Lu C

References (56)

Title : Mitochondrial Esterase Activity Measured at the Single Organelle Level by Nano-flow Cytometry - Su_2024_Anal.Chem__
Author(s) : Su L , Gao K , Tian Y , Xiao X , Lu C , Xu J , Yan X
Ref : Analytical Chemistry , : , 2024
Abstract : Monitoring mitochondrial esterase activity is crucial not only for investigating mitochondrial metabolism but also for assessing the effectiveness of mitochondrial-targeting prodrugs. However, accurately detecting esterase activity within mitochondria poses challenges due to its ubiquitous presence in cells and the uncontrolled localization of fluorogenic probes. To overcome this hurdle and reveal variations among different mitochondria, we isolated mitochondria and preserved their activity and functionality in a buffered environment. Subsequently, we utilized a laboratory-built nano-flow cytometer in conjunction with an esterase-responsive calcein-AM fluorescent probe to measure the esterase activity of individual mitochondria. This approach enabled us to investigate the influence of temperature, pH, metal ions, and various compounds on the mitochondrial esterase activity without any interference from other cellular constituents. Interestingly, we observed a decline in the mitochondrial esterase activity following the administration of mitochondrial respiratory chain inhibitors. Furthermore, we found that mitochondrial esterase activity was notably higher in the presence of a high concentration of ATP compared to that of ADP and AMP. Additionally, we noticed a correlation between elevated levels of complex IV and increased mitochondrial esterase activity. These findings suggest a functional connection between the mitochondrial respiratory chain and mitochondrial esterase activity. Moreover, we detected an upsurge in mitochondrial esterase activity during the early stages of apoptosis, while cellular esterase activity decreased. This highlights the significance of analyzing enzyme activity within specific organelle subregions. In summary, the integration of a nano-flow cytometer and fluorescent dyes introduces a novel method for quantifying mitochondrial enzyme activity with the potential to uncover the alterations and unique functions of other mitochondrial enzymes.
ESTHER : Su_2024_Anal.Chem__
PubMedSearch : Su_2024_Anal.Chem__
PubMedID: 38173421

Title : Effect of in vitro simulated digestion on the physicochemical properties and pancreatic lipase inhibitory activity of fucoidan - Lu_2024_J.Sci.Food.Agric__
Author(s) : Lu C , Gu Q , Yu X
Ref : J Sci Food Agric , : , 2024
Abstract : BACKGROUND: Fucoidan has an anti-obesity effect. However, there are few studies on its mechanism. In this study, we investigated the in vitro and in silico inhibitory properties of fucoidan against pancreatic lipase for the first time. We examined the changes in composition, structure, and pancreatic lipase inhibition of fucoidan during in vitro digestion. RESULTS: Simulated saliva-gastrointestinal digestion resulted in a slight decrease in the molecular weight of fucoidan but no significant changes in the monosaccharide composition, sulfate content, and functional groups. Moreover, the digestion process significantly increased the inhibition of pancreatic lipase by fucoidan. The study on the type of inhibition showed that the inhibition of pancreatic lipase by fucoidan belonged to mixed inhibition with competitive inhibition. Molecular docking analysis showed that fucoidan could bind to the active site of pancreatic lipase. CONCLUSION: This study indicates that fucoidan can be a potential functional food for anti-obesity.
ESTHER : Lu_2024_J.Sci.Food.Agric__
PubMedSearch : Lu_2024_J.Sci.Food.Agric__
PubMedID: 38284513

Title : Biodegradation of phthalic acid esters (PAEs) by Janthinobacterium sp. strain E1 under stress conditions - Zhang_2024_J.Gen.Appl.Microbiol__
Author(s) : Zhang K , Zhou H , Ke J , Feng H , Lu C , Chen S , Liu A
Ref : J Gen Appl Microbiol , : , 2024
Abstract : Phthalates esters (PAEs) are a kind of polymeric material additives widely been added into plastics to improve products' flexibility. It can easily cause environmental pollution which are hazards to public health. In this study, we isolated an efficient PAEs degrading strain, Janthinobacterium sp. E1, and determined its degradation effect of di-2-ethylhexyl phthalate (DEHP) under stress conditions. Strain E1 showed an obvious advantage in pollutants degradation under various environmental stress conditions. Degradation halo clearly occurred around the colony of strain E1 on agar plate supplemented with triglyceride. Strain E1's esterase is a constitutively expressed intracellular enzyme. The esterase purified from strain E1 showed a higher catalytic effect on short-chain PAEs than long-chain PAEs. The input of DEHP, DBP (dibutyl phthalate) and DMP (dimethyl phthalate) into the tested soil did not change the species composition of soil prokaryotic community, but altered the dominant species in specific environmental conditions. And the community diversity and richness decreased to a certain extent. However, the diversity and richness of the microbial community were improved after the contaminated soil was treated with the strain E1. Our results also suggested that strain E1 exhibited a tremendous potential in environmental bioremediation in the real environment, which provides a new insight into the elimination of the pollutants contamination in the urban environment.
ESTHER : Zhang_2024_J.Gen.Appl.Microbiol__
PubMedSearch : Zhang_2024_J.Gen.Appl.Microbiol__
PubMedID: 38220211

Title : Near-infrared-excitable acetylcholinesterase-activated fluorescent probe for sensitive and anti-interference detection of pesticides in colored food - Wu_2023_Biosens.Bioelectron_233_115341
Author(s) : Wu Z , Hao Z , Chai Y , Li A , Wang C , Zhang X , Chen H , Lu C
Ref : Biosensors & Bioelectronics , 233 :115341 , 2023
Abstract : The development of a common and anti-interference acetylcholinesterase (AChE) inhibition assay for plant-originated food samples has been of great challenge because of the prevalent and strong signal interferences from natural pigments. Plant pigments normally exhibit non-negligible absorbance in the UV-visible region. As a result, the signals of a typical near-infrared (NIR) fluorescent probe could be disturbed through primary inner filter effect if it is excited by UV-visible light during plant sample analysis. In this work, an NIR-excitable AChE-activated fluorescent probe was biomimetically designed and synthesized. And the NIR-excitation strategy was utilized for the anti-interference detection of organophosphate and carbamate pesticides in colored samples with this probe. Sensitive and rapid response to AChE and pesticides was achieved due to the high affinity of the biomimetic recognition unit in the probe. The limits of detection for four representative pesticides including dichlorvos, carbofuran, chlorpyrifos and methamidophos reached 0.0186 microg/L, 2.20 microg/L, 12.3 microg/L and 13.6 microg/L, respectively. Most importantly, fluorescent response to pesticide contents could be accurately measured in the coexistence of different plant pigments by this probe, and the measured results showed completely irrelevance to the plant pigments and their colors. Taking advantage of such probe, the new developed AChE inhibition assay showed good sensitivity and anti-interference ability in the detection of organophosphate and carbamate pesticides in real samples.
ESTHER : Wu_2023_Biosens.Bioelectron_233_115341
PubMedSearch : Wu_2023_Biosens.Bioelectron_233_115341
PubMedID: 37099980

Title : Genome-wide identification and expression analysis of the cotton patatin-related phospholipase A genes and response to stress tolerance - Wei_2023_Planta_257_49
Author(s) : Wei Y , Chong Z , Lu C , Li K , Liang C , Meng Z , Wang Y , Guo S , He L , Zhang R
Ref : Planta , 257 :49 , 2023
Abstract : Patatin-related phospholipase A genes were involved in the response of Gossypium hirsutum to drought and salt tolerance. pPLA (patatin-related phospholipase A) is a key enzyme that catalyzes the initial step of lipid hydrolysis, which is involved in biological processes, such as drought, salt stress, and freezing injury. However, a comprehensive analysis of the pPLA gene family in cotton, especially the role of pPLA in the response to drought and salt tolerance, has not been reported so far. A total of 33 pPLA genes were identified in this study using a genome-wide search approach, and phylogenetic analysis classified these genes into three groups. These genes are unevenly distributed on the 26 chromosomes of cotton, and most of them contain a few introns. The results of the collinear analysis showed that G. hirsutum contained 1-5 copies of each pPLA gene found in G. arboreum and G. raimondii. The subcellular localization analysis of Gh_D08G061200 showed that the protein was localized in the nucleus. In addition, analysis of published upland cotton transcriptome data revealed that six GhPLA genes were expressed in various tissues and organs. Two genes (Gh_A04G142100.1 and Gh_D04G181000.1) were highly expressed in all tissues under normal conditions, showing the expression characteristics of housekeeping genes. Under different drought and salt tolerance stresses, we detected four genes with different expression levels. This study helps to clarify the role of pPLA in the response to drought and salt tolerance.
ESTHER : Wei_2023_Planta_257_49
PubMedSearch : Wei_2023_Planta_257_49
PubMedID: 36752875

Title : Repetitive transcranial magnetic stimulation may be superior to drug therapy in the treatment of Alzheimer's disease: A systematic review and Bayesian network meta-analysis - Wei_2023_CNS.Neurosci.Ther__
Author(s) : Wei N , Liu H , Ye W , Xu S , Lu C , Dai A , Hou T , Zeng X , Wu J , Chen J
Ref : CNS Neurosci Ther , : , 2023
Abstract : BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive brain stimulation therapy that is primarily used to treat a variety of neuropsychiatric conditions. Recently, previous research reports stated that rTMS have the characteristics of neurorestorative in Alzheimer's disease (AD). However, the relevant clinical research evidence has not been fully summarized. METHODS: This article performed a network meta-analysis of individual participant data from eligible studies searched in PubMed, Embase, and the Cochrane Library from inception to March 31, 2022. The drug treatments involved were acetylcholinesterase inhibitors (AChEIs), N-methyl-d-aspartate (NMDA), anti-amyloid-beta (Abeta), and some new targeted therapeutic drugs. RESULTS: A total of 15, 548 individuals with AD disease in 57 randomized clinical trials (RCTs) were included in this meta-analysis. The results indicated that the patients who received rTMS treatment (standard mean difference [SMD]: 0.65; 95% confidence interval [CI]: 0.22-1.07) had a better MMSE score than placebo. Treatment outcome analysis showed that, compared with multiple pharmacological interventions, rTMS acquired the greatest probability rank with the best cognitive improvement in MMSE score [the surface under the cumulative ranking curve (SUCRA) 93.3%] and ADAS-cog score (SUCRA 86.7%). At the same time, rTMS treatment had the lowest rank in the adverse events (SUCRA 24.1%) except for the placebo group (SUCRA 19.1%). CONCLUSION: Compared with the current clinical drug treatment, rTMS demonstrated better cognitive function improvement and fewer adverse events in AD patients. Therefore, rTMS shows broad prospects in the treatment of Alzheimer's disease, and it is worth being widely popularized in clinic.
ESTHER : Wei_2023_CNS.Neurosci.Ther__
PubMedSearch : Wei_2023_CNS.Neurosci.Ther__
PubMedID: 37088953

Title : Role of soluble epoxide hydrolase in the abnormal activation of fibroblast-like synoviocytes from patients with rheumatoid arthritis - Pu_2023_Clin.Immunol__109850
Author(s) : Pu Y , Cheng R , Zhang Q , Huang T , Lu C , Tang Z , Zhong Y , Wu L , Hammock BD , Hashimoto K , Luo Y , Liu Y
Ref : Clin Immunol , :109850 , 2023
Abstract : Rheumatoid arthritis (RA) is an autoimmune disease characterized by enigmatic pathogenesis. Polyunsaturated fatty acids (PUFAs) are implicated in RA's development and progression, yet their exact mechanisms of influence are not fully understood. Soluble epoxide hydrolase (sEH) is an enzyme that metabolizes anti-inflammatory epoxy fatty acids (EpFAs), derivatives of PUFAs. In this study, we report elevated sEH expression in the joints of CIA (collagen-induced arthritis) rats, concomitant with diminished levels of two significant EpFAs. Additionally, increased sEH expression was detected in both the synovium of CIA rats and in the synovium and fibroblast-like synoviocytes (FLS) of RA patients. The sEH inhibitor TPPU attenuated the migration and invasion capabilities of FLS derived from RA patients and to reduce the secretion of inflammatory factors by these cells. Our findings indicate a pivotal role for sEH in RA pathogenesis and suggest that sEH inhibitors offer a promising new therapeutic strategy for managing RA.
ESTHER : Pu_2023_Clin.Immunol__109850
PubMedSearch : Pu_2023_Clin.Immunol__109850
PubMedID: 38013165

Title : New neo-Clerodane diterpenoids isolated from Ajuga decumbens Thunb., planted in Pingtan island of Fujian Province with the potent anticancer activity - Zacchaeus_2022_Anticancer.Agents.Med.Chem__
Author(s) : Zacchaeus Olatunde O , Yong J , Lu C
Ref : Anticancer Agents Med Chem , : , 2022
Abstract : AIMS: To find the anticancer lead compounds or drug candidates from Chinese Traditional Plant Medicine of Ajuga decumbens Thunb. BACKGROUND: Ajuga decumbens Thunb., has been used in clinical for a long history in China and selected in "Chinses Pharmacopoeia" (part I in 1977) for its wide spectrum biological activities: such as anticancer, antioxidant, antifeedant, antibacterial, anti-inflammatory, antihyperlipidemic, anti-cholinesterase and cytotoxicity activities. However, there are relatively fewer studies of Ajuga decumbens Thunb. have been carried out till now. These years, our research group focus on the discovery of new anticancer agents, so we studied the chemical compositions of Ajuga decumbens Thunb., planted in Pingtan island of Fujian Province, to discover new anticancer lead compounds or candidates from this Chinese Traditional Plant Medicine. OBJECTIVE: To discovery new lead compounds from this Chinese Traditional Plant Medicine for the development of anticancer agents. METHODS: The dichloromethane (DCM) extract was obtained in this work, and then this extract was performed on silica gel column chromatography to obtain different polar fractions. Several similar fractions were combined according to TLC or HPLC analysis. The combined fractions were isolated by preparative TLC or preparative HPLC to obtain the pure compounds and HPLC was used to detect the purity. All isolated compounds were determined by NMR (1HNMR, 13CNMR, DEPT, HMBC, HSQC, 1H-1H COSY and NOESY), HRESIMS and single crystal X-ray diffraction methods. The in vitro anticancer activity was evaluated using CCK8 method. RESULT: Seven compounds[three new compounds 1-3and four known compounds (Ajugacumbins A, Ajugacumbin B, Ajugamarin A2 and Ajugamarin A1)] were isolated from Ajuga decumbens Thunb. in this work, and their structures were confirmed. The biological evaluation showed that 3 and Ajugamarin A1 exhibited potent in vitro anticancer activity both against A549 cell lines with IC50s=71.4microM and 76.7microM; and against Hela cell lines with IC50s=71.6mM and 5.39x10-7microM respectively. CONCLUSION: Compounds (3 and Ajugamarin A1) can be regarded as the lead compounds for the development of anticancer agents.
ESTHER : Zacchaeus_2022_Anticancer.Agents.Med.Chem__
PubMedSearch : Zacchaeus_2022_Anticancer.Agents.Med.Chem__
PubMedID: 35726426

Title : Spleen volume-based non-invasive tool for predicting hepatic decompensation in people with compensated cirrhosis (CHESS1701) - Yu_2022_JHEP.Rep_4_100575
Author(s) : Yu Q , Xu C , Li Q , Ding Z , Lv Y , Liu C , Huang Y , Zhou J , Huang S , Xia C , Meng X , Lu C , Li Y , Tang T , Wang Y , Song Y , Qi X , Ye J , Ju S
Ref : JHEP Rep , 4 :100575 , 2022
Abstract : BACKGROUND & AIMS: Non-invasive stratification of the liver decompensation risk remains unmet in people with compensated cirrhosis. This study aimed to develop a non-invasive tool (NIT) to predict hepatic decompensation. METHODS: This retrospective study recruited 689 people with compensated cirrhosis (median age, 54 years; 441 men) from 5 centres from January 2016 to June 2020. Baseline abdominal computed tomography (CT), clinical features, and liver stiffness were collected, and then the first decompensation was registered during the follow-up. The spleen-based model was designed for predicting decompensation based on a deep learning segmentation network to generate the spleen volume and least absolute shrinkage and selection operator (LASSO)-Cox. The spleen-based model was trained on the training cohort of 282 individuals (Institutions I-III) and was validated in 2 external validation cohorts (97 and 310 individuals from Institutions IV and V, respectively) and compared with the conventional serum-based models and the Baveno VII criteria. RESULTS: The decompensation rate at 3 years was 23%, with a 37.6-month median (IQR 21.1-52.1 months) follow-up. The proposed model showed good performance in predicting decompensation (C-index <=0.84) and outperformed the serum-based models (C-index comparison test p <0.05) in both the training and validation cohorts. The hazard ratio (HR) for decompensation in individuals with high risk was 7.3 (95% CI 4.2-12.8) in the training and 5.8 (95% CI 3.9-8.6) in the validation (log-rank test, p <0.05) cohorts. The low-risk group had a negligible 3-year decompensation risk (>=1%), and the model had a competitive performance compared with the Baveno VII criteria. CONCLUSIONS: This spleen-based model provides a non-invasive and user-friendly method to help predict decompensation in people with compensated cirrhosis in diverse healthcare settings where liver stiffness is not available. LAY SUMMARY: People with compensated cirrhosis with larger spleen volume would have a higher risk of decompensation. We developed a spleen-based model and validated it in external validation cohorts. The proposed model might help predict hepatic decompensation in people with compensated cirrhosis when invasive tools are unavailable.
ESTHER : Yu_2022_JHEP.Rep_4_100575
PubMedSearch : Yu_2022_JHEP.Rep_4_100575
PubMedID: 36204707

Title : Transcriptome analysis and the identification of genes involved in the metabolic pathways of fenoxaprop-P-ethyl in rice treated with isoxadifen-ethyl hydrolysate - Zhao_2022_Pestic.Biochem.Physiol_183_105057
Author(s) : Zhao Y , Li W , Sun L , Xu H , Su W , Xue F , Wu R , Lu C
Ref : Pestic Biochem Physiol , 183 :105057 , 2022
Abstract : Fenoxaprop-P-ethyl (FE) is a highly effective weed control agent for rice fields, but it causes phytotoxicity in crops. A whole-plant bioassay has revealed that isoxadifen-ethyl hydrolysate (IH) can significantly improve the tolerance of rice to FE, but the molecular mechanisms underlying this phenomenon are still unclear. In this study, we performed RNA-Seq analysis using rice seedlings treated with FE and IH to determine the IH-regulated candidate genes involved in metabolic resistance to FE. We also analyzed spatiotemporal expression using quantitative reverse transcription polymerase chain reaction to reveal the expression patterns of these genes under different treatments. The results showed that genes encoding metabolic enzymes, such as cytochrome P450 monooxygenases, glutathione-s-transferases, UDP-glycosyltransferase, carboxylesterase, and ATP-binding cassette transporter, were influenced by the application of IH. Most of these genes were upregulated, and their products were involved in various stages of FE metabolism. Tolerance to FE was primarily mediated by CarE15, CYP86A1, GSTU6, GST4, UGT13248, UGT79, and ABCC4, all of which played a vital role in regulating the detoxification process of FE. Our findings elucidated the protective mechanisms of IH, which can help alleviate the phytotoxic effects of FE and expand its potential for application in agriculture.
ESTHER : Zhao_2022_Pestic.Biochem.Physiol_183_105057
PubMedSearch : Zhao_2022_Pestic.Biochem.Physiol_183_105057
PubMedID: 35430061

Title : A distal regulatory strategy of enzymes: from local to global conformational dynamics - Peng_2021_Phys.Chem.Chem.Phys__
Author(s) : Peng X , Lu C , Pang J , Liu Z , Lu D
Ref : Phys Chem Chem Phys , : , 2021
Abstract : Modulating the distribution of various states in protein ensembles through distal sites may be promising in the evolution of enzymes in desired directions. However, the prediction of distal mutation hotspots that stabilize the favoured states from a computational perspective remains challenging. Here, we presented a strategy based on molecular dynamics (MD) and Markov state models (MSM) to predict distal mutation sites. Extensive MD combined with MSM was applied to determine the principally distributed metastable states interconverting at a slow timescale. Then, molecular docking was used to classify these states into active states and inactive ones. Distal mutation hotspots were targeted based on comparing the conformational features between active and inactive states, where mutations destabilize the inactive states and show little influence on the active state. The proposed strategy was used to explore the highly dynamic MHETase, which shows a potential application in the biodegradation of poly(ethylene terephthalate) (PET). Seven principally populated interrelated metastable states were identified, and the atomistic picture of their conformational changes was unveiled. Several residues at distal positions were found to adopt more H-bond occupancies in inactive states than active states, making them potential mutation hotspots for stabilizing the favoured conformations. In addition, the detailed mechanism revealed the significance of calcium ions at a distance from the catalytic centre in reshaping the free energy landscape. This study deepens the understanding of the conformational dynamics of alpha/beta hydrolases containing a lid domain and advances the study of enzymatic plastic degradation.
ESTHER : Peng_2021_Phys.Chem.Chem.Phys__
PubMedSearch : Peng_2021_Phys.Chem.Chem.Phys__
PubMedID: 34585687

Title : [Computation-aided design of the flexible region of zearalenone hydrolase improves its thermal stability] - Chen_2021_Sheng.Wu.Gong.Cheng.Xue.Bao_37_4415
Author(s) : Chen Q , Lu C , Xu F
Ref : Sheng Wu Gong Cheng Xue Bao , 37 :4415 , 2021
Abstract : The zearalenone hydrolase (ZHD101) derived from Clonostachys rosea can effectively degrade the mycotoxin zearalenone (ZEN) present in grain by-products and feed. However, the low thermal stability of ZHD101 hampers its applications. High throughput screening of variants using spectrophotometer is challenging because the reaction of hydrolyzing ZEN does not change absorbance. In this study, we used ZHD101 as a model enzyme to perform computation-aided design followed by experimental verification. By comparing the molecular dynamics simulation trajectories of ZHD101 at different temperatures, 32 flexible sites were selected. 608 saturated mutations were introduced into the 32 flexible sites virtually, from which 12 virtual mutants were screened according to the position specific score and enzyme conformation free energy calculation. Three of the mutants N156F, S194T and T259F showed an increase in thermal melting temperature (deltaTm>4 degreesC), and their enzyme activities were similar to or even higher than that of the wild type (relative enzyme activity 95.8%, 131.6% and 169.0%, respectively). Molecular dynamics simulation analysis showed that the possible mechanisms leading to the improved thermal stability were NH-Pi force, salt bridge rearrangement, and hole filling on the molecular surface. The three mutants were combined iteratively, and the combination of N156F/S194T showed the highest thermal stability (deltaTm=6.7 degreesC). This work demonstrated the feasibility of engineering the flexible region to improve enzyme performance by combining virtual computational mutations with experimental verification.
ESTHER : Chen_2021_Sheng.Wu.Gong.Cheng.Xue.Bao_37_4415
PubMedSearch : Chen_2021_Sheng.Wu.Gong.Cheng.Xue.Bao_37_4415
PubMedID: 34984886

Title : Arabidopsis Carboxylesterase 20 Binds Strigolactone and Increases Branches and Tillers When Ectopically Expressed in Arabidopsis and Maize - Roesler_2021_Front.Plant.Sci_12_639401
Author(s) : Roesler K , Lu C , Thomas J , Xu Q , Vance P , Hou Z , Williams RW , Liu L , Owens MA , Habben JE
Ref : Front Plant Sci , 12 :639401 , 2021
Abstract : Severe drought stress can delay maize silk emergence relative to the pollen shedding period, resulting in poor fertilization and reduced grain yield. Methods to minimize the delay in silking could thus improve yield stability. An Arabidopsis enhancer-tagged carboxylesterase 20 (AtCXE20) line was identified in a drought tolerance screen. Ectopic expression of AtCXE20 in Arabidopsis and maize resulted in phenotypes characteristic of strigolactone (SL)-deficient mutants, including increased branching and tillering, decreased plant height, delayed senescence, hyposensitivity to ethylene, and reduced flavonols. Maize silk growth was increased by AtCXE20 overexpression, and this phenotype was partially complemented by exogenous SL treatments. In drought conditions, the transgenic maize plants silked earlier than controls and had decreased anthesis-silking intervals. The purified recombinant AtCXE20 protein bound SL in vitro, as indicated by SL inhibiting AtCXE20 esterase activity and altering AtCXE20 intrinsic fluorescence. Homology modeling of the AtCXE20 three-dimensional (3D) protein structure revealed a large hydrophobic binding pocket capable of accommodating, but not hydrolyzing SLs. The AtCXE20 protein concentration in transgenic maize tissues was determined by mass spectrometry to be in the micromolar range, well-above known endogenous SL concentrations. These results best support a mechanism where ectopic expression of AtCXE20 with a strong promoter effectively lowers the concentration of free SL by sequestration. This study revealed an agriculturally important role for SL in maize silk growth and provided a new approach for altering SL levels in plants.
ESTHER : Roesler_2021_Front.Plant.Sci_12_639401
PubMedSearch : Roesler_2021_Front.Plant.Sci_12_639401
PubMedID: 33986761
Gene_locus related to this paper: arath-AT5G62180

Title : Global and Kinetic Profiles of Substrate Diffusion in Candida antarctica Lipase B: Molecular Dynamics with the Markov-State Model - Lu_2020_ACS.Omega_5_9806
Author(s) : Lu C , Peng X , Lu D , Liu Z
Ref : ACS Omega , 5 :9806 , 2020
Abstract : Profiling substrate diffusion pathways with kinetic information, which accounts for the dynamic nature of enzyme-substrate interaction, can enable molecular reengineering of enzymes and process optimization of enzymatic catalysis. Candida antarctica lipase B (CALB) is extensively used for producing various chemicals because of its rich catalytic mechanisms, broad substrate spectrum, thermal stability, and tolerance to organic solvents. In this study, an all-atom molecular dynamics (MD) combined with Markov-state models (MSMs) implemented in pyEMMA was proposed to simulate diffusion pathways of 4-nitrophenyl ester (4NPE), a commonly used substrate, from the surface into the active site of CALB. Six important metastable conformations of CALB were identified in the diffusion process, including a closed state. An induced-fit mechanism incorporating multiple pathways with molecular information was proposed, which might find unprecedented applications for the rational design of lipase for green catalysis.
ESTHER : Lu_2020_ACS.Omega_5_9806
PubMedSearch : Lu_2020_ACS.Omega_5_9806
PubMedID: 32391467
Gene_locus related to this paper: canar-LipB

Title : A facile microfluidic paper-based analytical device for acetylcholinesterase inhibition assay utilizing organic solvent extraction in rapid detection of pesticide residues in food - Jin_2020_Anal.Chim.Acta_1100_215
Author(s) : Jin L , Hao Z , Zheng Q , Chen H , Zhu L , Wang C , Liu X , Lu C
Ref : Anal Chim Acta , 1100 :215 , 2020
Abstract : The incompatibility of most organic solvents with acetylcholinesterase (AChE) inhibition assay normally limits pesticide extraction efficiency in sample pretreatment, which might cause false negatives in real world sample assessment. Herein, a novel method has been developed for an improved AChE inhibition assay via organic solvent extraction combined spontaneous in situ solvent evaporation on microfluidic paper-based analytical devices. Enzyme pre-immobilization procedure was spared and AChE was added to the system after sampling step until a complete in-situ solvent evaporation process was performed on chip. IC50 levels of the six investigated organophosphate and carbamate pesticides indicated a completely eliminated influence of solvents on AChE behavior with the new method. Most importantly, analytical performances were significantly improved in food sample measurements. Reduction in matrix effect was observed when acetonitrile was adopted for lettuce sample pretreatment instead of water. Studies on different pesticides suggested a remarkably decreased discrimination effect on recoveries from sample pretreatment with the new developed method. The recovery level for phoxim spiked head lettuce samples reached (107.5 +/- 14.2) %, in comparison with that of (18.6 +/- 1.4) % from water-based extraction. Spiked water and apple juice samples with carbaryl concentration of as low as 0.02 mg L(-1) were also successfully recognized with the present method by visual detection. This is the first report on direct sampling of organic extracts for AChE inhibition assay on-chip and it might provide a new perspective for real world sample assessments involving bio-reagents.
ESTHER : Jin_2020_Anal.Chim.Acta_1100_215
PubMedSearch : Jin_2020_Anal.Chim.Acta_1100_215
PubMedID: 31987143

Title : Epigenetic mechanisms underlying the effects of triptolide and tripchlorolide on the expression of neuroligin-1 in the hippocampus of APP\/PS1 transgenic mice - Lu_2019_Pharm.Biol_57_453
Author(s) : Lu X , Yang B , Yu H , Hu X , Nie J , Wan B , Zhang M , Lu C
Ref : Pharm Biol , 57 :453 , 2019
Abstract : Context: Neuroligin-1 (NLGN1) is a cell adhesion protein located on the excitatory postsynaptic membrane. beta-Amyloid (Abeta)-induced neuroinflammation decreases NLGN1 expression through epigenetic mechanisms. Triptolide (T10) and tripchlorolide (T4) exert protective effects on synapses in Alzheimer's disease (AD) mice, but the mechanisms remain unclear. Objective: The effects of T10 and T4 on hippocampal NLGN1 expression in AD mice and the epigenetic mechanisms were assessed using chromatin immunoprecipitation and methylated DNA immunoprecipitation. Materials and methods: Sixty APP/PS1 transgenic mice were randomly divided into an AD model group, a T10-treated group and a T4-treated group (n = 20); 20 wild-type littermates served as the control group. APP/PS1 transgenic mice were intraperitoneally injected with T10 (0.1 mg/kg) and T4 (25 mug/kg) once per day for 60 days. NLGN1 expression was examined using western blotting and quantitative PCR. Results: T10 and T4 increased the levels of the NLGN1 protein and mRNA in hippocampus of AD mice. T10 and T4 inhibited the binding of HDAC2 (p< 0.01) and MeCP2 (p< 0.01 and p< 0.05, respectively) to the NLGN1 promoter, and cytosine methylation (1.2305 +/- 0.1482/1.2554 +/- 0.3570 vs. 1.6578 +/- 0.1818, p< 0.01) at the NLGN1 promoter in the hippocampus of AD mice. T10 and T4 increased the level of acetylated histone H3 (0.7733 +/- 0.1611/0.8241 +/- 0.0964 vs. 0.5587 +/- 0.0925, p< 0.01) at the NLGN1 promoter in the hippocampus of AD mice. Conclusions: T10 and T4 may increase hippocampal NLGN1 expression in AD mice through epigenetic mechanisms, providing a new explanation for the mechanism underlying the protective effects of T10 and T4 on synapses.
ESTHER : Lu_2019_Pharm.Biol_57_453
PubMedSearch : Lu_2019_Pharm.Biol_57_453
PubMedID: 31311385

Title : Neuroprotective effects of 20(S)-protopanaxatriol (PPT) on scopolamine-induced cognitive deficits in mice - Lu_2018_Phytother.Res_32_1056
Author(s) : Lu C , Lv J , Dong L , Jiang N , Wang Y , Wang Q , Li Y , Chen S , Fan B , Wang F , Liu X
Ref : Phytother Res , 32 :1056 , 2018
Abstract : 20(S)-protopanaxatriol (PPT), one of the ginsenosides from Panax ginseng, has been reported to have neuroprotective effects and to improve memory. The present study was designed to investigate the protective effect of PPT on scopolamine-induced cognitive deficits in mice. Male Institute of Cancer Research mice were pretreated with 2 different doses of PPT (20 and 40 mumol/kg) for 27 days by intraperitoneal injection, and scopolamine (0.75 mg/kg) was injected intraperitoneally for 9 days to induce memory impairment. Thirty minutes after the last pretreatment, the locomotor activity was firstly examined to evaluate the motor function of mice. Then, memory-related behaviors were evaluated, and the related mechanism was further researched. It was founded that PPT treatment significantly reversed scopolamine-induced cognitive impairment in the object location recognition experiment, the Morris water maze test, and the passive avoidance task, showing memory-improving effects. PPT also significantly improved cholinergic system reactivity and suppressed oxidative stress, indicated by inhibition of acetylcholinesterase activity, elevation of acetylcholine levels, increasing superoxide dismutase activity and lowering levels of malondialdehyde in the hippocampus. In addition, the expression levels of Egr-1, c-Jun, and cAMP responsive element binding in the hippocampus were significantly elevated by PPT administration. These results suggest that PPT may be a potential drug candidate for the treatment of cognitive deficit in Alzheimer's disease.
ESTHER : Lu_2018_Phytother.Res_32_1056
PubMedSearch : Lu_2018_Phytother.Res_32_1056
PubMedID: 29468740

Title : Studies on the lipid-regulating mechanism of alisol-based compounds on lipoprotein lipase - Xu_2018_Bioorg.Chem_80_347
Author(s) : Xu F , Lu C , Wu Q , Gu W , Chen J , Fang F , Zhao B , Du W , You M
Ref : Bioorg Chem , 80 :347 , 2018
Abstract : Studies on the lipid-regulating effects of alisol compounds are reported that include alisol B, alisol A 24-acetate (24A), alisol A and an alisol B - 24A - alisol A mixture (content ratio=1:1:1). The effects on the activity of lipoprotein lipase (LPL), a key lipid-modulating enzyme, were studied to investigate the molecular mechanism of lipid-regulating activity of alisols. The effects of alisols on regulating blood lipids and the activities of LPL were determined using a reagent kit method. The structure of LPL was obtained by homology modeling and the interactive mechanism of alisol monomers and the mixture with LPL was investigated by molecular simulation. The alisol monomer and mixture were shown to regulate blood lipids, suggesting that alisols may decrease the level of triglyceride (TG) by improving the activity of LPL. The order of intensity was: mixture>alisol A>alisol B>24A, indicating that alisols of alismatis rhizoma feature a synergistic effect on LPL. The N- and C-terminus of LPL both represented the catalytic active domains of this lipid-regulating effect. Cys306, Gln129 and Ser166 were the key amino acid residues resulting in the lipid-regulating effect of the alisol monomer while Ser166 and Arg18 were found to be responsible for the lipid-regulating effect of the mixture. The C-terminus of LPL was indirectly involved in the enzymatic process. A folded side chain of alisols or the parent ring was found to bind somewhat weaker to LPL than an open side chain or parent ring. The hydroxyl groups on the C14-, C22-, C28-, C30- and C31-terminus in the side chain, the ring ether structure in C23-position, and the acetyl group in C29-position represented the key sites for the lipid-regulating action of alisols. Meanwhile, the C30-site hydroxyl group played an important role in the synergistic effect of the alisol mixture.
ESTHER : Xu_2018_Bioorg.Chem_80_347
PubMedSearch : Xu_2018_Bioorg.Chem_80_347
PubMedID: 29986183

Title : Hydrogen peroxide redistributes the localization of protein phosphatase methylesterase 1 - Tang_2018_Life.Sci_213_166
Author(s) : Tang S , Lu C , Mo L , Wang X , Liang Z , Qin F , Liu Y , Huang H , Huang Y , Cai H , Xiao D , Guo S , Ouyang Y , Sun B , Li X
Ref : Life Sciences , 213 :166 , 2018
Abstract : AIMS: Protein phosphatase methylesterase-1 (PME-1) is a serine hydrolase that catalyzes protein phosphatase 2A (PP2A) demethylation and negatively regulates its activity. PME-1 is compartmentalized within cells to precisely control the demethylation of PP2A. This study investigated the localization of PME-1 in human fibroblast cells (HDF) under oxidative stress. MAIN METHODS: Alkaline demethylation and peptide competition assays were applied to detect the methylation sensitivity of anti-PP2Ac. The localization of PME-1, leucine carboxyl methyltransferase 1 (LCMT1), demethylated-phosphorylated-PP2Ac (dem-p-PP2Ac) and total PP2Ac was determined by immunofluorescence analysis, and protein expression was measured by Western blot. A HEK293 cell line stably expressing constructed PME-1-EGFP was used to dynamically monitor the nuclear export of PME-1 under oxidative stress. KEY RESULTS: After hydrogen peroxide (H(2)O(2)) treatment, the protein expression of PME-1 remained unchanged, while PME-1 facilitated redistribution from the nucleus to the cytoplasm in HDF according to immunofluorescence analysis. In constructed HEK293 cells, the EGFP-tagged PME-1 was exported from the nucleus to the cytoplasm after H(2)O(2) treatment, and nuclear export was eliminated after leptomycin B additions. Our observation of dem-p-PP2Ac species relocation from the nucleus to the cytoplasm under oxidative stress is consistent with the redistribution patterns of PME-1. Antioxidant N-acetyl cysteine can reverse the nuclear to cytoplasmic ratio of PME-1 proteins and dem-p-PP2Ac after H(2)O(2) exposure. SIGNIFICANCE: We found that PME-1 is exported from the nucleus to the cytoplasm upon H(2)O(2) treatment and redistributes dem-p-PP2Ac in subcellular compartments. These findings offer new insight into the regulation of PME-1 localization and PP2A demethylation under oxidative stress.
ESTHER : Tang_2018_Life.Sci_213_166
PubMedSearch : Tang_2018_Life.Sci_213_166
PubMedID: 30340029
Gene_locus related to this paper: human-PPME1

Title : 20(S)-protopanaxadiol (PPD) alleviates scopolamine-induced memory impairment via regulation of cholinergic and antioxidant systems, and expression of Egr-1, c-Fos and c-Jun in mice - Lu_2017_Chem.Biol.Interact_279_64
Author(s) : Lu C , Dong L , Lv J , Wang Y , Fan B , Wang F , Liu X
Ref : Chemico-Biological Interactions , 279 :64 , 2017
Abstract : 20(S)-protopanaxadiol (PPD) possesses various biological properties, including anti-inflammatory, antitumor and anti-fatigue properties. Recent studies found that PPD functioned as a neurotrophic agent to ameliorate the sensory deficit caused by glutamate-induced excitotoxicity through its antioxidant effects and exhibited strong antidepressant-like effects in vivo. The objective of the present study was first to investigate the effect of PPD in scopolamine (SCOP)-induced memory deficit in mice and the potential mechanisms involved. In this study, mice were pretreated with PPD (20 and 40 mumol/kg) and donepezil (1.6 mg/kg) intraperitoneally (i.p) for 14 days. Then, open field test was used to assess the effect of PPD on the locomotor activity and mice were daily injected with SCOP (0.75 mg/kg) to induce cognitive deficits and then subjected to behavioral tests by object location recognition (OLR) experiment and Morris water maze (MWM) task. The cholinergic system function, oxidative stress biomarkers and protein expression of Egr-1, c-Fos, and c-Jun in mouse hippocampus were examined. PPD was found to significantly improve the performance of amnesia mice in OLR and MWM tests. PPD regulated cholinergic function by inhibiting SCOP-induced elevation of acetylcholinesterase (AChE) activity, decline of choline acetyltransferase (ChAT) activity and decrease of acetylcholine (Ach) level. PPD suppressed oxidative stress by increasing activities of antioxidant enzymes such as superoxide dismutase (SOD) and lowering maleic diadehyde (MDA) level. Additionally, PPD significantly elevated the expression of Egr-1, c-Fos, and c-Jun in hippocampus at protein level. Taken together, all these results suggested that 20(S)-protopanaxadiol (PPD) may be a candidate compound for the prevention against memory loss in some neurodegenerative diseases such as Alzheimer's disease (AD).
ESTHER : Lu_2017_Chem.Biol.Interact_279_64
PubMedSearch : Lu_2017_Chem.Biol.Interact_279_64
PubMedID: 29133030

Title : The Protective Effect of Lavender Essential Oil and Its Main Component Linalool against the Cognitive Deficits Induced by D-Galactose and Aluminum Trichloride in Mice - Xu_2017_Evid.Based.Complement.Alternat.Med_2017_7426538
Author(s) : Xu P , Wang K , Lu C , Dong L , Gao L , Yan M , Aibai S , Yang Y , Liu X
Ref : Evid Based Complement Alternat Med , 2017 :7426538 , 2017
Abstract : Lavender essential oil (LO) is a traditional medicine used for the treatment of Alzheimer's disease (AD). It was extracted from Lavandula angustifolia Mill. This study was designed to investigate the effects of lavender essential oil (LO) and its active component, linalool (LI), against cognitive impairment induced by D-galactose (D-gal) and AlCl3 in mice and to explore the related mechanisms. Our results revealed that LO (100 mg/kg) or LI (100 mg/kg) significantly protected the cognitive impairments as assessed by the Morris water maze test and step-though test. The mechanisms study demonstrated that LO and LI significantly protected the decreased activity of superoxide dismutase (SOD), glutathione peroxidase (GPX), and protected the increased activity of acetylcholinesterase (AChE) and content of malondialdehyde (MDA). Besides, they protected the suppressed nuclear factor-erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) expression significantly. Moreover, the decreased expression of synapse plasticity-related proteins, calcium-calmodulin-dependent protein kinase II (CaMKII), p-CaMKII, brain-derived neurotrophic factor (BDNF), and TrkB in the hippocampus were increased with drug treatment. In conclusion, LO and its active component LI have protected the oxidative stress, activity of cholinergic function and expression of proteins of Nrf2/HO-1 pathway, and synaptic plasticity. It suggest that LO, especially LI, could be a potential agent for improving cognitive impairment in AD.
ESTHER : Xu_2017_Evid.Based.Complement.Alternat.Med_2017_7426538
PubMedSearch : Xu_2017_Evid.Based.Complement.Alternat.Med_2017_7426538
PubMedID: 28529531

Title : Identification and functional characterization of two missense mutations in NDRG1 associated with Charcot-Marie-Tooth disease type 4D - Li_2017_Hum.Mutat_38_1569
Author(s) : Li LX , Liu GL , Liu ZJ , Lu C , Wu ZY
Ref : Hum Mutat , 38 :1569 , 2017
Abstract : Charcot-Marie-Tooth disease type 4D (CMT4D) is an autosomal-recessive demyelinating form of CMT characterized by a severe distal motor and sensory neuropathy. NDRG1 is the causative gene for CMT4D. To date, only four mutations in NDRG1 -c.442C>T (p.Arg148*), c.739delC (p.His247Thrfs*74), c.538-1G>A, and duplication of exons 6-8-have been described in CMT4D patients. Here, using targeted next-generation sequencing examination, we identified for the first time two homozygous missense variants in NDRG1, c.437T>C (p.Leu146Pro) and c.701G>A (p.Arg234Gln), in two Chinese CMT families with consanguineous histories. Further functional studies were performed to characterize the biological effects of these variants. Cell culture transfection studies showed that mutant NDRG1 carrying p.Leu146Pro, p.Arg148*, or p.Arg234Gln variant degraded faster than wild-type NDRG1, resulting in lower protein levels. Live cell confocal microscopy and coimmunoprecipitation analysis indicated that these variants did not disrupt the interaction between NDRG1 and Rab4a protein. However, NDRG1-knockdown cells expressing mutant NDRG1 displayed enlarged Rab4a-positive compartments. Moreover, mutant NDRG1 could not enhance the uptake of DiI-LDL or increase the fraction of low-density lipoprotein receptor on the cell surface. Taken together, our study described two missense mutations in NDRG1 and emphasized the important role of NDRG1 in intracellular protein trafficking.
ESTHER : Li_2017_Hum.Mutat_38_1569
PubMedSearch : Li_2017_Hum.Mutat_38_1569
PubMedID: 28776325
Gene_locus related to this paper: human-NDRG1

Title : Protective effect of lavender oil on scopolamine induced cognitive deficits in mice and H2O2 induced cytotoxicity in PC12 cells - Xu_2016_J.Ethnopharmacol_193_408
Author(s) : Xu P , Wang K , Lu C , Dong L , Gao L , Yan M , Aibai S , Liu X
Ref : J Ethnopharmacol , 193 :408 , 2016
Abstract : ETHNOPHARMACOLOGICAL RELEVANCE: Lavender essential oil (LO), an aromatic liquid extracted from Lavandula angustifolia Mill., has been traditionally used in the treatments of many nervous system diseases, and recently LO also reported to be effective for the Alzheimer's disease (AD). AIM OF THE STUDY: The improvement effect of lavender oil (LO) on the scopolamine-induced cognitive deficits in mice and H2O2 induced cytotoxicity in PC12 cells have been evaluated. The relevant mechanism was also researched from the perspective of antioxidant effect and cholinergic system modulation. MATERIALS AND
METHODS: Cognitive deficits were induced in C57BL/6J mice treated with scopolamine (1mg/kg, i.p.) and were assessed by Morris water maze (MWM) and step-through passive avoidance tests. Then their hippocampus were removed for biochemical assays (acetylcholinesterase (AChE), superoxide dismutase (SOD), glutathione peroxidase (GPX) and malondialdehyde (MDA)). In vitro, the cytotoxicity were induced by 4h exposure to H2O2 in PC12 and evaluated by cell viability (MTT), lactate dehydrogenase (LDH) level, nitric oxide (NO) release, reactive oxygen species (ROS) production and mitochondrial membrane potential (MMP).
RESULTS: The results demonstrated that LO (100mg/kg) could improve the cognitive performance of scopolamine induced mice in behavioral tests. Meanwhile, it significantly decreased the AChE activity, MDA level, and increase SOD and GPX activities of the model. Moreover, LO (12mug/mL) protected PC12 cells from H2O2 induced cytotoxicity by reducing LDH, NO release, intracellular ROS accumulation and MMP loss.
CONCLUSIONS: It was suggested that LO could show neuroprotective effect in AD model in vivo (scopolamine-treated mice) and in vitro (H2O2 induced PC12 cells) via modulating oxidative stress and AChE activity.
ESTHER : Xu_2016_J.Ethnopharmacol_193_408
PubMedSearch : Xu_2016_J.Ethnopharmacol_193_408
PubMedID: 27558947

Title : Acetylcholinesterase Inhibitors for Alzheimer's Disease Treatment Ameliorate Acetaminophen-Induced Liver Injury in Mice via Central Cholinergic System Regulation - Zhang_2016_J.Pharmacol.Exp.Ther_359_374
Author(s) : Zhang J , Zhang L , Sun X , Yang Y , Kong L , Lu C , Lv G , Wang T , Wang H , Fu F
Ref : Journal of Pharmacology & Experimental Therapeutics , 359 :374 , 2016
Abstract : Acetaminophen (APAP) is widely used as an analgesic and antipyretic agent, but it may induce acute liver injury at high doses. Alzheimer's disease patients, while treated with acetylcholinesterase inhibitor (AChEI), may take APAP when they suffer from cold or pain. It is generally recognized that inhibiting acetylcholinesterase activity may also result in liver injury. To clarify whether AChEI could deteriorate or attenuate APAP hepatotoxicity, the effects of AChEI on APAP hepatotoxicity were investigated. Male C57BL/6J mice were administrated with the muscarinic acetylcholine receptor (mAChR) blocker atropine (Atr), or classic alpha7 nicotine acetylcholine receptor (alpha7nAChR) antagonist methyllycaconitine (MLA) 1 hour before administration of AChEIs-donepezil (4 mg/kg), rivastigmine (2 mg/kg), huperzine A (0.2 mg/kg), or neostigmine (0.15 mg/kg)-followed by APAP (300 mg/kg). Eight hours later, the mice were euthanized for histopathologic examination and biochemical assay. The results demonstrated that the tested AChEIs, excluding neostigmine, could attenuate APAP-induced liver injury, accompanied by reduced reactive oxygen species formation, adenosine triphosphate and cytochrome C loss, c-Jun N-terminal kinase 2 (JNK2) phosphorylation, and cytokines. However, Atr or MLA significantly weakened the protective effect of AChEI by affecting mitochondrial function or JNK2 phosphorylation and inflammation response. These results suggest that central mAChR and alpha7nAChR, which are activated by accumulated acetylcholine resulting from AChEI, were responsible for the protective effect of AChEIs on APAP-induced liver injury. This indicates that Alzheimer's patients treated with AChEI could take APAP, as AChEI is unlikely to deteriorate the hepatotoxicity of APAP.
ESTHER : Zhang_2016_J.Pharmacol.Exp.Ther_359_374
PubMedSearch : Zhang_2016_J.Pharmacol.Exp.Ther_359_374
PubMedID: 27535978

Title : Population pharmacokinetic modeling and simulation of huperzine A in elderly Chinese subjects - Sheng_2016_Acta.Pharmacol.Sin_37_994
Author(s) : Sheng L , Qu Y , Yan J , Liu GY , Wang WL , Wang YJ , Wang HY , Zhang MQ , Lu C , Liu Y , Jia JY , Hu CY , Li XN , Yu C , Xu HR
Ref : Acta Pharmacol Sin , 37 :994 , 2016
Abstract : AIM: Our preliminary results show that huperzine A, an acetylcholinesterase inhibitor used to treat Alzheimer's disease (AD) patients in China, exhibits different pharmacokinetic features in elderly and young healthy subjects. However, its pharmacokinetic data in elderly subjects remains unavailable to date. Thus, we developed a population pharmacokinetic (PPK) model of huperzine A in elderly Chinese people, and identified the covariate affecting its pharmacokinetics for optimal individual administration.
METHODS: A total of 341 serum huperzine A concentration records was obtained from 2 completed clinical trials (14 elderly healthy subjects in a phase I pharmacokinetic study; 35 elderly AD patients in a phase II study). Population pharmacokinetic analysis was performed using the non-linear mixed-effect modeling software Phoenix NLME1.1.1. The effects of age, gender, body weight, height, creatinine, endogenous creatinine clearance rate as well as drugs administered concomitantly were analyzed. Bootstrap and visual predictive checks were used simultaneously to validate the final population pharmacokinetics models.
RESULTS: The plasma concentration-time profile of huperzine A was best described by a one-compartment model with first-order absorption and elimination. Age was identified as the covariate having significant influence on huperzine A clearance. The final PPK model of huperzine A was: CL (L/h)=2.4649(*)(age/86)((-3.3856)), Ka=0.6750 h(-1), V (L)=104.216. The final PPK model was demonstrated to be suitable and effective by the bootstrap and visual predictive checks. CONCLUSION: A PPK model of huperzine A in elderly Chinese subjects is established, which can be used to predict PPK parameters of huperzine A in the treatment of elderly AD patients.
ESTHER : Sheng_2016_Acta.Pharmacol.Sin_37_994
PubMedSearch : Sheng_2016_Acta.Pharmacol.Sin_37_994
PubMedID: 27180987

Title : Avertoxins A-D, Prenyl Asteltoxin Derivatives from Aspergillus versicolor Y10, an Endophytic Fungus of Huperzia serrata - Wang_2015_J.Nat.Prod_78_3067
Author(s) : Wang M , Sun M , Hao H , Lu C
Ref : Journal of Natural Products , 78 :3067 , 2015
Abstract : Aspergillus versicolor Y10 is an endophytic fungus isolated from Huperzia serrata, which showed inhibitory activity against acetylcholinesterase. An investigation of the chemical constituents of Y10 led to the isolation of four new prenylated asteltoxin derivatives, named avertoxins A-D (2-5), together with the known mycotoxin asteltoxin (1). In the present study, we report structure elucidation for 2-5 and the revised NMR assignments for asteltoxin and demonstrated that avertoxin B (3) is an active inhibitor against human acetylcholinesterase with the IC50 value of 14.9 muM (huperzine A as the positive control had an IC50 of 0.6 muM). In addition, the cytotoxicity of asteltoxin (1) and avertoxins A-D (2-5) against MDA-MB-231, HCT116, and HeLa cell lines was evaluated.
ESTHER : Wang_2015_J.Nat.Prod_78_3067
PubMedSearch : Wang_2015_J.Nat.Prod_78_3067
PubMedID: 26618211

Title : Genome sequence of cultivated Upland cotton (Gossypium hirsutum TM-1) provides insights into genome evolution - Li_2015_Nat.Biotechnol_33_524
Author(s) : Li F , Fan G , Lu C , Xiao G , Zou C , Kohel RJ , Ma Z , Shang H , Ma X , Wu J , Liang X , Huang G , Percy RG , Liu K , Yang W , Chen W , Du X , Shi C , Yuan Y , Ye W , Liu X , Zhang X , Liu W , Wei H , Wei S , Zhu S , Zhang H , Sun F , Wang X , Liang J , Wang J , He Q , Huang L , Cui J , Song G , Wang K , Xu X , Yu JZ , Zhu Y , Yu S
Ref : Nat Biotechnol , 33 :524 , 2015
Abstract : Gossypium hirsutum has proven difficult to sequence owing to its complex allotetraploid (AtDt) genome. Here we produce a draft genome using 181-fold paired-end sequences assisted by fivefold BAC-to-BAC sequences and a high-resolution genetic map. In our assembly 88.5% of the 2,173-Mb scaffolds, which cover 89.6% approximately 96.7% of the AtDt genome, are anchored and oriented to 26 pseudochromosomes. Comparison of this G. hirsutum AtDt genome with the already sequenced diploid Gossypium arboreum (AA) and Gossypium raimondii (DD) genomes revealed conserved gene order. Repeated sequences account for 67.2% of the AtDt genome, and transposable elements (TEs) originating from Dt seem more active than from At. Reduction in the AtDt genome size occurred after allopolyploidization. The A or At genome may have undergone positive selection for fiber traits. Concerted evolution of different regulatory mechanisms for Cellulose synthase (CesA) and 1-Aminocyclopropane-1-carboxylic acid oxidase1 and 3 (ACO1,3) may be important for enhanced fiber production in G. hirsutum.
ESTHER : Li_2015_Nat.Biotechnol_33_524
PubMedSearch : Li_2015_Nat.Biotechnol_33_524
PubMedID: 25893780
Gene_locus related to this paper: gosra-a0a0d2rxs2 , gosra-a0a0d2tng2 , gosra-a0a0d2twz7 , goshi-a0a1u8hr03 , gosra-a0a0d2vdc5 , goshi-a0a1u8ljh5 , gosra-a0a0d2vj24 , goshi-a0a1u8pxd3 , gosra-a0a0d2sr31 , goshi-a0a1u8knd1 , goshi-a0a1u8nhw9 , goshi-a0a1u8mt09 , goshi-a0a1u8kis4 , goshi-a0a1u8ibk3 , goshi-a0a1u8ieg2 , goshi-a0a1u8iki6 , goshi-a0a1u8jvp4 , goshi-a0a1u8jw35 , gosra-a0a0d2pzd7 , goshi-a0a1u8ied7

Title : Contribution of carboxylesterase and cytochrome p450 to the bioactivation and detoxification of isocarbophos and its enantiomers in human liver microsomes - Zhuang_2014_Toxicol.Sci_140_40
Author(s) : Zhuang XM , Wei X , Tan Y , Xiao WB , Yang HY , Xie JW , Lu C , Li H
Ref : Toxicol Sci , 140 :40 , 2014
Abstract : Organophosphorus pesticides are the most widely used pesticides in modern agricultural systems to ensure good harvests. Isocarbophos (ICP), with a potent acetylcholinesterase inhibitory effect is widely utilized to control a variety of leaf-eating and soil insects. However, the characteristics of the bioactivation and detoxification of ICP in humans remain unclear. In this study, the oxidative metabolism, esterase hydrolysis, and chiral inversion of ICP in human liver microsomes (HLMs) were investigated with the aid of a stereoselective LC/MS/MS method. The depletion of ICP in HLMs was faster in the absence of carboxylesterase inhibitor (BNPP) than in the presence of NADPH and BNPP, with t1/2 of 5.2 and 90 min, respectively. Carboxylesterase was found to be responsible for the hydrolysis of ICP, the major metabolic pathway. CYP3A4, CYP1A2, CYP2D6, CYP2C9, and CYP2C19 were all involved in the secondary metabolism pathway of desulfuration of ICP. Flavin-containing monooxygenase (FMO) did not contribute to the clearance of ICP. The hydrolysis and desulfuration of (+/-)ICP, (+)ICP, and (-)ICP in HLMs follow Michaelis-Menten kinetics. Individual enantiomers of ICP and its oxidative desulfuration metabolite isocarbophos oxon (ICPO) were found to be inhibitors of acetylcholinesterases at different extents. For example, (+/-)ICPO is more potent than ICP (IC50 0.031muM vs. 192muM), whereas (+)ICPO is more potent than (-)ICPO (IC50 0.017muM vs. 1.55muM). Given the finding of rapid hydrolysis of ICP and low abundance of oxidative metabolites presence in human liver, the current study highlights that human liver has a greater capacity for detoxification of ICP.
ESTHER : Zhuang_2014_Toxicol.Sci_140_40
PubMedSearch : Zhuang_2014_Toxicol.Sci_140_40
PubMedID: 24752505

Title : Whole Genome Sequence of the Probiotic Strain Lactobacillus paracasei N1115, Isolated from Traditional Chinese Fermented Milk - Wang_2014_Genome.Announc_2_e00059
Author(s) : Wang S , Zhu H , He F , Luo Y , Kang Z , Lu C , Feng L , Lu X , Xue Y , Wang H
Ref : Genome Announc , 2 : , 2014
Abstract : Lactobacillus paracasei N1115 is a new strain with probiotic properties isolated from traditional homemade dairy products in Inner Mongolia, China. Here, we report the complete genome sequence of L. paracasei N1115, which shows high similarity to the well-studied probiotic Lactobacillus rhamnosus GG, and 3 structures turned out to be inversions, according to the colinearity analysis of the BLAST alignment.
ESTHER : Wang_2014_Genome.Announc_2_e00059
PubMedSearch : Wang_2014_Genome.Announc_2_e00059
PubMedID: 24625864
Gene_locus related to this paper: lacc3-q03b36 , lacrh-pepr , lacca-b5qt93 , lacca-k0n1x0 , lacpa-s2ter8 , lacpa-s2rz88

Title : Comparative genomic analysis shows that Streptococcus suis meningitis isolate SC070731 contains a unique 105K genomic island - Wu_2014_Gene_535_156
Author(s) : Wu Z , Wang W , Tang M , Shao J , Dai C , Zhang W , Fan H , Yao H , Zong J , Chen D , Wang J , Lu C
Ref : Gene , 535 :156 , 2014
Abstract : Streptococcus suis (SS) is an important swine pathogen worldwide that occasionally causes serious infections in humans. SS infection may result in meningitis in pigs and humans. The pathogenic mechanisms of SS are poorly understood. Here, we provide the complete genome sequence of S. suis serotype 2 (SS2) strain SC070731 isolated from a pig with meningitis. The chromosome is 2,138,568bp in length. There are 1933 predicted protein coding sequences and 96.7% (57/59) of the known virulence-associated genes are present in the genome. Strain SC070731 showed similar virulence with SS2 virulent strains HA9801 and ZY05719, but was more virulent than SS2 virulent strain P1/7 in the zebrafish infection model. Comparative genomic analysis revealed a unique 105K genomic island in strain SC070731 that is absent in seven other sequenced SS2 strains. Further analysis of the 105K genomic island indicated that it contained a complete nisin locus similar to the nisin U locus in S. uberis strain 42, a prophage similar to S. oralis phage PH10 and several antibiotic resistance genes. Several proteins in the 105K genomic island, including nisin and RelBE toxin-antitoxin system, contribute to the bacterial fitness and virulence in other pathogenic bacteria. Further investigation of newly identified gene products, including four putative new virulence-associated surface proteins, will improve our understanding of SS pathogenesis.
ESTHER : Wu_2014_Gene_535_156
PubMedSearch : Wu_2014_Gene_535_156
PubMedID: 24316490
Gene_locus related to this paper: strej-e8uk64

Title : A novel oil-body nanoemulsion formulation of ginkgolide B: pharmacokinetics study and in vivo pharmacodynamics evaluations - Yang_2014_J.Pharm.Sci_103_1075
Author(s) : Yang P , Cai X , Zhou K , Lu C , Chen W
Ref : J Pharm Sci , 103 :1075 , 2014
Abstract : The goal of this study was to develop a novel oil-body nanoemulsion (ONE) for Ginkgolide B (GB) and to conduct pharmacokinetics and pharmacodynamics evaluations. GB-ONE was prepared by O/O emulsion method. The differences in pharmacokinetics parameters and tissue distribution of rats after oral administrated with GB-ONE were investigated by liquid chromatography-tandem mass spectrometry. Changes in the ethological and pathological characterizations of the Alzheimer's disease rats after treated with GB-ONE were evaluated by Morris water maze (MWM) and pathological section, respectively. Furthermore, choline acetyltransferase (ChAT) and acetylcholinesterase (AchE) activity in hippocampus was analyzed by spectrophotometric method. The results indicated that the AUC of GB in rats' plasma was significantly improved after incorporated into ONE, and GB-ONE was significantly targeted into brain. In MWM experiment, memory improvement of rats with cognition impaired was confirmed after administrated with GB-ONE. Furthermore, GB-ONE significantly inhibited AchE activity and enhanced the activity of ChAT in the hippocampus. The overall results implicated that the novel ONE was effective for improving the drawbacks of GB and showed great potential for clinical application. (c) 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 103:1075-1084, 2014.
ESTHER : Yang_2014_J.Pharm.Sci_103_1075
PubMedSearch : Yang_2014_J.Pharm.Sci_103_1075
PubMedID: 24496859

Title : Whole-Genome Sequence of Streptococcus suis Serotype 4 Reference Strain 6407 - Wang_2014_Genome.Announc_2_e00770
Author(s) : Wang K , Chen J , Yao H , Lu C
Ref : Genome Announc , 2 : , 2014
Abstract : We report here the second complete genome sequence of Streptococcus suis serotype 4 (strain 6407). The genome is 2,292,360 bp in length, covering 2,239 coding sequences, 58 tRNAs, and 4 rRNA loci.
ESTHER : Wang_2014_Genome.Announc_2_e00770
PubMedSearch : Wang_2014_Genome.Announc_2_e00770
PubMedID: 25125641
Gene_locus related to this paper: strsu-b9wvz1

Title : A novel series of tacrine-selegiline hybrids with cholinesterase and monoamine oxidase inhibition activities for the treatment of Alzheimer's disease - Lu_2013_Eur.J.Med.Chem_62C_745
Author(s) : Lu C , Zhou Q , Yan J , Du Z , Huang L , Li X
Ref : Eur Journal of Medicinal Chemistry , 62C :745 , 2013
Abstract : A novel series of tacrine-selegiline hybrids was synthesised and evaluated for application as inhibitors of cholinesterase (AChE/BCHE) and monoamine oxidase (MAO-A/B). The results demonstrate that most of the synthesised compounds exhibit high inhibitory activity. Among these compounds, compound 8g provided a good balance of activity towards all targets (with IC50 values of 22.6 nM, 9.37 nM, 0.3724 muM, and 0.1810 muM for AChE, BCHE, MAO-A and MAO-B, respectively). These results indicated that 8g has the potential to be a multi-functional candidate for Alzheimer's disease.
ESTHER : Lu_2013_Eur.J.Med.Chem_62C_745
PubMedSearch : Lu_2013_Eur.J.Med.Chem_62C_745
PubMedID: 23454517

Title : Synthesis and Evaluation of Multi-Target-Directed Ligands against Alzheimer's Disease Based on the Fusion of Donepezil and Ebselen - Luo_2013_J.Med.Chem_56_9089
Author(s) : Luo Z , Sheng J , Sun Y , Lu C , Yan J , Liu A , Luo HB , Huang L , Li X
Ref : Journal of Medicinal Chemistry , 56 :9089 , 2013
Abstract : A novel series of compounds obtained by fusing the cholinesterase inhibitor donepezil and the antioxidant ebselen were designed as multi-target-directed ligands against Alzheimer's disease. An in vitro assay showed that some of these molecules did not exhibit highly potent cholinesterase inhibitory activity but did have various other ebselen-related pharmacological effects. Among the molecules, compound 7d, one of the most potent acetylcholinesterase inhibitors (IC50 values of 0.042 muM for Electrophorus electricus acetylcholinesterase and 0.097 muM for human acetylcholinesterase), was found to be a strong butyrylcholinesterase inhibitor (IC50 = 1.586 muM), to possess rapid H2O2 and peroxynitrite scavenging activity and glutathione peroxidase-like activity (nu0 = 123.5 muM min(-1)), and to be a substrate of mammalian TrxR. A toxicity test in mice showed no acute toxicity at doses of up to 2000 mg/kg. According to an in vitro blood-brain barrier model, 7d is able to penetrate the central nervous system.
ESTHER : Luo_2013_J.Med.Chem_56_9089
PubMedSearch : Luo_2013_J.Med.Chem_56_9089
PubMedID: 24160297

Title : The effects of huperzine A on gastrointestinal acetylcholinesterase activity and motility after single and multiple dosing in mice - Zhang_2013_Exp.Ther.Med_5_793
Author(s) : Zhang L , Song Y , Lu C , Zhang J , Yuan J , Wang T , Fu F
Ref : Exp Ther Med , 5 :793 , 2013
Abstract : The acetylcholinesterase inhibitor (AChEI), huperzine A has been used in the treatment of the cognitive deterioration associated with Alzheimer's disease (AD). However, the side-effects of huperzine A associated with increased cholinergic activity, particularly in the gastrointestinal system, are evident. It is not yet known how quickly these side-effects become tolerated; this information would provide guidance to doctors on how to use huperzine A so as to attenuate the adverse events. The present study aimed to observe the effects of huperzine A on gastrointestinal motility and acetylcholinesterase (AChE) activity in mice. After oral administration of huperzine A with single and multiple dosing, the gastrointestinal motility and AChE activity of the mice were examined. The results revealed that, following a single dose of huperzine A, the AChE activity in the stomach and duodenum were significantly inhibited and the gastrointestinal motility was significantly increased. However, following multiple doses (7 or 28 doses, one dose per day), no significant changes in the AChE activity and gastrointestinal motility were identified. These findings indicate that the gastrointestinal adverse effects of huperzine A may be well-tolerated relatively quickly and do not recur. Additionally, it suggests that patients with AD are likely to have minimal gastrointestinal side-effects after taking multiple doses of huperzine A.
ESTHER : Zhang_2013_Exp.Ther.Med_5_793
PubMedSearch : Zhang_2013_Exp.Ther.Med_5_793
PubMedID: 23403922

Title : Complete Genome Sequence of Streptococcus suis Serotype 16 Strain TL13 - Wang_2013_Genome.Announc_1_e00394
Author(s) : Wang K , Yao H , Lu C , Chen J
Ref : Genome Announc , 1 : , 2013
Abstract : We report here the first complete genome sequence of Streptococcus suis serotype 16, which has been identified to be zoonotic. The sequenced strain TL13 was isolated from a pig in China. The genome is 2,038,146 bp in length, covering 1,950 coding sequences, 53 tRNAs, and 4 rRNA loci.
ESTHER : Wang_2013_Genome.Announc_1_e00394
PubMedSearch : Wang_2013_Genome.Announc_1_e00394
PubMedID: 23814033
Gene_locus related to this paper: strsu-b9wvz1

Title : Whole-Genome Sequence of Streptococcus suis Serotype 3 Strain YB51 - Wang_2013_Genome.Announc_1_e00884
Author(s) : Wang K , Chen J , Yao H , Lu C
Ref : Genome Announc , 1 : , 2013
Abstract : We report here the second complete genome sequence of Streptococcus suis serotype 3 (strain YB51). The genome is 2,043,655 bp in length, which is 14,840 bp longer than the first reported genome of the same serotype, and it covers 2,012 coding sequences, 56 tRNAs, and 4 rRNA loci.
ESTHER : Wang_2013_Genome.Announc_1_e00884
PubMedSearch : Wang_2013_Genome.Announc_1_e00884
PubMedID: 24179118
Gene_locus related to this paper: strsu-b9wvz1

Title : Genomic and transcriptomic insights into the thermo-regulated biosynthesis of validamycin in Streptomyces hygroscopicus 5008 - Wu_2012_BMC.Genomics_13_337
Author(s) : Wu H , Qu S , Lu C , Zheng H , Zhou X , Bai L , Deng Z
Ref : BMC Genomics , 13 :337 , 2012
Abstract : BACKGROUND: Streptomyces hygroscopicus 5008 has been used for the production of the antifungal validamycin/jinggangmycin for more than 40 years. A high yield of validamycin is achieved by culturing the strain at 37 degreesC, rather than at 30 degreesC for normal growth and sporulation. The mechanism(s) of its thermo-regulated biosynthesis was largely unknown. RESULTS: The 10,383,684-bp genome of strain 5008 was completely sequenced and composed of a linear chromosome, a 164.57-kb linear plasmid, and a 73.28-kb circular plasmid. Compared with other Streptomyces genomes, the chromosome of strain 5008 has a smaller core region and shorter terminal inverted repeats, encodes more alpha/beta hydrolases, major facilitator superfamily transporters, and Mg2+/Mn2+-dependent regulatory phosphatases. Transcriptomic analysis revealed that the expression of 7.5% of coding sequences was increased at 37 degreesC, including biosynthetic genes for validamycin and other three secondary metabolites. At 37 degreesC, a glutamate dehydrogenase was transcriptionally up-regulated, and further proved its involvement in validamycin production by gene replacement. Moreover, efficient synthesis and utilization of intracellular glutamate were noticed in strain 5008 at 37 degreesC, revealing glutamate as the nitrogen source for validamycin biosynthesis. Furthermore, a SARP-family regulatory gene with enhanced transcription at 37 degreesC was identified and confirmed to be positively involved in the thermo-regulation of validamycin production by gene inactivation and transcriptional analysis. CONCLUSIONS: Strain 5008 seemed to have evolved with specific genomic components to facilitate the thermo-regulated validamycin biosynthesis. The data obtained here will facilitate future studies for validamycin yield improvement and industrial bioprocess optimization.
ESTHER : Wu_2012_BMC.Genomics_13_337
PubMedSearch : Wu_2012_BMC.Genomics_13_337
PubMedID: 22827618
Gene_locus related to this paper: strhj-h2k4a5

Title : Eight genetic loci associated with variation in lipoprotein-associated phospholipase A2 mass and activity and coronary heart disease: meta-analysis of genome-wide association studies from five community-based studies - Grallert_2012_Eur.Heart.J_33_238
Author(s) : Grallert H , Dupuis J , Bis JC , Dehghan A , Barbalic M , Baumert J , Lu C , Smith NL , Uitterlinden AG , Roberts R , Khuseyinova N , Schnabel RB , Rice KM , Rivadeneira F , Hoogeveen RC , Fontes JD , Meisinger C , Keaney JF, Jr. , Lemaitre R , Aulchenko YS , Vasan RS , Ellis S , Hazen SL , van Duijn CM , Nelson JJ , Marz W , Schunkert H , McPherson RM , Stirnadel-Farrant HA , Psaty BM , Gieger C , Siscovick D , Hofman A , Illig T , Cushman M , Yamamoto JF , Rotter JI , Larson MG , Stewart AF , Boerwinkle E , Witteman JC , Tracy RP , Koenig W , Benjamin EJ , Ballantyne CM
Ref : Eur Heart J , 33 :238 , 2012
Abstract : AIMS: Lipoprotein-associated phospholipase A2 (Lp-PLA2) generates proinflammatory and proatherogenic compounds in the arterial vascular wall and is a potential therapeutic target in coronary heart disease (CHD). We searched for genetic loci related to Lp-PLA2 mass or activity by a genome-wide association study as part of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. METHODS AND RESULTS: In meta-analyses of findings from five population-based studies, comprising 13 664 subjects, variants at two loci (PLA2G7, CETP) were associated with Lp-PLA2 mass. The strongest signal was at rs1805017 in PLA2G7 [P = 2.4 x 10(-23), log Lp-PLA2 difference per allele (beta): 0.043]. Variants at six loci were associated with Lp-PLA2 activity (PLA2G7, APOC1, CELSR2, LDL, ZNF259, SCARB1), among which the strongest signals were at rs4420638, near the APOE-APOC1-APOC4-APOC2 cluster [P = 4.9 x 10(-30); log Lp-PLA2 difference per allele (beta): -0.054]. There were no significant gene-environment interactions between these eight polymorphisms associated with Lp-PLA2 mass or activity and age, sex, body mass index, or smoking status. Four of the polymorphisms (in APOC1, CELSR2, SCARB1, ZNF259), but not PLA2G7, were significantly associated with CHD in a second study. CONCLUSION: Levels of Lp-PLA2 mass and activity were associated with PLA2G7, the gene coding for this protein. Lipoprotein-associated phospholipase A2 activity was also strongly associated with genetic variants related to low-density lipoprotein cholesterol levels.
ESTHER : Grallert_2012_Eur.Heart.J_33_238
PubMedSearch : Grallert_2012_Eur.Heart.J_33_238
PubMedID: 22003152
Gene_locus related to this paper: human-PLA2G7

Title : O-Hydroxyl- or o-amino benzylamine-tacrine hybrids: multifunctional biometals chelators, antioxidants, and inhibitors of cholinesterase activity and amyloid-beta aggregation - Mao_2012_Bioorg.Med.Chem_20_5884
Author(s) : Mao F , Huang L , Luo Z , Liu A , Lu C , Xie Z , Li X
Ref : Bioorganic & Medicinal Chemistry , 20 :5884 , 2012
Abstract : In an effort to identify novel multifunctional drug candidates for the treatment of Alzheimer's disease (AD), a series of hybrid molecules were synthesised by reacting N-(aminoalkyl)tacrine with salicylic aldehyde or derivatives of 2-aminobenzaldehyde. These compounds were then evaluated as multifunctional anti-Alzheimer's disease agents. All of the hybrids are potential biometal chelators, and in addition, most of them were better antioxidants and inhibitors of cholinesterases and amyloid-beta (Abeta) aggregation than the lead compound tacrine. Compound 7c has the potential to be a candidate for AD therapy: it is a much better inhibitor of acetylcholinesterase (AChE) than tacrine (IC(50): 0.55 nM vs 109 nM), has good biometal chelation ability, is able to inhibit Abeta aggregation and has moderate antioxidant activity (1.22 Trolox equivalents).
ESTHER : Mao_2012_Bioorg.Med.Chem_20_5884
PubMedSearch : Mao_2012_Bioorg.Med.Chem_20_5884
PubMedID: 22944335

Title : Dipeptidyl peptidases as survival factors in Ewing sarcoma family of tumors: implications for tumor biology and therapy - Lu_2011_J.Biol.Chem_286_27494
Author(s) : Lu C , Tilan JU , Everhart L , Czarnecka M , Soldin SJ , Mendu DR , Jeha D , Hanafy J , Lee CK , Sun J , Izycka-Swieszewska E , Toretsky JA , Kitlinska J
Ref : Journal of Biological Chemistry , 286 :27494 , 2011
Abstract : Ewing sarcoma family of tumors (ESFT) is a group of aggressive pediatric malignancies driven by the EWS-FLI1 fusion protein, an aberrant transcription factor up-regulating specific target genes, such as neuropeptide Y (NPY) and its Y1 and Y5 receptors (Y5Rs). Previously, we have shown that both exogenous NPY and endogenous NPY stimulate ESFT cell death via its Y1 and Y5Rs. Here, we demonstrate that this effect is prevented by dipeptidyl peptidases (DPPs), which cleave NPY to its shorter form, NPY(3-36), not active at Y1Rs. We have shown that NPY-induced cell death can be abolished by overexpression of DPPs and enhanced by their down-regulation. Both NPY treatment and DPP blockade activated the same cell death pathway mediated by poly(ADP-ribose) polymerase (PARP-1) and apoptosis-inducing factor (AIF). Moreover, the decrease in cell survival induced by DPP inhibition was blocked by Y1 and Y5R antagonists, confirming its dependence on endogenous NPY. Interestingly, similar levels of NPY-driven cell death were achieved by blocking membrane DPPIV and cytosolic DPP8 and DPP9. Thus, this is the first evidence of these intracellular DPPs cleaving releasable peptides, such as NPY, in live cells. In contrast, another membrane DPP, fibroblast activation protein (FAP), did not affect NPY actions. In conclusion, DPPs act as survival factors for ESFT cells and protect them from cell death induced by endogenous NPY. This is the first demonstration that intracellular DPPs are involved in regulation of ESFT growth and may become potential therapeutic targets for these tumors.
ESTHER : Lu_2011_J.Biol.Chem_286_27494
PubMedSearch : Lu_2011_J.Biol.Chem_286_27494
PubMedID: 21680731

Title : Possible ligand release pathway of dipeptidyl peptidase IV investigated by molecular dynamics simulations - Li_2011_Proteins_79_1800
Author(s) : Li C , Shen J , Li W , Lu C , Liu G , Tang Y
Ref : Proteins , 79 :1800 , 2011
Abstract : Dipeptidyl peptidase IV (DPP4) is an important target for the treatment of Type II diabetes mellitus. The crystal structure of DPP4 demonstrates that there are two possible pathways to the active site, a side opening and a beta propeller opening. However, it still lacks quantitative evidence to illustrate which pathway is more favorable for inhibitor to enter into or release from the active site. In this study, conventional and steered molecular dynamics simulations were performed to explore the details of inhibitor Q448 release from the active site of DPP4 via the two potential pathways. The comparisons of force and work together with potentials of mean force results suggested that the side opening might be more favorable for the inhibitor to pass through. Moreover, Glu205-Glu206 and Phe357 were recognized as two "key residues" in the active site for inhibitor binding. Accordingly, suggestions for further inhibitor design were provided.
ESTHER : Li_2011_Proteins_79_1800
PubMedSearch : Li_2011_Proteins_79_1800
PubMedID: 21465558

Title : Synthesis, biological evaluation and molecular modeling of novel triazole-containing berberine derivatives as acetylcholinesterase and beta-amyloid aggregation inhibitors - Shi_2011_Bioorg.Med.Chem_19_2298
Author(s) : Shi A , Huang L , Lu C , He F , Li X
Ref : Bioorganic & Medicinal Chemistry , 19 :2298 , 2011
Abstract : A series of novel triazole-containing berberine derivatives were synthesized via the azide-alkyne cycloaddition reaction. Their biological activity as inhibitors of both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) were evaluated. Among them, compound 16d, which featured a diisopropylamino substitution at the 4-position of triazole ring, was found to be a potent inhibitor of AChE, with IC(50) value of 0.044 uM. Compound 18d, which beares a butyl at the 4-position of the triazole ring, showed the highest potency of beta-amyloid aggregation inhibition (77.9% at 20 uM). Molecular modeling studies indicated that the triazole moiety of berberine derivatives displayed a face-to-face - stacking interaction in a 'sandwich' form with the Trp84 (4.09 ) and Phe330 (4.33 ) in catalytic sites of AChE.
ESTHER : Shi_2011_Bioorg.Med.Chem_19_2298
PubMedSearch : Shi_2011_Bioorg.Med.Chem_19_2298
PubMedID: 21397508

Title : Ablation of ligament of Marshall attenuates atrial vulnerability to fibrillation induced by inferior left atrial fat pad stimulation in dogs - Liu_2010_J.Cardiovasc.Electrophysiol_21_1024
Author(s) : Liu X , Yan Q , Li H , Tian Y , Su J , Tang R , Lu C , Dong J , Ma C
Ref : J Cardiovasc Electrophysiol , 21 :1024 , 2010
Abstract : BACKGROUND: The role of ligament of Marshall (LOM) in the mechanism of "vagal" atrial fibrillation (AF) is still unknown. OBJECTIVE: To investigate the impact of LOM ablation on atrial vulnerability to AF induced by inferior left atrial fat pad (ILAFP) stimulation in dogs. METHODS: AF inducibility and atrial effective refractory period (ERP) were elevated before and after LOM ablation in 8 of 14 dogs (the ablation group). Same protocol but without LOM ablation was conducted in the remaining 6 dogs (the control group). The activation patterns of LOM and left pulmonary veins (LPVs) during sustained AF were analyzed. The distribution of epicardial cholinergic nerve fibers between LOM and ILAFP was investigated in the control group. RESULTS: Ablation of LOM significantly attenuated AF inducibility (87.5% vs 33.3%, P < 0.001) and prolonged ERPs of the structures in contiguity with LOM (P < 0.05) in the ablation group. In contrast, there was no significant change in ERPs and AF inducibility in the control group. During sustained AF, fractionated atrial electrograms were more common in the LOM area than the LPVs (84% vs 18% of the analyzed episodes, P < 0.001). In 46.7% of the episodes with identifiable LOM spikes, atrial potentials, and LOM spikes were related in 2:1 or 3:2 pattern during the intermittent organized activity. Acetylcholinesterase staining revealed a close cholinergic nerved relationship between LOM and ILAFP. CONCLUSIONS: LOM plays a critical role in maintaining AF induced by stimulation of ILAFP. Ablation of LOM can markedly attenuate AF inducibility in this model.
ESTHER : Liu_2010_J.Cardiovasc.Electrophysiol_21_1024
PubMedSearch : Liu_2010_J.Cardiovasc.Electrophysiol_21_1024
PubMedID: 20367662

Title : Construction of a full-length cDNA Library from Chinese oak silkworm pupa and identification of a KK-42-binding protein gene in relation to pupa-diapause termination - Li_2009_Int.J.Biol.Sci_5_451
Author(s) : Li YP , Xia RX , Wang H , Li XS , Liu YQ , Wei ZJ , Lu C , Xiang ZH
Ref : Int J Biol Sci , 5 :451 , 2009
Abstract : In this study we successfully constructed a full-length cDNA library from Chinese oak silkworm, Antheraea pernyi, the most well-known wild silkworm used for silk production and insect food. Total RNA was extracted from a single fresh female pupa at the diapause stage. The titer of the library was 5 x 10(5) cfu/ml and the proportion of recombinant clones was approximately 95%. Expressed sequence tag (EST) analysis was used to characterize the library. A total of 175 clustered ESTs consisting of 24 contigs and 151 singlets were generated from 250 effective sequences. Of the 175 unigenes, 97 (55.4%) were known genes but only five from A. pernyi, 37 (21.2%) were known ESTs without function annotation, and 41 (23.4%) were novel ESTs. By EST sequencing, a gene coding KK-42-binding protein in A. pernyi (named as ApKK42-BP; GenBank accession no. FJ744151) was identified and characterized. Protein sequence analysis showed that ApKK42-BP was not a membrane protein but an extracellular protein with a signal peptide at position 1-18, and contained two putative conserved domains, abhydro_lipase and abhydrolase_1, suggesting it may be a member of lipase superfamily. Expression analysis based on number of ESTs showed that ApKK42-BP was an abundant gene in the period of diapause stage, suggesting it may also be involved in pupa-diapause termination.
ESTHER : Li_2009_Int.J.Biol.Sci_5_451
PubMedSearch : Li_2009_Int.J.Biol.Sci_5_451
PubMedID: 19564928

Title : Annotation and expression of carboxylesterases in the silkworm, Bombyx mori - Yu_2009_BMC.Genomics_10_553
Author(s) : Yu QY , Lu C , Li WL , Xiang ZH , Zhang Z
Ref : BMC Genomics , 10 :553 , 2009
Abstract : BACKGROUND: Carboxylesterase is a multifunctional superfamily and ubiquitous in all living organisms, including animals, plants, insects, and microbes. It plays important roles in xenobiotic detoxification, and pheromone degradation, neurogenesis and regulating development. Previous studies mainly used Dipteran Drosophila and mosquitoes as model organisms to investigate the roles of the insect COEs in insecticide resistance. However, genome-wide characterization of COEs in phytophagous insects and comparative analysis remain to be performed. RESULTS: Based on the newly assembled genome sequence, 76 putative COEs were identified in Bombyx mori. Relative to other Dipteran and Hymenopteran insects, alpha-esterases were significantly expanded in the silkworm. Genomics analysis suggested that BmCOEs showed chromosome preferable distribution and 55% of which were tandem arranged. Sixty-one BmCOEs were transcribed based on cDNA/ESTs and microarray data. Generally, most of the COEs showed tissue specific expressions and expression level between male and female did not display obvious differences. Three main patterns could be classified, i.e. midgut-, head and integument-, and silk gland-specific expressions. Midgut is the first barrier of xenobiotics peroral toxicity, in which COEs may be involved in eliminating secondary metabolites of mulberry leaves and contaminants of insecticides in diet. For head and integument-class, most of the members were homologous to odorant-degrading enzyme (ODE) and antennal esterase. RT-PCR verified that the ODE-like esterases were also highly expressed in larvae antenna and maxilla, and thus they may play important roles in degradation of plant volatiles or other xenobiotics. CONCLUSION: B. mori has the largest number of insect COE genes characterized to date. Comparative genomic analysis suggested that the gene expansion mainly occurred in silkworm alpha-esterases. Expression evidence indicated that the expanded genes were specifically expressed in midgut, integument and head, implying that these genes may have important roles in detoxifying secondary metabolites of mulberry leaves, contaminants in diet, and odorants. Our results provide some new insights into functions and evolutionary characteristics of COEs in phytophagous insects.
ESTHER : Yu_2009_BMC.Genomics_10_553
PubMedSearch : Yu_2009_BMC.Genomics_10_553
PubMedID: 19930670

Title : The genome of a lepidopteran model insect, the silkworm Bombyx mori - Xia_2008_Insect.Biochem.Mol.Biol_38_1036
Author(s) : Xia Q , Wang J , Zhou Z , Li R , Fan W , Cheng D , Cheng T , Qin J , Duana J , Xu H , Li Q , Li N , Wang M , Dai F , Liu C , Lin Y , Zhao P , Zhang H , Liu S , Zha X , Li C , Zhao A , Pan M , Pan G , Shen Y , Gao Z , Wang Z , Wang G , Wu Z , Hou Y , Chai C , Yu Q , He N , Zhang Z , Li S , Yang H , Lu C , Xiang Z , Mita K , Kasahara M , Nakatani Y , Yamamoto K , Abe H , Ahsan B , Daimoni T , Doi K , Fujii T , Fujiwara H , Fujiyama A , Futahashi R , Hashimotol S , Ishibashi J , Iwami M , Kadono-Okuda K , Kanamori H , Kataoka H , Katsuma S , Kawaoka S , Kawasaki H , Kohara Y , Kozaki T , Kuroshu RM , Kuwazaki S , Matsushima K , Minami H , Nagayasu Y , Nakagawa T , Narukawa J , Nohata J , Ohishi K , Ono Y , Osanai-Futahashi M , Ozaki K , Qu W , Roller L , Sasaki S , Sasaki T , Seino A , Shimomura M , Shin-I T , Shinoda T , Shiotsuki T , Suetsugu Y , Sugano S , Suwa M , Suzuki Y , Takiya S , Tamura T , Tanaka H , Tanaka Y , Touhara K , Yamada T , Yamakawa M , Yamanaka N , Yoshikawa H , Zhong YS , Shimada T , Morishita S
Ref : Insect Biochemistry & Molecular Biology , 38 :1036 , 2008
Abstract : Bombyx mori, the domesticated silkworm, is a major insect model for research, and the first lepidopteran for which draft genome sequences became available in 2004. Two independent data sets from whole-genome shotgun sequencing were merged and assembled together with newly obtained fosmid- and BAC-end sequences. The remarkably improved new assembly is presented here. The 8.5-fold sequence coverage of an estimated 432 Mb genome was assembled into scaffolds with an N50 size of approximately 3.7 Mb; the largest scaffold was 14.5 million base pairs. With help of a high-density SNP linkage map, we anchored 87% of the scaffold sequences to all 28 chromosomes. A particular feature was the high repetitive sequence content estimated to be 43.6% and that consisted mainly of transposable elements. We predicted 14,623 gene models based on a GLEAN-based algorithm, a more accurate prediction than the previous gene models for this species. Over three thousand silkworm genes have no homologs in other insect or vertebrate genomes. Some insights into gene evolution and into characteristic biological processes are presented here and in other papers in this issue. The massive silk production correlates with the existence of specific tRNA clusters, and of several sericin genes assembled in a cluster. The silkworm's adaptation to feeding on mulberry leaves, which contain toxic alkaloids, is likely linked to the presence of new-type sucrase genes, apparently acquired from bacteria. The silkworm genome also revealed the cascade of genes involved in the juvenile hormone biosynthesis pathway, and a large number of cuticular protein genes.
ESTHER : Xia_2008_Insect.Biochem.Mol.Biol_38_1036
PubMedSearch : Xia_2008_Insect.Biochem.Mol.Biol_38_1036
PubMedID: 19121390
Gene_locus related to this paper: bommo-a0mnw6 , bommo-a1yw85 , bommo-a9ls22 , bommo-ACHE1 , bommo-ACHE2 , bommo-b0fgv8 , bommo-b1q137 , bommo-b1q139 , bommo-b1q140 , bommo-b1q141 , bommo-b2zdz0 , bommo-b3gef6 , bommo-b3gef7 , bommo-b3gs55 , bommo-b3gs56 , bommo-d2ktu3 , bommo-d2ktu5 , bommo-d9ile0 , bommo-e1cga5 , bommo-e1cga6 , bommo-g8fpz6 , bommo-h9iu43 , bommo-h9iu46 , bommo-h9iu47.1 , bommo-h9iu47.2 , bommo-h9iue5 , bommo-h9ivg2 , bommo-h9iwj7 , bommo-h9iwj8 , bommo-h9ix58 , bommo-h9ixi1.1 , bommo-h9ixi1.2 , bommo-h9iy47 , bommo-h9izw1 , bommo-h9j0s4 , bommo-h9j1y0 , bommo-h9j3r0 , bommo-h9j3w6 , bommo-h9j3w7 , bommo-h9j5t0 , bommo-h9j8g3 , bommo-h9j9k9 , bommo-h9j066 , bommo-h9j067 , bommo-h9j593 , bommo-h9j594 , bommo-h9j990 , bommo-h9jde8 , bommo-h9jde9 , bommo-h9jdf0 , bommo-h9jds4 , bommo-h9jle7 , bommo-h9jn83 , bommo-h9jn85 , bommo-h9jrg2 , bommo-h9jyh9 , bommo-JHE , bommo-m1rmh6 , bommo-q1hq05 , bommo-q4tte1 , bommo-h9j592 , bommo-h9j604 , bommo-h9jpm8 , bommo-h9iss4 , bommo-h9j2c7

Title : The Rice Annotation Project Database (RAP-DB): 2008 update - Tanaka_2008_Nucleic.Acids.Res_36_D1028
Author(s) : Tanaka T , Antonio BA , Kikuchi S , Matsumoto T , Nagamura Y , Numa H , Sakai H , Wu J , Itoh T , Sasaki T , Aono R , Fujii Y , Habara T , Harada E , Kanno M , Kawahara Y , Kawashima H , Kubooka H , Matsuya A , Nakaoka H , Saichi N , Sanbonmatsu R , Sato Y , Shinso Y , Suzuki M , Takeda J , Tanino M , Todokoro F , Yamaguchi K , Yamamoto N , Yamasaki C , Imanishi T , Okido T , Tada M , Ikeo K , Tateno Y , Gojobori T , Lin YC , Wei FJ , Hsing YI , Zhao Q , Han B , Kramer MR , McCombie RW , Lonsdale D , O'Donovan CC , Whitfield EJ , Apweiler R , Koyanagi KO , Khurana JP , Raghuvanshi S , Singh NK , Tyagi AK , Haberer G , Fujisawa M , Hosokawa S , Ito Y , Ikawa H , Shibata M , Yamamoto M , Bruskiewich RM , Hoen DR , Bureau TE , Namiki N , Ohyanagi H , Sakai Y , Nobushima S , Sakata K , Barrero RA , Souvorov A , Smith-White B , Tatusova T , An S , An G , S OO , Fuks G , Messing J , Christie KR , Lieberherr D , Kim H , Zuccolo A , Wing RA , Nobuta K , Green PJ , Lu C , Meyers BC , Chaparro C , Piegu B , Panaud O , Echeverria M
Ref : Nucleic Acids Research , 36 :D1028 , 2008
Abstract : The Rice Annotation Project Database (RAP-DB) was created to provide the genome sequence assembly of the International Rice Genome Sequencing Project (IRGSP), manually curated annotation of the sequence, and other genomics information that could be useful for comprehensive understanding of the rice biology. Since the last publication of the RAP-DB, the IRGSP genome has been revised and reassembled. In addition, a large number of rice-expressed sequence tags have been released, and functional genomics resources have been produced worldwide. Thus, we have thoroughly updated our genome annotation by manual curation of all the functional descriptions of rice genes. The latest version of the RAP-DB contains a variety of annotation data as follows: clone positions, structures and functions of 31 439 genes validated by cDNAs, RNA genes detected by massively parallel signature sequencing (MPSS) technology and sequence similarity, flanking sequences of mutant lines, transposable elements, etc. Other annotation data such as Gnomon can be displayed along with those of RAP for comparison. We have also developed a new keyword search system to allow the user to access useful information. The RAP-DB is available at: and
ESTHER : Tanaka_2008_Nucleic.Acids.Res_36_D1028
PubMedSearch : Tanaka_2008_Nucleic.Acids.Res_36_D1028
PubMedID: 18089549
Gene_locus related to this paper: orysa-Q9FW17 , orysa-Q0JK71 , orysa-B9EWJ8 , orysa-Q5N7L1 , orysa-pir7a , orysa-q2qyj1 , orysj-q6yse8 , orysa-q6yzk1 , orysa-Q8S0U8 , orysa-q33aq0 , orysa-Q0J0A4 , orysi-a2z179 , orysi-a2zef2 , orysi-b8a7e6 , orysi-b8a7e7 , orysi-b8bfe5 , orysi-b8bhp9 , orysj-b9fi05 , orysj-b9fkb0 , orysj-cgep , orysj-q0djj0 , orysj-q0dud7 , orysj-q0jaf0 , orysj-q0jga1 , orysj-q5jl22 , orysj-q5jlw7 , orysj-q6h7q9 , orysj-q6yvk6 , orysj-q7f8x1 , orysj-q7xcx3 , orysj-q9fwm6 , orysj-q10j20 , orysj-q10ss2 , orysj-q69uw6 , orysj-q94d71 , orysj-q0iq98 , orysj-b9gbs4 , orysj-b9gbs1 , orysj-pla4 , orysj-pla1

Title : The presence of dialkylphosphates in fresh fruit juices: implication for organophosphorus pesticide exposure and risk assessments - Lu_2005_J.Toxicol.Environ.Health.A_68_209
Author(s) : Lu C , Bravo R , Caltabiano LM , Irish RM , Weerasekera G , Barr DB
Ref : J Toxicol Environ Health A , 68 :209 , 2005
Abstract : This study was designed to determine whether dialkylphosphates (DAPs) are present in fresh fruit juices, as a result of organophosphorus (OP) pesticides degradation. Fresh conventional and organic fruit (apple and orange) juices were purchased from local grocery stores. DAPs were found in both conventional and organic juices, and the original levels were higher, for both apple and orange juices, in conventional than in organic juices. Additional DAPs were found in OP pesticide fortified juices after 72 h of storage at 4 degrees C, suggesting a degradation of OP pesticides in juices. Overall, 12% and 36.2% of fortified azinphosmethyl, a dimethyl OP pesticide, and the combination of fortified diazinon and chlorpyrifos, both diethyl OP pesticides, were degraded to dimethyl and diethyl DAPs, respectively. Although the exact mechanism of the degradation is unknown, hydrolysis is likely the cause of OP pesticide degradation in juice. The presence of DAPs in fresh fruit juices clouds the validity of using urinary DAP measurements for estimating OP pesticide exposures in humans, particularly in children. The overestimated OP pesticide exposures based on urinary DAPs reported in other studies is likely due to the coexistence of preformed DAPs and DAPs resulting from OP pesticide exposures. Thus, before urinary DAP concentrations can be reliably used in exposure and risk assessment, the proportion of the concentration attributable to environmental DAP exposure, particularly through the diet, must be ascertained. In conclusion, urinary DAPs have many limitations when being used as biomarkers for OP pesticides in exposure and risk assessment, and caution should be exercised when interpreting DAPs results.
ESTHER : Lu_2005_J.Toxicol.Environ.Health.A_68_209
PubMedSearch : Lu_2005_J.Toxicol.Environ.Health.A_68_209
PubMedID: 15762180

Title : Genome sequence of Theileria parva, a bovine pathogen that transforms lymphocytes - Gardner_2005_Science_309_134
Author(s) : Gardner MJ , Bishop R , Shah T , de Villiers EP , Carlton JM , Hall N , Ren Q , Paulsen IT , Pain A , Berriman M , Wilson RJ , Sato S , Ralph SA , Mann DJ , Xiong Z , Shallom SJ , Weidman J , Jiang L , Lynn J , Weaver B , Shoaibi A , Domingo AR , Wasawo D , Crabtree J , Wortman JR , Haas B , Angiuoli SV , Creasy TH , Lu C , Suh B , Silva JC , Utterback TR , Feldblyum TV , Pertea M , Allen J , Nierman WC , Taracha EL , Salzberg SL , White OR , Fitzhugh HA , Morzaria S , Venter JC , Fraser CM , Nene V
Ref : Science , 309 :134 , 2005
Abstract : We report the genome sequence of Theileria parva, an apicomplexan pathogen causing economic losses to smallholder farmers in Africa. The parasite chromosomes exhibit limited conservation of gene synteny with Plasmodium falciparum, and its plastid-like genome represents the first example where all apicoplast genes are encoded on one DNA strand. We tentatively identify proteins that facilitate parasite segregation during host cell cytokinesis and contribute to persistent infection of transformed host cells. Several biosynthetic pathways are incomplete or absent, suggesting substantial metabolic dependence on the host cell. One protein family that may generate parasite antigenic diversity is not telomere-associated.
ESTHER : Gardner_2005_Science_309_134
PubMedSearch : Gardner_2005_Science_309_134
PubMedID: 15994558
Gene_locus related to this paper: thepa-q4mzr2 , thepa-q4n0b4 , thepa-q4n2i4 , thepa-q4n4i8 , thepa-q4n5d6 , thepa-q4n5m4 , thepa-q4n006 , thepa-q4n9g7 , thepa-q4n315 , thepa-q4n349 , thepa-q4n803

Title : Genomic sequence of the pathogenic and allergenic filamentous fungus Aspergillus fumigatus - Nierman_2005_Nature_438_1151
Author(s) : Nierman WC , Pain A , Anderson MJ , Wortman JR , Kim HS , Arroyo J , Berriman M , Abe K , Archer DB , Bermejo C , Bennett J , Bowyer P , Chen D , Collins M , Coulsen R , Davies R , Dyer PS , Farman M , Fedorova N , Feldblyum TV , Fischer R , Fosker N , Fraser A , Garcia JL , Garcia MJ , Goble A , Goldman GH , Gomi K , Griffith-Jones S , Gwilliam R , Haas B , Haas H , Harris D , Horiuchi H , Huang J , Humphray S , Jimenez J , Keller N , Khouri H , Kitamoto K , Kobayashi T , Konzack S , Kulkarni R , Kumagai T , Lafon A , Latge JP , Li W , Lord A , Lu C , Majoros WH , May GS , Miller BL , Mohamoud Y , Molina M , Monod M , Mouyna I , Mulligan S , Murphy L , O'Neil S , Paulsen I , Penalva MA , Pertea M , Price C , Pritchard BL , Quail MA , Rabbinowitsch E , Rawlins N , Rajandream MA , Reichard U , Renauld H , Robson GD , Rodriguez de Cordoba S , Rodriguez-Pena JM , Ronning CM , Rutter S , Salzberg SL , Sanchez M , Sanchez-Ferrero JC , Saunders D , Seeger K , Squares R , Squares S , Takeuchi M , Tekaia F , Turner G , Vazquez de Aldana CR , Weidman J , White O , Woodward J , Yu JH , Fraser C , Galagan JE , Asai K , Machida M , Hall N , Barrell B , Denning DW
Ref : Nature , 438 :1151 , 2005
Abstract : Aspergillus fumigatus is exceptional among microorganisms in being both a primary and opportunistic pathogen as well as a major allergen. Its conidia production is prolific, and so human respiratory tract exposure is almost constant. A. fumigatus is isolated from human habitats and vegetable compost heaps. In immunocompromised individuals, the incidence of invasive infection can be as high as 50% and the mortality rate is often about 50% (ref. 2). The interaction of A. fumigatus and other airborne fungi with the immune system is increasingly linked to severe asthma and sinusitis. Although the burden of invasive disease caused by A. fumigatus is substantial, the basic biology of the organism is mostly obscure. Here we show the complete 29.4-megabase genome sequence of the clinical isolate Af293, which consists of eight chromosomes containing 9,926 predicted genes. Microarray analysis revealed temperature-dependent expression of distinct sets of genes, as well as 700 A. fumigatus genes not present or significantly diverged in the closely related sexual species Neosartorya fischeri, many of which may have roles in the pathogenicity phenotype. The Af293 genome sequence provides an unparalleled resource for the future understanding of this remarkable fungus.
ESTHER : Nierman_2005_Nature_438_1151
PubMedSearch : Nierman_2005_Nature_438_1151
PubMedID: 16372009
Gene_locus related to this paper: aspfc-b0xp50 , aspfc-b0xu40 , aspfc-b0xzj6 , aspfc-dpp5 , aspfu-apth1 , aspfu-axe1 , aspfu-CBPYA , aspfu-faec , aspfu-kex1 , aspfu-ppme1 , aspfu-q4wa39 , aspfu-q4wa78 , aspfu-q4wf56 , aspfu-q4wg73 , aspfu-q4wk44 , aspfu-q4wkh6 , aspfu-q4wnx3 , aspfu-q4wpb9 , aspfu-q4wqv2 , aspfu-q4wub2 , aspfu-q4wxr1 , aspfu-q4x0n6 , aspfu-q4x1n0 , aspfu-q5vjg7 , neofi-a1cwa6 , neofi-a1dfr9 , aspfm-a0a084bf80 , aspfu-fmac

Title : Children's exposure to chlorpyrifos and parathion in an agricultural community in central Washington State - Fenske_2002_Environ.Health.Perspect_110_549
Author(s) : Fenske RA , Lu C , Barr D , Needham L
Ref : Environmental Health Perspectives , 110 :549 , 2002
Abstract : We measured two diethyl organophosphorus (OP) pesticides--chlorpyrifos and parathion--in residences, and their metabolic by-products, in the urine of children 6 years old or younger in a central Washington State agricultural community. Exposures to two dimethyl OP pesticides (azinphos-methyl and phosmet) in this same population have been reported previously. We categorized children by parental occupation and by household proximity to pesticide-treated farmland. Median chlorpyrifos house dust concentrations were highest for the 49 applicator homes (0.4 microg/g), followed by the 12 farm-worker homes (0.3 microg/g) and the 14 nonagricultural reference homes (0.1 microg/g), and were statistically different (p < 0.001); we observed a similar pattern for parathion in house dust. Chlorpyrifos was measurable in the house dust of all homes, whereas we found parathion in only 41% of the homes. Twenty-four percent of the urine samples from study children had measurable 3,5,6-trichloro-2-pyridinol (TCPy) concentrations [limits of quantitation (LOQ) = 8 microg/L], and 7% had measurable 4-nitrophenol concentrations (LOQ = 9 microg/L). Child urinary metabolite concentrations did not differ across parental occupational classifications. Homes in close proximity (200 ft/60 m) to pesticide-treated farmland had higher chlorpyrifos (p = 0.01) and parathion (p = 0.014) house dust concentrations than did homes farther away, but this effect was not reflected in the urinary metabolite data. Use of OP pesticides in the garden was associated with an increase in TCPy concentrations in children's urine. Parathion concentrations in house dust decreased 10-fold from 1992 to 1995, consistent with the discontinued use of this product in the region in the early 1990s.
ESTHER : Fenske_2002_Environ.Health.Perspect_110_549
PubMedSearch : Fenske_2002_Environ.Health.Perspect_110_549
PubMedID: 12003762

Title : Biological monitoring survey of organophosphorus pesticide exposure among pre-school children in the Seattle metropolitan area - Lu_2001_Environ.Health.Perspect_109_299
Author(s) : Lu C , Knutson DE , Fisker-Andersen J , Fenske RA
Ref : Environmental Health Perspectives , 109 :299 , 2001
Abstract : In this study we assessed organophosphorus (OP) pesticide exposure among children living in two Seattle metropolitan area communities by measuring urinary metabolites, and identified possible exposure risk factors through a parental interview. We recruited children in clinic and outpatient waiting rooms. We obtained spot urine samples in the spring and fall of 1998 from 110 children ages 2-5 years, from 96 households. We analyzed urine samples for six dialkylphosphate (DAP) compounds, the common metabolites of the OP pesticides. Through parental interviews we gathered demographic and residential pesticide use data. At least one of the DAP metabolites was measured in 99% of the children, and the two predominant metabolites (DMTP and DETP) were measured in 70-75% of the children. We found no significant differences in DAP concentrations related to season, community, sex, age, family income, or housing type. Median concentrations of dimethyl and diethyl DAPs were 0.11 and 0.04 micromol/L, respectively (all children). Concentrations were significantly higher in children whose parents reported pesticide use in the garden (0.19 vs. 0.09 micromol/L for dimethyl metabolites, p = 0.05; 0.04 vs. 0.03 micromol/L for diethyl metabolites, p = 0.02), but were not different based on reported pet treatment or indoor residential use. Nearly all children in this study had measurable levels of OP pesticide metabolites. Some of this exposure was likely due to diet. Garden pesticide use was associated with elevated metabolite levels. It is unlikely that these exposure levels would cause acute intoxication, but the long-term health effects of such exposures are unknown. We recommend that OP pesticide use be avoided in areas where children are likely to play.
ESTHER : Lu_2001_Environ.Health.Perspect_109_299
PubMedSearch : Lu_2001_Environ.Health.Perspect_109_299
PubMedID: 11333193

Title : Open-loop and closed-loop optokinetic nystagmus (OKN) in myasthenia gravis and nonmyasthenic subjects - Yang_2000_Exp.Neurol_166_166
Author(s) : Yang Q , Wei M , Sun F , Tian J , Chen X , Lu C
Ref : Experimental Neurology , 166 :166 , 2000
Abstract : Optokinetic nystagmus (OKN) eye movements of myasthenia gravis (MG) and nonmyasthenic ocular palsies, and normal subjects were examined under closed-loop and open-loop conditions. The open-loop OKN condition was achieved by adding the signal of eye-movement velocity of OKN to the computer-generated signal controlling the stimulus grating moving. The OKN was recorded by means of electromagnetic search scleral coil technique. In MG patients, the open-loop gains of OKN increased significantly after the intramuscular injection of an acetylcholinesterase inhibitor, neostigmine, while the closed-loop OKN gains were not significantly changed. Both the closed-loop and open-loop OKN gains of normal subjects and nonmyasthenic patients were not increased for the administration of neostigmine. The experimental results indicated that the open-loop OKN gain could be sensitive to reflect the changes of the function of neuromuscular junction in MG patients.
ESTHER : Yang_2000_Exp.Neurol_166_166
PubMedSearch : Yang_2000_Exp.Neurol_166_166
PubMedID: 11031092

Title : Improved cleanup and determination of dialkyl phosphates in the urine of children exposed to organophosphorus insecticides - Moate_1999_J.Anal.Toxicol_23_230
Author(s) : Moate TF , Lu C , Fenske RA , Hahne RM , Kalman DA
Ref : J Anal Toxicol , 23 :230 , 1999
Abstract : Analysis of dialkylphosphate urinary metabolites of organophosphorus insecticides has been used to estimate dose in nonoccupationally exposed populations, including children. Analytical methods must continue to be improved in order to accurately and reproducibly measure less than 10 ng/mL of these metabolites. Dialkyl phosphates are commonly determined as their pentafluorobenzyl bromide derivatives via gas chromatography (GC) with flame photometric detection. Presented here is an improved method for precleanup of urine using solid-phase extraction, followed by derivatization and GC analysis. The method includes the quantitative determination of the following dialkyl phosphate metabolites: dimethylphosphate, diethylphosphate, dimethylthiophosphate, diethylthiophosphate, and dimethyldithiophosphate. Additional cleanup of urine samples allows for increasing sample size and improving sensitivity while minimizing interferences and variability associated with derivatization. Sample aliquot size was 5 mL with limits of quantitation of 10 ng/mL of urine for dimethylphosphate and diethylphosphate and 2 ng/mL of urine for dimethylthiophosphate, diethylthiophosphate, and dimethyldithiophosphate. This level of method sensitivity allows for quantitative determination of trace dialkyl phosphates in approximately 75% of individuals in nonoccupationally exposed populations. This streamlined method increases sample throughput, provides a clean extract for analysis, and requires no custom glassware.
ESTHER : Moate_1999_J.Anal.Toxicol_23_230
PubMedSearch : Moate_1999_J.Anal.Toxicol_23_230
PubMedID: 10445484

Title : Tissue-specific regulation of G-protein-coupled inwardly rectifying K+ channel expression by muscarinic receptor activation in ovo - Thomas_1997_J.Biol.Chem_272_29958
Author(s) : Thomas SL , Chmelar RS , Lu C , Halvorsen SW , Nathanson NM
Ref : Journal of Biological Chemistry , 272 :29958 , 1997
Abstract : We investigated the effects of muscarinic acetylcholine receptor stimulation on the expression levels of the G-protein-coupled inwardly rectifying K+ channel (GIRK) subunits using solution hybridization and immunoblot analyses. We report here that treatment of chick embryos in ovo with muscarinic agonist causes decreases in mRNA levels encoding GIRK1 and GIRK4 in atria but does not alter GIRK1 expression in ventricles. In addition, GIRK1 protein levels also demonstrate a decrease in atria upon muscarinic acetylcholine receptor stimulation. Numerous receptors couple to the activation of the GIRK family of inwardly rectifying K+ channels; thus, these decreases represent a novel mechanism for regulating physiological responses to chronic agonist exposure.
ESTHER : Thomas_1997_J.Biol.Chem_272_29958
PubMedSearch : Thomas_1997_J.Biol.Chem_272_29958
PubMedID: 9368074