Author Report for: Kim JNo contact information in database for Kim J
Fortibui MM, Jang M, Lee S, Ryoo IJ, Ahn JS, Ko SK, Kim J Ref: ACS Appl Bio Mater, :, 2022 : PubMed ESTHER: Fortibui_2022_ACS.Appl.Bio.Mater__ PubMedSearch: Fortibui 2022 ACS.Appl.Bio.Mater PubMedID: 35446530 Abstract Acetylcholinesterase (AChE) is a pivotal enzyme that is closely related with multiple neurological diseases, such as brain disorders or alterations in the neurotransmission and cancer. The development of convenient methods for imaging AChE activity in biological samples is very important to understand its mechanisms and functions in a living system. Herein, a fluorescent probe exhibiting emission in the near-infrared (NIR) region is developed to detect AChE and visualize biological AChE activities. This probe exhibits a quick response time, reasonable detection limit, and a large Stokes shift accompanied by the NIR emission. The probe has much better reactivity toward AChE than butyrylcholinesterase, which is one of the significant interfering substances. The outstanding specificity of the probe is proved by cellular imaging AChE activity and successful mapping in different regions of zebrafish. Such an effective probe can greatly contribute to ongoing efforts to design emission probes that have distinct properties to assay AChE in biological systems. Title: Insecticide resistance in pepper greenhouse populations of Aphis gossypii (Hemiptera: Aphididae) in Korea Nam HY, Kim S, Lee SH, Lee JH, Kim J Ref: Pestic Biochem Physiol, 182:105033, 2022 : PubMed ESTHER: Nam_2022_Pestic.Biochem.Physiol_182_105033 PubMedSearch: Nam 2022 Pestic.Biochem.Physiol 182 105033 PubMedID: 35249654 Abstract The cotton aphid or melon aphid, Aphis gossypii Glover (Hemiptera: Aphididae), is a polyphagous insect pest with a wide host range. Two distinct genetic clusters were found in A. gossypii populations in Korea. To determine whether the division of the genetic clusters was driven by insecticide selection pressure, the frequencies of insecticide resistance-associated mutations on three representative insecticide target genes [i.e., nicotinic acetylcholine receptor gene (nAChR), voltage-gated sodium channel gene (vgsc), and acetylcholinesterase 1 gene (ace-1)] were predicted in A. gossypii populations with known genetic structures. Most populations revealed heterozygosity-resistant alleles for the nAChR R81T and vgsc M918L mutations, but homozygous-resistant alleles for the ace-1 S431F mutation. However, assessment of the three mutation frequencies revealed no apparent correlation between the genetic structures and the resistance profiles. The regression analysis revealed no correlation between the genetic cluster ratios and resistance allele frequencies (R81T, S431F, and M918L). We used three insecticides that are commonly used in greenhouses: imidacloprid (neonicotinoid), acephate (organophosphate), and esfenvalerate (pyrethroid), to test resistance and susceptibility in A. gossypii populations. The bioassay results revealed that the BS_19 (Busan) and JE_19 (Jeongeup) populations were resistant to imidacloprid and acephate, the HS_19 (Honseong) population was resistant to acephate and esfenvalerate, and susceptible lab strains only exhibited resistance to acephate. The bioassay results were correlated with mutation frequency, but no correlation was detected among genetic clusters. These results suggest that the distinct genetic structure observed in the Korean populations of A. gossypii is not likely influenced by insecticide resistance traits, but rather by other factors. Title: Epoxyeicosatrienoic Acid administration or Soluble Epoxide Hydrolase inhibition attenuates renal fibrogenesis in obstructive nephropathy Noh MR, Jang HS, Salem FE, Ferrer FA, Kim J, Padanilam BJ Ref: American Journal of Physiology Renal Physiol, :, 2022 : PubMed ESTHER: Noh_2022_Am.J.Physiol.Renal.Physiol__ PubMedSearch: Noh 2022 Am.J.Physiol.Renal.Physiol PubMedID: 36475868 Abstract Epoxyeicosatrienoic acids (EETs) are arachidonic acid metabolites with biological effects, including anti-apoptotic, anti-inflammatory, and anti-fibrotic functions. Soluble epoxide hydrolase (sEH)-mediated hydrolysis of EETs to dihydroxyeicosatrienoic acids (DHET) attenuates these effects. Recent studies have demonstrated inhibition of sEH prevents renal tubulointerstitial fibrosis and inflammation in chronic kidney disease (CKD) model. Given the pathophysiological role of the EET pathway in CKD, we investigated if administration of EETs regioisomers and/or sEH inhibition will promote anti-fibrotic and reno-protective effects in renal fibrosis following UUO. EETs administration abolished tubulointerstitial fibrogenesis, as demonstrated by reduced fibroblast activation and collagen deposition after UUO. Inflammatory response was prevented as demonstrated by decreased neutrophil and macrophage infiltration and expression of cytokines in EETs-administered UUO kidneys. EETs administration and/or sEH inhibition significantly reduced M1 macrophage markers while M2 macrophage markers were highly upregulated. Furthermore, UUO-induced oxidative stress, tubular injury, and apoptosis were all downregulated following EETs administration. Combined EETs administration and sEH inhibition however, had no additive effect in attenuating inflammation and renal interstitial fibrogenesis after UUO. Taken together, our findings provide a mechanistic understanding of how EETs prevent kidney fibrogenesis during obstructive nephropathy, and suggest EETs treatment as a potential therapeutic strategy to treat fibrotic diseases. Title: Esculetin and Fucoidan Attenuate Autophagy and Apoptosis Induced by Zinc Oxide Nanoparticles through Modulating Reactive Astrocyte and Proinflammatory Cytokines in the Rat Brain Song WJ, Kim J, Shin T, Jeong MS, Kim KN, Yun JH, Wie MB Ref: Toxics, 10:, 2022 : PubMed ESTHER: Song_2022_Toxics_10_ PubMedSearch: Song 2022 Toxics 10 PubMedID: 35448455 Abstract We examined the protective effects of esculetin and fucoidan against the neurotoxicity of ZnO NPs in rats. Ninety rats were divided into nine groups and pre-treated with esculetin or fucoidan 1 h before ZnO NP administration on a daily basis for 2 weeks. Serum and brain homogenates were examined by enzyme-linked immunosorbent assay (ELISA), and neurons, microglia, and astrocytes in the hippocampal region were examined with immunohistochemical analysis. The serum levels of interleukin-1-beta (IL-1beta), 3-nitrotyrosine (3-NT), superoxide dismutase (SOD), and 8-hydroxy-2'-deoxyguanosine (8-OHdG) were altered in the ZnO NP treatment groups. Brain IL-1beta and TNF-alpha levels were elevated after ZnO NP administration, and these effects were inhibited by esculetin and fucoidan. SOD, 8-OHdG, and acetylcholinesterase (AChE) levels in the brain were decreased after ZnO NP administration. The brain levels of beclin-1 and caspase-3 were elevated after ZnO NP treatment, and these effects were significantly ameliorated by esculetin and fucoidan. The number of reactive astrocytes measured by counting glial fibrillary acidic protein (GFAP)-positive cells, but not microglia, increased following ZnO NP treatment, and esculetin and fucoidan ameliorated the changes. Esculetin and fucoidan may be beneficial for preventing ZnO NP-mediated autophagy and apoptosis by the modulation of reactive astrocyte and proinflammatory cytokines in the rat brain. Title: Nematicidal Activity of Benzyloxyalkanols against Pine Wood Nematode Kim J, Lee SJ, Park JO, Yoon KA Ref: Biomolecules, 11:, 2021 : PubMed ESTHER: Kim_2021_Biomolecules_11_ PubMedSearch: Kim 2021 Biomolecules 11 PubMedID: 33807784 Abstract Pine wilt disease (PWD) is caused by the pine wood nematode (PWN; Bursaphelenchus xylophilus) and causes severe environmental damage to global pine forest ecosystems. The current strategies used to control PWN are mainly chemical treatments. However, the continuous use of these reagents could result in the development of pesticide-resistant nematodes. Therefore, the present study was undertaken to find potential alternatives to the currently used PWN control agents abamectin and emamectin. Benzyloxyalkanols (BzOROH; R = C(2)-C(9)) were synthesized and the nematicidal activity of the synthetic compounds was investigated. Enzymatic inhibitory assays (acetylcholinesterase (AChE) and glutathione S-transferase (GST)) were performed with BzOC8OH and BzOC9OH to understand their mode of action. The benzyloxyalkanols showed higher nematicidal activity than did benzyl alcohol. Among the tested BzOROHs, BzC8OH and BzC9OH showed the strongest nematicidal activity. The LD(50) values of BzC8OH and BzC9OH were 246.1 and 158.0 ppm, respectively. No enzyme inhibitory activity was observed for BzC8OH and BzC9OH. The results suggested that benzyloxyalcohols could be an alternative nematicidal agent. Title: Donepezil Regulates LPS and Abeta-Stimulated Neuroinflammation through MAPK/NLRP3 Inflammasome/STAT3 Signaling Kim J, Lee HJ, Park SK, Park JH, Jeong HR, Lee S, Lee H, Seol E, Hoe HS Ref: Int J Mol Sci, 22:, 2021 : PubMed ESTHER: Kim_2021_Int.J.Mol.Sci_22_ PubMedSearch: Kim 2021 Int.J.Mol.Sci 22 PubMedID: 34638977 Abstract The acetylcholinesterase inhibitors donepezil and rivastigmine have been used as therapeutic drugs for Alzheimer's disease (AD), but their effects on LPS- and Abeta-induced neuroinflammatory responses and the underlying molecular pathways have not been studied in detail in vitro and in vivo. In the present study, we found that 10 or 50 microM donepezil significantly decreased the LPS-induced increases in the mRNA levels of a number of proinflammatory cytokines in BV2 microglial cells, whereas 50 microM rivastigmine significantly diminished only LPS-stimulated IL-6 mRNA levels. In subsequent experiments in primary astrocytes, donepezil suppressed only LPS-stimulated iNOS mRNA levels. To identify the molecular mechanisms by which donepezil regulates LPS-induced neuroinflammation, we examined whether donepezil alters LPS-stimulated proinflammatory responses by modulating LPS-induced downstream signaling and the NLRP3 inflammasome. Importantly, we found that donepezil suppressed LPS-induced AKT/MAPK signaling, the NLRP3 inflammasome, and transcription factor NF-kB/STAT3 phosphorylation to reduce neuroinflammatory responses. In LPS-treated wild-type mice, a model of neuroinflammatory disease, donepezil significantly attenuated LPS-induced microglial activation, microglial density/morphology, and proinflammatory cytokine COX-2 and IL-6 levels. In a mouse model of AD (5xFAD mice), donepezil significantly reduced Abeta-induced microglial and astrocytic activation, density, and morphology. Taken together, our findings indicate that donepezil significantly downregulates LPS- and Abeta-evoked neuroinflammatory responses in vitro and in vivo and may be a therapeutic agent for neuroinflammation-associated diseases such as AD. Title: Effects of Inoculants Producing Antifungal and Carboxylesterase Activities on Corn Silage and Its Shelf Life against Mold Contamination at Feed-Out Phase Paradhipta DHV, Joo YH, Lee HJ, Lee SS, Noh HT, Choi JS, Kim J, Min HG, Kim SC Ref: Microorganisms, 9:, 2021 : PubMed ESTHER: Paradhipta_2021_Microorganisms_9_ PubMedSearch: Paradhipta 2021 Microorganisms 9 PubMedID: 33800497 Abstract The present study aimed to investigate effects of dual-purpose inoculants (antifungal and carboxylesterase activities) not only on corn silage quality, but also its shelf life against mold contamination at feed-out phase. Corn forage was ensiled for 252 d with different inoculants of the following: control (CON), Lactobacillus brevis 5M2 (5M), Lactobacillus buchneri 6M1 (6M), and mixture of 5M and 6M at 1:1 ratio (MIX). After ensiling, corn silage was contaminated with Fusarium graminearum. Silages applied inoculants had positive effects by increased organic acid and lactic acid bacteria, and decreased undesirable microbes. At feed-out phase, contamination of F. graminearum into corn silage had a negative effect on aerobic stability caused by increased growth of undesirable microbes. However, silages applied inoculants had positive effects by decreased undesirable microbes and extended lactic acid bacteria and aerobic stability. Generally, MIX silage presented better effects on organic acid production, rumen degradation, inhibition of undesirable microbes, and aerobic stability than 5M silage and 6M silage. The present study concluded that application of inoculants into corn silage had positive effects on fermentation characteristics and extended shelf life against mold contamination at feed-out phase. A mixed inoculant appeared to have better effects of antifungal and carboxylesterase than a single inoculant. Title: Investigation of Lipolytic-Secreting Bacteria from an Artificially Polluted Soil Using a Modified Culture Method and Optimization of Their Lipase Production Pham VHT, Kim J, Chang S, Chung W Ref: Microorganisms, 9:, 2021 : PubMed ESTHER: Pham_2021_Microorganisms_9_ PubMedSearch: Pham 2021 Microorganisms 9 PubMedID: 34946192 Abstract Compared to lipases from plants or animals, microbial lipases play a vital role in different industrial applications and biotechnological perspectives due to their high stability and cost-effectiveness. Therefore, numerous lipase producers have been investigated in a variety of environments in the presence of lipidic carbon and organic nitrogen sources. As a step in the development of cultivating the unculturable functional bacteria in this study, the forest soil collected from the surrounding plant roots was used to create an artificially contaminated environment for lipase-producing bacterial isolation. The ten strongest active bacterial strains were tested in an enzyme assay supplemented with metal ions such as Ca(2+), Zn(2+), Cu(2+), Fe(2+), Mg(2+), K(+), Co(2+), Mn(2+), and Sn(2+) to determine bacterial tolerance and the effect of these metal ions on enzyme activity. Lipolytic bacteria in this study tended to grow and achieved a high lipase activity at temperatures of 35-40 degreesC and at pH 6-7, reaching a peak of 480 U/mL and 420 U/mL produced by Lysinibacillus PL33 and Lysinibacillus PL35, respectively. These potential lipase-producing bacteria are excellent candidates for large-scale applications in the future. Title: Sugammadex is associated with shorter hospital length of stay after open lobectomy for lung cancer: a retrospective observational study Song SW, Yoo KY, Ro YS, Pyeon T, Bae HB, Kim J Ref: J Cardiothorac Surg, 16:45, 2021 : PubMed ESTHER: Song_2021_J.Cardiothorac.Surg_16_45 PubMedSearch: Song 2021 J.Cardiothorac.Surg 16 45 PubMedID: 33757525 Abstract BACKGROUND: Sugammadex is associated with few postoperative complications. Postoperative pulmonary complications (PPC) are related to prolonged hospitalizations. Present study explored whether the use of sugammadex could reduce PPCs and thereby reduce hospital length of stay (LOS) after lung surgery. METHODS: We reviewed the medical records of patients who underwent elective open lobectomy for lung cancer from January 2010 to December 2015. Patients were divided into the sugammadex group and pyridostigmine group. The primary outcome was hospital LOS and secondary outcomes were postoperative complications and overall survival at 1 year. The cohort was subdivided into patients with and without prolonged LOS to explore the effects of sugammadex on outcomes in each group. Risk factors for LOS were determined via multivariate analyses. After propensity score matching, 127 patients were assigned to each group. RESULTS: Median hospital LOS was shorter (10.0 vs. 12.0 days) and the incidence of postoperative atelectasis was lower (18.1 vs. 29.9%) in the sugammadex group. However, no significant difference in overall survival between the groups was seen over 1 year (hazard ratio, 0.967; 95% confidence interval, 0.363 to 2.577). Sugammadex was a predictor related to LOS (exponential coefficient 0.88; 95% CI 0.82-0.95). CONCLUSIONS: Our data suggest that sugammadex is a preferable agent for neuromuscular blockade (NMB) reversal than cholinesterase inhibitors in this patient population. TRIAL REGISTRATION: This study registered in the Clinical Research Information Service of the Korea National Institute of Health (approval number: KCT0004735 , Date of registration: 21 January 2020, Retrospectively registered). Title: Transcriptome-Based Identification of Genes Responding to the Organophosphate Pesticide Phosmet in Danio rerio Vasamsetti BMK, Chon K, Kim J, Oh JA, Yoon CY, Park HH Ref: Genes (Basel), 12:, 2021 : PubMed ESTHER: Vasamsetti_2021_Genes.(Basel)_12_ PubMedSearch: Vasamsetti 2021 Genes.(Basel) 12 PubMedID: 34828343 Abstract Organophosphate pesticides (OPPs) are one of the most widely used insecticides. OPPs exert their neurotoxic effects by inhibiting acetylcholine esterase (AChE). Most of the gross developmental abnormalities observed in OPP-treated fish, on the other hand, may not be explained solely by AChE inhibition. To understand the overall molecular mechanisms involved in OPP toxicity, we used the zebrafish (ZF) model. We exposed ZF embryos to an OPP, phosmet, for 96 h, and then analyzed developmental abnormalities and performed whole transcriptome analysis. Phenotypic abnormalities, such as bradycardia, spine curvature, and growth retardation, were observed in phosmet-treated ZF (PTZF). Whole transcriptome analysis revealed 2190 differentially expressed genes (DEGs), with 822 and 1368 significantly up-and downregulated genes, respectively. System process and sensory and visual perception were among the top biological pathways affected by phosmet toxicity. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed significant enrichment of metabolic pathways, calcium signaling pathway, regulation of actin cytoskeleton, cardiac muscle contraction, drug metabolism-other enzymes, and phototransduction. Quantitative real-time PCR results of six DEGs agreed with the sequencing data expression profile trend. Our findings provide insights into the consequences of phosmet exposure in ZF, as well as an estimate of the potential risk of OPPs to off-target species. Title: Canonical versus non-canonical transsynaptic signaling of neuroligin 3 tunes development of sociality in mice Yoshida T, Yamagata A, Imai A, Kim J, Izumi H, Nakashima S, Shiroshima T, Maeda A, Iwasawa-Okamoto S and Fukai S <16 more author(s)> Yoshida T, Yamagata A, Imai A, Kim J, Izumi H, Nakashima S, Shiroshima T, Maeda A, Iwasawa-Okamoto S, Azechi K, Osaka F, Saitoh T, Maenaka K, Shimada T, Fukata Y, Fukata M, Matsumoto J, Nishijo H, Takao K, Tanaka S, Okabe S, Tabuchi K, Uemura T, Mishina M, Mori H, Fukai S (- 16) Ref: Nat Commun, 12:1848, 2021 : PubMed ESTHER: Yoshida_2021_Nat.Commun_12_1848 PubMedSearch: Yoshida 2021 Nat.Commun 12 1848 PubMedID: 33758193 Abstract Neuroligin 3 (NLGN3) and neurexins (NRXNs) constitute a canonical transsynaptic cell-adhesion pair, which has been implicated in autism. In autism spectrum disorder (ASD) development of sociality can be impaired. However, the molecular mechanism underlying NLGN3-mediated social development is unclear. Here, we identify non-canonical interactions between NLGN3 and protein tyrosine phosphatase delta (PTPdelta) splice variants, competing with NRXN binding. NLGN3-PTPdelta complex structure revealed a splicing-dependent interaction mode and competition mechanism between PTPdelta and NRXNs. Mice carrying a NLGN3 mutation that selectively impairs NLGN3-NRXN interaction show increased sociability, whereas mice where the NLGN3-PTPdelta interaction is impaired exhibit impaired social behavior and enhanced motor learning, with imbalance in excitatory/inhibitory synaptic protein expressions, as reported in the Nlgn3 R451C autism model. At neuronal level, the autism-related Nlgn3 R451C mutation causes selective impairment in the non-canonical pathway. Our findings suggest that canonical and non-canonical NLGN3 pathways compete and regulate the development of sociality. Title: Middle East Respiratory Syndrome-Coronavirus Infection into Established hDPP4-Transgenic Mice Accelerates Lung Damage Via Activation of the Pro-Inflammatory Response and Pulmonary Fibrosis Kim J, Yang YL, Jeong Y, Jang YS Ref: J Microbiol Biotechnol, 30:427, 2020 : PubMed ESTHER: Kim_2020_J.Microbiol.Biotechnol_30_427 PubMedSearch: Kim 2020 J.Microbiol.Biotechnol 30 427 PubMedID: 31838832 Abstract Middle East respiratory syndrome coronavirus (MERS-CoV) infects the lower respiratory airway of humans, leading to severe acute respiratory failure. Unlike human dipeptidyl peptidase 4 (hDPP4), a receptor for MERS-CoV, mouse DPP4 (mDPP4) failed to support MERS-CoV infection. Consequently, diverse transgenic mouse models expressing hDPP4 have been developed using diverse methods, although some models show no mortality and/or only transient and mild-to-moderate clinical signs following MERS-CoV infection. Additionally, overexpressed hDPP4 is associated with neurological complications and breeding difficulties in some transgenic mice, resulting in impeding further studies. Here, we generated stable hDPP4-transgenic mice that were sufficiently susceptible to MERS-CoV infection. The transgenic mice showed weight loss, decreased pulmonary function, and increased mortality with minimal perturbation of overexpressed hDPP4 after MERS-CoV infection. In addition, we observed histopathological signs indicative of progressive pulmonary fibrosis, including thickened alveolar septa, infiltration of inflammatory monocytes, and macrophage polarization as well as elevated expression of profibrotic molecules and acute inflammatory response in the lung of MERS-CoV-infected hDPP4-transgenic mice. Collectively, we suggest that this hDPP4-transgenic mouse is useful in understanding the pathogenesis of MERS-CoV infection and for antiviral research and vaccine development against the virus. Title: Casticin ameliorates scopolamine-induced cognitive dysfunction in mice Kim J, Seo YH, Goo N, Jeong Y, Bae HJ, Jung SY, Lee J, Ryu JH Ref: J Ethnopharmacol, :112843, 2020 : PubMed ESTHER: Kim_2020_J.Ethnopharmacol__112843 PubMedSearch: Kim 2020 J.Ethnopharmacol 112843 PubMedID: 32380246 Abstract ETHNOPHARMACOLOGICAL RELEVANCE: The fruit of Vitex rotundifolia L. (Verbenaceae) has been used in traditional medicine as sedative or analgesic agent for headache. Recent population-based cohort studies have shown that headache including migraines is a risk factor for dementia. Thus, the fruit of V. rotundifolia may be useful for treating cognitive dysfunction observed in dementia. AIM OF THE STUDY: We had previously found that the ethanolic extract of the fruit of V. rotundifolia ameliorated cognitive dysfunction and isolated casticin as an active compound. In the present study, we studied the effect of casticin on a mouse model of cognitive impairment induced by scopolamine. MATERIALS AND METHODS: Mice were treated with the ethanolic extract of the fruit of V. rotundifolia (EEVR; 30, 100 or 300mg/kg, p.o.) or casticin (0.3, 1 or 3mg/kg, p.o.). We examined the effect of casticin or EEVR using the passive avoidance test, the Morris water maze test and the novel object recognition test. Scopolamine (1mg/kg, i.p.) was used to induce cognitive impairment by blocking cholinergic neurotransmitter system. We investigated the effects of casticin on acetylcholinesterase (AchE) activity and the phosphorylation levels of extracellular signal-regulated kinase (ERK), cAMP response element binding protein (CREB), and the expression levels of brain-derived neurotrophic factor (BDNF). RESULTS: EEVR (100 and 300mg/kg, p.o.) significantly ameliorated the latency in the passive avoidance test, and casticin (1 and 3mg/kg, p.o.) also significantly improved the latency in the passive avoidance test, novel object preference in the novel object recognition test, and swimming time in the target quadrant of the Morris water maze test. Casticin also decreased AChE activity in ex vivo analysis and increased the phosphorylation levels of memory-related signaling molecules, such as ERK, CREB and BDNF in the cortex. CONCLUSION: These results suggest that casticin ameliorates cholinergic blockade-induced cognitive impairment, in part, through the inhibition of AChE and the activation of the ERK-CREB-BDNF signaling pathway. Taken together, the results suggest that casticin may be useful for treating the cognitive dysfunction observed during cholinergic impairment. Title: Dual-Purpose Inoculants and Their Effects on Corn Silage Paradhipta DHV, Lee SS, Kang B, Joo YH, Lee HJ, Lee Y, Kim J, Kim SC Ref: Microorganisms, 8:, 2020 : PubMed ESTHER: Paradhipta_2020_Microorganisms_8_ PubMedSearch: Paradhipta 2020 Microorganisms 8 PubMedID: 32443787 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. Title: Comparison of recovery profiles in patients with Parkinson's disease for 2 types of neuromuscular blockade reversal agent following deep brain stimulator implantation Park YS, Kim J, Kim SH, Moon YJ, Kwon HM, Park HS, Kim WJ, Ha S Ref: Medicine (Baltimore), 98:e18406, 2019 : PubMed ESTHER: Park_2019_Medicine.(Baltimore)_98_e18406 PubMedSearch: Park 2019 Medicine.(Baltimore) 98 e18406 PubMedID: 31876713 Abstract As an anesthetic reversal agent, there are concerns with cholinesterase inhibitors regarding worsening of Parkinson's disease (PD)-related symptoms. Sugammadex, a relatively new reversal agent, does not inhibit acetylcholinesterase and does not require co-administration of an antimuscarinic agent. The present study compared the recovery profiles of 2 agents initially administered for reversal of neuromuscular blockade in patients with advanced PD who underwent deep brain stimulator implantation.A total of 121 patients with PD who underwent deep brain stimulator implantation were retrospectively analyzed. Patients were divided into 1 of 2 groups according to the type of neuromuscular blockade reversal agent (pyridostigmine vs sugammadex) initially administered. Recovery profiles reflecting time to extubation, reversal failure at first attempt, and hemodynamic stability, including incidence of hypertension or tachycardia during the emergence period, were compared.Time to extubation in the sugammadex group was significantly shorter (P < .001). In the sugammadex group, reversal failure at first attempt did not occur in any patient, while it occurred in seven (9.7%) patients in the pyridostigmine group (P = .064), necessitating an additional dose of pyridostigmine (n = 3) or sugammadex (n = 4). The incidence of hemodynamic instability during anesthetic emergence was significantly lower in the sugammadex group than in the pyridostigmine group (P = .019).Sugammadex yielded a recovery profile superior to that of pyridostigmine during the anesthesia emergence period in advanced PD patients. Sugammadex is also likely to be associated with fewer adverse effects than traditional reversal agents, which in turn would also improve overall postoperative management in this patient population. Title: Comprehensive genomic and transcriptomic analysis of polycyclic aromatic hydrocarbon degradation by a mycoremediation fungus, Dentipellis sp. KUC8613 Park H, Min B, Jang Y, Kim J, Lipzen A, Sharma A, Andreopoulos B, Johnson J, Riley R and Choi IG <5 more author(s)> Park H, Min B, Jang Y, Kim J, Lipzen A, Sharma A, Andreopoulos B, Johnson J, Riley R, Spatafora JW, Henrissat B, Kim KH, Grigoriev IV, Kim JJ, Choi IG (- 5) Ref: Applied Microbiology & Biotechnology, 103:8145, 2019 : PubMed ESTHER: Park_2019_Appl.Microbiol.Biotechnol_103_8145 PubMedSearch: Park 2019 Appl.Microbiol.Biotechnol 103 8145 PubMedID: 31482283 Gene_locus related to this paper: 9agam-a0a5b1qnb8, 9agam-a0a5b1qwq3, 9agam-a0a5b1qh04, 9agam-a0a5b1qyk1, 9agam-a0a5b1qmi3, 9agam-a0a5b1qi91, 9agam-a0a5b1qhi2 Abstract The environmental accumulation of polycyclic aromatic hydrocarbons (PAHs) is of great concern due to potential carcinogenic and mutagenic risks, as well as their resistance to remediation. While many fungi have been reported to break down PAHs in environments, the details of gene-based metabolic pathways are not yet comprehensively understood. Specifically, the genome-scale transcriptional responses of fungal PAH degradation have rarely been reported. In this study, we report the genomic and transcriptomic basis of PAH bioremediation by a potent fungal degrader, Dentipellis sp. KUC8613. The genome size of this fungus was 36.71 Mbp long encoding 14,320 putative protein-coding genes. The strain efficiently removed more than 90% of 100 mg/l concentration of PAHs within 10 days. The genomic and transcriptomic analysis of this white rot fungus highlights that the strain primarily utilized non-ligninolytic enzymes to remove various PAHs, rather than typical ligninolytic enzymes known for playing important roles in PAH degradation. PAH removal by non-ligninolytic enzymes was initiated by both different PAH-specific and common upregulation of P450s, followed by downstream PAH-transforming enzymes such as epoxide hydrolases, dehydrogenases, FAD-dependent monooxygenases, dioxygenases, and glycosyl- or glutathione transferases. Among the various PAHs, phenanthrene induced a more dynamic transcriptomic response possibly due to its greater cytotoxicity, leading to highly upregulated genes involved in the translocation of PAHs, a defense system against reactive oxygen species, and ATP synthesis. Our genomic and transcriptomic data provide a foundation of understanding regarding the mycoremediation of PAHs and the application of this strain for polluted environments. Title: Newly developed reversible MAO-B inhibitor circumvents the shortcomings of irreversible inhibitors in Alzheimer's disease Park JH, Ju YH, Choi JW, Song HJ, Jang BK, Woo J, Chun H, Kim HJ, Shin SJ and Park KD <17 more author(s)> Park JH, Ju YH, Choi JW, Song HJ, Jang BK, Woo J, Chun H, Kim HJ, Shin SJ, Yarishkin O, Jo S, Park M, Yeon SK, Kim S, Kim J, Nam MH, Londhe AM, Cho SJ, Cho S, Lee C, Hwang SY, Kim SW, Oh SJ, Cho J, Pae AN, Lee CJ, Park KD (- 17) Ref: Sci Adv, 5:eaav0316, 2019 : PubMed ESTHER: Park_2019_Sci.Adv_5_eaav0316 PubMedSearch: Park 2019 Sci.Adv 5 eaav0316 PubMedID: 30906861 Abstract Monoamine oxidase-B (MAO-B) has recently emerged as a potential therapeutic target for Alzheimer's disease (AD) because of its association with aberrant gamma-aminobutyric acid (GABA) production in reactive astrocytes. Although short-term treatment with irreversible MAO-B inhibitors, such as selegiline, improves cognitive deficits in AD patients, long-term treatments have shown disappointing results. We show that prolonged treatment with selegiline fails to reduce aberrant astrocytic GABA levels and rescue memory impairment in APP/PS1 mice, an animal model of AD, because of increased activity in compensatory genes for a GABA-synthesizing enzyme, diamine oxidase (DAO). We have developed a potent, highly selective, and reversible MAO-B inhibitor, KDS2010 (IC(50) = 7.6 nM; 12,500-fold selectivity over MAO-A), which overcomes the disadvantages of the irreversible MAO-B inhibitor. Long-term treatment with KDS2010 does not induce compensatory mechanisms, thereby significantly attenuating increased astrocytic GABA levels and astrogliosis, enhancing synaptic transmission, and rescuing learning and memory impairments in APP/PS1 mice. Title: Cholinesterase inhibitory alkaloids from the rhizomes of Coptis chinensis Cao TQ, Ngo QT, Seong SH, Youn UJ, Kim JA, Kim J, Kim JC, Woo MH, Choi JS, Min BS Ref: Bioorg Chem, 77:625, 2018 : PubMed ESTHER: Cao_2018_Bioorg.Chem_77_625 PubMedSearch: Cao 2018 Bioorg.Chem 77 625 PubMedID: 29502023 Abstract Coptis chinensis has been used as a medicinal herb in traditional oriental medicine. In this study, chemical investigation of a water extract of C. chinensis identified two new quaternary protoberberines (1, 2), a new tricyclic amide (3), together with five known compounds. Their chemical structures were elucidated by analysis with 1D and 2D NMR and high-resolution mass spectroscopy, as well as by comparison with those reported in the literature. Compounds 4, 5, and 7 showed potent inhibition against acetylcholinesterase (AChE) with IC50 values of 1.1, 5.6, and 12.9muM, respectively. Compounds 2 and 4 showed inhibition of butyrylcholinesterase (BChE) with IC50 values of 11.5 and 27.8muM, respectively. The kinetic activities were investigated to find out the type of enzyme inhibition involved. The types of AChE inhibition shown by compounds 5 and 7 were noncompetitive; BChE inhibition by compound 2 was also noncompetitive. Title: The genome of the marine medaka Oryzias melastigma Kim HS, Lee BY, Han J, Jeong CB, Hwang DS, Lee MC, Kang HM, Kim DH, Lee D and Lee JS <2 more author(s)> Kim HS, Lee BY, Han J, Jeong CB, Hwang DS, Lee MC, Kang HM, Kim DH, Lee D, Kim J, Choi IY, Lee JS (- 2) Ref: Mol Ecol Resour, 18:656, 2018 : PubMed ESTHER: Kim_2018_Mol.Ecol.Resour_18_656 PubMedSearch: Kim 2018 Mol.Ecol.Resour 18 656 PubMedID: 29451363 Gene_locus related to this paper: oryme-a0a3b3dpk3, oryme-a0a3b3c959, oryme-a0a3b3d3r3, oryme-a0a3b3d4c8, oryme-a0a3b3bnt1, oryme-a0a3b3caa8, oryme-a0a3b3bl32, oryme-a0a3b3da95, oryme-a0a3b3dps7, oryme-a0a3b3dej7, oryme-a0a3b3bpw5, oryme-a0a3b3c014 Abstract Marine medaka (Oryzias melastigma) is considered to be a useful fish model for marine and estuarine ecotoxicology studies and has good potential for field-based population genomics because of its geographical distribution in Asian estuarine and coastal areas. In this study, we present the first whole-genome draft of O. melastigma. The genome assembly consists of 8,602 scaffolds (N50 = 23.737 Mb) and a total genome length of 779.4 Mb. A total of 23,528 genes were predicted, and 12,670 gene families shared with three teleost species (Japanese medaka, mangrove killifish and zebrafish) were identified. Genome analyses revealed that the O. melastigma genome is highly heterozygous and contains a large number of repeat sequences. This assembly represents a useful genomic resource for fish scientists. Title: Novel tacrine-pyridinium hybrid reactivators of organophosphorus-inhibited acetylcholinesterase: Synthesis, molecular docking, and in vitro reactivation study Kim J, Malpani YR, Lee J, Shin JS, Han SB, Jung YS Ref: Bioorganic & Medicinal Chemistry Lett, 28:3784, 2018 : PubMed ESTHER: Kim_2018_Bioorg.Med.Chem.Lett_28_3784 PubMedSearch: Kim 2018 Bioorg.Med.Chem.Lett 28 3784 PubMedID: 30301674 Abstract First-line medical treatment against nerve agents consists of co-administration of anticholinergic agents and oxime reactivators, which reactivate inhibited AChE. Pralidoxime, a commonly used oxime reactivator, is effective against some nerve agents but not against others; thus, new oxime reactivators are needed. Novel tacrine-pyridinium hybrid reactivators in which 4-pyridinealdoxime derivatives are connected to tacrine moieties by linear carbon chains of different lengths (C2-C7) were prepared (Scheme 1, 5a-f). Their binding affinities to electric eel AChE were tested because oximes can inhibit free AChE, and the highest AChE activity (95%, 92%, and 90%) was observed at 1muM concentrations of the oximes (5a, 5b, and 5c, respectively). Based on their inhibitory affinities towards free AChE, 1muM concentrations of the oxime derivatives (5) were used to examine reactivation of paraoxon-inhibited AChE. Reactivation ability increased as the carbon linker chains lengthened (n=2-5), and 5c and 5d showed remarkable reactivation ability (41%) compared to that of 2-PAM (16%) and HI-6 (4%) against paraoxon-inhibited electric eel AChE at 1muM concentrations. Molecular docking simulation showed that the most stable binding free energy was observed in 5c at 73.79kcalmol(-1), and the binding mode of 5c is acceptable for the oxygen atom of oximate to attack the phosphorus atom of paraoxon and reactivate paraoxon-inhibited eel AChE model structure. Title: Enzymatic Synthesis of Structured Monogalactosyldiacylglycerols Enriched in Pinolenic Acid Kim J, Chung MY, Choi HD, Choi IW, Kim BH Ref: Journal of Agricultural and Food Chemistry, 66:8079, 2018 : PubMed ESTHER: Kim_2018_J.Agric.Food.Chem_66_8079 PubMedSearch: Kim 2018 J.Agric.Food.Chem 66 8079 PubMedID: 29998729 Abstract We enzymatically prepared structured monogalactosydiacylglycerols (MGDGs) enriched in pinolenic acid (PLA). PLA-enriched free fatty acids~ (FFAs) containing ~86 mol % PLA were produced from an FFA fraction obtained from pine nut oil (PLA content, ~13 mol %) by urea crystallization. Commercial MGDGs (5 mg) were acidolyzed with PLA-enriched FFAs using four commercial immobilized lipases as biocatalysts. The reaction was performed in acetone (4 mL) in a stirred-batch reactor. Lipozyme RM IM (immobilized Rhizomucor miehei lipase) was the most effective biocatalyst for the reaction. Structured MGDGs containing 42.1 mol % PLA were obtained under optimal reaction conditions: temperature, 25 degreeC; substrate molar ratio, 1:30 (MGDGs/PLA-enriched FFAs); enzyme loading, 20 wt % of total substrates; and reaction time, 36 h. The structured MGDGs were separated from the reaction products at a purity of 96.6 wt % using silica column chromatography. The structured MGDGs could be possibly used as emulsifiers with appetite-suppression effects. Title: A missense allele of KARRIKIN-INSENSITIVE2 impairs ligand-binding and downstream signaling in Arabidopsis thaliana Lee I, Kim K, Lee S, Hwang E, Shin K, Kim D, Choi J, Choi H, Cha JS and Soh MS <8 more author(s)> Lee I, Kim K, Lee S, Hwang E, Shin K, Kim D, Choi J, Choi H, Cha JS, Kim H, Lee RA, Jeong S, Kim J, Kim Y, Nam HG, Park SK, Cho HS, Soh MS (- 8) Ref: J Exp Bot, 69:3609, 2018 : PubMed ESTHER: Lee_2018_J.Exp.Bot_69_3609 PubMedSearch: Lee 2018 J.Exp.Bot 69 3609 PubMedID: 29722815 Gene_locus related to this paper: arath-KAI2.D14L Abstract A smoke-derived compound, karrikin (KAR), and an endogenous but as yet unidentified KARRIKIN INSENSITIVE2 (KAI2) ligand (KL) have been identified as chemical cues in higher plants that impact on multiple aspects of growth and development. Genetic screening of light-signaling mutants in Arabidopsis thaliana has identified a mutant designated as ply2 (pleiotropic long hypocotyl2) that has pleiotropic light-response defects. In this study, we used positional cloning to identify the molecular lesion of ply2 as a missense mutation of KAI2/HYPOSENSITIVE TO LIGHT, which causes a single amino acid substitution, Ala219Val. Physiological analysis and genetic epistasis analysis with the KL-signaling components MORE AXILLARY GROWTH2 (MAX2) and SUPPRESSOR OF MAX2 1 suggested that the pleiotropic phenotypes of the ply2 mutant can be ascribed to a defect in KL-signaling. Molecular and biochemical analyses revealed that the mutant KAI2ply2 protein is impaired in its ligand-binding activity. In support of this conclusion, X-ray crystallography studies suggested that the KAI2ply2 mutation not only results in a narrowed entrance gate for the ligand but also alters the structural flexibility of the helical lid domains. We discuss the structural implications of the Ala219 residue with regard to ligand-specific binding and signaling of KAI2, together with potential functions of KL-signaling in the context of the light-regulatory network in Arabidopsis thaliana. Title: Development of a diagnostic system for detection of specific antibodies and antigens against Middle East respiratory syndrome coronavirus Lee K, Ko HL, Lee EY, Park HJ, Kim YS, Cho NH, Park MS, Lee SM, Kim J and Nam JH <2 more author(s)> Lee K, Ko HL, Lee EY, Park HJ, Kim YS, Cho NH, Park MS, Lee SM, Kim J, Kim H, Seong BL, Nam JH (- 2) Ref: Microbiol Immunol, 62:574, 2018 : PubMed ESTHER: Lee_2018_Microbiol.Immunol_62_574 PubMedSearch: Lee 2018 Microbiol.Immunol 62 574 PubMedID: 30117617 Abstract Middle East respiratory syndrome coronavirus (MERS-CoV) is a single-stranded RNA virus that causes severe respiratory disease in humans with a high fatality rate. Binding of the receptor binding domain (RBD) of the spike (S) glycoprotein to dipeptidyl peptidase 4 is the critical step in MERS-CoV infection of a host cell. No vaccines or clinically applicable treatments are currently available for MERS-CoV. Therefore, rapid diagnosis is important for improving patient outcomes through prompt treatment and protection against viral outbreaks. In this study, the aim was to establish two ELISA systems for detecting antigens and antibodies against MERS-CoV. Using a recombinant full-length S protein, an indirect ELISA was developed and found to detect MERS-CoV-specific antibodies in animal sera and sera of patient with MERS. Moreover, MAbs were induced with the recombinant S protein and RBD and used for sandwich ELISA to detect the MERS-CoV S protein. Neither ELISA system exhibited significant intra-assay or inter-assay variation, indicating good reproducibility. Moreover, the inter-day precision and sensitivity were adequate for use as a diagnostic kit. Thus, these ELISAs can be used clinically to diagnose MERS-CoV. Title: Lipoprotein lipase regulates hematopoietic stem progenitor cell maintenance through DHA supply Liu C, Han T, Stachura DL, Wang H, Vaisman BL, Kim J, Klemke RL, Remaley AT, Rana TM and Miller YI <1 more author(s)> Liu C, Han T, Stachura DL, Wang H, Vaisman BL, Kim J, Klemke RL, Remaley AT, Rana TM, Traver D, Miller YI (- 1) Ref: Nat Commun, 9:1310, 2018 : PubMed ESTHER: Liu_2018_Nat.Commun_9_1310 PubMedSearch: Liu 2018 Nat.Commun 9 1310 PubMedID: 29615667 Abstract Lipoprotein lipase (LPL) mediates hydrolysis of triglycerides (TGs) to supply free fatty acids (FFAs) to tissues. Here, we show that LPL activity is also required for hematopoietic stem progenitor cell (HSPC) maintenance. Knockout of Lpl or its obligatory cofactor Apoc2 results in significantly reduced HSPC expansion during definitive hematopoiesis in zebrafish. A human APOC2 mimetic peptide or the human very low-density lipoprotein, which carries APOC2, rescues the phenotype in apoc2 but not in lpl mutant zebrafish. Creating parabiotic apoc2 and lpl mutant zebrafish rescues the hematopoietic defect in both. Docosahexaenoic acid (DHA) is identified as an important factor in HSPC expansion. FFA-DHA, but not TG-DHA, rescues the HSPC defects in apoc2 and lpl mutant zebrafish. Reduced blood cell counts are also observed in Apoc2 mutant mice at the time of weaning. These results indicate that LPL-mediated release of the essential fatty acid DHA regulates HSPC expansion and definitive hematopoiesis. Title: NOTUM Is Involved in the Progression of Colorectal Cancer Yoon JH, Kim D, Kim J, Lee H, Ghim J, Kang BJ, Song P, Suh PG, Ryu SH, Lee TG Ref: Cancer Genomics Proteomics, 15:485, 2018 : PubMed ESTHER: Yoon_2018_Cancer.Genomics.Proteomics_15_485 PubMedSearch: Yoon 2018 Cancer.Genomics.Proteomics 15 485 PubMedID: 30343282 Abstract BACKGROUND: There are limitations to current colorectal cancer (CRC)-specific diagnostic methods and therapies. Tumorigenesis proceeds because of interaction between cancer cells and various surrounding cells; discovering new molecular mediators through studies of the CRC secretome is a promising approach for the development of CRC diagnostics and therapies. MATERIALS AND METHODS: A comparative secretomic analysis was performed using primary and metastatic human isogenic CRC cells. Proliferation was determined by MTT and thymidine incorporation assay, migration was determined by wound-healing assay (ELISA). The level of palmitoleoyl-protein carboxylesterase (NOTUM) in plasma from patients with CRC was determined by enzyme-linked immunosorbent assay. RESULTS: NOTUM expression was increased in metastatic cells. Proliferation was suppressed by inhibiting expression of NOTUM. Knockdown of NOTUM genes inhibited proliferation as well as migration, with possible involvement of p38 and c-JUN N-terminal kinase in this process. The result was verified in patients with CRC. CONCLUSION: NOTUM may be a new candidate for diagnostics and therapy of CRC. Title: Biological activity of Myrtaceae plant essential oils and their major components against Drosophila suzukii (Diptera: Drosophilidae) Jang M, Kim J, Yoon KA, Lee SH, Park CG Ref: Pest Manag Sci, 73:404, 2017 : PubMed ESTHER: Jang_2017_Pest.Manag.Sci_73_404 PubMedSearch: Jang 2017 Pest.Manag.Sci 73 404 PubMedID: 27607409 Abstract BACKGROUND: The spotted-wing drosophila (SWD), Drosophila suzukii (Matsumura), is a globally invasive and serious pest of numerous soft-skinned fruit crops. Assessments were made of fumigant and contact toxicities of 12 Myrtaceae plant essential oils (EOs) and their components. For determining the mode of action of major components of active EOs, their activities against acetylcholinesterase (AChE) and Glutathione S-transferase (GST) were also assessed. Title: Crystal structure and characterization of esterase Est25 mutants reveal improved enantioselectivity toward (S)-ketoprofen ethyl ester Kim J, Seok SH, Hong E, Yoo TH, Seo MD, Ryu Y Ref: Applied Microbiology & Biotechnology, 101:2333, 2017 : PubMed ESTHER: Kim_2017_Appl.Microbiol.Biotechnol_101_2333 PubMedSearch: Kim 2017 Appl.Microbiol.Biotechnol 101 2333 PubMedID: 27915377 Gene_locus related to this paper: 9bact-q4tzq3 Abstract Esterases comprise a group of enzymes that catalyze the cleavage and synthesis of ester bonds. They are important in biotechnological applications owing to their enantioselectivity, regioselectivity, broad substrate specificity, and the fact that they do not require cofactors. In a previous study, we isolated the esterase Est25 from a metagenomic library. Est25 showed catalytic activity toward the (R,S)-ketoprofen ethyl ester but had low enantioselectivity toward the (S)-ketoprofen ethyl ester. Because (S)-ketoprofen has stronger anti-inflammatory effects and fewer side effects than (R)-ketoprofen, enantioselectivity of this esterase is important. In this study, we generated Est25 mutants with improved enantioselectivity toward the (S)-ketoprofen ethyl ester; improved enantioselectivity of mutants was established by analysis of their crystal structures. The enantioselectivity of mutants was influenced by substitution of Phe72 and Leu255. Substituting these residues changed the size of the binding pocket and the entrance hole that leads to the active site. The enantioselectivity of Est25 (E = 1.1 +/- 0.0) was improved in the mutants F72G (E = 1.9 +/- 0.2), L255W (E = 16.1 +/- 1.1), and F72G/L255W (E = 60.1 +/- 0.5). Finally, characterization of Est25 mutants was performed by determining the optimum reaction conditions, thermostability, effect of additives, and substrate specificity after substituting Phe72 and Leu255. Title: Structure and function of the N-terminal domain of Ralstonia eutropha polyhydroxyalkanoate synthase, and the proposed structure and mechanisms of the whole enzyme Kim YJ, Choi SY, Kim J, Jin KS, Lee SY, Kim KJ Ref: Biotechnol J, 12:, 2017 : PubMed ESTHER: Kim_2017_Biotechnol.J_12_1 PubMedSearch: Kim 2017 Biotechnol.J 12 1 PubMedID: 27808475 Gene_locus related to this paper: alceu-phbc Abstract Polyhydroxyalkanoates (PHAs) are natural polyesters synthesized by numerous microorganisms as energy and reducing power storage materials, and have attracted much attention as substitutes for petroleum-based plastics. In an accompanying paper, the authors reported the crystal structure of the C-terminal domain of Ralstonia eutropha PHA synthase (PhaC1). Here, the authors report the 3D reconstructed model of full-length of R. eutropha PhaC1 (RePhaC1F ) by small angle X-ray scattering (SAXS) analysis. The catalytic C-terminal domain of RePhaC1 (RePhaC1CD ) dimer is located at the center of RePhaC1F , and the N-terminal domain of RePhaC1 (RePhaC1ND ) is located opposite the dimerization subdomain of RePhaC1CD , indicating that RePhaC1ND is not directly involved in the enzyme catalysis. The localization studies using RePhaC1F , RePhaC1ND and RePhaC1CD revealed that RePhaC1ND plays important roles in PHA polymerization by localizing the enzyme to the PHA granules and stabilizing the growing PHA polymer near the active site of RePhaC1CD . The serial truncation study on RePhaC1ND suggested that the predicted five alpha-helices (N-alpha3 to N-alpha7) are required for proper folding and granule binding function of RePhaC1ND . In addition, the authors also report the SAXS 3D reconstructed model of the RePhaC1F /RePhaMDeltaC complex (RePhaMDeltaC , PAKKA motif-truncated version of RePhaM). RePhaM forms a complex with RePhaC1 by interacting with RePhaC1ND and activates RePhaC1 by providing a more extensive surface area for interaction with the growing PHA polymer. Title: Crystal structure of Ralstonia eutropha polyhydroxyalkanoate synthase C-terminal domain and reaction mechanisms Kim J, Kim YJ, Choi SY, Lee SY, Kim KJ Ref: Biotechnol J, 12:, 2017 : PubMed ESTHER: Kim_2017_Biotechnol.J_12_2 PubMedSearch: Kim 2017 Biotechnol.J 12 2 PubMedID: 27808482 Gene_locus related to this paper: alceu-phbc Abstract Polyhydroxyalkanoates (PHAs) are natural polyesters synthesized by numerous microorganisms as energy and reducing power storage materials, and have attracted much attention as substitutes for petroleum-based plastics. Here, we report the first crystal structure of Ralstonia eutropha PHA synthase at 1.8 A resolution and structure-based mechanisms for PHA polymerization. RePhaC1 contains two distinct domains, the N-terminal (RePhaC1ND ) and C-terminal domains (RePhaC1CD ), and exists as a dimer. RePhaC1CD catalyzes polymerization via non-processive ping-pong mechanism using a Cys-His-Asp catalytic triad. Molecular docking simulation of 3-hydroxybutyryl-CoA to the active site of RePhaC1CD reveals residues involved in the formation of 3-hydroxybutyryl-CoA binding pocket and substrate binding tunnel. Comparative analysis with other polymerases elucidates how different classes of PHA synthases show different substrate specificities. Furthermore, we attempted structure-based protein engineering and developed a RePhaC1 mutant with enhanced PHA synthase activity. Title: Alantolactone and Isoalantolactone Prevent Amyloid beta25-35 -induced Toxicity in Mouse Cortical Neurons and Scopolamine-induced Cognitive Impairment in Mice Seo JY, Lim SS, Kim J, Lee KW, Kim JS Ref: Phytother Res, 31:801, 2017 : PubMed ESTHER: Seo_2017_Phytother.Res_31_801 PubMedSearch: Seo 2017 Phytother.Res 31 801 PubMedID: 28326625 Abstract Given the evidence for detoxifying/antioxidant enzyme-inducing activities by alantolactone (AL) and isoalantolactone (IAL), the purpose of this study was to investigate the effects of AL and IAL on Abeta25-35 -induced cell death in mouse cortical neuron cells and to determine their effects on scopolamine-induced amnesia in mice. Our data demonstrated that both compounds effectively attenuated the cytotoxicity of Abeta25-35 (10 muM) in neuronal cells derived from the mouse cerebral cortex. It was also found that the production of intracellular reactive oxygen species, including superoxide anion induced by Abeta25-35 , was inhibited. Moreover, the administration of the sesquiterpenes reversed scopolamine-induced cognitive impairments as assessed by Morris water, Y-maze, and the passive avoidance tests, and the compounds decreased acetylcholinesterase (AChE) activities in a dose-dependent manner. Interestingly, AL and IAL did not improve scopolamine-induced cognitive deficit in Nrf2-/- mice, suggesting that memory improvement by sesquiterpenes was mediated not only by the activation of the Nrf2 signaling pathway but also by their inhibitory activity against AChE. In conclusion, our results showed that AL and IAL had neuroprotective effects and reversed cognitive impairments induced by scopolamine in a mouse model. Therefore, AL and IAL deserve further study as potential therapeutic agents for reactive oxygen species-related neurodegenerative diseases. Copyright (c) 2017 John Wiley & Sons, Ltd. Title: A Screen for Protein-Protein Interactions in Live Mycobacteria Reveals a Functional Link between the Virulence-Associated Lipid Transporter LprG and the Mycolyltransferase Antigen 85A Touchette MH, Van Vlack ER, Bai L, Kim J, Cognetta AB, 3rd, Previti ML, Backus KM, Martin DW, Cravatt BF, Seeliger JC Ref: ACS Infect Dis, 3:336, 2017 : PubMed ESTHER: Touchette_2017_ACS.Infect.Dis_3_336 PubMedSearch: Touchette 2017 ACS.Infect.Dis 3 336 PubMedID: 28276676 Gene_locus related to this paper: myctu-a85a Abstract Outer membrane lipids in pathogenic mycobacteria are important for virulence and survival. Although the biosynthesis of these lipids has been extensively studied, mechanisms responsible for their assembly in the outer membrane are not understood. In the study of Gram-negative outer membrane assembly, protein-protein interactions define transport mechanisms, but analogous interactions have not been explored in mycobacteria. Here we identified interactions with the lipid transport protein LprG. Using site-specific photo-cross-linking in live mycobacteria, we mapped three major interaction interfaces within LprG. We went on to identify proteins that cross-link at the entrance to the lipid binding pocket, an area likely relevant to LprG transport function. We verified LprG site-specific interactions with two hits, the conserved lipoproteins LppK and LppI. We further showed that LprG interacts physically and functionally with the mycolyltransferase Ag85A, as loss of either protein leads to similar defects in cell growth and mycolylation. Overall, our results support a model in which protein interactions coordinate multiple pathways in outer membrane biogenesis and connect lipid biosynthesis to transport. Title: Rg3-enriched ginseng extract ameliorates scopolamine-induced learning deficits in mice Kim J, Shim J, Lee S, Cho WH, Hong E, Lee JH, Han JS, Lee HJ, Lee KW Ref: BMC Complement Altern Med, 16:66, 2016 : PubMed ESTHER: Kim_2016_BMC.Complement.Altern.Med_16_66 PubMedSearch: Kim 2016 BMC.Complement.Altern.Med 16 66 PubMedID: 26887326 Abstract BACKGROUND: Ginseng (Panax ginseng C.A. Meyer) has been used as a traditional herb in the treatment of many medical disorders. Ginsenosides, which are triterpene derivatives that contain sugar moieties, are the main pharmacological ingredients in ginseng. This study was designed to investigate the effect of ginsenoside Rg3-enriched ginseng extract (Rg3GE) on scopolamine-induced memory impairment in mice. Title: Insecticidal and Enzyme Inhibitory Activities of Sparassol and Its Analogues against Drosophila suzukii Kim J, Jang M, Lee KT, Yoon KA, Park CG Ref: Journal of Agricultural and Food Chemistry, 64:5479, 2016 : PubMed ESTHER: Kim_2016_J.Agric.Food.Chem_64_5479 PubMedSearch: Kim 2016 J.Agric.Food.Chem 64 5479 PubMedID: 27327201 Abstract Drosophila suzukii is an economically important pest in America and Europe as well as in Asia. Sparassol and methyl orsellinate are naturally produced by the cultivating mushrooms Sparassis cripta and Sparassis latifolia. Fumigant and contact toxicities of synthetic sparassol and its analogues, methyl orsellinate and methyl 2,4-dimethoxy-6-methylbenzoate (DMB), were investigated. Negligible fumigant activity was observed from the tested compounds. However, DMB showed the strongest contact toxicity, followed by sparassol and methyl orsellinate. The possible modes of action of the compounds were assessed for their acetylcholinesterase (AChE)- and glutathione S-transferase (GST)-inhibiting activities. AChE activity was weakly inhibited by methyl orsellinate and DMB, but GST was inhibited by sparassol, methyl orsellinate, and DMB. Thus, DMB could be a promising alternative to common insecticides as it can be easily synthesized from sparassol, which is the natural product of Sparassis species. Sparassis species could be an industrial resource of DMB. Title: Strategies for increasing heterologous expression of a thermostable esterase from Archaeoglobus fulgidus in Escherichia coli Kim J, Kim SI, Hong E, Ryu Y Ref: Protein Expr Purif, 127:98, 2016 : PubMed ESTHER: Kim_2016_Protein.Expr.Purif_127_98 PubMedSearch: Kim 2016 Protein.Expr.Purif 127 98 PubMedID: 27449918 Abstract Heterologous proteins expressed in bacteria are used for numerous biotechnological applications. Escherichia coli is the most commonly used host for heterologous protein expression because of its many advantages. Researchers have been studying proteins from extremophiles heterologously expressed in E. coli because the proteins of extremophiles are strongly resistant to extreme conditions. In a previous study, a thermostable esterase Est-AF was isolated from Archaeoglobus fulgidus and expressed in E. coli. However, further studies of Est-AF were difficult owing to its low expression levels in E. coli. In this study, we used various strategies, such as changing the expression vector and host strain, codon optimization, and optimization of induction conditions, to increase the expression of Est-AF. Through codon optimization and by changing the vector and host strain, Est-AF expression was increased from 31.50 +/- 0.35 mg/L to 61.75 +/- 0.28 mg/L. The optimized expression system consisted of a codon-optimized Est-AF gene in a pET28a(+)-based expression plasmid in E. coli Rosetta cells. The expression level was further increased by optimizing the induction conditions. The optimized conditions were induction with 0.4 mM isopropyl-b-d-1-thiogalactoside (IPTG) at 37 degrees C for 5 h. Under these conditions, the expression level of Est-AF was increased from 31.5 +/- 0.35 mg/L to 119.52 +/- 0.34 mg/L. Title: Pharmacological profiles of gemigliptin (LC15-0444), a novel dipeptidyl peptidase-4 inhibitor, in vitro and in vivo Kim SH, Jung E, Yoon MK, Kwon OH, Hwang DM, Kim DW, Kim J, Lee SM, Yim HJ Ref: European Journal of Pharmacology, 788:54, 2016 : PubMed ESTHER: Kim_2016_Eur.J.Pharmacol_788_54 PubMedSearch: Kim 2016 Eur.J.Pharmacol 788 54 PubMedID: 27298192 Inhibitor(s) related to this paper: Gemigliptin Abstract Gemigliptin, a novel dipeptidyl peptidase (DPP)-4 inhibitor, is approved for use as a monotherapy or in combination therapy to treat hyperglycemia in patients with type 2 diabetes mellitus. In this study, we investigated the pharmacological profiles of gemigliptin in vitro and in vivo and compared them to those of the other DPP-4 inhibitors. Gemigliptin was a reversible and competitive inhibitor with a Ki value of 7.25+/-0.67nM. Similar potency was shown in plasma from humans, rats, dogs, and monkeys. The kinetics of DPP-4 inhibition by gemigliptin was characterized by a fast association and a slow dissociation rate compared to sitagliptin (fast on and fast off rate) or vildagliptin (slow on and slow off rate). In addition, gemigliptin showed at least >23,000-fold selectivity for DPP-4 over various proteases and peptidases, including DPP-8, DPP-9, and fibroblast activation protein (FAP)-alpha. In the rat, dog, and monkey, gemigliptin showed more potent DPP-4 inhibitory activity in vivo compared with sitagliptin. In mice and dogs, gemigliptin prevented the degradation of active glucagon-like peptide-1 by DPP-4 inhibition, which improved glucose tolerance by increasing insulin secretion and reducing glucagon secretion during an oral glucose tolerance test. The long-term anti-hyperglycemic effect of gemigliptin was evaluated in diet-induced obese mice and high-fat diet/streptozotocin-induced diabetic mice. Gemigliptin dose-dependently decreased hemoglobin A1c (HbA1c) levels and ameliorated beta-cell damage. In conclusion, gemigliptin is a potent, long-acting, and highly selective DPP-4 inhibitor and can be a safe and effective drug for the long-term treatment of type 2 diabetes. Title: NORE1/SAUL1 integrates temperature-dependent defense programs involving SGT1b and PAD4 pathways and leaf senescence in Arabidopsis Lee IH, Lee IC, Kim J, Kim JH, Chung EH, Kim HJ, Park SJ, Kim YM, Kang SK and Lim PO <2 more author(s)> Lee IH, Lee IC, Kim J, Kim JH, Chung EH, Kim HJ, Park SJ, Kim YM, Kang SK, Nam HG, Woo HR, Lim PO (- 2) Ref: Physiol Plant, 158:180, 2016 : PubMed ESTHER: Lee_2016_Physiol.Plant_158_180 PubMedSearch: Lee 2016 Physiol.Plant 158 180 PubMedID: 26910207 Abstract Leaf senescence is not only primarily governed by developmental age but also influenced by various internal and external factors. Although some genes that control leaf senescence have been identified, the detailed regulatory mechanisms underlying integration of diverse senescence-associated signals into the senescence programs remain to be elucidated. To dissect the regulatory pathways involved in leaf senescence, we isolated the not oresara1-1 (nore1-1) mutant showing accelerated leaf senescence phenotypes from an EMS-mutagenized Arabidopsis thaliana population. We found that altered transcriptional programs in defense response-related processes were associated with the accelerated leaf senescence phenotypes observed in nore1-1 through microarray analysis. The nore1-1 mutation activated defense program, leading to enhanced disease resistance. Intriguingly, high ambient temperature effectively suppresses the early senescence and death phenotypes of nore1-1. The gene responsible for the phenotypes of nore1-1 contains a missense mutation in SENESCENCE-ASSOCIATED E3 UBIQUITIN LIGASE 1 (SAUL1), which was reported as a negative regulator of premature senescence in the light intensity- and PHYTOALEXIN DEFICIENT 4 (PAD4)-dependent manner. Through extensive double mutant analyses, we recently identified suppressor of the G2 Allele of SKP1b (SGT1b), one of the positive regulators for disease resistance conferred by many resistance (R) proteins, as a downstream signaling component in NORE1-mediated senescence and cell death pathways. In conclusion, NORE1/SAUL1 is a key factor integrating signals from temperature-dependent defense programs and leaf senescence in Arabidopsis. These findings provide a new insight that plants might utilize defense response program in regulating leaf senescence process, possibly through recruiting the related genes during the evolution of the leaf senescence program. Title: Gemigliptin, a dipeptidyl peptidase-4 inhibitor, inhibits retinal pericyte injury in db/db mice and retinal neovascularization in mice with ischemic retinopathy Jung E, Kim J, Kim CS, Kim SH, Cho MH Ref: Biochimica & Biophysica Acta, 1852:2618, 2015 : PubMed ESTHER: Jung_2015_Biochim.Biophys.Acta_1852_2618 PubMedSearch: Jung 2015 Biochim.Biophys.Acta 1852 2618 PubMedID: 26391252 Inhibitor(s) related to this paper: Gemigliptin Abstract Retinal pericyte loss and neovascularization are characteristic features of diabetic retinopathy. Gemigliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, has shown robust blood-glucose lowering effects in type 2 diabetic patients, but its effects on diabetic retinopathy have not yet been reported. We evaluated the efficacy of gemigliptin on retinal vascular leakage in db/db mice, which is an animal model for type 2 diabetes, and neovascularization in oxygen-induced retinopathy (OIR) mice, which is an animal model for ischemic proliferative retinopathy. Gemigliptin (100mg/kg/day) was orally administered to the db/db mice for 12weeks. C57BL/6 mice on postnatal day 7 (P7) were exposed to 75% hyperoxia for 5days, followed by exposure to room air from P12 to P17 to induce OIR. Gemigliptin (50mg/kg/day) was intraperitoneally injected daily from P12 to P17. Retinal neovascularization was analyzed in flat-mounted retinas on P17. We determined the efficacy and possible mechanism of gemigliptin on high glucose-induced apoptosis of primary human retinal pericytes. The oral administration of gemigliptin for 4months significantly ameliorated retinal pericyte apoptosis and vascular leakage in the db/db mice. Gemigliptin also ameliorated retinal neovascularization in the OIR mice. Gemigliptin attenuated the overexpression of plasminogen activator inhibitor-1 (PAI-1) in the retinas of diabetic and OIR mice. Gemigliptin and PAI-1 siRNA significantly inhibited pericyte apoptosis by inhibiting the overexpression of PAI-1, which is induced by high glucose. Our results suggest that gemigliptin has potent anti-angiogenic and anti-apoptotic activities via suppressing DPP-4 and PAI-1, and the results support the direct retinoprotective action of gemigliptin. Title: Improved enantioselectivity of thermostable esterase from Archaeoglobus fulgidus toward (S)-ketoprofen ethyl ester by directed evolution and characterization of mutant esterases Kim J, Kim S, Yoon S, Hong E, Ryu Y Ref: Applied Microbiology & Biotechnology, 99:6293, 2015 : PubMed ESTHER: Kim_2015_Appl.Microbiol.Biotechnol_99_6293 PubMedSearch: Kim 2015 Appl.Microbiol.Biotechnol 99 6293 PubMedID: 25661815 Abstract Thermostable esterases have potential applications in various biotechnology industries because of their resistance to high temperature and organic solvents. In a previous study, we isolated an esterase from Archaeoglobus fulgidus DSM 4304 (Est-AF), which showed high thermostability but low enantioselectivity toward (S)-ketoprofen ethyl ester. (R)-ketoprofenor (S)-ketoprofenis produced by esterase hydrolysis of the ester bond of (R,S)-ketoprofen ethyl ester and (S)-ketoprofen has better pharmaceutical activity and lower side effects than (R)-ketoprofen. Therefore, we have generated mutants of Est-AF that retained high thermostability whilst improving enantioselectivity. A library of Est-AF mutants was created by error-prone polymerase chain reaction, and mutants with improved enantioselectivity were isolated by site-saturation mutagenesis. The regions of Est-AF containing amino acid mutations were analyzed by homology modeling of its three-dimensional structure, and structure-based explanations for the changes in enantioselectivity are proposed. Finally, we isolated two mutants showing improved enantioselectivity over Est-AF (ee% = -16.2 +/- 0.2 and E = 0.7 +/- 0.0): V138G (ee% = 35.9 +/- 1.0 and E = 3.0 +/- 0.1) and V138G/L200R (ee% = 89.2 +/- 0.2 and E = 19.5 +/- 0.5). We also investigated various characteristics of these mutants and found that the mutants showed similar thermostability and resistance to additives or organic solvents to Est-AF, without a significant trade-off between activity and stability. Title: Cloning and characterization of a novel thermostable esterase from Bacillus gelatini KACC 12197 Kim J, Deng L, Hong E, Ryu Y Ref: Protein Expr Purif, 116:90, 2015 : PubMed ESTHER: Kim_2015_Protein.Expr.Purif_116_90 PubMedSearch: Kim 2015 Protein.Expr.Purif 116 90 PubMedID: 26276473 Abstract A novel gene encoding a thermostable esterase (designated as Est-gela) was isolated from the moderate thermophile Bacillus gelatini KACC 12197. The open reading frame of this gene (1170bp) encodes 389 amino acid residues, and the molecular weight of Est-gela is approximately 42kDa. The protein sequence of Est-gela shows similarity with beta-lactamases and esterases (43%). Est-gela contains the Ser-X-X-Lys conserved sequence (Ser58-Met59-Thr60-Lys61) and belongs to family VIII of esterases. We overexpressed Est-gela in Escherichia coli XL1-blue and purified this protein using a His tag. Est-gela showed a strong enzymatic activity toward p-nitrophenyl esters with short acyl chains (C4) and the strongest activity toward p-nitrophenyl butyrate. Est-gela showed an enhanced enzymatic activity at 65-75 degrees C and retained more than 90% of the activity after incubation at 65 degrees C for 180min. These results indicated that Est-gela was thermostable. In addition, Est-gela showed the maximal activity at pH 10. We also evaluated the effects of surfactants and organic solvents. Surfactants were more effective at improving the enzymatic activity than were organic solvents. Finally, Est-gela hydrolyzed (R,S)-ketoprofen ethyl ester (Kcat/Km=5.0+/-0.2s(-1)mM(-1), mean+/-standard error) with enantioselectivity toward (S)-ketoprofen ethyl ester rather than (R)-ketoprofen ethyl ester. Title: Characterization of Novel Family IV Esterase and Family I.3 Lipase from an Oil-Polluted Mud Flat Metagenome Kim HJ, Jeong YS, Jung WK, Kim SK, Lee HW, Kahng HY, Kim J, Kim H Ref: Mol Biotechnol, 57:781, 2015 : PubMed ESTHER: Kim_2015_Mol.Biotechnol_57_781 PubMedSearch: Kim 2015 Mol.Biotechnol 57 781 PubMedID: 25943044 Abstract Two genes encoding lipolytic enzymes were isolated from a metagenomic library constructed from oil-polluted mud flats. An esterase gene, est3K, encoded a protein of 299 amino acids (ca. 32,364 Da). Est3K was a family IV esterase with typical motifs, HGGG, and HGF. Although est3K showed high identity to many genes with no information on their enzymatic properties, Est3K showed the highest identity (36 %) to SBLip5.1 from forest soil metagenome when compared to the enzymes with reported properties. A lipase gene, lip3K, encoded a protein of 616 amino acids (ca. 64,408 Da). Lip3K belonged to family I.3 lipase with a C-terminal secretion signal and showed the highest identity (93 %) to the lipase of Pseudomonas sp. MIS38. The presence of several newly identified conserved motifs in Est3K and Lip3K are suggested. Both Est3K and Lip3K exerted their maximal activity at pH 9.0 and 50 degrees C. The activity of Lip3K was significantly increased by the presence of 30 % methanol. The ability of the enzymes to retain activities in the presence of methanol and the substrates may offer a merit to the biotechnological applications of the enzymes such as transesterification. The activity and the thermostability of Lip3K were increased by Ca(2+). Est3K and Lip3K preferred p-nitrophenyl butyrate (C4) and octanoate (C8), respectively, as the substrate and acted independently on the substrates with no synergistic effect. Title: A randomized, placebo-controlled, double-blind, phase 3 trial to evaluate the efficacy and safety of anagliptin in drug-naive patients with type 2 diabetes Yang HK, Min KW, Park SW, Chung CH, Park KS, Choi SH, Song KH, Kim DM, Lee MK and Yoon KH <11 more author(s)> Yang HK, Min KW, Park SW, Chung CH, Park KS, Choi SH, Song KH, Kim DM, Lee MK, Sung YA, Baik SH, Kim IJ, Cha BS, Park JH, Ahn YB, Lee IK, Yoo SJ, Kim J, Park Ie B, Park TS, Yoon KH (- 11) Ref: Endocrine Journal, 62:449, 2015 : PubMed ESTHER: Yang_2015_Endocr.J_62_449 PubMedSearch: Yang 2015 Endocr.J 62 449 PubMedID: 25819061 Abstract The aim of this study was to evaluate the efficacy and safety of anagliptin in drug-naive patients with type 2 diabetes in a double-blind randomized placebo-controlled study. A total of 109 patients were randomized to 100 mg (n=37) or 200 mg (n=33) anagliptin twice daily or placebo (n=39). The primary objective was to alter HbA1c levels from baseline at a 24-week endpoint. The overall baseline mean age and body mass index were 56.20 +/- 9.77 years and 25.01 +/- 2.97 kg/m(2), respectively, and the HbA1c level was of 7.14 +/- 0.69 %. Anagliptin at 100 mg and 200 mg produced significant reductions in HbA1c (-0.50 +/- 0.45 % and -0.51 +/- 0.55%, respectively), and the placebo treatment resulted in an increase in HbA1c by 0.23 +/- 0.62 %. Both doses of anagliptin produced significant decreases in fasting plasma glucose (-0.53 +/- 1.25 mmol/L and -0.72 +/- 1.25 mmol/L, respectively) and the proinsulin/insulin ratio (-0.04 +/- 0.15 and -0.07 +/- 0.18, respectively) compared with placebo. No meaningful body weight changes from baseline were observed in three groups. Plasma dipeptidyl peptidase (DPP)-4 activity was significantly inhibited after 24 weeks of anagliptin treatment, and >75% and >90% inhibitions were observed during the meal tolerance tests with 100 mg and 200 mg anagliptin, respectively. The incidences of adverse or serious adverse events were similar among the three study groups. Twice-daily anagliptin therapy effectively inhibited DPP-4 activity and improved glycemic control and was well-tolerated in patients with type 2 diabetes. Title: Insecticidal and Acetylcholine Esterase Inhibition Activity of Asteraceae Plant Essential Oils and Their Constituents against Adults of the German Cockroach (Blattella germanica) Yeom HJ, Jung CS, Kang J, Kim J, Lee JH, Kim DS, Kim HS, Park PS, Kang KS, Park IK Ref: Journal of Agricultural and Food Chemistry, 63:2241, 2015 : PubMed ESTHER: Yeom_2015_J.Agric.Food.Chem_63_2241 PubMedSearch: Yeom 2015 J.Agric.Food.Chem 63 2241 PubMedID: 25664467 Abstract The fumigant and contact toxicities of 16 Asteraceae plant essential oils and their constituents against adult male and female Blattella germanica were examined. In a fumigant toxicity test, tarragon oil exhibited 100% and 90% fumigant toxicity against adult male German cockroaches at 5 and 2.5 mg/filter paper, respectively. Fumigant toxicities of Artemisia arborescens and santolina oils against adult male German cockroaches were 100% at 20 mg/filter paper, but were reduced to 60% and 22.5% at 10 mg/filter paper, respectively. In contact toxicity tests, tarragon and santolina oils showed potent insecticidal activity against adult male German cockroaches. Components of active oils were analyzed using gas chromatography, gas chromatography-mass spectrometry, or nuclear magnetic resonance spectrometer. Among the identified compounds from active essential oils, estragole demonstrated potent fumigant and contact toxicity against adult German cockroaches. beta-Phellandrene exhibited inhibition of male and female German cockroach acetylcholinesterase activity with IC50 values of 0.30 and 0.28 mg/mL, respectively. Title: Neurons in the basal forebrain project to the cortex in a complex topographic organization that reflects corticocortical connectivity patterns: an experimental study based on retrograde tracing and 3D reconstruction Zaborszky L, Csordas A, Mosca K, Kim J, Gielow MR, Vadasz C, Nadasdy Z Ref: Cerebral Cortex, 25:118, 2015 : PubMed ESTHER: Zaborszky_2015_Cereb.Cortex_25_118 PubMedSearch: Zaborszky 2015 Cereb.Cortex 25 118 PubMedID: 23964066 Abstract The most prominent feature of the Basal Forebrain (BF) is the collection of large cortically projecting neurons (basal nucleus of Meynert) that serve as the primary source of cholinergic input to the entire cortical mantle. Despite its broad involvement in cortical activation, attention, and memory, the functional details of the BF are not well understood due to the anatomical complexity of the region. This study tested the hypothesis that basalocortical connections reflect cortical connectivity patterns. Distinct retrograde tracers were deposited into various frontal and posterior cortical areas, and retrogradely labeled cholinergic and noncholinergic neurons were mapped in the BF. Concurrently, we mapped retrogradely labeled cells in posterior cortical areas that project to various frontal areas, and all cell populations were combined in the same coordinate system. Our studies suggest that the cholinergic and noncholinergic projections to the neocortex are not diffuse, but instead, are organized into segregated or overlapping pools of projection neurons. The extent of overlap between BF populations projecting to the cortex depends on the degree of connectivity between the cortical targets of these projection populations. We suggest that the organization of projections from the BF may enable parallel modulation of multiple groupings of interconnected yet nonadjacent cortical areas. Title: Enhanced catalytic site thermal stability of cold-adapted esterase EstK by a W208Y mutation Boyineni J, Kim J, Kang BS, Lee C, Jang SH Ref: Biochimica & Biophysica Acta, 1844:1076, 2014 : PubMed ESTHER: Boyineni_2014_Biochim.Biophys.Acta_1844_1076 PubMedSearch: Boyineni 2014 Biochim.Biophys.Acta 1844 1076 PubMedID: 24667115 Abstract Hydrophobic interactions are known to play an important role for cold-adaptation of proteins; however, the role of amino acid residue, Trp, has not been systematically investigated. The extracellular esterase, EstK, which was isolated from the cold-adapted bacterium Pseudomonas mandelii, has 5 Trp residues. In this study, the effects of Trp mutation on thermal stability, catalytic activity, and conformational change of EstK were investigated. Among the 5 Trp residues, W(208) was the most crucial in maintaining structural conformation and thermal stability of the enzyme. Surprisingly, mutation of W(208) to Tyr (W(208)Y) showed an increased catalytic site thermal stability at ambient temperatures with a 13-fold increase in the activity at 40 degrees C compared to wild-type EstK. The structure model of W(208)Y suggested that Y(208) could form a hydrogen bond with D(308), which is located next to catalytic residue H(307), stabilizing the catalytic domain. Interestingly, Tyr was conserved in the corresponding position of hyper-thermophilic esterases EstE1 and AFEST, which are active at high temperatures. Our study provides a novel insight into the engineering of the catalytic site of cold-adapted enzymes with increased thermal stability and catalytic activity at ambient temperatures. Title: Highly stabilized lipase in polyaniline nanofibers for surfactant-mediated esterification of ibuprofen Hong SG, Kim HS, Kim J Ref: Langmuir, 30:911, 2014 : PubMed ESTHER: Hong_2014_Langmuir_30_911 PubMedSearch: Hong 2014 Langmuir 30 911 PubMedID: 24417226 Abstract Lipase (LP) from Candida rugosa was immobilized and stabilized in polyaniline nanofibers (PANFs) via a three-step process of enzyme adsorption, precipitation, and cross-linking, which generates the final immobilization called "EAPC". The activity of EAPC was 5.1 and 5.9 times higher than those of LP immobilizations via enzyme adsorption (EA) and enzyme adsorption/cross-linking (EAC), respectively. After incubation in an aqueous buffer under shaking (200 rpm) for 84 days, EAPC maintained 74% of its initial activity, while EA and EAC retained 11 and 24% of their initial activities, respectively. Highly stable and active EAPC was employed for the resolution of racemic ibuprofen via esterification of S-(+)-ibuprofen with 1-propanol in isooctane. The addition of 100 mM dioctyl sulfosuccinate (AOT) into the reaction medium increased the esterification activity by 61-fold, which can be explained by the better dispersion of EAPC in isooctane. EAPC showed 42% conversion in the esterification of racemic ibuprofen after 102 h, whereas EA and EAC showed only 1.2 and 1.4% conversion in the same condition, respectively. The EAPC approach increases both loading and stability of LP, and the combination of EAPC with the surfactant addition can be employed for efficient enzymatic reactions in organic solvents. Title: Preclinical activity of nanoliposomal irinotecan is governed by tumor deposition and intratumor prodrug conversion Kalra AV, Kim J, Klinz SG, Paz N, Cain J, Drummond DC, Nielsen UB, Fitzgerald JB Ref: Cancer Research, 74:7003, 2014 : PubMed ESTHER: Kalra_2014_Cancer.Res_74_7003 PubMedSearch: Kalra 2014 Cancer.Res 74 7003 PubMedID: 25273092 Abstract A major challenge in the clinical use of cytotoxic chemotherapeutics is maximizing efficacy in tumors while sparing normal tissue. Irinotecan is used for colorectal cancer treatment but the extent of its use is limited by toxic side effects. Liposomal delivery systems offer tools to modify pharmacokinetic and safety profiles of cytotoxic drugs. In this study, we defined parameters that maximize the antitumor activity of a nanoliposomal formulation of irinotecan (nal-IRI). In a mouse xenograft model of human colon carcinoma, nal-IRI dosing could achieve higher intratumoral levels of the prodrug irinotecan and its active metabolite SN-38 compared with free irinotecan. For example, nal-IRI administered at doses 5-fold lower than free irinotecan achieved similar intratumoral exposure of SN-38 but with superior antitumor activity. Tumor response and pharmacokinetic modeling identified the duration for which concentrations of SN-38 persisted above a critical intratumoral threshold of 120 nmol/L as determinant for antitumor activity. We identified tumor permeability and carboxylesterase activity needed for prodrug activation as critical factors in achieving longer duration of SN-38 in tumors. Simulations varying tumor permeability and carboxylesterase activity predicted a concave increase in tumor SN-38 duration, which was confirmed experimentally in 13 tumor xenograft models. Tumors in which higher SN-38 duration was achieved displayed more robust growth inhibition compared with tumors with lower SN-38 duration, confirming the importance of this factor in drug response. Overall, our work shows how liposomal encapsulation of irinotecan can safely improve its antitumor activity in preclinical models by enhancing accumulation of its active metabolite within the tumor microenvironment. Cancer Res; 74(23); 7003-13. (c)2014 AACR. Title: Pharmacological inhibition of soluble epoxide hydrolase prevents renal interstitial fibrogenesis in obstructive nephropathy Kim J, Yoon SP, Toews ML, Imig JD, Hwang SH, Hammock BD, Padanilam BJ Ref: American Journal of Physiology Renal Physiol, :ajprenal 00531 2014, 2014 : PubMed ESTHER: Kim_2014_Am.J.Physiol.Renal.Physiol__ajprenal 00531 2014 PubMedSearch: Kim 2014 Am.J.Physiol.Renal.Physiol ajprenal 00531 2014 PubMedID: 25377915 Abstract Treating chronic kidney disease (CKD) has been challenging because of its pathogenic complexity. Epoxyeicosatrienoic acids (EETs) are cytochrome P450-dependent derivatives of arachidonic acid with anti-hypertensive, anti-inflammatory and profibrinolytic functions. We recently reported that genetic ablation of soluble epoxide hydrolase (sEH), an enzyme that converts EETs to less active dihydroxyeicosatrienoic acids, prevents renal tubulointerstitial fibrosis and inflammation in experimental mouse models of CKD. Here, we tested the hypothesis that pharmacological inhibition of sEH post-unilateral ureteral obstruction (UUO) would attenuate tubulointerstitial fibrosis and inflammation in mouse kidneys and may provide a novel approach to manage the progression of CKD. Inhibition of sEH enhanced levels of EET regioisomers and abolished tubulointerstitial fibrosis as demonstrated by reduced collagen deposition and myofibroblast formation after UUO. The inflammatory response was also attenuated as demonstrated by decreased influx of neutrophils and macrophages and decreased expression of inflammatory cytokines KC, MIP-2, MCP-1, TNF-alpha and ICAM-1 in kidneys after UUO . UUO upregulated TGF-beta1/Smad3 signaling and induced NF-kappaB activation, oxidative stress, tubular injury, apoptosis; in contrast it downregulated antifibrotic factors including peroxisome proliferators-activated receptor (PPAR) isoforms, especially PPARgamma. sEH inhibition mitigated the aforementioned malevolent effects in UUO kidneys. These data demonstrate that pharmacological inhibition of sEH promotes anti-inflammatory and fibroprotective effects in UUO kidneys by preventing tubular injury, downregulation of NF-kappaB, TGF-beta1/Smad3 and inflammatory signaling pathways and activation of PPAR isoforms. Our data suggest the potential use of sEH inhibitors in treating fibrogenesis in CKD. Title: Sulforaphane alleviates scopolamine-induced memory impairment in mice Lee S, Kim J, Seo SG, Choi BR, Han JS, Lee KW Ref: Pharmacol Res, 85:23, 2014 : PubMed ESTHER: Lee_2014_Pharmacol.Res_85_23 PubMedSearch: Lee 2014 Pharmacol.Res 85 23 PubMedID: 24836869 Abstract Sulforaphane, an organosulfur compound present in cruciferous vegetables, has been shown to exert neuroprotective effects in experimental in vitro and in vivo models of neurodegeneration. To determine whether sulforaphane can preserve cognitive function, we examined its effects on scopolamine-induced memory impairment in mice using the Morris water maze test. Sulforaphane (10 or 50mg/kg) was administered to C57BL/6 mice by oral gavage for 14 days (days 1-14), and memory impairment was induced by intraperitoneal injection of scopolamine (1mg/kg) for 7 days (days 8-14). Mice that received scopolamine alone showed impaired learning and memory retention and considerably decreased cholinergic system reactivity in the hippocampus and frontal cortex, as indicated by a decreased acetylcholine (ACh) level and an increased acetylcholinesterase (AChE) activity. Sulforaphane significantly attenuated the scopolamine-induced memory impairment and improved cholinergic system reactivity, as indicated by an increased ACh level, decreased AChE activity, and increased choline acetyltransferase (ChAT) expression in the hippocampus and frontal cortex. These effects of sulforaphane on cholinergic system reactivity were confirmed in vitro. Sulforaphane (10 or 20muM) increased the ACh level, decreased the AChE activity, and increased ChAT expression in scopolamine-treated primary cortical neurons. These observations suggest that sulforaphane might exert a significant neuroprotective effect on cholinergic deficit and cognitive impairment. Title: Monoacylglycerol lipase inhibitor JZL184 improves behavior and neural properties in Ts65Dn mice, a model of down syndrome Lysenko LV, Kim J, Henry C, Tyrtyshnaia A, Kohnz RA, Madamba F, Simon GM, Kleschevnikova NE, Nomura DK and Kleschevnikov AM <1 more author(s)> Lysenko LV, Kim J, Henry C, Tyrtyshnaia A, Kohnz RA, Madamba F, Simon GM, Kleschevnikova NE, Nomura DK, Ezekowitz RA, Kleschevnikov AM (- 1) Ref: PLoS ONE, 9:e114521, 2014 : PubMed ESTHER: Lysenko_2014_PLoS.One_9_e114521 PubMedSearch: Lysenko 2014 PLoS.One 9 e114521 PubMedID: 25474204 Inhibitor(s) related to this paper: JZL184 Abstract Genetic alterations or pharmacological treatments affecting endocannabinoid signaling have profound effects on synaptic and neuronal properties and, under certain conditions, may improve higher brain functions. Down syndrome (DS), a developmental disorder caused by triplication of chromosome 21, is characterized by deficient cognition and inevitable development of the Alzheimer disease (AD) type pathology during aging. Here we used JZL184, a selective inhibitor of monoacylglycerol lipase (MAGL), to examine the effects of chronic MAGL inhibition on the behavioral, biochemical, and synaptic properties of aged Ts65Dn mice, a genetic model of DS. In both Ts65Dn mice and their normosomic (2N) controls, JZL184-treatment increased brain levels of 2-arachidonoylglycerol (2-AG) and decreased levels of its metabolites such as arachidonic acid, prostaglandins PGD2, PGE2, PGFalpha, and PGJ2. Enhanced spontaneous locomotor activity of Ts65Dn mice was reduced by the JZL184-treatement to the levels observed in 2N animals. Deficient long-term memory was also improved, while short-term and working types of memory were unaffected. Furthermore, reduced hippocampal long-term potentiation (LTP) was increased in the JZL184-treated Ts65Dn mice to the levels observed in 2N mice. Interestingly, changes in synaptic plasticity and behavior were not observed in the JZL184-treated 2N mice suggesting that the treatment specifically attenuated the defects in the trisomic animals. The JZL184-treatment also reduced the levels of Abeta40 and Abeta42, but had no effect on the levels of full length APP and BACE1 in both Ts65Dn and 2N mice. These data show that chronic MAGL inhibition improves the behavior and brain functions in a DS model suggesting that pharmacological targeting of MAGL may be considered as a perspective new approach for improving cognition in DS. Title: Fumigant toxicity and acetylcholinesterase inhibitory activity of 4 Asteraceae plant essential oils and their constituents against Japanese termite (Reticulitermes speratus Kolbe) Seo SM, Kim J, Kang J, Koh SH, Ahn YJ, Kang KS, Park IK Ref: Pestic Biochem Physiol, 113:55, 2014 : PubMed ESTHER: Seo_2014_Pestic.Biochem.Physiol_113_55 PubMedSearch: Seo 2014 Pestic.Biochem.Physiol 113 55 PubMedID: 25052527 Abstract This study investigated the fumigant toxicity of 4 Asteraceae plant essential oils and their constituents against the Japanese termite Reticulitermes speratus Kolbe. Fumigant toxicity varied with plant essential oils or constituents, exposure time, and concentration. Among the tested essential oils, those from Chamaemelum nobile exhibited the strongest fumigant toxicity, followed by those from Santolina chamaecyparissus, Ormenis multicaulis, and Eriocephalus punctulatus at 2days after treatment. In all, 15, 24, 19, and 9 compounds were identified in the essential oils from C. nobile, E. punctulatus, O. multicaulis, and S. chamaecyparissus, respectively, by using gas chromatography, gas chromatography-mass spectrometry, or open-column chromatography. The identified compounds were tested individually for their fumigant toxicity against Japanese termites. Among the test compounds, trans-pinocarveol, caryophyllene oxide, sabinene hydrate, and santolina alcohol showed strong fumigant toxicity against Japanese termites. Acetylcholinesterase (AChE) inhibition activity of the identified compounds from C. nobile, E. punctulatus, O. multicaulis, and S. chamaecyparissus essential oils were tested to determine the mode of their action. The IC50 values of (+)-alpha-pinene, (-)-limonene, (-)-alpha-pinene, beta-pinene, and beta-phellandrene against Japanese termite AChE were 0.03, 0.13, 0.41, 0.42, and 0.67mg/mL, respectively. Further studies are warranted to determine the potential of these essential oils and their constituents as fumigants for termite control. Title: The transgenic expression of LARGE exacerbates the muscle phenotype of dystroglycanopathy mice Whitmore C, Fernandez-Fuente M, Booler H, Parr C, Kavishwar M, Ashraf A, Lacey E, Kim J, Terry R and Brown SC <4 more author(s)> Whitmore C, Fernandez-Fuente M, Booler H, Parr C, Kavishwar M, Ashraf A, Lacey E, Kim J, Terry R, Ackroyd MR, Wells KE, Muntoni F, Wells DJ, Brown SC (- 4) Ref: Hum Mol Genet, 23:1842, 2014 : PubMed ESTHER: Whitmore_2014_Hum.Mol.Genet_23_1842 PubMedSearch: Whitmore 2014 Hum.Mol.Genet 23 1842 PubMedID: 24234655 Abstract Mutations in fukutin-related protein (FKRP) underlie a group of muscular dystrophies associated with the hypoglycosylation of alpha-dystroglycan (alpha-DG), a proportion of which show central nervous system involvement. Our original FKRP knock-down mouse (FKRP(KD)) replicated many of the characteristics seen in patients at the severe end of the dystroglycanopathy spectrum but died perinatally precluding its full phenotyping and use in testing potential therapies. We have now overcome this by crossing FKRP(KD) mice with those expressing Cre recombinase under the Sox1 promoter. Owing to our original targeting strategy, this has resulted in the restoration of Fkrp levels in the central nervous system but not the muscle, thereby generating a new model (FKRP(MD)) which develops a progressive muscular dystrophy resembling what is observed in limb girdle muscular dystrophy. Like-acetylglucosaminyltransferase (LARGE) is a bifunctional glycosyltransferase previously shown to hyperglycosylate alpha-DG. To investigate the therapeutic potential of LARGE up-regulation, we have now crossed the FKRP(MD) line with one overexpressing LARGE and show that, contrary to expectation, this results in a worsening of the muscle pathology implying that any future strategies based upon LARGE up-regulation require careful management. Title: Neuregulin-1 impairs the long-term depression of hippocampal inhibitory synapses by facilitating the degradation of endocannabinoid 2-AG Du H, Kwon IK, Kim J Ref: Journal of Neuroscience, 33:15022, 2013 : PubMed ESTHER: Du_2013_J.Neurosci_33_15022 PubMedSearch: Du 2013 J.Neurosci 33 15022 PubMedID: 24048832 Abstract Endocannabinoids play essential roles in synaptic plasticity; thus, their dysfunction often causes impairments in memory or cognition. However, it is not well understood whether deficits in the endocannabinoid system account for the cognitive symptoms of schizophrenia. Here, we show that endocannabinoid-mediated synaptic regulation is impaired by the prolonged elevation of neuregulin-1, the abnormality of which is a hallmark in many patients with schizophrenia. When rat hippocampal slices were chronically treated with neuregulin-1, the degradation of 2-arachidonoylglycerol (2-AG), one of the major endocannabinoids, was enhanced due to the increased expression of its degradative enzyme, monoacylglycerol lipase. As a result, the time course of depolarization-induced 2-AG signaling was shortened, and the magnitude of 2-AG-dependent long-term depression of inhibitory synapses was reduced. Our study reveals that an alteration in the signaling of 2-AG contributes to hippocampal synaptic dysfunction in a hyper-neuregulin-1 condition and thus provides novel insights into potential schizophrenic therapeutics that target the endocannabinoid system. Title: Propionibacterium acnes strain populations in the human skin microbiome associated with acne Fitz-Gibbon S, Tomida S, Chiu BH, Nguyen L, Du C, Liu M, Elashoff D, Erfe MC, Loncaric A and Li H <6 more author(s)> Fitz-Gibbon S, Tomida S, Chiu BH, Nguyen L, Du C, Liu M, Elashoff D, Erfe MC, Loncaric A, Kim J, Modlin RL, Miller JF, Sodergren E, Craft N, Weinstock GM, Li H (- 6) Ref: Journal of Investigative Dermatology, 133:2152, 2013 : PubMed ESTHER: Fitz-Gibbon_2013_J.Invest.Dermatol_133_2152 PubMedSearch: Fitz-Gibbon 2013 J.Invest.Dermatol 133 2152 PubMedID: 23337890 Gene_locus related to this paper: proac-q6a5t3, proac-q6a981 Abstract The human skin microbiome has important roles in skin health and disease. However, bacterial population structure and diversity at the strain level is poorly understood. We compared the skin microbiome at the strain level and genome level of Propionibacterium acnes, a dominant skin commensal, between 49 acne patients and 52 healthy individuals by sampling the pilosebaceous units on their noses. Metagenomic analysis demonstrated that although the relative abundances of P. acnes were similar, the strain population structures were significantly different in the two cohorts. Certain strains were highly associated with acne, and other strains were enriched in healthy skin. By sequencing 66 previously unreported P. acnes strains and comparing 71 P. acnes genomes, we identified potential genetic determinants of various P. acnes strains in association with acne or health. Our analysis suggests that acquired DNA sequences and bacterial immune elements may have roles in determining virulence properties of P. acnes strains, and some could be future targets for therapeutic interventions. This study demonstrates a previously unreported paradigm of commensal strain populations that could explain the pathogenesis of human diseases. It underscores the importance of strain-level analysis of the human microbiome to define the role of commensals in health and disease. Title: Improvement of the Oryza sativa Nipponbare reference genome using next generation sequence and optical map data Kawahara Y, de la Bastide M, Hamilton JP, Kanamori H, McCombie WR, Ouyang S, Schwartz DC, Tanaka T, Wu J and Matsumoto T <12 more author(s)> Kawahara Y, de la Bastide M, Hamilton JP, Kanamori H, McCombie WR, Ouyang S, Schwartz DC, Tanaka T, Wu J, Zhou S, Childs KL, Davidson RM, Lin H, Quesada-Ocampo L, Vaillancourt B, Sakai H, Lee SS, Kim J, Numa H, Itoh T, Buell CR, Matsumoto T (- 12) Ref: Rice (N Y), 6:4, 2013 : PubMed ESTHER: Kawahara_2013_Rice.(N.Y)_6_4 PubMedSearch: Kawahara 2013 Rice.(N.Y) 6 4 PubMedID: 24280374 Gene_locus related to this paper: orysa-Q0JK71, orysj-q6yse8, orysa-q6yzk1, orysa-q7xej4, orysa-q7xem8, orysa-q7xr64, orysj-a0a0p0y6l9, orysj-pla4, orysj-pla1 Abstract BACKGROUND: Rice research has been enabled by access to the high quality reference genome sequence generated in 2005 by the International Rice Genome Sequencing Project (IRGSP). To further facilitate genomic-enabled research, we have updated and validated the genome assembly and sequence for the Nipponbare cultivar of Oryza sativa (japonica group). RESULTS: The Nipponbare genome assembly was updated by revising and validating the minimal tiling path of clones with the optical map for rice. Sequencing errors in the revised genome assembly were identified by re-sequencing the genome of two different Nipponbare individuals using the Illumina Genome Analyzer II/IIx platform. A total of 4,886 sequencing errors were identified in 321 Mb of the assembled genome indicating an error rate in the original IRGSP assembly of only 0.15 per 10,000 nucleotides. A small number (five) of insertions/deletions were identified using longer reads generated using the Roche 454 pyrosequencing platform. As the re-sequencing data were generated from two different individuals, we were able to identify a number of allelic differences between the original individual used in the IRGSP effort and the two individuals used in the re-sequencing effort. The revised assembly, termed Os-Nipponbare-Reference-IRGSP-1.0, is now being used in updated releases of the Rice Annotation Project and the Michigan State University Rice Genome Annotation Project, thereby providing a unified set of pseudomolecules for the rice community. CONCLUSIONS: A revised, error-corrected, and validated assembly of the Nipponbare cultivar of rice was generated using optical map data, re-sequencing data, and manual curation that will facilitate on-going and future research in rice. Detection of polymorphisms between three different Nipponbare individuals highlights that allelic differences between individuals should be considered in diversity studies. Title: An Organic Solvent-Tolerant Alkaline Lipase from Cold-Adapted Pseudomonas mandelii: Cloning, Expression, and Characterization Kim J, Jang SH, Lee C Ref: Biosci Biotechnol Biochem, 77:320, 2013 : PubMed ESTHER: Kim_2013_Biosci.Biotechnol.Biochem_77_320 PubMedSearch: Kim 2013 Biosci.Biotechnol.Biochem 77 320 PubMedID: 23391923 Abstract A gene encoding a novel organic solvent-tolerant alkaline lipase, lipS (GenBank ID JQ071496), was cloned from cold-adapted Pseudomonas mandelii. Recombinant LipS was expressed in Escherichia coli as a 32-kDa soluble protein and was purified by standard procedures. It maintained more than 80% of its activity under alkaline conditions, pH 8-10.5, with an apparent optimum temperature range of 40-50 degrees C. It maintained thermal stability from 4 to 50 degrees C. After 1 h of incubation at 60 degrees C, approximately 50% of its activity remained. It retained its activity in organic solvents, and activity increased in the presence of ethanol and of DMSO. Our data indicate that LipS is an alkaline lipase with relatively high thermal stability and notable tolerance of organic solvents. Title: Cloning, expression, and characterization of a recombinant esterase from cold-adapted Pseudomonas mandelii Lee C, Kim J, Hong S, Goo B, Lee S, Jang SH Ref: Appl Biochem Biotechnol, 169:29, 2013 : PubMed ESTHER: Lee_2013_Appl.Biochem.Biotechnol_169_29 PubMedSearch: Lee 2013 Appl.Biochem.Biotechnol 169 29 PubMedID: 23117417 Abstract A gene coding for the extracellular esterase (EstK) was cloned from the psychrotrophic bacterium Pseudomonas mandelii based on its partial amino acid sequence as determined by mass spectrometry. The entire open reading frame consisting of 1,011 bp was expressed in Escherichia coli as a soluble protein and purified by nickel-chelated affinity chromatography and Capto Q column chromatography. Here, we show that the 33-kDa recombinant EstK protein (rEstKsp) had a substrate preference for esters of short-chain fatty acids, especially, p-nitrophenyl acetate. Optimum activity of rEstKsp was at pH 8.5 and 40 degrees C. The esterase activity remained similar from a range of 4 approximately 20 degrees C, but the maximum activity varied depending upon pH. With p-nitrophenyl acetate as the substrate, K (M) was 210 muM and k (cat) was 3.4 s(-1). Circular dichroism and fluorescence spectroscopy results revealed that rEstKsp had a predominantly alpha-helical structure and maintained its folded state at 4 approximately 40 degrees C. Interestingly, the tertiary structure of rEstKsp was predicted based on the structures of other hyperthermophilic esterases. Our results demonstrated that both native and rEstKsp are active at low temperatures and have a unique substrate preference for p-nitrophenyl acetate. Title: Rice Annotation Project Database (RAP-DB): an integrative and interactive database for rice genomics Sakai H, Lee SS, Tanaka T, Numa H, Kim J, Kawahara Y, Wakimoto H, Yang CC, Iwamoto M and Itoh T <7 more author(s)> Sakai H, Lee SS, Tanaka T, Numa H, Kim J, Kawahara Y, Wakimoto H, Yang CC, Iwamoto M, Abe T, Yamada Y, Muto A, Inokuchi H, Ikemura T, Matsumoto T, Sasaki T, Itoh T (- 7) Ref: Plant Cell Physiol, 54:e6, 2013 : PubMed ESTHER: Sakai_2013_Plant.Cell.Physiol_54_E6 PubMedSearch: Sakai 2013 Plant.Cell.Physiol 54 E6 PubMedID: 23299411 Gene_locus related to this paper: orysa-Q0JK71, orysj-q6yse8, orysa-q6yzk1 Abstract The Rice Annotation Project Database (RAP-DB, http://rapdb.dna.affrc.go.jp/) has been providing a comprehensive set of gene annotations for the genome sequence of rice, Oryza sativa (japonica group) cv. Nipponbare. Since the first release in 2005, RAP-DB has been updated several times along with the genome assembly updates. Here, we present our newest RAP-DB based on the latest genome assembly, Os-Nipponbare-Reference-IRGSP-1.0 (IRGSP-1.0), which was released in 2011. We detected 37,869 loci by mapping transcript and protein sequences of 150 monocot species. To provide plant researchers with highly reliable and up to date rice gene annotations, we have been incorporating literature-based manually curated data, and 1,626 loci currently incorporate literature-based annotation data, including commonly used gene names or gene symbols. Transcriptional activities are shown at the nucleotide level by mapping RNA-Seq reads derived from 27 samples. We also mapped the Illumina reads of a Japanese leading japonica cultivar, Koshihikari, and a Chinese indica cultivar, Guangluai-4, to the genome and show alignments together with the single nucleotide polymorphisms (SNPs) and gene functional annotations through a newly developed browser, Short-Read Assembly Browser (S-RAB). We have developed two satellite databases, Plant Gene Family Database (PGFD) and Integrative Database of Cereal Gene Phylogeny (IDCGP), which display gene family and homologous gene relationships among diverse plant species. RAP-DB and the satellite databases offer simple and user-friendly web interfaces, enabling plant and genome researchers to access the data easily and facilitating a broad range of plant research topics. Title: A novel synthesis of (-)-huperzine A via tandem intramolecular aza-Prins cyclization-cyclobutane fragmentation White JD, Li Y, Kim J, Terinek M Ref: Org Lett, 15:882, 2013 : PubMed ESTHER: White_2013_Org.Lett_15_882 PubMedSearch: White 2013 Org.Lett 15 882 PubMedID: 23346936 Abstract The acetylcholinesterase inhibitor (-)-huperzine A was synthesized from (S)-4-hydroxycyclohex-2-enone in 17 steps by a route that involved two cyclobutane fragmentations. The first of these employed a retro-aldol cleavage to generate the alpha-pyridone ring of huperzine A, and the second invoked a novel intramolecular aza-Prins reaction in tandem with stereocontrolled scission of a cyclobutylcarbinyl cation to create the aminobicyclo[3.3.1]nonene framework of the natural alkaloid. Title: Epimediphine, a novel alkaloid from Epimedium koreanum inhibits acetylcholinesterase Zhang X, Oh M, Kim S, Kim J, Kim H, Houghton PJ, Whang W Ref: Nat Prod Res, 27:1067, 2013 : PubMed ESTHER: Zhang_2013_Nat.Prod.Res_27_1067 PubMedSearch: Zhang 2013 Nat.Prod.Res 27 1067 PubMedID: 22823459 Abstract A novel aporphine alkaloid was isolated from the leaves of Epimedium koreanum Nakai during activity-guided fractionation in search of compounds with an anticholinesterase activity. The structure of the new compound was assigned as 1,10-methoxy-7-hydroxy-aporphine (1), which we have named epimediphine. Unambiguous (1)H-NMR and (13)C-NMR data for epimediphine are described. Epimediphine inhibited an acetylcholinesterase (AchE) activity in a dose-dependent manner with an IC50 value of 3.1 microM. Meanwhile, tacrine, dehydroevodiamine and physostigmine, which are therapeutic drugs or candidates for AD, exhibited an anti-AchE activity with IC50 values of 0.4, 37.9 and 0.12 microM, respectively. Title: Complete genome sequence of the rice pathogen Pantoea ananatis strain PA13 Choi O, Lim JY, Seo YS, Hwang I, Kim J Ref: Journal of Bacteriology, 194:531, 2012 : PubMed ESTHER: Choi_2012_J.Bacteriol_194_531 PubMedSearch: Choi 2012 J.Bacteriol 194 531 PubMedID: 22207741 Gene_locus related to this paper: panam-d4gf31, panam-d4gn21, panan-g7uev1, panan-u4w979 Abstract Pantoea ananatis is the causative agent of sheath and grain rot in rice. Here, we present the complete genome sequence of P. ananatis strain PA13, originally isolated from a diseased rice grain. Title: Genome sequence of cold-adapted Pseudomonas mandelii strain JR-1 Jang SH, Kim J, Hong S, Lee C Ref: Journal of Bacteriology, 194:3263, 2012 : PubMed ESTHER: Jang_2012_J.Bacteriol_194_3263 PubMedSearch: Jang 2012 J.Bacteriol 194 3263 PubMedID: 22628497 Gene_locus related to this paper: 9psed-w6ve15, 9psed-a0a024ebb1, 9psed-a0a024e9h9 Abstract Pseudomonas mandelii is a cold-adapted bacterium that can grow at 4 degrees C but not at 37 degrees C. Here we report the draft genome sequence of P. mandelii strain JR-1. Title: Inhibitory Activities of Cudrania tricuspidata Leaves on Pancreatic Lipase In Vitro and Lipolysis In Vivo Kim YS, Lee Y, Kim J, Sohn E, Kim CS, Lee YM, Jo K, Shin S, Song Y and Kim JS <1 more author(s)> Kim YS, Lee Y, Kim J, Sohn E, Kim CS, Lee YM, Jo K, Shin S, Song Y, Kim JH, Kim JS (- 1) Ref: Evid Based Complement Alternat Med, 2012:878365, 2012 : PubMed ESTHER: Kim_2012_Evid.Based.Complement.Alternat.Med_2012_878365 PubMedSearch: Kim 2012 Evid.Based.Complement.Alternat.Med 2012 878365 PubMedID: 23365603 Abstract To identify effective herb to treat obesity, we screened 115 herbal extracts for inhibition of porcine pancreatic lipase (triacylg-ycerol acylhydrolase, EC 3.1.1.3) 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. Title: Genome sequence of pectin-degrading Alishewanella agri, isolated from landfill soil Kim J, Jung J, Sung JS, Chun J, Park W Ref: Journal of Bacteriology, 194:5135, 2012 : PubMed ESTHER: Kim_2012_J.Bacteriol_194_5135 PubMedSearch: Kim 2012 J.Bacteriol 194 5135 PubMedID: 22933763 Gene_locus related to this paper: 9alte-i9p3n1, 9alte-h3zi92, 9alte-i9nzs4, 9alte-i8u2j8, 9alte-h3zb04 Abstract Alishewanella agri BL06(T) (= KCTC 22400(T) = JCM 15597(T)) was isolated from landfill soil in Pohang, South Korea. A. agri showed the ability to degrade pectin, a structural heteropolysaccharide present in the cell wall of plants. Here we report the genome sequence of Alishewanella agri BL06(T), the second sequenced strain in the genus Alishewanella. Title: Cloning and identification of a new group esterase (Est5S) from noncultured rumen bacterium Kim MK, Kang TH, Kim J, Kim H, Yun HD Ref: J Microbiol Biotechnol, 22:1044, 2012 : PubMed ESTHER: Kim_2012_J.Microbiol.Biotechnol_22_1044 PubMedSearch: Kim 2012 J.Microbiol.Biotechnol 22 1044 PubMedID: 22713979 Gene_locus related to this paper: 9bact-q0gpb3 Abstract The gene encoding an esterase enzyme was cloned from a metagenomic library of cow rumen bacteria. The esterase gene (est5S) was 1,026 bp in length, encoding a protein of 366 amino acid residues with a calculated molecular mass of 40,168 Da. The molecular mass of the enzyme was estimated to be 40,000 Da. The Est5S protein contains the Gly-X-Ser-X-Gly motif found in most bacterial and eukaryotic serine hydrolases. However, the Asp or Glu necessary for the catalytic triad [Ser-Asp-(Glu)-His] was not present, indicating Est5S represents a novel member of the GHSQG family of esterolytic enzymes. BlastP in the NCBI database analysis of Est5S revealed homology to hypothetical proteins and it had no homology to previous known lipases and esterases. Est5S was optimally active at pH 7.0 and 40 degrees C. Among the p-nitrophenyl acylesters tested, high enzymatic activities were observed on the short-chain p-nitrophenyl acylesters, such as p-nitrophenyl acetate, etc. The conserved serine residue (Ser190) was shown to be important for Est5S activity. The primers that amplified the est5S gene did not show any relative band with 49 species of culturable rumen bacteria. This implies that a new group esterase gene, est5S, may have come from a noncultured cow rumen bacterium. Title: The yak genome and adaptation to life at high altitude Qiu Q, Zhang G, Ma T, Qian W, Wang J, Ye Z, Cao C, Hu Q, Kim J and Liu J <35 more author(s)> Qiu Q, Zhang G, Ma T, Qian W, Wang J, Ye Z, Cao C, Hu Q, Kim J, Larkin DM, Auvil L, Capitanu B, Ma J, Lewin HA, Qian X, Lang Y, Zhou R, Wang L, Wang K, Xia J, Liao S, Pan S, Lu X, Hou H, Wang Y, Zang X, Yin Y, Ma H, Zhang J, Wang Z, Zhang Y, Zhang D, Yonezawa T, Hasegawa M, Zhong Y, Liu W, Huang Z, Zhang S, Long R, Yang H, Lenstra JA, Cooper DN, Wu Y, Shi P, Liu J (- 35) Ref: Nat Genet, 44:946, 2012 : PubMed ESTHER: Qiu_2012_Nat.Genet_44_946 PubMedSearch: Qiu 2012 Nat.Genet 44 946 PubMedID: 22751099 Gene_locus related to this paper: bosmu-l8ic43, bovin-2neur, bovin-balip, bovin-BCHE, bovin-e1bbv2, bovin-e1bn79, bovin-est8, bovin-f1mi11, bovin-f1n385, bovin-g3mxp5, bovin-lipli, bovin-lipr2, bovin-q2kj30, bovin-q3sz79, bovin-q3t0r6, bovin-ABHDA, bovin-q08dw9, bovin-ABHD16B, bovin-SPG21, bovin-TEX30, 9ceta-l8iwv2, 9ceta-l8idy3, 9ceta-l8hsi3, bovin-e1bjq9, bovin-f1mc21, 9ceta-l8hyl8, bovin-LIPG, bovin-a0a3q1nm09, bovin-f1n2i5 Abstract Domestic yaks (Bos grunniens) provide meat and other necessities for Tibetans living at high altitude on the Qinghai-Tibetan Plateau and in adjacent regions. Comparison between yak and the closely related low-altitude cattle (Bos taurus) is informative in studying animal adaptation to high altitude. Here, we present the draft genome sequence of a female domestic yak generated using Illumina-based technology at 65-fold coverage. Genomic comparisons between yak and cattle identify an expansion in yak of gene families related to sensory perception and energy metabolism, as well as an enrichment of protein domains involved in sensing the extracellular environment and hypoxic stress. Positively selected and rapidly evolving genes in the yak lineage are also found to be significantly enriched in functional categories and pathways related to hypoxia and nutrition metabolism. These findings may have important implications for understanding adaptation to high altitude in other animal species and for hypoxia-related diseases in humans. Title: The evolution of host specialization in the vertebrate gut symbiont Lactobacillus reuteri Frese SA, Benson AK, Tannock GW, Loach DM, Kim J, Zhang M, Oh PL, Heng NC, Patil PB and Walter J <11 more author(s)> Frese SA, Benson AK, Tannock GW, Loach DM, Kim J, Zhang M, Oh PL, Heng NC, Patil PB, Juge N, Mackenzie DA, Pearson BM, Lapidus A, Dalin E, Tice H, Goltsman E, Land M, Hauser L, Ivanova N, Kyrpides NC, Walter J (- 11) Ref: PLoS Genet, 7:e1001314, 2011 : PubMed ESTHER: Frese_2011_PLoS.Genet_7_E1001314 PubMedSearch: Frese 2011 PLoS.Genet 7 E1001314 PubMedID: 21379339 Gene_locus related to this paper: lacre-b3xl60, lacrj-b2g622, lacre-a0a0s4nmr3 Abstract Recent research has provided mechanistic insight into the important contributions of the gut microbiota to vertebrate biology, but questions remain about the evolutionary processes that have shaped this symbiosis. In the present study, we showed in experiments with gnotobiotic mice that the evolution of Lactobacillus reuteri with rodents resulted in the emergence of host specialization. To identify genomic events marking adaptations to the murine host, we compared the genome of the rodent isolate L. reuteri 100-23 with that of the human isolate L. reuteri F275, and we identified hundreds of genes that were specific to each strain. In order to differentiate true host-specific genome content from strain-level differences, comparative genome hybridizations were performed to query 57 L. reuteri strains originating from six different vertebrate hosts in combination with genome sequence comparisons of nine strains encompassing five phylogenetic lineages of the species. This approach revealed that rodent strains, although showing a high degree of genomic plasticity, possessed a specific genome inventory that was rare or absent in strains from other vertebrate hosts. The distinct genome content of L. reuteri lineages reflected the niche characteristics in the gastrointestinal tracts of their respective hosts, and inactivation of seven out of eight representative rodent-specific genes in L. reuteri 100-23 resulted in impaired ecological performance in the gut of mice. The comparative genomic analyses suggested fundamentally different trends of genome evolution in rodent and human L. reuteri populations, with the former possessing a large and adaptable pan-genome while the latter being subjected to a process of reductive evolution. In conclusion, this study provided experimental evidence and a molecular basis for the evolution of host specificity in a vertebrate gut symbiont, and it identified genomic events that have shaped this process. Title: Complete genome sequence of the metabolically versatile plant growth-promoting endophyte Variovorax paradoxus S110 Han JI, Choi HK, Lee SW, Orwin PM, Kim J, Laroe SL, Kim TG, O'Neil J, Leadbetter JR and Han C <5 more author(s)> Han JI, Choi HK, Lee SW, Orwin PM, Kim J, Laroe SL, Kim TG, O'Neil J, Leadbetter JR, Lee SY, Hur CG, Spain JC, Ovchinnikova G, Goodwin L, Han C (- 5) Ref: Journal of Bacteriology, 193:1183, 2011 : PubMed ESTHER: Han_2011_J.Bacteriol_193_1183 PubMedSearch: Han 2011 J.Bacteriol 193 1183 PubMedID: 21183664 Gene_locus related to this paper: varps-c5cla8, varps-c5cld3, varps-c5cle8, varps-c5cmg7, varps-c5cmn3, varps-c5cmq5, varps-c5cn77, varps-c5cpt8, varps-c5cqf4, varps-c5crj1, varps-c5crm2, varps-c5csa3, varps-c5csp0, varps-c5ct29, varps-c5ct59, varps-c5ctz6, varps-c5cu01, varps-c5cu02, varps-c5cuk9, varps-c5cw29, varps-c5czm3, varps-c5czm7, varps-c5czs2, varps-c5czw9, varps-c5czx0, varps-c5czz1, varps-c5d0w2, varps-c5d1f5, varps-c5d1m4, varps-c5d1p7, varps-c5d1r3, varps-c5d033, varpd-t1x730, varps-c5cyt5, varps-rutd Abstract Variovorax paradoxus is a microorganism of special interest due to its diverse metabolic capabilities, including the biodegradation of both biogenic compounds and anthropogenic contaminants. V. paradoxus also engages in mutually beneficial interactions with both bacteria and plants. The complete genome sequence of V. paradoxus S110 is composed of 6,754,997 bp with 6,279 predicted protein-coding sequences within two circular chromosomes. Genomic analysis has revealed multiple metabolic features for autotrophic and heterotrophic lifestyles. These metabolic diversities enable independent survival, as well as a symbiotic lifestyle. Consequently, S110 appears to have evolved into a superbly adaptable microorganism that is able to survive in ever-changing environmental conditions. Based on our findings, we suggest V. paradoxus S110 as a potential candidate for agrobiotechnological applications, such as biofertilizer and biopesticide. Because it has many associations with other biota, it is also suited to serve as an additional model system for studies of microbe-plant and microbe-microbe interactions. Title: Pharmacogenetic Regulation of Acetylcholinesterase Activity in Drosophila Reveals the Regulatory Mechanisms of AChE Inhibitors in Synaptic Plasticity Kim W, Lee D, Choi J, Kim A, Han S, Park K, Kim J, Choi Y, Lee SH, Koh YH Ref: Neurochem Res, 36:879, 2011 : PubMed ESTHER: Kim_2011_Neurochem.Res_36_879 PubMedSearch: Kim 2011 Neurochem.Res 36 879 PubMedID: 21305389 Abstract We conducted experiments in Drosophila to investigate the consequences of altered acetylcholinesterase (AChE) activity in the nervous system. In ace hypomorphic mutant larvae, the amount of ace mRNA and the activity of AChE both in vivo and in vitro were significantly reduced compared with those of controls. Reduced Ace in Drosophila larvae resulted in significant down-regulation of branch length and the number of boutons in Type 1 glutamatergic neuromuscular junctions (NMJs). These defects in ace hypomorphic mutant larvae were suppressed when Musca domestica AChE was transgenically expressed. Because AChE inhibitors are utilized for medications for Alzheimer's disease, we investigated whether pharmacological inhibition of AChE activity induced any synaptic defects. We found that controls exposed to a sublethal dose of DDVP phenocopied the synaptic structural defects of the ace hypomorphic mutant. These results suggest that down-regulation of AChE activity, regardless of whether it is due to genetic or pharmacological manipulations, results in altered synaptic architecture. Our study suggests that exposure to AChE inhibitors for 6-12 months may induce altered synaptic architectures in human brains with Alzheimer's diseases, similar to those reported here. These changes may underlie or contribute to the loss of efficacy of AChE inhibitors after prolonged treatment. Title: Expanding the diversity of mycobacteriophages: insights into genome architecture and evolution Pope WH, Jacobs-Sera D, Russell DA, Peebles CL, Al-Atrache Z, Alcoser TA, Alexander LM, Alfano MB, Alford ST and Hatfull GF <182 more author(s)> Pope WH, Jacobs-Sera D, Russell DA, Peebles CL, Al-Atrache Z, Alcoser TA, Alexander LM, Alfano MB, Alford ST, Amy NE, Anderson MD, Anderson AG, Ang AA, Ares M, Jr., Barber AJ, Barker LP, Barrett JM, Barshop WD, Bauerle CM, Bayles IM, Belfield KL, Best AA, Borjon A, Jr., Bowman CA, Boyer CA, Bradley KW, Bradley VA, Broadway LN, Budwal K, Busby KN, Campbell IW, Campbell AM, Carey A, Caruso SM, Chew RD, Cockburn CL, Cohen LB, Corajod JM, Cresawn SG, Davis KR, Deng L, Denver DR, Dixon BR, Ekram S, Elgin SC, Engelsen AE, English BE, Erb ML, Estrada C, Filliger LZ, Findley AM, Forbes L, Forsyth MH, Fox TM, Fritz MJ, Garcia R, George ZD, Georges AE, Gissendanner CR, Goff S, Goldstein R, Gordon KC, Green RD, Guerra SL, Guiney-Olsen KR, Guiza BG, Haghighat L, Hagopian GV, Harmon CJ, Harmson JS, Hartzog GA, Harvey SE, He S, He KJ, Healy KE, Higinbotham ER, Hildebrandt EN, Ho JH, Hogan GM, Hohenstein VG, Holz NA, Huang VJ, Hufford EL, Hynes PM, Jackson AS, Jansen EC, Jarvik J, Jasinto PG, Jordan TC, Kasza T, Katelyn MA, Kelsey JS, Kerrigan LA, Khaw D, Kim J, Knutter JZ, Ko CC, Larkin GV, Laroche JR, Latif A, Leuba KD, Leuba SI, Lewis LO, Loesser-Casey KE, Long CA, Lopez AJ, Lowery N, Lu TQ, Mac V, Masters IR, McCloud JJ, McDonough MJ, Medenbach AJ, Menon A, Miller R, Morgan BK, Ng PC, Nguyen E, Nguyen KT, Nguyen ET, Nicholson KM, Parnell LA, Peirce CE, Perz AM, Peterson LJ, Pferdehirt RE, Philip SV, Pogliano K, Pogliano J, Polley T, Puopolo EJ, Rabinowitz HS, Resiss MJ, Rhyan CN, Robinson YM, Rodriguez LL, Rose AC, Rubin JD, Ruby JA, Saha MS, Sandoz JW, Savitskaya J, Schipper DJ, Schnitzler CE, Schott AR, Segal JB, Shaffer CD, Sheldon KE, Shepard EM, Shepardson JW, Shroff MK, Simmons JM, Simms EF, Simpson BM, Sinclair KM, Sjoholm RL, Slette IJ, Spaulding BC, Straub CL, Stukey J, Sughrue T, Tang TY, Tatyana LM, Taylor SB, Taylor BJ, Temple LM, Thompson JV, Tokarz MP, Trapani SE, Troum AP, Tsay J, Tubbs AT, Walton JM, Wang DH, Wang H, Warner JR, Weisser EG, Wendler SC, Weston-Hafer KA, Whelan HM, Williamson KE, Willis AN, Wirtshafter HS, Wong TW, Wu P, Yang Y, Yee BC, Zaidins DA, Zhang B, Zuniga MY, Hendrix RW, Hatfull GF (- 182) Ref: PLoS ONE, 6:e16329, 2011 : PubMed ESTHER: Pope_2011_PLoS.ONE_6_E16329 PubMedSearch: Pope 2011 PLoS.ONE 6 E16329 PubMedID: 21298013 Gene_locus related to this paper: 9caud-g1jvt5, 9caud-e0ypf9 Abstract Mycobacteriophages are viruses that infect mycobacterial hosts such as Mycobacterium smegmatis and Mycobacterium tuberculosis. All mycobacteriophages characterized to date are dsDNA tailed phages, and have either siphoviral or myoviral morphotypes. However, their genetic diversity is considerable, and although sixty-two genomes have been sequenced and comparatively analyzed, these likely represent only a small portion of the diversity of the mycobacteriophage population at large. Here we report the isolation, sequencing and comparative genomic analysis of 18 new mycobacteriophages isolated from geographically distinct locations within the United States. Although no clear correlation between location and genome type can be discerned, these genomes expand our knowledge of mycobacteriophage diversity and enhance our understanding of the roles of mobile elements in viral evolution. Expansion of the number of mycobacteriophages grouped within Cluster A provides insights into the basis of immune specificity in these temperate phages, and we also describe a novel example of apparent immunity theft. The isolation and genomic analysis of bacteriophages by freshman college students provides an example of an authentic research experience for novice scientists. Title: Complete genome sequence of Burkholderia gladioli BSR3 Seo YS, Lim J, Choi BS, Kim H, Goo E, Lee B, Lim JS, Choi IY, Moon JS and Hwang I <1 more author(s)> Seo YS, Lim J, Choi BS, Kim H, Goo E, Lee B, Lim JS, Choi IY, Moon JS, Kim J, Hwang I (- 1) Ref: Journal of Bacteriology, 193:3149, 2011 : PubMed ESTHER: Seo_2011_J.Bacteriol_193_3149 PubMedSearch: Seo 2011 J.Bacteriol 193 3149 PubMedID: 21478339 Gene_locus related to this paper: burgs-f2lad2, burgs-f2lc33, burgs-f2lje5, burgs-f2lka6, burgs-f2lp50, burgs-f2lkq2, burgs-f2l922, burgs-f2ld85, burgs-f2lqm0, burgs-f2la46, burgs-f2ljj1 Abstract We report the complete genome sequence of Burkholderia gladioli BSR3, isolated from a diseased rice sheath in South Korea. Title: The genome sequence of the leaf-cutter ant Atta cephalotes reveals insights into its obligate symbiotic lifestyle Suen G, Teiling C, Li L, Holt C, Abouheif E, Bornberg-Bauer E, Bouffard P, Caldera EJ, Cash E and Currie CR <39 more author(s)> Suen G, Teiling C, Li L, Holt C, Abouheif E, Bornberg-Bauer E, Bouffard P, Caldera EJ, Cash E, Cavanaugh A, Denas O, Elhaik E, Fave MJ, Gadau J, Gibson JD, Graur D, Grubbs KJ, Hagen DE, Harkins TT, Helmkampf M, Hu H, Johnson BR, Kim J, Marsh SE, Moeller JA, Munoz-Torres MC, Murphy MC, Naughton MC, Nigam S, Overson R, Rajakumar R, Reese JT, Scott JJ, Smith CR, Tao S, Tsutsui ND, Viljakainen L, Wissler L, Yandell MD, Zimmer F, Taylor J, Slater SC, Clifton SW, Warren WC, Elsik CG, Smith CD, Weinstock GM, Gerardo NM, Currie CR (- 39) Ref: PLoS Genet, 7:e1002007, 2011 : PubMed ESTHER: Suen_2011_PLoS.Genet_7_e1002007 PubMedSearch: Suen 2011 PLoS.Genet 7 e1002007 PubMedID: 21347285 Gene_locus related to this paper: acrec-f4w848, acrec-f4wah1, acrec-f4wai9, acrec-f4wda7, acrec-f4wfh7, acrec-f4wk54, acrec-f4wng2, acrec-f4wpb7, acrec-f4wpb8, acrec-f4wpb9, acrec-f4x2j7, acrec-f4x3l5, acrec-f4x6y6, acrec-f4x7w5, acrec-f4x7w6, acrec-f4x378, acrec-f4x808, attce-h9hc46, solin-e9ige7, attce-w4wts9, attce-w4x506, attce-w4vya2, attce-w4vyi5, attce-w4wib4, attce-w4wkj3, attce-w4x3s7, attce-w4x3u4, attce-w4wu92, attce-w4w1m9, attce-w4x2m8, attce-w4w776, attce-w4x1t1, attce-a0a158nl98, attce-a0a158nmi0, attce-a0a158nqx5, attce-a0a158nr47.2, attce-a0a158ns84, attce-a0a158nvq4, attce-a0a158nij4, attce-a0a158nhg2, attce-a0a158nhn7, attce-a0a158nbh6, attce-a0a158ne04, attce-a0a158nyf0 Abstract Leaf-cutter ants are one of the most important herbivorous insects in the Neotropics, harvesting vast quantities of fresh leaf material. The ants use leaves to cultivate a fungus that serves as the colony's primary food source. This obligate ant-fungus mutualism is one of the few occurrences of farming by non-humans and likely facilitated the formation of their massive colonies. Mature leaf-cutter ant colonies contain millions of workers ranging in size from small garden tenders to large soldiers, resulting in one of the most complex polymorphic caste systems within ants. To begin uncovering the genomic underpinnings of this system, we sequenced the genome of Atta cephalotes using 454 pyrosequencing. One prediction from this ant's lifestyle is that it has undergone genetic modifications that reflect its obligate dependence on the fungus for nutrients. Analysis of this genome sequence is consistent with this hypothesis, as we find evidence for reductions in genes related to nutrient acquisition. These include extensive reductions in serine proteases (which are likely unnecessary because proteolysis is not a primary mechanism used to process nutrients obtained from the fungus), a loss of genes involved in arginine biosynthesis (suggesting that this amino acid is obtained from the fungus), and the absence of a hexamerin (which sequesters amino acids during larval development in other insects). Following recent reports of genome sequences from other insects that engage in symbioses with beneficial microbes, the A. cephalotes genome provides new insights into the symbiotic lifestyle of this ant and advances our understanding of host-microbe symbioses. Title: Input-specific synaptic plasticity in the amygdala is regulated by neuroligin-1 via postsynaptic NMDA receptors Jung SY, Kim J, Kwon OB, Jung JH, An K, Jeong AY, Lee CJ, Choi YB, Bailey CH and Kim JH <1 more author(s)> Jung SY, Kim J, Kwon OB, Jung JH, An K, Jeong AY, Lee CJ, Choi YB, Bailey CH, Kandel ER, Kim JH (- 1) Ref: Proc Natl Acad Sci U S A, 107:4710, 2010 : PubMed ESTHER: Jung_2010_Proc.Natl.Acad.Sci.U.S.A_107_4710 PubMedSearch: Jung 2010 Proc.Natl.Acad.Sci.U.S.A 107 4710 PubMedID: 20176955 Abstract Despite considerable evidence for a critical role of neuroligin-1 in the specification of excitatory synapses, the cellular mechanisms and physiological roles of neuroligin-1 in mature neural circuits are poorly understood. In mutant mice deficient in neuroligin-1, or adult rats in which neuroligin-1 was depleted, we have found that neuroligin-1 stabilizes the NMDA receptors residing in the postsynaptic membrane of amygdala principal neurons, which allows for a normal range of NMDA receptor-mediated synaptic transmission. We observed marked decreases in NMDA receptor-mediated synaptic currents at afferent inputs to the amygdala of neuroligin-1 knockout mice. However, the knockout mice exhibited a significant impairment in spike-timing-dependent long-term potentiation (STD-LTP) at the thalamic but not the cortical inputs to the amygdala. Subsequent electrophysiological analyses indicated that STD-LTP in the cortical pathway is largely independent of activation of postsynaptic NMDA receptors. These findings suggest that neuroligin-1 can modulate, in a pathway-specific manner, synaptic plasticity in the amygdala circuits of adult animals, likely by regulating the abundance of postsynaptic NMDA receptors. Title: Naturally occurring phytochemicals for the prevention of Alzheimer's disease Kim J, Lee HJ, Lee KW Ref: Journal of Neurochemistry, 112:1415, 2010 : PubMed ESTHER: Kim_2010_J.Neurochem_112_1415 PubMedSearch: Kim 2010 J.Neurochem 112 1415 PubMedID: 20050972 Abstract Alzheimer's disease (AD) is an age-related neurodegenerative disease increasingly recognized as one of the most important medical problems affecting the elderly. Although a number of drugs, including several cholinesterase inhibitors and an NMDA receptor antagonist, have been approved for use, they have been shown to produce diverse side effects and yield relatively modest benefits. To overcome these limitations of current therapeutics for AD, extensive research and development are underway to identify drugs that are effective and free of undesirable side effects. Certain naturally occurring dietary polyphenolic phytochemicals have received considerable recent attention as alternative candidates for AD therapy. In particular, curcumin, resveratrol, and green tea catechins have been suggested to have the potential to prevent AD because of their anti-amyloidogenic, anti-oxidative, and anti-inflammatory properties. These polyphenolic phytochemicals also activate adaptive cellular stress responses, called 'neurohormesis', and suppress disease processes. In this commentary, we describe the amyloid-beta-induced pathogenesis of AD, and summarize the intracellular and molecular targets of selected dietary phytochemicals that might slow the progression of AD. Title: Neutral lipid storage leads to acylceramide deficiency, likely contributing to the pathogenesis of Dorfman-Chanarin syndrome Uchida Y, Cho Y, Moradian S, Kim J, Nakajima K, Crumrine D, Park K, Ujihara M, Akiyama M and Elias PM <3 more author(s)> Uchida Y, Cho Y, Moradian S, Kim J, Nakajima K, Crumrine D, Park K, Ujihara M, Akiyama M, Shimizu H, Holleran WM, Sano S, Elias PM (- 3) Ref: Journal of Investigative Dermatology, 130:2497, 2010 : PubMed ESTHER: Uchida_2010_J.Invest.Dermatol_130_2497 PubMedSearch: Uchida 2010 J.Invest.Dermatol 130 2497 PubMedID: 20520629 Title: Functional and evolutionary insights from the genomes of three parasitoid Nasonia species Werren JH, Richards S, Desjardins CA, Niehuis O, Gadau J, Colbourne JK, Beukeboom LW, Desplan C, Elsik CG and Williamson M <147 more author(s)> Werren JH, Richards S, Desjardins CA, Niehuis O, Gadau J, Colbourne JK, Beukeboom LW, Desplan C, Elsik CG, Grimmelikhuijzen CJ, Kitts P, Lynch JA, Murphy T, Oliveira DC, Smith CD, van de Zande L, Worley KC, Zdobnov EM, Aerts M, Albert S, Anaya VH, Anzola JM, Barchuk AR, Behura SK, Bera AN, Berenbaum MR, Bertossa RC, Bitondi MM, Bordenstein SR, Bork P, Bornberg-Bauer E, Brunain M, Cazzamali G, Chaboub L, Chacko J, Chavez D, Childers CP, Choi JH, Clark ME, Claudianos C, Clinton RA, Cree AG, Cristino AS, Dang PM, Darby AC, de Graaf DC, Devreese B, Dinh HH, Edwards R, Elango N, Elhaik E, Ermolaeva O, Evans JD, Foret S, Fowler GR, Gerlach D, Gibson JD, Gilbert DG, Graur D, Grunder S, Hagen DE, Han Y, Hauser F, Hultmark D, Hunter HCt, Hurst GD, Jhangian SN, Jiang H, Johnson RM, Jones AK, Junier T, Kadowaki T, Kamping A, Kapustin Y, Kechavarzi B, Kim J, Kiryutin B, Koevoets T, Kovar CL, Kriventseva EV, Kucharski R, Lee H, Lee SL, Lees K, Lewis LR, Loehlin DW, Logsdon JM, Jr., Lopez JA, Lozado RJ, Maglott D, Maleszka R, Mayampurath A, Mazur DJ, McClure MA, Moore AD, Morgan MB, Muller J, Munoz-Torres MC, Muzny DM, Nazareth LV, Neupert S, Nguyen NB, Nunes FM, Oakeshott JG, Okwuonu GO, Pannebakker BA, Pejaver VR, Peng Z, Pratt SC, Predel R, Pu LL, Ranson H, Raychoudhury R, Rechtsteiner A, Reese JT, Reid JG, Riddle M, Robertson HM, Romero-Severson J, Rosenberg M, Sackton TB, Sattelle DB, Schluns H, Schmitt T, Schneider M, Schuler A, Schurko AM, Shuker DM, Simoes ZL, Sinha S, Smith Z, Solovyev V, Souvorov A, Springauf A, Stafflinger E, Stage DE, Stanke M, Tanaka Y, Telschow A, Trent C, Vattathil S, Verhulst EC, Viljakainen L, Wanner KW, Waterhouse RM, Whitfield JB, Wilkes TE, Williamson MS, Willis JH, Wolschin F, Wyder S, Yamada T, Yi SV, Zecher CN, Zhang L, Gibbs RA, Williamson M (- 147) Ref: Science, 327:343, 2010 : PubMed ESTHER: Werren_2010_Science_327_343 PubMedSearch: Werren 2010 Science 327 343 PubMedID: 20075255 Gene_locus related to this paper: nasvi-ACHE1, nasvi-ACHE2, nasvi-k7in31, nasvi-k7iwl9, nasvi-k7iyk8, nasvi-k7jlv1, nasvi-k7in32, nasvi-k7ind2, nasvi-k7inh0, nasvi-k7inh1, nasvi-k7inh2, nasvi-k7inp9, nasvi-k7iun7, nasvi-k7iv21, nasvi-k7ivn5, nasvi-k7ivn6, nasvi-k7iw29, nasvi-k7iwk5, nasvi-k7iwl8, nasvi-k7iz24, nasvi-k7izb4, nasvi-k7j5u6, nasvi-k7j6y1, nasvi-k7j6y2, nasvi-k7j6y4, nasvi-k7j718, nasvi-k7j755, nasvi-k7j756, nasvi-k7j757, nasvi-k7j7k5, nasvi-k7j7n7, nasvi-k7j7r8, nasvi-k7j7s8, nasvi-k7j7s9, nasvi-k7j811, nasvi-k7iny8, nasvi-k7izf2, nasvi-k7iwe2, nasvi-k7j6w4, nasvi-k7izl9, nasvi-k7jf39, nasvi-k7izl8, nasvi-k7irf1, nasvi-k7j7l1 Abstract We report here genome sequences and comparative analyses of three closely related parasitoid wasps: Nasonia vitripennis, N. giraulti, and N. longicornis. Parasitoids are important regulators of arthropod populations, including major agricultural pests and disease vectors, and Nasonia is an emerging genetic model, particularly for evolutionary and developmental genetics. Key findings include the identification of a functional DNA methylation tool kit; hymenopteran-specific genes including diverse venoms; lateral gene transfers among Pox viruses, Wolbachia, and Nasonia; and the rapid evolution of genes involved in nuclear-mitochondrial interactions that are implicated in speciation. Newly developed genome resources advance Nasonia for genetic research, accelerate mapping and cloning of quantitative trait loci, and will ultimately provide tools and knowledge for further increasing the utility of parasitoids as pest insect-control agents. Title: A comparative study of alpha-dystroglycan glycosylation in dystroglycanopathies suggests that the hypoglycosylation of alpha-dystroglycan does not consistently correlate with clinical severity Jimenez-Mallebrera C, Torelli S, Feng L, Kim J, Godfrey C, Clement E, Mein R, Abbs S, Brown SC and Muntoni F <9 more author(s)> Jimenez-Mallebrera C, Torelli S, Feng L, Kim J, Godfrey C, Clement E, Mein R, Abbs S, Brown SC, Campbell KP, Kroger S, Talim B, Topaloglu H, Quinlivan R, Roper H, Childs AM, Kinali M, Sewry CA, Muntoni F (- 9) Ref: Brain Pathology, 19:596, 2009 : PubMed ESTHER: Jimenez-Mallebrera_2009_Brain.Pathol_19_596 PubMedSearch: Jimenez-Mallebrera 2009 Brain.Pathol 19 596 PubMedID: 18691338 Abstract Hypoglycosylation of alpha-dystroglycan underpins a subgroup of muscular dystrophies ranging from congenital onset of weakness, severe brain malformations and death in the perinatal period to mild weakness in adulthood without brain involvement. Mutations in six genes have been identified in a proportion of patients. POMT1, POMT2 and POMGnT1 encode for glycosyltransferases involved in the mannosylation of alpha-dystroglycan but the function of fukutin, FKRP and LARGE is less clear. The pathological hallmark is reduced immunolabeling of skeletal muscle with antibodies recognizing glycosylated epitopes on alpha-dystroglycan. If the common pathway of these conditions is the hypoglycosyation of alpha-dystroglycan, one would expect a correlation between clinical severity and the extent of hypoglycosylation. By studying 24 patients with mutations in these genes, we found a good correlation between reduced alpha-dystroglycan staining and clinical course in patients with mutations in POMT1, POMT2 and POMGnT1. However, this was not always the case in patients with defects in fukutin and FKRP, as we identified patients with mild limb-girdle phenotypes without brain involvement with profound depletion of alpha-dystroglycan. These data indicate that it is not always possible to correlate clinical course and alpha-dystroglycan labeling and suggest that there might be differences in alpha-dystroglycan processing in these disorders. Title: A new pancreatic lipase inhibitor isolated from the roots of Actinidia arguta Jang DS, Lee GY, Kim J, Lee YM, Kim JM, Kim YS, Kim JS Ref: Arch Pharm Res, 31:666, 2008 : PubMed ESTHER: Jang_2008_Arch.Pharm.Res_31_666 PubMedSearch: Jang 2008 Arch.Pharm.Res 31 666 PubMedID: 18481026 Abstract A new coumaroyl triterpene, 3-O-trans-p-coumaroyl actinidic acid (1), as well as five known triterpenes, ursolic acid (2), 23-hydroxyursolic acid (3), corosolic acid (4), asiatic acid (5) and betulinic acid (6) were isolated from an EtOAc-soluble extract of the roots of Actinidia arguta. The structure of compound 1 was elucidated from interpretation of the spectroscopic data, particularly by extensive 1D and 2D NMR studies. All the isolates (1-6) were evaluated in vitro for their inhibitory activities on pancreatic lipase (PL). Of the isolates, the new compound 1 possessed the highest inhibitory activity on PL, with an IC(50) of 14.95 microM, followed by ursolic acid (2, IC(50) = 15.83 microM). The other four triterpenes (3-6) also showed significant PL inhibitory activity, with IC(50) values ranging from 20.42 to 76.45 microM. Title: Neuroligin-1 is required for normal expression of LTP and associative fear memory in the amygdala of adult animals Kim J, Jung SY, Lee YK, Park S, Choi JS, Lee CJ, Kim HS, Choi YB, Scheiffele P and Kim JH <2 more author(s)> Kim J, Jung SY, Lee YK, Park S, Choi JS, Lee CJ, Kim HS, Choi YB, Scheiffele P, Bailey CH, Kandel ER, Kim JH (- 2) Ref: Proc Natl Acad Sci U S A, 105:9087, 2008 : PubMed ESTHER: Kim_2008_Proc.Natl.Acad.Sci.U.S.A_105_9087 PubMedSearch: Kim 2008 Proc.Natl.Acad.Sci.U.S.A 105 9087 PubMedID: 18579781 Abstract Neuroligin-1 is a potent trigger for the de novo formation of synaptic connections, and it has recently been suggested that it is required for the maturation of functionally competent excitatory synapses. Despite evidence for the role of neuroligin-1 in specifying excitatory synapses, the underlying molecular mechanisms and physiological consequences that neuroligin-1 may have at mature synapses of normal adult animals remain unknown. By silencing endogenous neuroligin-1 acutely in the amygdala of live behaving animals, we have found that neuroligin-1 is required for the storage of associative fear memory. Subsequent cellular physiological studies showed that suppression of neuroligin-1 reduces NMDA receptor-mediated currents and prevents the expression of long-term potentiation without affecting basal synaptic connectivity at the thalamo-amygdala pathway. These results indicate that persistent expression of neuroligin-1 is required for the maintenance of NMDAR-mediated synaptic transmission, which enables normal development of synaptic plasticity and long-term memory in the amygdala of adult animals. Title: Kv4 accessory protein DPPX (DPP6) is a critical regulator of membrane excitability in hippocampal CA1 pyramidal neurons Kim J, Nadal MS, Clemens AM, Baron M, Jung SC, Misumi Y, Rudy B, Hoffman DA Ref: Journal of Neurophysiology, 100:1835, 2008 : PubMed ESTHER: Kim_2008_J.Neurophysiol_100_1835 PubMedSearch: Kim 2008 J.Neurophysiol 100 1835 PubMedID: 18667548 Abstract A-type K+ currents have unique kinetic and voltage-dependent properties that allow them to finely tune synaptic integration, action potential (AP) shape and firing patterns. In hippocampal CA1 pyramidal neurons, Kv4 channels make up the majority of the somatodendritic A-type current. Studies in heterologous expression systems have shown that Kv4 channels interact with transmembrane dipeptidyl-peptidase-like proteins (DPPLs) to regulate the surface trafficking and biophysical properties of Kv4 channels. To investigate the influence of DPPLs in a native system, we conducted voltage-clamp experiments in patches from CA1 pyramidal neurons expressing short-interfering RNA (siRNA) targeting the DPPL variant known to be expressed in hippocampal pyramidal neurons, DPPX (siDPPX). In accordance with heterologous studies, we found that DPPX downregulation in neurons resulted in depolarizing shifts of the steady-state inactivation and activation curves, a shallower conductance-voltage slope, slowed inactivation, and a delayed recovery from inactivation for A-type currents. We carried out current-clamp experiments to determine the physiological effect of the A-type current modifications by DPPX. Neurons expressing siDPPX exhibited a surprisingly large reduction in subthreshold excitability as measured by a decrease in input resistance, delayed time to AP onset, and an increased AP threshold. Suprathreshold DPPX downregulation resulted in slower AP rise and weaker repolarization. Computer simulations supported our experimental results and demonstrated how DPPX remodeling of A-channel properties can result in opposing sub- and suprathreshold effects on excitability. The Kv4 auxiliary subunit DPPX thus acts to increase neuronal responsiveness and enhance signal precision by advancing AP initiation and accelerating both the rise and repolarization of APs. Title: Structure of diethyl phosphate bound to the binuclear metal center of phosphotriesterase Kim J, Tsai PC, Chen SL, Himo F, Almo SC, Raushel FM Ref: Biochemistry, 47:9497, 2008 : PubMed ESTHER: Kim_2008_Biochemistry_47_9497 PubMedSearch: Kim 2008 Biochemistry 47 9497 PubMedID: 18702530 Abstract The bacterial phosphotriesterase (PTE) from Pseudomonas diminuta catalyzes the hydrolysis of organophosphate esters at rates close to the diffusion limit. X-ray diffraction studies have shown that a binuclear metal center is positioned in the active site of PTE and that this complex is responsible for the activation of the nucleophilic water from solvent. In this paper, the three-dimensional structure of PTE was determined in the presence of the hydrolysis product, diethyl phosphate (DEP), and a product analogue, cacodylate. In the structure of the PTE-diethyl phosphate complex, the DEP product is found symmetrically bridging the two divalent cations. The DEP displaces the hydroxide from solvent that normally bridges the two divalent cations in structures determined in the presence or absence of substrate analogues. One of the phosphoryl oxygen atoms in the PTE-DEP complex is 2.0 A from the alpha-metal ion, while the other oxygen is 2.2 A from the beta-metal ion. The two metal ions are separated by a distance of 4.0 A. A similar structure is observed in the presence of cacodylate. Analogous complexes have previously been observed for the product complexes of isoaspartyl dipeptidase, d-aminoacylase, and dihydroorotase from the amidohydrolase superfamily of enzymes. The experimentally determined structure of the PTE-diethyl phosphate product complex is inconsistent with a recent proposal based upon quantum mechanical/molecular mechanical simulations which postulated the formation of an asymmetrical product complex bound exclusively to the beta-metal ion with a metal-metal separation of 5.3 A. This structure is also inconsistent with a chemical mechanism for substrate hydrolysis that utilizes the bridging hydroxide as a base to abstract a proton from a water molecule loosely associated with the alpha-metal ion. Density functional theory (DFT) calculations support a reaction mechanism that utilizes the bridging hydroxide as the direct nucleophile in the hydrolysis of organophosphate esters by PTE. Title: Development of magnetically separable immobilized lipase by using cellulose derivatives and their application in enantioselective esterification of ibuprofen Lee G, Joo H, Kim J, Lee JH Ref: J Microbiol Biotechnol, 18:465, 2008 : PubMed ESTHER: Lee_2008_J.Microbiol.Biotechnol_18_465 PubMedSearch: Lee 2008 J.Microbiol.Biotechnol 18 465 PubMedID: 18388463 Abstract Highly active, stable, and magnetically separable immobilized enzymes were developed using carboxymethyl cellulose (CMC) and diethylaminoethyl cellulose DEAE-C; hereafter designated "DEAE" as supporting materials. Iron oxide nanoparticles penetrated the micropores of the supporting materials, rendering them magnetically separable. Lipase (LP) was immobilized on the surface of the supporting materials by using cross-linked enzyme aggregation (CLEA) by glutaraldehyde. The activity of enzyme aggregates coated on DEAE was approximately 2 times higher than that of enzyme aggregates coated on CMC. This is explained by the fact that enzyme aggregates with amine residues are more efficient than those with carboxyl residues. After a 96-h enantioselective ibuprofen esterification reaction, 6% ibuprofen propyl ester was produced from the racemic mixture of ibuprofen by using DEAE-LP, and 2.8% using CMC-LP. Title: Omentum transposition surgery for patients with Alzheimer's disease: a case series Shankle WR, Hara J, Bjornsen L, Gade GF, Leport PC, Ali MB, Kim J, Raimo M, Reyes L and O'Heany T <2 more author(s)> Shankle WR, Hara J, Bjornsen L, Gade GF, Leport PC, Ali MB, Kim J, Raimo M, Reyes L, Amen D, Rudy L, O'Heany T (- 2) Ref: Neurol Res, 30:313, 2008 : PubMed ESTHER: Shankle_2008_Neurol.Res_30_313 PubMedSearch: Shankle 2008 Neurol.Res 30 313 PubMedID: 17767812 Abstract OBJECTIVE: To examine effect of omentum transposition surgery (OT) in Alzheimer's disease (AD). Title: The Orientia tsutsugamushi genome reveals massive proliferation of conjugative type IV secretion system and host-cell interaction genes Cho NH, Kim HR, Lee JH, Kim SY, Kim J, Cha S, Darby AC, Fuxelius HH, Yin J and Kim IS <7 more author(s)> Cho NH, Kim HR, Lee JH, Kim SY, Kim J, Cha S, Darby AC, Fuxelius HH, Yin J, Kim JH, Lee SJ, Koh YS, Jang WJ, Park KH, Andersson SG, Choi MS, Kim IS (- 7) Ref: Proc Natl Acad Sci U S A, 104:7981, 2007 : PubMed ESTHER: Cho_2007_Proc.Natl.Acad.Sci.U.S.A_104_7981 PubMedSearch: Cho 2007 Proc.Natl.Acad.Sci.U.S.A 104 7981 PubMedID: 17483455 Abstract Scrub typhus is caused by the obligate intracellular rickettsia Orientia tsutsugamushi (previously called Rickettsia tsutsugamushi). The bacterium is maternally inherited in trombicuid mites and transmitted to humans by feeding larvae. We report here the 2,127,051-bp genome of the Boryong strain, which represents the most highly repeated bacterial genome sequenced to date. The repeat density of the scrub typhus pathogen is 200-fold higher than that of its close relative Rickettsia prowazekii, the agent of epidemic typhus. A total of 359 tra genes for components of conjugative type IV secretion systems were identified at 79 sites in the genome. Associated with these are >200 genes for signaling and host-cell interaction proteins, such as histidine kinases, ankyrin-repeat proteins, and tetratrico peptide-repeat proteins. Additionally, the O. tsutsugamushi genome contains >400 transposases, 60 phage integrases, and 70 reverse transcriptases. Deletions and rearrangements have yielded unique gene combinations as well as frequent pseudogenization in the tra clusters. A comparative analysis of the tra clusters within the genome and across strains indicates sequence homogenization by gene conversion, whereas complexity, diversity, and pseudogenization are acquired by duplications, deletions, and transposon integrations into the amplified segments. The results suggest intragenomic duplications or multiple integrations of a massively proliferating conjugative transfer system. Diversifying selection on host-cell interaction genes along with repeated population bottlenecks may drive rare genome variants to fixation, thereby short-circuiting selection for low complexity in bacterial genomes. Title: Multiple mechanisms of endocannabinoid response initiation in hippocampus Edwards DA, Kim J, Alger BE Ref: Journal of Neurophysiology, 95:67, 2006 : PubMed ESTHER: Edwards_2006_J.Neurophysiol_95_67 PubMedSearch: Edwards 2006 J.Neurophysiol 95 67 PubMedID: 16207781 Abstract Endocannabinoids (eCBs) act as retrograde messengers at inhibitory synapses of the hippocampal CA1 region. Current models place eCB synthesis in the postsynaptic pyramidal cell and the site of eCB action at cannabinoid receptors located on presynaptic interneuron terminals. Four responses at the CA1-interneuron synapse are attributed to eCBs: depolarization-induced suppression of inhibition (DSI), G-protein-coupled receptor-mediated enhancement of DSI (DeltaDSI), persistent suppression of evoked inhibitory postsynaptic currents (eIPSCs), and finally, mGluR-dependent long-term depression (iLTD). It has been proposed that all are mediated by the eCB, 2-arachidonoyl glycerol, yet there is evidence that DSI does not arise from the same underlying biochemical processes as the other responses. In view of the increasing importance of eCB effects in the brain, it will be essential to understand the mechanisms by which eCB effects are produced. Our results reveal new differences in the biochemical pathways by which the eCB-dependent responses are initiated. Both U73122, a phospholipase C antagonist, and RHC-80267, a diacylglycerol (DAG) lipase antagonist, prevented eCB-dependent iLTD induction by 3,5-dihydroxyphenylglycine (DHPG). However, mAChR activation does not cause eCB-dependent iLTD. Neither enzyme inhibitor affects DSI, and persistent eCB-dependent eIPSC suppression induced by either mGluRs or mAChRs is unaffected by U73122. On the other hand, inhibition of DAG lipase prevents persistent eCB-dependent eIPSC suppression triggered by mAChRs. The results show that the biochemical pathways for the various eCB-dependent responses differ and might therefore be independently manipulated. Title: Stimulation of endocannabinoid formation in brain slice cultures through activation of group I metabotropic glutamate receptors Jung KM, Mangieri R, Stapleton C, Kim J, Fegley D, Wallace M, Mackie K, Piomelli D Ref: Molecular Pharmacology, 68:1196, 2005 : PubMed ESTHER: Jung_2005_Mol.Pharmacol_68_1196 PubMedSearch: Jung 2005 Mol.Pharmacol 68 1196 PubMedID: 16051747 Gene_locus related to this paper: rat-dglb Abstract Activation of group I metabotropic glutamate (mGlu) receptors drives the endocannabinoid system to cause both short- and long-term changes of synaptic strength in the striatum, hippocampus, and other brain areas. Although there is strong electrophysiological evidence for a role of endocannabinoid release in mGlu receptor-dependent plasticity, the identity of the endocannabinoid transmitter mediating this phenomenon remains undefined. In this study, we show that activation of group I mGlu receptors triggers the biosynthesis of the endocannabinoid 2-arachidonoylglycerol (2-AG), but not anandamide, in primary cultures of corticostriatal and hippocampal slices prepared from early postnatal rat brain. Pharmacological studies suggest that 2-AG biosynthesis is initiated by activation of mGlu5 receptors, is catalyzed by phospholipase C (PLC) and 1,2-diacylglycerol lipase (DGL) activities, and is dependent on intracellular Ca2+ ions. Realtime polymerase chain reaction and immunostaining analyses indicate that DGL-beta is the predominant DGL isoform expressed in corticostriatal and hippocampal slices and that this enzyme is highly expressed in striatal neurons, where it is colocalized with PLC-beta1. The results suggest that 2-AG is a primary endocannabinoid mediator of mGlu receptor-dependent neuronal plasticity. Title: Protection by sustained release of physostigmine and procyclidine of soman poisoning in rats Choi EK, Park D, Yon JM, Hur GH, Ha YC, Che JH, Kim J, Shin S, Jang JY and Kim YB <4 more author(s)> Choi EK, Park D, Yon JM, Hur GH, Ha YC, Che JH, Kim J, Shin S, Jang JY, Hwang SY, Seong YH, Kim DJ, Kim JC, Kim YB (- 4) Ref: European Journal of Pharmacology, 505:83, 2004 : PubMed ESTHER: Choi_2004_Eur.J.Pharmacol_505_83 PubMedSearch: Choi 2004 Eur.J.Pharmacol 505 83 PubMedID: 15556140 Abstract The efficacy of a combinational prophylactic regimen on the lethality, convulsions, and loss of morphological and functional integrities of the brain induced by an organophosphate soman was investigated in rats. The rats were implanted subcutaneously with osmotic minipumps containing the combinational prophylactic regimen composed of physostigmine, a reversible cholinesterase inhibitor, and procyclidine, an N-methyl-D-aspartate antagonist possessing anticholinergic action, for 3 days, and intoxicated subcutaneously with soman (160 microg/kg, 1.3 LD50). The doses of combinational regimen in minipumps were optimized to achieve 30-35% inhibition of blood cholinesterase activity by physostigmine and 50-100 ng/ml of blood concentrations of procyclidine as clinically available doses, respectively. In comparison, 1-[([4-(aminocarbonyl)pyridinio]methoxy)methyl]-2-[(hydroxyimino)methyl]pyridiniu m (HI-6, 125 mg/kg) was administered intraperitoneally 30 min prior to the soman challenge in control groups to reduce mortality of rats without affecting convulsions. Soman induced profound limbic convulsions and 30% mortality, leading to increased blood-brain barrier permeability, neural injuries, learning and memory impairments, and physical incapacitation of survived rats pretreated with HI-6. The combinational regimen, at optimal doses without adverse effects on passive avoidance performances (72 microg/kg/h of physostigmine plus 432 microg/kg/h of procyclidine), exerted full protective effects against lethality, convulsions, blood-brain barrier opening, brain injuries, learning and memory impairments, and physical incapacitation induced by soman. Taken together, it is suggested that the combination of physostigmine and procyclidine, at adequate doses, could be a choice to provide the victims of organophosphate poisoning with chance of intensive care for survival and neuroprotection. Title: Access to the carbamate tunnel of carbamoyl phosphate synthetase Kim J, Raushel FM Ref: Archives of Biochemistry & Biophysics, 425:33, 2004 : PubMed ESTHER: Kim_2004_Arch.Biochem.Biophys_425_33 PubMedSearch: Kim 2004 Arch.Biochem.Biophys 425 33 PubMedID: 15081891 Abstract The X-ray crystal structure of carbamoyl phosphate synthetase (CPS) from Escherichia coli revealed the existence of a molecular tunnel that has been proposed to facilitate the translocation of reaction intermediates between remotely located active sites. Five highly conserved glutamate residues, including Glu-25, Glu-383, Glu-577, Glu-604, and Glu-916, are close together in two clusters in the interior wall of the molecular tunnel that enables the intermediate carbamate to migrate from the site of synthesis to the site of utilization. Two arginines, Arg-306 and Arg-848, are located at either end of the carbamate tunnel and participate in the binding of ATP at each of the two active sites within the large subunit of CPS. The mutation of Glu-25 or Glu-577 results in a diminution in the overall rate of carbamoyl phosphate formation. Similar effects are observed upon mutation of Arg-306 and Arg-848 to alanine residues. The conserved glutamate and arginine residues may function in concert with one another to control entry of carbamate into the tunnel prior to phosphorylation to carbamoyl phosphate. The electrostatic environment of tunnel interior may help to stabilize the tunnel architecture and prevent decomposition of carbamate through protonation. Title: Activation of muscarinic acetylcholine receptors enhances the release of endogenous cannabinoids in the hippocampus Kim J, Isokawa M, Ledent C, Alger BE Ref: Journal of Neuroscience, 22:10182, 2002 : PubMed ESTHER: Kim_2002_J.Neurosci_22_10182 PubMedSearch: Kim 2002 J.Neurosci 22 10182 PubMedID: 12451119 Abstract Endogenous cannabinoids (endocannabinoids) are endogenous compounds that resemble the active ingredient of marijuana and activate the cannabinoid receptor in the brain. They mediate retrograde signaling from principal cells to both inhibitory ["depolarization-induced suppression of inhibition" (DSI)] and excitatory ("depolarization-induced suppression of excitation") afferent fibers. Transient endocannabinoid release is triggered by voltage-dependent Ca(2+) influx and is upregulated by group I metabotropic glutamate receptor activation. Here we show that muscarinic acetylcholine receptor (mAChR) activation also enhances transient endocannabinoid release (DSI) and induces persistent release. Inhibitory synapses in the rat hippocampal CA1 region of acute slices were studied using whole-cell patch-clamp techniques. We found that low concentrations (0.2-0.5 microm) of carbachol (CCh) enhanced DSI without affecting basal evoked IPSCs (eIPSCs) by activating mAChRs on postsynaptic cells. Higher concentrations of CCh (> or =1 microm) enhanced DSI and also persistently depressed basal eIPSCs, mainly by releasing endocannabinoids. Persistent CCh-induced endocannabinoid release did not require an increase in [Ca2+]i but was dependent on G-proteins. Although they were independent at the receptor level, muscarinic and glutamatergic mechanisms of endocannabinoid release shared intracellular machinery. Replication of the effects of CCh by blocking acetylcholinesterase with eserine suggests that mAChR-mediated endocannabinoid release is physiologically relevant. This study reveals a new role of the muscarinic cholinergic system in mammalian brain. Title: (+)-Alpha-viniferin, a stilbene trimer from Caragana chamlague, inhibits acetylcholinesterase Sung SH, Kang SY, Lee KY, Park MJ, Kim JH, Park JH, Kim YC, Kim J Ref: Biol Pharm Bull, 25:125, 2002 : PubMed ESTHER: Sung_2002_Biol.Pharm.Bull_25_125 PubMedSearch: Sung 2002 Biol.Pharm.Bull 25 125 PubMedID: 11824541 Abstract In the course of screening natural products for anti-acetylcholinesterase (AChE) activity, we found that a total methanolic extract of the underground parts of Caragana chamlague (Leguminosae) had significant inhibition towards AChE. Bioactivity-guided fractionation of the total methanolic extract resulted in the isolation and identification of two active stilbene oligomers, (+)-alpha-viniferin (1) and kobophenol A (2). Both 1 and 2 inhibited AChE activity in a dose-dependent manner, and the IC50 values of 1 and 2 were 2.0 and 115.8 microM, respectively. The AChE inhibitory activity of 1 was specific, reversible and noncompetitive. Title: Genes affecting the activity of nicotinic receptors involved in Caenorhabditis elegans egg-laying behavior Kim J, Poole DS, Waggoner LE, Kempf A, Ramirez DS, Treschow PA, Schafer WR Ref: Genetics, 157:1599, 2001 : PubMed ESTHER: Kim_2001_Genetics_157_1599 PubMedSearch: Kim 2001 Genetics 157 1599 PubMedID: 11290716 Abstract Egg-laying behavior in Caenorhabditis elegans is regulated by multiple neurotransmitters, including acetylcholine and serotonin. Agonists of nicotinic acetylcholine receptors such as nicotine and levamisole stimulate egg laying; however, the genetic and molecular basis for cholinergic neurotransmission in the egg-laying circuitry is not well understood. Here we describe the egg-laying phenotypes of eight levamisole resistance genes, which affect the activity of levamisole-sensitive nicotinic receptors in nematodes. Seven of these genes, including the nicotinic receptor subunit genes unc-29, unc-38, and lev-1, were essential for the stimulation of egg laying by levamisole, though they had only subtle effects on egg-laying behavior in the absence of drug. Thus, these genes appear to encode components of a nicotinic receptor that can promote egg laying but is not necessary for egg-laying muscle contraction. Since the levamisole-receptor mutants responded to other cholinergic drugs, other acetylcholine receptors are likely to function in parallel with the levamisole-sensitive receptors to mediate cholinergic neurotransmission in the egg-laying circuitry. In addition, since expression of functional unc-29 in muscle cells restored levamisole sensitivity under some but not all conditions, both neuronal and muscle cell UNC-29 receptors are likely to contribute to the regulation of egg-laying behavior. Mutations in one levamisole receptor gene, unc-38, also conferred both hypersensitivity and reduced peak response to serotonin; thus nicotinic receptors may play a role in regulating serotonin response pathways in the egg-laying neuromusculature. Title: Degradation of lipid vesicles in the yeast vacuole requires function of Cvt17, a putative lipase Teter SA, Eggerton KP, Scott SV, Kim J, Fischer AM, Klionsky DJ Ref: Journal of Biological Chemistry, 276:2083, 2001 : PubMed ESTHER: Teter_2001_J.Biol.Chem_276_2083 PubMedSearch: Teter 2001 J.Biol.Chem 276 2083 PubMedID: 11085977 Gene_locus related to this paper: yeast-ATG15 Abstract The vacuole/lysosome serves an essential role in allowing cellular components to be degraded and recycled under starvation conditions. Vacuolar hydrolases are key proteins in this process. In Saccharyomces cerevisiae, some resident vacuolar hydrolases are delivered by the cytoplasm to vacuole targeting (Cvt) pathway, which shares mechanistic features with autophagy. Autophagy is a degradative pathway that is used to degrade and recycle cellular components under starvation conditions. Both the Cvt pathway and autophagy employ double-membrane cytosolic vesicles to deliver cargo to the vacuole. As a result, these pathways share a common terminal step, the degradation of subvacuolar vesicles. We have identified a protein, Cvt17, which is essential for this membrane lytic event. Cvt17 is a membrane glycoprotein that contains a motif conserved in esterases and lipases. The active-site serine of this motif is required for subvacuolar vesicle lysis. This is the first characterization of a putative lipase implicated in vacuolar function in yeast. Title: Combined pyridostigmine-thyrotrophin-releasing hormone test for the evaluation of hypothalamic somatostatinergic activity in healthy normal men Yang I, Woo J, Kim S, Kim J, Kim Y, Choi Y Ref: European Journal of Endocrinology, 133:457, 1995 : PubMed ESTHER: Yang_1995_Eur.J.Endocrinol_133_457 PubMedSearch: Yang 1995 Eur.J.Endocrinol 133 457 PubMedID: 7581970 Inhibitor(s) related to this paper: Pyridostigmine Abstract Pyridostigmine (PST), a cholinesterase inhibitor, induces a clear growth hormone (GH) release in man by suppression of hypothalamic somatostatin (SRIH). Somatostatin suppresses thyrotrophin (TSH) release in rats and men. Earlier studies showed that the thryotrophin-releasing hormone (TRH)-induced TSH response was not altered by 60-120 mg of PST. We studied whether a larger dose (180 mg) of PST can increase the TSH response to TRH. Six healthy young men were studied with the following six tests: (Test 1) 200 micrograms of TRH i.v.; (Test 2) 180 mg of PST po; (Test 3) three different doses of PST (60, 120, 180 mg) + TRH; (Test 4) 100 micrograms of octreotide (SMS) i.v.; (Test 5) SMS + TRH; (Test 6) PST + SMS + TRH. A large dose of PST (180 mg) significantly augmented GH, TSH and prolactin responses to TRH, while smaller doses of PST (60 and 120 mg) did not significantly increase the responses of GH and TSH. While the increased TRH-induced prolactin response by PST was not suppressed by SMS, the increased responses of GH and TSH were suppressed remarkably by SMS. Most of the subjects noticed a mild to moderate abdominal pain, nausea and muscular fasciculation after the administration of a large dose of PST administration. These data suggest that suppression of hypothalamic SRIH secretion by 180 mg of PST can augment the TSH response to TRH. However, the considerable side effects should be minimized before clinical application of the combined PST-TRH test. | |||||||
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