain neuropathies. Ginsenosides decrease amyloid beta-protein (Abeta) formation by inhibiting beta- and gamma-secretase activity or by activating the nonamyloidogenic pathway, inhibit acetylcholinesterase activity and Abeta-induced neurotoxicity, and decrease Abeta-induced production of reactive oxygen species and neuroinflammatory reactions. Oral administration of ginsenosides increases the expression levels of enzymes involved in acetylcholine synthesis in the brain and alleviates Abeta-induced cholinergic deficits in AD models. Similarly, gintonin inhibits Abeta-induced neurotoxicity and activates the nonamyloidogenic pathway to reduce Abeta formation and to increase acetylcholine and choline acetyltransferase expression in the brain through lysophosphatidic acid receptors. Oral administration of gintonin attenuates brain amyloid plaque deposits, boosting hippocampal cholinergic systems and neurogenesis, thereby ameliorating learning and memory impairments. It also improves cognitive functions in patients with AD. Ginsenosides and gintonin attenuate AD-related neuropathology through multiple routes. This review focuses research demonstrating that ginseng constituents could be a candidate as an adjuvant for AD treatment. However, clinical investigations including efficacy and tolerability analyses may be necessary for the clinical acceptance of ginseng components in combination with conventional AD drugs.
ESTHER : Kim_2018_J.Ginseng.Res_42_401
PubMedSearch : Kim_2018_J.Ginseng.Res_42_401
PubMedID: 30337800

Title : Signal-amplifying nanoparticle\/hydrogel hybrid microarray biosensor for metal-enhanced fluorescence detection of organophosphorus compounds - Kim_2018_Biofabrication_10_035002
Author(s) : Kim M , Kwon JE , Lee K , Koh WG
Ref : Biofabrication , 10 :035002 , 2018
Abstract : In this study, we developed an enzyme-based miniaturized fluorescence biosensor to detect paraoxon, one of the most well-known neurotoxic organophosphorus compounds. The biosensor was fabricated with poly(ethylene glycol) (PEG) hydrogel microarrays that entrapped acetylcholinesterase (AChE) and quantum dots (QDs) as fluorescence reporters. Metal-enhanced fluorescence (MEF) was utilized to amplify the fluorescence signal, which was achieved by decorating QDs on the surface of silica-coated silver nanoparticles (Ag@Silica). The MEF effects of Ag@Silica were optimized by tuning the thickness of the silica shells, and under the optimized conditions, the fluorescence intensity was shown to be increased 5 fold, compared with the system without MEF. PEG hydrogel microarray entrapping QD-decorated Ag@Silica and AChE was prepared via photopatterning process. The entrapped AChE hydrolyzed paraoxon to produce p-nitrophenol within the hydrogel microstructure, which subsequently quenched the fluorescence of the QDs on the surface of Ag@Silica. The MEF-assisted fluorescence detection resulted in a significant enhancement of paraoxon detection. The detection limit was approximately 1.0 x 10(-10) M and 2.0 x 10(-7) M for sensing with and without MEF, respectively. The successful integration of a hydrogel microarray system with a microfluidic system was demonstrated to be a potential application for the MEF-based micro-total-analysis-system.
ESTHER : Kim_2018_Biofabrication_10_035002
PubMedSearch : Kim_2018_Biofabrication_10_035002
PubMedID: 29451128

Title : Constant exposure to environmental concentrations of the antifouling biocide Sea-Nine retards growth and reduces acetylcholinesterase activity in a marine mysid - Do_2018_Aquat.Toxicol_205_165
Author(s) : Do JW , Haque MN , Lim HJ , Min BH , Lee DH , Kang JH , Kim M , Jung JH , Rhee JS
Ref : Aquat Toxicol , 205 :165 , 2018
Abstract : Sea-Nine (4,5-dichloro-2-n-octyl-4-isothiazoline3-one; DCOIT) antifoulant has been widely used owing to its broad spectrum of biocide activity against major fouling organisms. In this study, several physiological parameters of a marine mysid were analyzed upon exposure to sublethal environmental concentrations (1 and 100 ng L(-1)) of Sea-Nine in two exposure conditions, intermittent (weekly; once per week) and constant (daily; once per 24 h) exposure, for 4 weeks. In both experimental conditions, growth retardation, acetylcholinesterase (AChE) activity, glutathione S-transferase (GST) activity, and number of newborn juveniles as second generation, together with their survival were measured. Morphometric parameters of total body, antennal scale, exopod, endopod, and telson were significantly retarded by 22%, 14%, 13%, and 24%, respectively, by daily exposure to 100 ng L(-1) Sea-Nine for 4 weeks. Significant inhibition of AChE activity was observed at week 4 in the 100 ng L(-1) daily Sea-Nine-exposed groups, whereas no significant GST activity was measured at the same experimental conditions. Inhibition of AChE activity would be associated with impairment of cholinergic system and may adversely modulate growth parameters of the mysid. The number of newly hatched juveniles from females that were exposed daily to 100 ng L(-1) Sea-Nine was significantly lower than that of the control. Although no significant differences were observed between survival percentages of newborn juveniles for 30 days, mortality (NOEC and LC50) increased in the surviving offspring from the 100 ng L(-1)-exposed 1st generation of mysids. These findings suggested that constant exposure to Sea-Nine has detrimental effects on the growth parameters of marine mysids with inhibition of AChE activity.
ESTHER : Do_2018_Aquat.Toxicol_205_165
PubMedSearch : Do_2018_Aquat.Toxicol_205_165
PubMedID: 30391725

Title : DPP9 enzymatic activity in hematopoietic cells is dispensable for mouse hematopoiesis - Kim_2018_Immunol.Lett_198_60
Author(s) : Kim M , von Muenchow L , Le Meur T , Kueng B , Gapp B , Weber D , Dietrich W , Kovarik J , Rolink AG , Ksiazek I
Ref : Immunol Lett , 198 :60 , 2018
Abstract : Dipeptidyl peptidase 9 (DPP9) is a ubiquitously expressed intracellular prolyl peptidase implicated in immunoregulation. However, its physiological relevance in the immune system remains largely unknown. We investigated the role of DPP9 enzyme in immune system by characterizing DPP9 knock-in mice expressing a catalytically inactive S729A mutant of DPP9 enzyme (DPP9(ki/ki) mice). DPP9(ki/ki) mice show reduced number of lymphoid and myeloid cells in fetal liver and postnatal blood but their hematopoietic cells are fully functional and able to reconstitute lymphoid and myeloid lineages even in competitive mixed chimeras. These studies demonstrate that inactivation of DPP9 enzymatic activity does not lead to any perturbations in mouse hematopoiesis.
ESTHER : Kim_2018_Immunol.Lett_198_60
PubMedSearch : Kim_2018_Immunol.Lett_198_60
PubMedID: 29709545
Gene_locus related to this paper: human-DPP9 , mouse-dpp9

Title : ULK1 prevents cardiac dysfunction in obesity through autophagy-meditated regulation of lipid metabolism - An_2017_Cardiovasc.Res_113_1137
Author(s) : An M , Ryu DR , Won Park J , Ha Choi J , Park EM , Eun Lee K , Woo M , Kim M
Ref : Cardiovascular Research , 113 :1137 , 2017
Abstract : Aims: Autophagy is essential to maintain tissue homeostasis, particularly in long-lived cells such as cardiomyocytes. Whereas many studies support the importance of autophagy in the mechanisms underlying obesity-related cardiac dysfunction, the role of autophagy in cardiac lipid metabolism remains unclear. In the heart, lipotoxicity is exacerbated by cardiac lipoprotein lipase (LPL), which mediates accumulation of fatty acids to the heart through intravascular triglyceride (TG) hydrolysis. Methods and results: In both genetic and dietary models of obesity, we observed a substantial increase in cardiac LPL protein levels without any change in messenger ribonucleic acid (mRNA). This was accompanied by a dramatic down-regulation of autophagy in the heart, as revealed by reduced levels of unc-51 like kinase-1 (ULK1) protein. To further explore the relationship between cardiac LPL and autophagy, we generated cardiomyocyte-specific knockout mice for ulk1 (Myh6-cre/ulk1fl/fl), Lpl (Myh6-cre/Lplfl/fl), and mice with a combined deficiency (Myh6-cre/ulk1fl/flLplfl/fl). Similar to genetic and dietary models of obesity, Myh6-cre/ulk1fl/fl mice had a substantial increase in cardiac LPL levels. When these mice were fed a high-fat diet (HFD), they showed elevated cardiac TG levels and deterioration in heart function. However, with combined deletion of LPL and ULK1 in Myh6-cre/ulk1fl/flLplfl/fl mice, HFD feeding did not lead to alterations in levels of TG or diacylglycerol, or in cardiac function. To further elucidate the role of autophagy in cardiac lipid metabolism, we infused a peptide that enhanced autophagy (D-Tat-beclin1). This effectively lowered LPL levels at the coronary lumen by restoring autophagy in the genetic model of obesity. This decrease in cardiac luminal LPL was associated with a reduction in TG levels and recovery of cardiac function. Conclusion: These results provide clear evidence of the critical role of modulating cardiac LPL activity through autophagy-mediated proteolytic clearance as a potential novel strategy to overcome obesity-related cardiomyopathy.
ESTHER : An_2017_Cardiovasc.Res_113_1137
PubMedSearch : An_2017_Cardiovasc.Res_113_1137
PubMedID: 28430962
Gene_locus related to this paper: mouse-lipli

Title : DPP9 enzyme activity controls survival of mouse migratory tongue muscle progenitors and its absence leads to neonatal lethality due to suckling defect - Kim_2017_Dev.Biol_431_297
Author(s) : Kim M , Minoux M , Piaia A , Kueng B , Gapp B , Weber D , Haller C , Barbieri S , Namoto K , Lorenz T , Wirsching J , Bassilana F , Dietrich W , Rijli FM , Ksiazek I
Ref : Developmental Biology , 431 :297 , 2017
Abstract : Dipeptidyl peptidase 9 (DPP9) is an intracellular N-terminal post-proline-cleaving enzyme whose physiological function remains largely unknown. We investigated the role of DPP9 enzyme in vivo by characterizing knock-in mice expressing a catalytically inactive mutant form of DPP9 (S729A; DPP9ki/ki mice). We show that DPP9ki/ki mice die within 12-18h after birth. The neonatal lethality can be rescued by manual feeding, indicating that a suckling defect is the primary cause of neonatal lethality. The suckling defect results from microglossia, and is characterized by abnormal formation of intrinsic muscles at the distal tongue. In DPP9ki/ki mice, the number of occipital somite-derived migratory muscle progenitors, forming distal tongue intrinsic muscles, is reduced due to increased apoptosis. In contrast, intrinsic muscles of the proximal tongue and extrinsic tongue muscles, which derive from head mesoderm, develop normally in DPP9ki/ki mice. Thus, lack of DPP9 activity in mice leads to impaired tongue development, suckling defect and subsequent neonatal lethality due to impaired survival of a specific subset of migratory tongue muscle progenitors.
ESTHER : Kim_2017_Dev.Biol_431_297
PubMedSearch : Kim_2017_Dev.Biol_431_297
PubMedID: 28887018
Gene_locus related to this paper: mouse-dpp9

Title : Effects of overweight and the PLA2G7 V279F polymorphism on the association of age with systolic blood pressure - Kim_2017_PLoS.One_12_e0173611
Author(s) : Kim M , Yoo HJ , Jang HY , Lee SH , Lee JH
Ref : PLoS ONE , 12 :e0173611 , 2017
Abstract : This prospective study aimed to determine the effects of the persistence of overweight for three years and the PLA2G7 V279F polymorphism, as well as the interaction between these factors, on the association of age with blood pressure (BP). Healthy middle-aged subjects with normotensive BP were divided into the normal-weight and overweight groups. The PLA2G7 V279F genotype, BP, lipoprotein-associated phospholipase A2 (Lp-PLA2) activity, and oxidized low-density lipoprotein (ox-LDL) were determined. Lp-PLA2 activity was lower in the F allele subjects (n = 111) than in those with the VV genotype (n = 389). The overweight individuals with the F allele had lower Lp-PLA2 activity and ox-LDL at both baseline and after three years and lower systolic and diastolic BP and LDL cholesterol after three years compared with those with the VV phenotype. After three years, the overweight subjects with the VV phenotype exhibited greater increases in Lp-PLA2 activity, systolic BP, and ox-LDL than those with the F allele and normal-weight subjects with the VV phenotype. A multivariate analysis revealed that the PLA2G7 V279F genotype, baseline BMI, changes in Lp-PLA2 activity and ox-LDL remained independently and positively associated with changes in systolic BP. The simultaneous presence of the PLA2G7 279VV genotype and persistence of overweight synergistically increases the risk for hypertension, whereas lower Lp-PLA2 activity in PLA2G7 279F allele carriers might offer certain protection against hypertension, even in individuals who have been overweight for over three years.
ESTHER : Kim_2017_PLoS.One_12_e0173611
PubMedSearch : Kim_2017_PLoS.One_12_e0173611
PubMedID: 28334001
Gene_locus related to this paper: human-PLA2G7

Title : Circulating Lp-PLA activity correlates with oxidative stress and cytokines in overweight\/obese postmenopausal women not using hormone replacement therapy - Paik_2015_Age.(Dordr)_37_32
Author(s) : Paik JK , Kim M , Yen Y , Ahn HY , Lee SH , Lee JH
Ref : Age (Dordr) , 37 :32 , 2015
Abstract : Controversy remains regarding whether there is an association between circulating lipoprotein-associated phospholipase A2 (Lp-PLA2), cytokines, and oxidative stress in healthy postmenopausal women. We investigated the influence of age on Lp-PLA2 activity in postmenopausal women not using hormone therapy and the relationship of Lp-PLA2 enzyme activity to serum cytokine levels and oxidative stress indices. Normal weight (n = 1284) and overweight/obese (n = 707) postmenopausal women not using hormone therapy were categorized into five age groups: 50-54, 55-59, 60-64, 65-69, and 70-89 years. Overweight-obese women showed higher plasma Lp-PLA2 activity, urinary 8-epi-prostaglandin F2alpha (8-epi-PGF2alpha), serum interleukin (IL)-6, and smaller LDL particles than normal-weight women after adjusting for age, years postmenopause, smoking, drinking, blood pressure, glucose, insulin, lipid profiles, BMI, and waist circumference. Overweight/obese women 70-89 years old showed higher Lp-PLA2 activity than those aged 50-54 years, whereas no significant difference in Lp-PLA2 activity existed across normal-weight female age groups. Overweight/obese women aged <= 65 years showed higher Lp-PLA2, oxidized LDL (ox-LDL), IL-6, and 8-epi-PGF2alpha than age-matched normal-weight controls. Overweight/obese women aged <= 70 years had higher ox-LDL levels than those aged 50-59, and overweight/obese women aged 65-89 showed higher IL-6 and 8-epi-PGF2alpha. There were strong positive correlations between Lp-PLA2 and ox-LDL (r = 0.385, P < 0.001), Lp-PLA2 and IL-6 (r = 0.293, P < 0.001), and ox-LDL and IL-6 (r = 0.303, P < 0.001) in overweight/obese women; however, these relationships were weak in normal-weight women. These results suggest that aging and obesity-related oxidative and inflammatory mediators are associated with Lp-PLA2 activity in overweight/obese postmenopausal women not using hormone therapy.
ESTHER : Paik_2015_Age.(Dordr)_37_32
PubMedSearch : Paik_2015_Age.(Dordr)_37_32
PubMedID: 25840804

Title : Draft Genome Sequences of Burkholderia cenocepacia ET12 Lineage Strains K56-2 and BC7 - Varga_2013_Genome.Announc_1_e00841
Author(s) : Varga JJ , Losada L , Zelazny AM , Kim M , McCorrison J , Brinkac L , Sampaio EP , Greenberg DE , Singh I , Heiner C , Ashby M , Nierman WC , Holland SM , Goldberg JB
Ref : Genome Announc , 1 : , 2013
Abstract : The Burkholderia cepacia complex (BCC) is a group of closely related bacteria that are responsible for respiratory infections in immunocompromised humans, most notably those with cystic fibrosis (CF). We report the genome sequences for Burkholderia cenocepacia ET12 lineage CF isolates K56-2 and BC7.
ESTHER : Varga_2013_Genome.Announc_1_e00841
PubMedSearch : Varga_2013_Genome.Announc_1_e00841
PubMedID: 24136849
Gene_locus related to this paper: 9burk-a0u8m3 , burcj-b4efi5 , burcj-b4ek59 , burce-a0a088tsj6

Title : Genome Sequences of 28 Bordetella pertussis U.S. Outbreak Strains Dating from 2010 to 2012 - Harvill_2013_Genome.Announc_1_e01075
Author(s) : Harvill ET , Goodfield LL , Ivanov Y , Meyer JA , Newth C , Cassiday P , Tondella ML , Liao P , Zimmerman J , Meert K , Wessel D , Berger J , Dean JM , Holubkov R , Burr J , Liu T , Brinkac L , Kim M , Losada L
Ref : Genome Announc , 1 : , 2013
Abstract : Despite the availability of highly effective vaccines, Bordetella pertussis incidence has been rapidly rising in highly vaccinated populations. Recent outbreaks have received media attention, feeding concerns about the emergence of dangerous new strains with increased virulence or that escape vaccine-induced immunity. To accelerate the study of this reemerging pathogen, we sequenced the genomes of 28 B. pertussis strains isolated during outbreaks from 2010 through 2012, making both strains and sequence data available to the scientific community.
ESTHER : Harvill_2013_Genome.Announc_1_e01075
PubMedSearch : Harvill_2013_Genome.Announc_1_e01075
PubMedID: 24356839

Title : Draft genome sequence of Escherichia coli W26, an enteric strain isolated from cow feces - Kim_2012_J.Bacteriol_194_5149
Author(s) : Kim M , Yi H , Cho YJ , Jang J , Hur HG , Chun J
Ref : Journal of Bacteriology , 194 :5149 , 2012
Abstract : An enteric bacterium, Escherichia coli W26 (KACC 16630), was isolated from feces from a healthy cow in South Korea. Here, we report the draft genome sequence of the isolate, which is closely affiliated with commensal strains belonging to E. coli phylogroup B1.
ESTHER : Kim_2012_J.Bacteriol_194_5149
PubMedSearch : Kim_2012_J.Bacteriol_194_5149
PubMedID: 22933771
Gene_locus related to this paper: ecoli-fes , ecoli-ycfp , ecoli-yiel , ecoli-yqia , ecoli-yuar

Title : Genome sequencing and analysis of Yersina pestis KIM D27, an avirulent strain exempt from select agent regulation - Losada_2011_PLoS.One_6_e19054
Author(s) : Losada L , Varga JJ , Hostetler J , Radune D , Kim M , Durkin S , Schneewind O , Nierman WC
Ref : PLoS ONE , 6 :e19054 , 2011
Abstract : Yersinia pestis is the causative agent of the plague. Y. pestis KIM 10+ strain was passaged and selected for loss of the 102 kb pgm locus, resulting in an attenuated strain, KIM D27. In this study, whole genome sequencing was performed on KIM D27 in order to identify any additional differences. Initial assemblies of 454 data were highly fragmented, and various bioinformatic tools detected between 15 and 465 SNPs and INDELs when comparing both strains, the vast majority associated with A or T homopolymer sequences. Consequently, Illumina sequencing was performed to improve the quality of the assembly. Hybrid sequence assemblies were performed and a total of 56 validated SNP/INDELs and 5 repeat differences were identified in the D27 strain relative to published KIM 10+ sequence. However, further analysis showed that 55 of these SNP/INDELs and 3 repeats were errors in the KIM 10+ reference sequence. We conclude that both 454 and Illumina sequencing were required to obtain the most accurate and rapid sequence results for Y. pestis KIMD27. SNP and INDELS calls were most accurate when both Newbler and CLC Genomics Workbench were employed. For purposes of obtaining high quality genome sequence differences between strains, any identified differences should be verified in both the new and reference genomes.
ESTHER : Losada_2011_PLoS.One_6_e19054
PubMedSearch : Losada_2011_PLoS.One_6_e19054
PubMedID: 21559501
Gene_locus related to this paper: yerpe-y3224

Title : Biomarker responses in pelagic and benthic fish over 1 year following the Hebei Spirit oil spill (Taean, Korea) - Jung_2011_Mar.Pollut.Bull_62_1859
Author(s) : Jung JH , Kim M , Yim UH , Ha SY , An JG , Won JH , Han GM , Kim NS , Addison RF , Shim WJ
Ref : Mar Pollut Bull , 62 :1859 , 2011
Abstract : After the Hebei Spirit oil spill incident (7th December, 2007) in the west coast of Korea, contamination of biliary PAH metabolite and hepatic biomarkers in a pelagic and a benthic fish was monitored for 1 year. Concentrations of 16 PAHs and alkylated PAHs in fish muscle were highest (22.0 ng/g d.w. for 16 PAHs and 284 ng/g d.w. for alkylated PAHs) at 5 days after the spill and then decreased rapidly to background levels at 11 months after the spill. Fish from the oiled site had elevated biliary PAH metabolite concentrations immediately after the spill; these declined steadily in both species, but were still above reference site concentrations 2 months after the spill. Oiled-site fish showed hepatic CYP 1A induction whose trend closely followed those of biliary PAH metabolite concentrations, implying continuous exposure to PAHs. Brain acetylcholinesterase activity was not related to oil exposure.
ESTHER : Jung_2011_Mar.Pollut.Bull_62_1859
PubMedSearch : Jung_2011_Mar.Pollut.Bull_62_1859
PubMedID: 21658730

Title : Acute up-regulation of adipose triglyceride lipase and release of non-esterified fatty acids by dexamethasone in chicken adipose tissue - Serr_2011_Lipids_46_813
Author(s) : Serr J , Suh Y , Oh SA , Shin S , Kim M , Latshaw JD , Lee K
Ref : Lipids , 46 :813 , 2011
Abstract : The mechanism of adipose tissue lipolysis has not been fully elucidated. Greater understanding of this process could allow for increased feed efficiency and reduced fat in poultry. Studies in avian species may provide important insight in developing therapies for human obesity, as lipolytic pathways are highly conserved. Adipose triglyceride lipase (ATGL) cleaves triacylglycols, releasing non-esterified fatty acids (NEFA) into the bloodstream. Glucocorticoids have been shown to elevate circulating NEFA. To determine the regulation of ATGL and regulator proteins comparative gene identification-58 (CGI-58) and G(0)/G(1) switch gene 2 (G0S2) by glucocorticoid, 36 chickens received an injection of dexamethasone (4 mg/kg). Saline was administered to an additional 12 birds to determine any effect of stress during handling. Dexamethasone-injected birds were harvested at 0, 0.5, 1, 2, 4, and 6 h after treatment; saline-treated birds were collected at 4 and 6 h. Abdominal and subcutaneous adipose tissue and blood were collected. Gene and protein expression were analyzed via quantitative real-time PCR and western blot. Compared with the saline group, ATGL expression increased in birds injected with dexamethasone. When dexamethasone response was compared to the untreated group up to 6 h following injection, an increase in ATGL protein was observed as quickly as 0.5 h and increased further from 1 to 6 h. Plasma NEFA and glucose increased gradually from 0 to 6 h, reaching statistical significance at 4 h. These data show that ATGL expression is stimulated by glucocorticoid in a time-dependent manner.
ESTHER : Serr_2011_Lipids_46_813
PubMedSearch : Serr_2011_Lipids_46_813
PubMedID: 21725859

Title : Immobilization of cross-linked lipase aggregates onto magnetic beads for enzymatic degradation of polycaprolactone - Kim_2010_J.Basic.Microbiol_50_218
Author(s) : Kim M , Park JM , Um HJ , Lee DH , Lee KH , Kobayashi F , Iwasaka Y , Hong CS , Min J , Kim YH
Ref : J Basic Microbiol , 50 :218 , 2010
Abstract : Candida rugosa lipase was immobilized on amino-functionalized magnetic supports via cross-linked enzyme aggregates (CLEA) and used to enhance the enzymatic degradation of polycaprolactone (PCL). The maximum amounts of lipase immobilized on the magnetic beads using glutaraldehyde as a coupling agent were determined to be 33.7 mg/g of beads with an 81% recovery of activity after immobilization. Compared to the free enzyme, the immobilized lipase showed the optimum pH at 1 unit higher (pH 8.0) and also retained its enzymatic activity at higher temperatures. There was 62.9% retention of lipase activity after 30 consecutive reuses, indicating its stability and reusability in aqueous media. Moreover, the immobilized lipase maintained more than 80% of its initial activity during 30 days storage period, while the free lipase lost all under same condition. In addition, the immobilized lipase showed a more than 6-fold increase in biodegradability over the free lipase when the immobilized lipase was used to degrade PCL in a batch system. Higher thermal and storage stability, as well as good durability after repeated use of the immobilized lipase CLEA, highlights its potential applicability as large scale continuous systems for the enzymatic degradation of PCL.
ESTHER : Kim_2010_J.Basic.Microbiol_50_218
PubMedSearch : Kim_2010_J.Basic.Microbiol_50_218
PubMedID: 20473952

Title : Complete genome sequence of Burkholderia glumae BGR1 - Lim_2009_J.Bacteriol_191_3758
Author(s) : Lim J , Lee TH , Nahm BH , Choi YD , Kim M , Hwang I
Ref : Journal of Bacteriology , 191 :3758 , 2009
Abstract : Burkholderia glumae is the causative agent of grain and seedling rot in rice and of bacterial wilt in many field crops. Here, we report the complete genome sequence of B. glumae BGR1 isolated from a diseased rice panicle in Korea.
ESTHER : Lim_2009_J.Bacteriol_191_3758
PubMedSearch : Lim_2009_J.Bacteriol_191_3758
PubMedID: 19329631
Gene_locus related to this paper: burgb-c5acc8 , burgb-c5acp4 , burgb-c5act2 , burgb-c5ae33 , burgb-c5aeb9 , burgb-c5ag69 , burgb-c5ail4 , burgb-c5ain7 , burgb-c5air4 , burgb-c5aji9 , burgb-c5ajv4 , burgb-c5ak59 , burgb-c5al55 , burgb-c5al59 , burgb-c5als0 , burgb-c5amb0 , burgb-c5amd6 , burgb-c5amf7 , burgb-c5aii1 , burgb-c5aaw5 , burgb-c5ag31

Title : White matter hyperintensities and cognitive dysfunction in Alzheimer disease - Heo_2009_J.Geriatr.Psychiatry.Neurol_22_207
Author(s) : Heo JH , Lee ST , Kon C , Park HJ , Shim JY , Kim M
Ref : J Geriatr Psychiatry Neurol , 22 :207 , 2009
Abstract : The effect of white matter lesions in magnetic resonance imaging or vascular atherosclerosis on cognitive function is not fully understood in Alzheimer disease (AD). In this investigation, we examined the influence of white matter lesions on cognitive decline in AD. A total of 142 patients with AD (44 men, mean age 65.7 + 7.6 years; mean education period 7.8 + 5.0 years) were included. Patients were divided into 4 groups based on the severities of white matter hyperintensities (WMH) in brain magnetic resonance images (MRI) using Fazekas scale. Cognitive functions were determined using the Korean version of the Mini-Mental State Examination (K-MMSE) and the Clinical Dementia Rating (CDR) scale before acetylcholinesterase inhibitors were administered. Of the 142 patients, 30% (43/142) had no white matter signal abnormality (grade 0). Fourteen percentage (20/142) were grade 1, 42% (59/142) grade 2, and 14% (20/142) were grade 3. Mean K-MMSE scores declined as MRI grades increased to grade 2 and 3 compared to grade 0 (P < .01). Clinical Dementia Ratings were also aggravated by MRI grade. These results remained significant after adjusting for compounding factors affecting cognitive functions; sex, age, number of years in full-time education, hypertension, diabetes, hypercholesterolemia, smoking, and atrial fibrillation. The presence of WMHs were associated with score of MMSE and CDR impairment in patients with AD. These features could be a correctable factor hastening cognitive decline in AD.
ESTHER : Heo_2009_J.Geriatr.Psychiatry.Neurol_22_207
PubMedSearch : Heo_2009_J.Geriatr.Psychiatry.Neurol_22_207
PubMedID: 19433863

Title : Galantamine reduces striatal degeneration in 3-nitropropionic acid model of Huntington's disease - Park_2008_Neurosci.Lett_448_143
Author(s) : Park JE , Lee ST , Im WS , Chu K , Kim M
Ref : Neuroscience Letters , 448 :143 , 2008
Abstract : The acetylcholinesterase inhibitor (AChEI) galantamine is currently used to treat mild to moderate Alzheimer's disease (AD), and it has been suggested to have several neuroprotective effects. To investigate the potential application of this drug to the treatment of Huntington's disease, we examined whether galantamine can reduce the striatal degeneration induced by the mitochondrial toxin, 3-nitropropionic acid (3NP). 3NP (63 mg/kg/day) was delivered to Lewis rats by osmotic pumps for 5 consecutive days, and the rats received intraperitoneal administration of either different concentrations of galantamine (1mg/kg/day or 10 mg/kg/day, twice daily) or vehicle (saline) throughout the experiment. Galantamine attenuated the 3NP-induced neurologic deficits on days 2-5. Galantamine-treated rats showed smaller striatal lesion volumes measured by Nissl staining and lower numbers of TUNEL(+) apoptotic cells when compared to the vehicle-treated rats. Galantamine failed to reduce the striatal lesion volume when co-administered with mecamylamine, a nicotinic acetylcholine receptor antagonist. Our data indicate that galantamine can attenuate neurodegeneration in a Huntington's disease model by modulating nAChR.
ESTHER : Park_2008_Neurosci.Lett_448_143
PubMedSearch : Park_2008_Neurosci.Lett_448_143
PubMedID: 18938211

Title : Genome sequence of Aeromonas hydrophila ATCC 7966T: jack of all trades - Seshadri_2006_J.Bacteriol_188_8272
Author(s) : Seshadri R , Joseph SW , Chopra AK , Sha J , Shaw J , Graf J , Haft D , Wu M , Ren Q , Rosovitz MJ , Madupu R , Tallon L , Kim M , Jin S , Vuong H , Stine OC , Ali A , Horneman AJ , Heidelberg JF
Ref : Journal of Bacteriology , 188 :8272 , 2006
Abstract : The complete genome of Aeromonas hydrophila ATCC 7966(T) was sequenced. Aeromonas, a ubiquitous waterborne bacterium, has been placed by the Environmental Protection Agency on the Contaminant Candidate List because of its potential to cause human disease. The 4.7-Mb genome of this emerging pathogen shows a physiologically adroit organism with broad metabolic capabilities and considerable virulence potential. A large array of virulence genes, including some identified in clinical isolates of Aeromonas spp. or Vibrio spp., may confer upon this organism the ability to infect a wide range of hosts. However, two recognized virulence markers, a type III secretion system and a lateral flagellum, that are reported in other A. hydrophila strains are not identified in the sequenced isolate, ATCC 7966(T). Given the ubiquity and free-living lifestyle of this organism, there is relatively little evidence of fluidity in terms of mobile elements in the genome of this particular strain. Notable aspects of the metabolic repertoire of A. hydrophila include dissimilatory sulfate reduction and resistance mechanisms (such as thiopurine reductase, arsenate reductase, and phosphonate degradation enzymes) against toxic compounds encountered in polluted waters. These enzymes may have bioremediative as well as industrial potential. Thus, the A. hydrophila genome sequence provides valuable insights into its ability to flourish in both aquatic and host environments.
ESTHER : Seshadri_2006_J.Bacteriol_188_8272
PubMedSearch : Seshadri_2006_J.Bacteriol_188_8272
PubMedID: 16980456
Gene_locus related to this paper: aerhh-a0kes5 , aerhh-a0keu7 , aerhh-a0kf11 , aerhh-a0kfl9 , aerhh-a0kfn7 , aerhh-a0kgz2 , aerhh-a0khk1 , aerhh-a0kin3 , aerhh-a0kiv7 , aerhh-a0kkc6 , aerhh-a0kkj8 , aerhh-a0klc3 , aerhh-a0kme3 , aerhh-a0knr1 , aerhh-a0knu8 , aerhh-a0kp50 , aerhh-a0kpk1 , aerhh-a0kr22 , aerhy-PHAC , aerpu-PEP , aerhh-a0khd8 , aerhh-a0kle4 , aerhy-a0a028v5g9

Title : Transient calcium and dopamine increase PKA activity and DARPP-32 phosphorylation - Lindskog_2006_PLoS.Comput.Biol_2_e119
Author(s) : Lindskog M , Kim M , Wikstrom MA , Blackwell KT , Kotaleski JH
Ref : PLoS Comput Biol , 2 :e119 , 2006
Abstract : Reinforcement learning theorizes that strengthening of synaptic connections in medium spiny neurons of the striatum occurs when glutamatergic input (from cortex) and dopaminergic input (from substantia nigra) are received simultaneously. Subsequent to learning, medium spiny neurons with strengthened synapses are more likely to fire in response to cortical input alone. This synaptic plasticity is produced by phosphorylation of AMPA receptors, caused by phosphorylation of various signalling molecules. A key signalling molecule is the phosphoprotein DARPP-32, highly expressed in striatal medium spiny neurons. DARPP-32 is regulated by several neurotransmitters through a complex network of intracellular signalling pathways involving cAMP (increased through dopamine stimulation) and calcium (increased through glutamate stimulation). Since DARPP-32 controls several kinases and phosphatases involved in striatal synaptic plasticity, understanding the interactions between cAMP and calcium, in particular the effect of transient stimuli on DARPP-32 phosphorylation, has major implications for understanding reinforcement learning. We developed a computer model of the biochemical reaction pathways involved in the phosphorylation of DARPP-32 on Thr34 and Thr75. Ordinary differential equations describing the biochemical reactions were implemented in a single compartment model using the software XPPAUT. Reaction rate constants were obtained from the biochemical literature. The first set of simulations using sustained elevations of dopamine and calcium produced phosphorylation levels of DARPP-32 similar to that measured experimentally, thereby validating the model. The second set of simulations, using the validated model, showed that transient dopamine elevations increased the phosphorylation of Thr34 as expected, but transient calcium elevations also increased the phosphorylation of Thr34, contrary to what is believed. When transient calcium and dopamine stimuli were paired, PKA activation and Thr34 phosphorylation increased compared with dopamine alone. This result, which is robust to variation in model parameters, supports reinforcement learning theories in which activity-dependent long-term synaptic plasticity requires paired glutamate and dopamine inputs.
ESTHER : Lindskog_2006_PLoS.Comput.Biol_2_e119
PubMedSearch : Lindskog_2006_PLoS.Comput.Biol_2_e119
PubMedID: 16965177

Title : A magnetic nanoprobe technology for detecting molecular interactions in live cells - Won_2005_Science_309_121
Author(s) : Won J , Kim M , Yi YW , Kim YH , Jung N , Kim TK
Ref : Science , 309 :121 , 2005
Abstract : Technologies to assess the molecular targets of biomolecules in living cells are lacking. We have developed a technology called magnetism-based interaction capture (MAGIC) that identifies molecular targets on the basis of induced movement of superparamagnetic nanoparticles inside living cells. Efficient intracellular uptake of superparamagnetic nanoparticles (coated with a small molecule of interest) was mediated by a transducible fusogenic peptide. These nanoprobes captured the small molecule's labeled target protein and were translocated in a direction specified by the magnetic field. Use of MAGIC in genome-wide expression screening identified multiple protein targets of a drug. MAGIC was also used to monitor signal-dependent modification and multiple interactions of proteins.
ESTHER : Won_2005_Science_309_121
PubMedSearch : Won_2005_Science_309_121
PubMedID: 15994554

Title : Sequence, annotation, and analysis of synteny between rice chromosome 3 and diverged grass species - Buell_2005_Genome.Res_15_1284
Author(s) : Buell CR , Yuan Q , Ouyang S , Liu J , Zhu W , Wang A , Maiti R , Haas B , Wortman J , Pertea M , Jones KM , Kim M , Overton L , Tsitrin T , Fadrosh D , Bera J , Weaver B , Jin S , Johri S , Reardon M , Webb K , Hill J , Moffat K , Tallon L , Van Aken S , Lewis M , Utterback T , Feldblyum T , Zismann V , Iobst S , Hsiao J , de Vazeille AR , Salzberg SL , White O , Fraser C , Yu Y , Kim H , Rambo T , Currie J , Collura K , Kernodle-Thompson S , Wei F , Kudrna K , Ammiraju JS , Luo M , Goicoechea JL , Wing RA , Henry D , Oates R , Palmer M , Pries G , Saski C , Simmons J , Soderlund C , Nelson W , de la Bastide M , Spiegel L , Nascimento L , Huang E , Preston R , Zutavern T , Palmer LE , O'Shaughnessy A , Dike S , McCombie WR , Minx P , Cordum H , Wilson R , Jin W , Lee HR , Jiang J , Jackson S
Ref : Genome Res , 15 :1284 , 2005
Abstract : Rice (Oryza sativa L.) chromosome 3 is evolutionarily conserved across the cultivated cereals and shares large blocks of synteny with maize and sorghum, which diverged from rice more than 50 million years ago. To begin to completely understand this chromosome, we sequenced, finished, and annotated 36.1 Mb ( approximately 97%) from O. sativa subsp. japonica cv Nipponbare. Annotation features of the chromosome include 5915 genes, of which 913 are related to transposable elements. A putative function could be assigned to 3064 genes, with another 757 genes annotated as expressed, leaving 2094 that encode hypothetical proteins. Similarity searches against the proteome of Arabidopsis thaliana revealed putative homologs for 67% of the chromosome 3 proteins. Further searches of a nonredundant amino acid database, the Pfam domain database, plant Expressed Sequence Tags, and genomic assemblies from sorghum and maize revealed only 853 nontransposable element related proteins from chromosome 3 that lacked similarity to other known sequences. Interestingly, 426 of these have a paralog within the rice genome. A comparative physical map of the wild progenitor species, Oryza nivara, with japonica chromosome 3 revealed a high degree of sequence identity and synteny between these two species, which diverged approximately 10,000 years ago. Although no major rearrangements were detected, the deduced size of the O. nivara chromosome 3 was 21% smaller than that of japonica. Synteny between rice and other cereals using an integrated maize physical map and wheat genetic map was strikingly high, further supporting the use of rice and, in particular, chromosome 3, as a model for comparative studies among the cereals.
ESTHER : Buell_2005_Genome.Res_15_1284
PubMedSearch : Buell_2005_Genome.Res_15_1284
PubMedID: 16109971
Gene_locus related to this paper: orysa-Q852M6 , orysa-Q8S5X5 , orysa-Q84QZ6 , orysa-Q84QY7 , orysa-Q851E3 , orysa-q6ave2 , orysj-cgep , orysj-q0dud7 , orysj-q10j20 , orysj-q10ss2

Title : Effects of green tea polyphenol on cognitive and acetylcholinesterase activities - Kim_2004_Biosci.Biotechnol.Biochem_68_1977
Author(s) : Kim HK , Kim M , Kim S , Chung JH
Ref : Biosci Biotechnol Biochem , 68 :1977 , 2004
Abstract : The effect of tea polyphenol (TP) on cognitive and anti-cholinesterase activity was examined in scopolamine-treated mice. Chronic administration of TP significantly reversed scopolamine-induced retention deficits in both step-through passive avoidance and spontaneous alternation behavior tasks. Furthermore, TP exhibited a dramatic inhibitory effect on acetylcholinesterase activity. This finding suggests that TP might be useful in the treatment of Alzheimer's disease.
ESTHER : Kim_2004_Biosci.Biotechnol.Biochem_68_1977
PubMedSearch : Kim_2004_Biosci.Biotechnol.Biochem_68_1977
PubMedID: 15388975