Li B


Full name : Li Bin

First name : Bin

Mail : Eppley Institute\; 986805 University of Nebraska Medical Center\; Omaha\; NE 68198

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Country : USA

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References (145)

Title : Significant but partial lipoprotein lipase functional loss caused by a novel occurrence of rare LPL biallelic variants - Hu_2024_Lipids.Health.Dis_23_92
Author(s) : Hu Y , Chen JM , Zuo H , Pu N , Zhang G , Duan Y , Li G , Tong Z , Li W , Li B , Yang Q
Ref : Lipids Health Dis , 23 :92 , 2024
Abstract : BACKGROUND: Lipoprotein lipase (LPL) plays a crucial role in triglyceride hydrolysis. Rare biallelic variants in the LPL gene leading to complete or near-complete loss of function cause autosomal recessive familial chylomicronemia syndrome. However, rare biallelic LPL variants resulting in significant but partial loss of function are rarely documented. This study reports a novel occurrence of such rare biallelic LPL variants in a Chinese patient with hypertriglyceridemia-induced acute pancreatitis (HTG-AP) during pregnancy and provides an in-depth functional characterization. METHODS: The complete coding sequences and adjacent intronic regions of the LPL, APOC2, APOA5, LMF1, and GPIHBP1 genes were analyzed by Sanger sequencing. The aim was to identify rare variants, including nonsense, frameshift, missense, small in-frame deletions or insertions, and canonical splice site mutations. The functional impact of identified LPL missense variants on protein expression, secretion, and activity was assessed in HEK293T cells through single and co-transfection experiments, with and without heparin treatment. RESULTS: Two rare LPL missense variants were identified in the patient: the previously reported c.809G > A (p.Arg270His) and a novel c.331G > C (p.Val111Leu). Genetic testing confirmed these variants were inherited biallelically. Functional analysis showed that the p.Arg270His variant resulted in a near-complete loss of LPL function due to effects on protein synthesis/stability, secretion, and enzymatic activity. In contrast, the p.Val111Leu variant retained approximately 32.3% of wild-type activity, without impacting protein synthesis, stability, or secretion. Co-transfection experiments indicated a combined activity level of 20.7%, suggesting no dominant negative interaction between the variants. The patient's post-heparin plasma LPL activity was about 35% of control levels. CONCLUSIONS: This study presents a novel case of partial but significant loss-of-function biallelic LPL variants in a patient with HTG-AP during pregnancy. Our findings enhance the understanding of the nuanced relationship between LPL genotypes and clinical phenotypes, highlighting the importance of residual LPL function in disease manifestation and severity. Additionally, our study underscores the challenges in classifying partial loss-of-function variants in classical Mendelian disease genes according to the American College of Medical Genetics and Genomics (ACMG)'s variant classification guidelines.
ESTHER : Hu_2024_Lipids.Health.Dis_23_92
PubMedSearch : Hu_2024_Lipids.Health.Dis_23_92
PubMedID: 38561841
Gene_locus related to this paper: human-LPL

Title : Carboxylesterase Activatable Molecular Probe for Personalized Treatment Guidance by Analyte-Induced Molecular Transformation - Li_2024_Angew.Chem.Int.Ed.Engl__e202404093
Author(s) : Li B , Liu H , Zhao M , Zhang X , Huang P , Chen X , Lin J
Ref : Angew Chem Int Ed Engl , :e202404093 , 2024
Abstract : Accurate visualization of tumor microenvironment is of great significance for personalized medicine. Here, we develop a near-infrared (NIR) fluorescence/photoacoustic (FL/PA) dual-mode molecular probe (denoted as NIR-CE) for distinguishing tumors based on carboxylesterase (CE) level by an analyte-induced molecular transformation (AIMT) strategy. The recognition moiety for CE activity is the acetyl unit of NIR-CE, generating the pre-product, NIR-CE-OH, which undergoes spontaneous hydrogen atom exchange between the nitrogen atoms in the indole group and the phenol hydroxyl group, eventually transforming into NIR-CE-H. In cellular experiments and in vivo blind studies, the human hepatoma cells and tumors with high level of CE were successfully distinguished by both NIR FL and PA imaging. Our findings provide a new molecular imaging strategy for personalized treatment guidance.
ESTHER : Li_2024_Angew.Chem.Int.Ed.Engl__e202404093
PubMedSearch : Li_2024_Angew.Chem.Int.Ed.Engl__e202404093
PubMedID: 38727540

Title : SlCarE054 in Spodoptera litura (Lepidoptera: Noctuidae) showed direct metabolic activity to beta-cypermethrin with stereoselectivity - Xu_2024_Bull.Entomol.Res__1
Author(s) : Xu L , Liu H , Li B , Li G , Liu R , Li D
Ref : Bull Entomol Res , :1 , 2024
Abstract : Carboxylesterases (CarEs) is an important detoxification enzyme system in phase participating in insecticides resistance. In our previous study, SlCarE054, a CarEs gene from lepidoptera class, was screened out to be upregulated in a pyrethroids and organophosphates resistant population. Its overexpression was verified in two field-collected populations of Spodoptera litura (Lepidoptera: Noctuidae) resistant to pyrethroids and organophosphates by qRT-PCR. Spatiotemporal expression results showed that SlCarE054 was highly expressed in the pupae stage and the digestive tissue midgut. To further explore its role in pyrethroids and organophosphates resistance, its metabolism activity to insecticides was determined by UPLC. Its recombinant protein showed significant metabolism activity to cyhalothrin and fenvalerate, but not to phoxim or chlorpyrifos. The metabolic activity of SlCarE054 to beta-cypermethrin showed stereoselectivity, with higher metabolic activity to -cypermethrin than the enantiomer alpha-cypermethrin. The metabolite of beta-cypermethrin was identified as 3-phenoxybenzaldehyde. Further modelling and docking analysis indicated that beta-cypermethrin, cyhalothrin and fenvalerate could bind with the catalytic triad of the 3D structure of SlCarE054. The interaction of beta-cypermethrin with SlCarE054 also showed the lowest binding energy. Our work provides evidence that SlCarE054 play roles in beta-cypermethrin resistance in S. litura.
ESTHER : Xu_2024_Bull.Entomol.Res__1
PubMedSearch : Xu_2024_Bull.Entomol.Res__1
PubMedID: 38708572
Gene_locus related to this paper: spolt-SlCarE054

Title : AAV-mediated hepatic expression of LPL ameliorates severe hypertriglyceridemia and its related acute pancreatitis in Gpihbp1 deficient mice and rats - Yuan_2023_Mol.Ther__
Author(s) : Yuan C , Xu Y , Lu G , Hu Y , Mao W , Ke L , Tong Z , Xia Y , Ma S , Dong X , Xian X , Wu X , Liu G , Li B , Li W
Ref : Mol Ther , : , 2023
Abstract : GPIHBP1 plays an important role in the hydrolysis of triglyceride (TG) lipoproteins by lipoprotein lipases (LPL). However, Gpihbp1 knockout mice did not develop hypertriglyceridemia (HTG) during the suckling period but developed severe HTG after weaning on a chow diet. It has been postulated that LPL expression in the liver of suckling mice may be involved. To determine whether hepatic LPL expression could correct severe HTG in Gpihbp1 deficiency, liver-targeted LPL expression was achieved via intravenous administration of the adeno-associated virus (AAV)-human LPL gene, and the effects of AAV-LPL on HTG and HTG-related acute pancreatitis (HTG-AP) were observed. Suckling Gpihbp1(-/-) mice with high hepatic LPL expression did not develop HTG, whereas Gpihbp1(-/-) rat pups, without hepatic LPL expression developed severe HTG. AAV-mediated liver-targeted LPL expression dose-dependently decreased plasma TG levels in Gpihbp1(-/-) mice and rats, increased post-heparin plasma LPL mass and activity, decreased mortality in Gpihbp1(-/-) rat pups, and reduced the susceptibility and severity of both Gpihbp1(-/-) animals to HTG-AP. However, the muscle expression of AAV-LPL had no significant effect on HTG. Targeted expression of LPL in the liver showed no obvious adverse reactions. Thus, liver-targeted LPL expression may be a new therapeutic approach for HTG-AP caused by GPIHBP1 deficiency.
ESTHER : Yuan_2023_Mol.Ther__
PubMedSearch : Yuan_2023_Mol.Ther__
PubMedID: 37974401

Title : JH degradation pathway participates in hormonal regulation of larval development of Bombyx mori following lambda-cyhalothrin exposure - Su_2023_Chemosphere_349_140871
Author(s) : Su Y , Wang W , Dai Y , Qi R , Gu H , Guo X , Liu X , Ren Y , Li F , Li B , Sun H
Ref : Chemosphere , 349 :140871 , 2023
Abstract : lambda-Cyhalothrin (lambda-cyh), a widely utilized pyrethroid insecticide, poses serious threats to non-target organisms due to its persistence nature in the environment. Exposure to low concentrations of lambda-cyh has been observed to result in prolonged larval development in Bombyx mori, leading to substantial financial losses in sericulture. The present study was undertaken to elucidate the underlying mechanisms for prolonged development caused by lambda-cyh (LC(10)) exposure. The results showed that the JH titer was significantly increased at 24 h of lambda-cyh exposure, and the JH interacting genes Methoprene-tolerant 2, Steroid Receptor Co-activator, Krppel-homolog 1, and JH binding proteins were also up-regulated. Although the target of rapamycin (Tor) genes were induced by lambda-cyh, the biosynthesis of JH in the corpora allata was not promoted. Notably, 13 JH degradation genes were found to be significantly down-regulated in the midgut of B. mori. The mRNA levels and enzyme activity assays indicated that lambda-cyh had inhibitory effects on JH esterase, JH epoxide hydrolase, and JH diol kinase (JHDK). Furthermore, the suppression of JHDK (KWMTBOMO01580) was further confirmed by both western blot and immunohistochemistry. This study has offered a comprehensive perspective on the mechanisms underlying the prolonged development caused by insecticides, and our results also hold significant implications for the safe production of sericulture.
ESTHER : Su_2023_Chemosphere_349_140871
PubMedSearch : Su_2023_Chemosphere_349_140871
PubMedID: 38056714

Title : The advantages of penehyclidine hydrochloride over atropine in acute organophosphorus pesticide poisoning: A meta-analysis - Zeng_2023_J.Intensive.Med_3_171
Author(s) : Zeng S , Ma L , Yang L , Hu X , Wang C , Guo X , Li Y , Gou Y , Zhang Y , Li S , Zhang S , Wu X , Li M , Lei J , Li B , Bi C , Luo Q
Ref : J Intensive Med , 3 :171 , 2023
Abstract : BACKGROUND: Penehyclidine hydrochloride (PHC) has been used for many years as an anticholinergic drug for the treatment of acute organophosphorus pesticide poisoning (AOPP). The purpose of this meta-analysis was to explore whether PHC has advantages over atropine in the use of anticholinergic drugs in AOPP. METHODS: We searched Scopus, Embase, Cochrane, PubMed, ProQuest, Ovid, Web of Science, China Science and Technology Journal Database (VIP), Duxiu, Chinese Biomedical literature (CBM), WanFang, and Chinese National Knowledge Infrastructure (CNKI), from inception to March 2022. After all qualified randomized controlled trials (RCTs) were included, we conducted quality evaluation, data extraction, and statistical analysis. Statistics using risk ratios (RR), weighted mean difference (WMD), and standard mean difference (SMD). RESULTS: Our meta-analysis included 20,797 subjects from 240 studies across 242 different hospitals in China. Compared with the atropine group, the PHC group showed decreased mortality rate (RR=0.20, 95% confidence intervals [CI]: 0.16-0.25, P <0.001), hospitalization time (WMD=-3.89, 95% CI: -4.37 to -3.41, P <0.001), overall incidence rate of complications (RR=0.35, 95% CI: 0.28-0.43, P <0.001), overall incidence of adverse reactions (RR=0.19, 95% CI: 0.17-0.22, P <0.001), total symptom disappearance time (SMD=-2.13, 95% CI: -2.35 to -1.90, P <0.001), time for cholinesterase activity to return to normal value 50-60% (SMD=-1.87, 95% CI: -2.03 to -1.70, P <0.001), coma time (WMD=-5.57, 95% CI: -7.20 to -3.95, P <0.001), and mechanical ventilation time (WMD=-2.16, 95% CI: -2.79 to -1.53, P <0.001). CONCLUSION: PHC has several advantages over atropine as an anticholinergic drug in AOPP.
ESTHER : Zeng_2023_J.Intensive.Med_3_171
PubMedSearch : Zeng_2023_J.Intensive.Med_3_171
PubMedID: 37188113

Title : (+)-\/(-)-Rutabenzofuran a and (+)-\/(-)- Rutabenzofuran b: Two unprecedented pairs of Z\/E isomeric benzofuran enantiomers from the aerial part of Ruta graveolens L - Liu_2023_Phytochemistry__113677
Author(s) : Liu Y , Peng J , Huang L , Li B , Ge C , Liu S , Jiang Y
Ref : Phytochemistry , :113677 , 2023
Abstract : Two pairs of Z/E isomeric benzofuran enantiomers possessing unprecedented carbon skeletons featuring ring cleavage and addition reactions in the alpha-pyrone ring of furocoumarin, named rutabenzofuran A [(+)-1 and (-)-1], and rutabenzofuran B [(+)-2 and (-)-2], respectively, were isolated as minor compounds from the water extract of the aerial part of Ruta graveolens L. Their structures were determined by extensive spectroscopic data analysis. The absolute configurations were assigned by comparing the optical rotation with previous research and the experimental circular dichroism (CD) spectra with the calculated electronic CD (ECD) spectra. (-)-1, (+)-2, and (-)-2 were evaluated for antibacterial, anticoagulant, anticancer, and acetylcholinesterase (AChE) inhibitory activities. No anticancer or anticoagulant activities were observed, yet (-)-2 exhibited weak antibacterial activity against Salmonella enterica subsp. Enterica. At the same time, (-)-1, (+)-2, and (-)-2 displayed weak inhibitory activity on AChE.
ESTHER : Liu_2023_Phytochemistry__113677
PubMedSearch : Liu_2023_Phytochemistry__113677
PubMedID: 37059286

Title : Self-ratiometric fluorescent platform based on upconversion nanoparticles for on-site detection of chlorpyrifos - Zhao_2023_Food.Chem_439_138100
Author(s) : Zhao X , Lu Y , Li B , Kong M , Sun Y , Li H , Liu X , Lu G
Ref : Food Chem , 439 :138100 , 2023
Abstract : Chromobacterium sp. USM2, a locally isolated bacterium was found to synthesize poly(3-hydroxybutyrate-co-3-hydroxyvalerate), P(3HB-co-3HV) copolymer with high 3HV monomer composition. The PHA synthase gene was cloned and expressed in Cupriavidus necator PHB4 to investigate the possibilities of incorporating other monomer. The recombinant successfully incorporated 3-hydroxyhexanoate (3HHx) monomer when fed with crude palm kernel oil (CPKO) as the sole carbon source. Approximately 63 2 wt% of P(3HB-co-3HHx) copolymer with 4 mol% of 3HHx was synthesized from 5 g/L of oil after 48 h of cultivation. In addition, P(3HB-co-3HV-co-3HHx) terpolymer with 9 mol% 3HV and 4 mol% 3HHx could be synthesized with a mixture of CPKO and sodium valerate. The presence of 3HV and 3HHx monomers in the copolymer and terpolymer was further confirmed with +H-NMR analysis. This locally isolated PHA synthase has demonstrated its ability to synthesize P(3HB-co-3HHx) copolymer from a readily available and renewable carbon source; CPKO, without the addition of 3HHx precursors.
ESTHER : Zhao_2023_Food.Chem_439_138100
PubMedSearch : Zhao_2023_Food.Chem_439_138100
PubMedID: 38041885

Title : Discovery of seven-membered ring berberine analogues as highly potent and specific hCES2A inhibitors - Yang_2023_Chem.Biol.Interact_378_110501
Author(s) : Yang Y , Xiong Y , Zhu G , Sun M , Zou K , Zhao Y , Zhang Y , Xu Z , Li Y , Zhu W , Jia Q , Li B , Ge G
Ref : Chemico-Biological Interactions , 378 :110501 , 2023
Abstract : Human carboxylesterase 2A (hCES2A) is a key serine hydrolase responsible for the metabolic clearance of large number of compounds bearing the ester- or amide-bond(s). Inhibition of hCES2A can relieve the chemotherapy-induced toxicity and alter the pharmacokinetic bahaviors of some orally administrate esters-containing agents. However, most of the hCES2A inhibitors show poor cell-membrane permeability and poor specificity. Herein, guided by the structure activity relationships (SAR) of fifteen natural alkaloids against hCES2A, fifteen new seven-membered ring berberine analogues were designed and synthesized, and their anti-hCES2A activities were evaluated. Among all tested compounds, compound 28 showed potent anti-hCES2A effect (IC(50) = 1.66 microM) and excellent selectivity over hCES1A (IC(50) > 100 microM). The SAR analysis revealed that the seven-membered ring of these berberine analogues was a crucial moiety for hCES2A inhibition, while the secondary amine group of the ring-C is important for improving their specificity over other serine hydrolases. Inhibition kinetic analyses and molecular dynamic simulation demonstrated that 28 strongly inhibited hCES2A in a mixed-inhibition manner, with an estimated K(i) value of 1.035 microM. Moreover, 28 could inhibit intracellular hCES2A in living HepG2 cells and exhibited suitable metabolic stability. Collectively, the SAR of seven-membered ring berberine analogues as hCES2A inhibitors were studied, while compound 28 acted as a promising candidate for developing highly selective hCES2A inhibitors.
ESTHER : Yang_2023_Chem.Biol.Interact_378_110501
PubMedSearch : Yang_2023_Chem.Biol.Interact_378_110501
PubMedID: 37080375

Title : The East Asian-specific LPL p.Ala288Thr (c.862G > A) missense variant exerts a mild effect on protein function - Hu_2023_Lipids.Health.Dis_22_119
Author(s) : Hu Y , Zhang G , Yang Q , Pu N , Li K , Li B , Cooper DN , Tong Z , Li W , Chen JM
Ref : Lipids Health Dis , 22 :119 , 2023
Abstract : BACKGROUND: Lipoprotein lipase (LPL) is the key enzyme responsible for the hydrolysis of triglycerides. Loss-of-function variants in the LPL gene are associated with hypertriglyceridemia (HTG) and HTG-related diseases. Unlike nonsense, frameshift and canonical GT-AG splice site variants, a pathogenic role for clinically identified LPL missense variants should generally be confirmed by functional analysis. Herein, we describe the clinical and functional analysis of a rare LPL missense variant. METHODS: Chinese patients with HTG-associated acute pancreatitis (HTG-AP) were screened for rare nonsense, frameshift, missense or canonical GT-AG splice site variants in LPL and four other lipid metabolism-related genes (APOC2, APOA5, GPIHBP1 and LMF1) by Sanger sequencing. The functional consequences of the LPL missense variant of interest were characterized by in vitro expression in HEK-293T and COS-7 cells followed by Western blot and LPL activity assays. RESULTS: Five unrelated HTG-AP patients were found to be heterozygous for a rare East Asian-specific LPL missense variant, c.862G > A (p.Ala288Thr). All five patients were adult males, and all were overweight and had a long history of alcohol consumption. Transfection of LPL wild-type and c.862G > A expression vectors into two cell lines followed by Western blot analysis served to exclude the possibility that the p.Ala288Thr missense variant either impaired protein synthesis or increased protein degradation. Contrary to a previous functional study that claimed that p.Ala288Thr had a severe impact on LPL function (reportedly having 36% normal activity), our experiments consistently demonstrated that the variant had a comparatively mild effect on LPL functional activity, which was mediated through its impact upon LPL protein secretion (~ 20% reduced secretion compared to wild-type). CONCLUSIONS: In this study, we identified the East Asian-specific LPL c.862G > A (p.Ala288Thr) missense variant in five unrelated HTG-AP patients. We demonstrated that this variant exerted only a relatively mild effect on LPL function in two cell lines. Heterozygosity for this LPL variant may have combined with alcohol consumption to trigger HTG-AP in these patients.
ESTHER : Hu_2023_Lipids.Health.Dis_22_119
PubMedSearch : Hu_2023_Lipids.Health.Dis_22_119
PubMedID: 37550668
Gene_locus related to this paper: human-LPL

Title : The sodium glucose co-transporter 2 inhibitor ertugliflozin for Alzheimer's disease: Inhibition of brain insulin signaling disruption-induced tau hyperphosphorylation - Pang_2023_Physiol.Behav_263_114134
Author(s) : Pang B , Zhang LL , Li B , Sun FX , Wang ZD
Ref : Physiol Behav , 263 :114134 , 2023
Abstract : An antidiabetic agent sodium glucose co-transporter 2 (SGLT2) inhibitor ertugliflozin has been revealed to bind to catalytic anionic site of acetylcholinesterase (AChE), which is considered to be associated with the cognitive decline in neurodegenerative diseases, such as Alzheimer's disease (AD). The aim of the present study was thus to probe the effect of ertugliflozin on AD. Intracerebroventricular injection of streptozotocin (STZ/i.c.v) (3 mg/kg) was done bilaterally in male Wistar rats at 7-8 weeks of age. Two treatment doses (5 mg/kg and 10 mg/kg) of ertugliflozin were given intragastrically to STZ/i.c.v-induced rats for 20 days daily for behavioral assessment. Biochemical estimations of cholinergic activity, neuronal apoptosis, mitochondrial function and synaptic plasticity were performed. Behavioral results with ertugliflozin treatment revealed attenuation of cognitive deficit. Ertugliflozin also inhibited hippocampal AChE activity, downregulated pro-apoptotic marker expression, as well as mitigated mitochondrial dysfunction and synaptic damage in STZ/i.c.v rats. Importantly, we found that the hyperphosphorylation of tau in the hippocampus of STZ/i.c.v rats was decreased after oral administration of ertugliflozin, which was accompanied by decreased Phospho.IRS-1(Ser307)/Total.IRS-1 ratio and increased Phospho.Akt(Ser473)/Total.Akt and Phospho.GSK3beta(Ser9)/Total.GSK3beta ratios. Our results indicated that treatment with ertugliflozin reversed AD pathology, which may be associated with inhibition of insulin signaling disruption-induced tau hyperphosphorylation.
ESTHER : Pang_2023_Physiol.Behav_263_114134
PubMedSearch : Pang_2023_Physiol.Behav_263_114134
PubMedID: 36809844

Title : The molecular mechanism of three novel peptides from C-phycocyanin alleviates MPTP-induced Parkinson's disease-like pathology in zebrafish - Xu_2023_Food.Funct__
Author(s) : Xu FH , Qiu YZ , Zhang Y , Yang FH , Ji MM , Liu KC , Jin M , Zhang SS , Li B
Ref : Food Funct , : , 2023
Abstract : Previous studies have shown that peptides isolated from C-phycocyanin (C-PC) possess various functions including antioxidant and anticancer activities. However, there is little research on C-PC peptides applied for the neuroprotective effect against a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease (PD) model. In this study, twelve novel peptides from C-PC were isolated, purified and identified, and the anti-PD effect of the synthesized peptides was evaluated in a zebrafish PD model. As a result, three of these peptides (MAAAHR, MPQPPAK, and MTAAAR) significantly reversed the loss of dopamine neurons and cerebral vessels, and reduced the locomotor impairment in PD zebrafish. In addition, three novel peptides could inhibit the MPTP-induced decrease of antioxidant enzymes (SOD, CAT, and GSH-Px) and increase the ROS and protein carbonylation content. In addition, they can also alleviate apoptosis of brain regions and acetylcholinesterase (AChE) activity in zebrafish. Further studies elucidated the potential molecular mechanism of peptides' anti-PD effects in the larvae. The results showed that C-PC peptides could modulate multiple genes associated with oxidative stress, autophagy and apoptosis signaling pathways, and thereby alleviate the occurrence of PD symptoms. Overall, our results highlight the neuroprotective effects of three novel peptides and provide valuable mechanistic insights and a promising drug target for the treatment of PD.
ESTHER : Xu_2023_Food.Funct__
PubMedSearch : Xu_2023_Food.Funct__
PubMedID: 37337786

Title : Transcriptional landscape of pathogen-responsive lncRNAs in tomato unveils the role of hydrolase encoding genes in response to Botrytis cinerea invasion - Chen_2023_Plant.Cell.Environ__
Author(s) : Chen D , Zhang Z , Chen Y , Li B , Chen T , Tian S
Ref : Plant Cell Environ , : , 2023
Abstract : LncRNAs have gained increasing attention owing to their important regulatory roles on growth and stress responses of plants. However, the mechanisms underlying the functions of lncRNAs in fruit-pathogen interaction are still largely unknown. In this study, a total of 273 lncRNAs responding to Botrytis cinerea infection were identified in tomato fruit, among which a higher percentage of antisense lncRNAs were targeted to the genes enriched in hydrolase activity. To ascertain the roles of these lncRNAs, seven hydrolase-related transcripts were transiently knocked-down by virus-induced gene silencing. Silencing of lncRNACXE20 reduced the expression level of a carboxylesterase gene, further enhancing the resistance of tomato to B. cinerea. In contrast, silencing of lncRNACHI, lncRNAMMP, lncRNASBT1.9 and lncRNAPME1.9 impaired the resistance to B. cinerea, respectively. Further RT-qPCR assay and enzymatic activity detection displayed that the attenuated resistance of lncRNAMMP and lncRNASBT1.9-silenced plants was associated with the inhibition on the expression of JA-related genes, while the decreased resistance of lncRNACHI-silenced plants resulted in reduced chitinase activity. Collectively, these results may provide references for deciphering the mechanisms underlying specific lncRNAs to interfere with B. cinerea infection by regulating the expression of defence-related genes or affecting hydrolase activity.
ESTHER : Chen_2023_Plant.Cell.Environ__
PubMedSearch : Chen_2023_Plant.Cell.Environ__
PubMedID: 37899711

Title : Design, synthesis and biological evaluation of salicylanilides as novel allosteric inhibitors of human pancreatic lipase - Zhao_2023_Bioorg.Med.Chem_91_117413
Author(s) : Zhao Y , Zhang M , Hou X , Han J , Qin X , Yang Y , Song Y , Liu Z , Zhang Y , Xu Z , Jia Q , Li Y , Chen K , Li B , Zhu W , Ge G
Ref : Bioorganic & Medicinal Chemistry , 91 :117413 , 2023
Abstract : Obesity is a growing global health problem and is associated with increased prevalence of many metabolic disorders, including diabetes, hypertension and cardiovascular disease. Pancreatic lipase (PL) has been validated as a key target for developing anti-obesity agents, owing to its crucial role in lipid digestion and absorption. In the past few decades, porcine PL (pPL) is always used as the enzyme source for screening PL inhibitors, which generate numerous pPL inhibitors but the potent inhibitors against human PL (hPL) are rarely reported. Herein, a series of salicylanilide derivatives were designed and synthesized, while their anti-hPL effects were assayed by a fluorescence-based biochemical approach. To investigate the structure-activity relationships of salicylanilide derivatives as hPL inhibitors in detail, structural modifications on three rings (A, B and C) of the salicylanilide skeleton were performed. Among all tested compounds, 2t and 2u were found possessing the most potent anti-PL activity, showing IC(50) values of 1.86 microM and 1.63 microM, respectively. Inhibition kinetic analyses suggested that both 2t and 2u could effectively inhibit hPL in a non-competitive manner, with the k(i) value of 1.67 microM and 1.70 microM, respectively. Fluorescence quenching assays suggested that two inhibitors could quench the fluorescence of hPL via a static quenching procedure. Molecular docking simulations suggested that 2t and 2u could tightly bind on an allosteric site of hPL. Collectively, the structure-activity relationships of salicylanilide derivatives as hPL inhibitors were carefully investigated, while two newly identified reversible hPL inhibitors (2t and 2u) could be used as promising lead compounds to develop novel anti-obesity drugs.
ESTHER : Zhao_2023_Bioorg.Med.Chem_91_117413
PubMedSearch : Zhao_2023_Bioorg.Med.Chem_91_117413
PubMedID: 37490786

Title : Green biosynthesis of DHA-phospholipids in tailor-made supersaturated DHA aqueous solution and catalytic mechanism study - Zhang_2023_Food.Chem_431_137164
Author(s) : Zhang T , Wang J , Zhao Y , Wang Z , Hu D , Liu Y , Zhang X , Li H , Zhao B , Li B
Ref : Food Chem , 431 :137164 , 2023
Abstract : Docosahexaenoic acid-phospholipids (DHA-PLs) were prepared via lipase-mediated transesterification of DHA donor and phosphatidylcholine (PC) in a purely aqueous solution. Pre-existing carriers would play the role as "artificial interfaces" to adsorb water-insoluble PC and made them disperse in water. DHA donors were concentrated by a pH-responsive method and presented as supersaturated salt solutions. 153 triacylglycerol lipase structures were analyzed and screened in silico. Transesterification was carried out to further evaluate the six lipase candidates. Lipase B from Candida antarctica (CALB) was the best biocatalyst with 34.8% of DHA incorporation and 80.0% of PLs yields (involving 38.1% PC and 41.9% sn-1 lyso-PC). Toxic organic solvents were avoided. Six possible microunits of our aqueous system consisting of three PLs donors (PC, lyso-PC, sn-glycero-3-PC) and two DHA donors (DHA and DHA salts), were simulated by molecular dynamics (MD) to illustrate the enzymatic mechanism based on diffusional channels, competitive bindings, and enzymatic structures.
ESTHER : Zhang_2023_Food.Chem_431_137164
PubMedSearch : Zhang_2023_Food.Chem_431_137164
PubMedID: 37607420

Title : Assessment of the therapeutic potential of probiotics against carbon quantum dots-induced neurotoxicity in common carp (Cyprinus carpio) - Cao_2023_Aquat.Toxicol_258_106508
Author(s) : Cao X , Yuan R , Sun D , Ji X , Wei Y , Li L , Guo S , Li B , Chen J
Ref : Aquat Toxicol , 258 :106508 , 2023
Abstract : Carbon quantum dots (CQDs) have received increasing attention in recent years for their potential toxicity. However, little is known about their neurobehavioral toxicity. This study aimed to investigate the potential mechanisms by which probiotics reduce CQDs neurotoxicity from a brain-gut axis perspective by exposing carp to CQDs and/or probiotics for five weeks. The results showed that CQDs accumulation in the brain reduces the expression of blood-brain-barrier (BBB) related genes in carp, leading to brain damage. In addition, CQDs impaired motor behavior and inhibited acetylcholinesterase activity. These abnormalities were alleviated by probiotic supplementation. Microbiomic analysis showed that probiotics improved the imbalance of intestinal flora caused by CQDs and increased the abundance of Firmicutes. Serum metabolomic analysis showed that probiotic supplementation restored the abnormal metabolic levels associated with neurological, inflammatory, and apoptotic cell death caused by CQDs. Overall, probiotic supplementation improved the CQDs-induced changes in brain damage, gut microbiology, and systemic metabolism. These results suggests that CQDs may cause neurotoxicity via the brain-gut microbial axis.
ESTHER : Cao_2023_Aquat.Toxicol_258_106508
PubMedSearch : Cao_2023_Aquat.Toxicol_258_106508
PubMedID: 37001197

Title : ANGPTL4 May Regulate the Crosstalk Between Intervertebral Disc Degeneration and Type 2 Diabetes Mellitus: A Combined Analysis of Bioinformatics and Rat Models - Chen_2023_J.Inflamm.Res_16_6361
Author(s) : Chen Y , Du H , Wang X , Li B , Chen X , Yang X , Zhao C , Zhao J
Ref : J Inflamm Res , 16 :6361 , 2023
Abstract : INTRODUCTION: The crosstalk between intervertebral disc degeneration (IVDD) and type 2 diabetes mellitus (T2DM) has been investigated. However, the common mechanism underlying this phenomenon has not been clearly elucidated. This study aimed to explore the shared gene signatures of IVDD and T2DM. METHODS: The expression profiles of IVDD (GSE27494) and T2DM (GSE20966) were acquired from the Gene Expression Omnibus database. Five hub genes including ANGPTL4, CCL2, CCN3, THBS2, and INHBA were preliminarily screened. GO (Gene Ontology) enrichment analysis, functional correlation analysis, immune filtration, Transcription factors (TFs)-mRNA-miRNA coregulatory network, and potential drugs prediction were performed following the identification of hub genes. RNA sequencing, in vivo and in vitro experiments on rats were further performed to validate the expression and function of the target gene. RESULTS: Five hub genes (ANGPTL4, CCL2, CCN3, THBS2, and INHBA) were identified. GO analysis demonstrated the regulation of the immune system, extracellular matrix (ECM), and SMAD protein signal transduction. There was a strong correlation between hub genes and different functions, including lipid metabolism, mitochondrial function, and ECM degradation. The immune filtration pattern grouped by disease and the expression of hub genes showed significant changes in the immune cell composition. TFs-mRNA-miRNA co-expression networks were constructed. In addition, pepstatin showed great drug-targeting relevance based on potential drugs prediction of hub genes. ANGPTL4, a gene that mediates the inhibition of lipoprotein lipase activity, was eventually determined after hub gene screening, validation by different datasets, RNA sequencing, and experiments. DISCUSSION: This study screened five hub genes and ANGPTL4 was eventually determined as a potential target for the regulation of the crosstalk in patients with IVDD and T2DM.
ESTHER : Chen_2023_J.Inflamm.Res_16_6361
PubMedSearch : Chen_2023_J.Inflamm.Res_16_6361
PubMedID: 38161353

Title : Low concentration of indoxacarb interferes with the growth and development of silkworm by damaging the structure of midgut cells - Wang_2023_Pestic.Biochem.Physiol_195_105567
Author(s) : Wang W , Su Y , Liu X , Qi R , Li F , Li B , Sun H
Ref : Pestic Biochem Physiol , 195 :105567 , 2023
Abstract : As an important economic insect, Bombyx mori plays an essential role in the development of the agricultural economy. Indoxacarb, a novel sodium channel blocker insecticide, has been widely used for the control of various pests in agriculture and forestry, and its environmental pollution caused by flight control operations has seriously affected the safe production of sericulture in recent years. However, the lethal toxicity and adverse effects of indoxacarb on silkworm remain largely unknown. In this study, the toxicity of indoxacarb on the 5th instar larvae of silkworm was determined, with an LC(50) (72 h) of 2.07 mg/L. Short-term exposure (24 h) to a low concentration of indoxacarb (1/2 LC(50)) showed significantly reduced body weight and survival rate of silkworm larvae. In addition, indoxacarb also led to decreased cocoon weight and cocoon shell weight, but had no significant effects on pupation, adult eclosion, and oviposition. Histopathological and ultrastructural analysis indicated that indoxacarb could severely damage the structure of the midgut epithelial cells, and lead to physiological impairment of the midgut. A total of 3883 differentially expressed genes (DEGs) were identified by midgut transcriptome sequencing and functionally annotated using GO and KEGG. Furthermore, the transcription level and enzyme activity of the detoxification related genes were determined, and our results suggested that esterases (ESTs) might play a major role in metabolism of indoxacarb in the midgut of B. mori. Future studies to examine the detoxification or biotransformation function of candidate genes will greatly enhance our understanding of indoxacarb metabolism in B. mori. The results of this study provide a theoretical basis for elucidating the mechanism of toxic effects of indoxacarb on silkworm by interfering with the normal physiological functions of the midgut.
ESTHER : Wang_2023_Pestic.Biochem.Physiol_195_105567
PubMedSearch : Wang_2023_Pestic.Biochem.Physiol_195_105567
PubMedID: 37666598

Title : Green biosynthesis of rare DHA-phospholipids by lipase-catalyzed transesterification with edible algal oil in solvent-free system and catalytic mechanism study - Zhang_2023_Front.Bioeng.Biotechnol_11_1158348
Author(s) : Zhang T , Li B , Wang Z , Hu D , Zhang X , Zhao B , Wang J
Ref : Front Bioeng Biotechnol , 11 :1158348 , 2023
Abstract : Docosahexaenoic acid (DHA)-enriched phosphatidylcholine (PC) has received significant scientific attention due to the health benefits in food and pharmaceutical products. In this work, the edible algal oil rich in DHA-triacylglycerol (DHA-TAG) without pretreatment was first used as the DHA donor for the transesterification of phospholipids (PLs) to prepare three kinds of rare PLs, including DHA-PC, DHA-phosphatidylethanolamine (DHA-PE), and DHA-phosphatidylserine (DHA-PS). Here, 153 protein structures of triacylglycerol lipase (EC were virtually screened and evaluated by transesterification. PLA1 was the best candidate due to a higher DHA incorporation. Results showed that the transesterification of PC with DHA-TAG at 45 degreesC and 0.7% water content (without additional water addition) could produce DHA-PC with 39.1% DHA incorporation at 30 min. The different DHA donors, including forms of fatty acid, methyl ester, and triglycerides, were compared. Molecular dynamics (MD) was used to illustrate the catalytic mechanism at the molecular level containing the diffusions of substrates, the structure-activity relationship of PLA1, and the effect of water content.
ESTHER : Zhang_2023_Front.Bioeng.Biotechnol_11_1158348
PubMedSearch : Zhang_2023_Front.Bioeng.Biotechnol_11_1158348
PubMedID: 37064237

Title : Anti-Oxidant and Pro-Oxidant Effects of Peroxiredoxin 6: A Potential Target in Respiratory Diseases - Jia_2023_Cells_12_
Author(s) : Jia W , Dong C , Li B
Ref : Cells , 12 : , 2023
Abstract : Peroxiredoxin 6 (PRDX6) is widely distributed in several organs, especially the lungs. The role of PRDX6 in oxidative stress is controversial and even contradictory, as indicated by research conducted over the past 20 years. PRDX6 has anti-oxidant or pro-oxidant effects on oxidative stress in different diseases. It can even exhibit both anti-oxidant and pro-oxidant effects in the same disease. These findings are attributed to the fact that PRDX6 is a multifunctional enzyme. The peroxidase and phospholipase A2 activity of PRDX6 is closely related to its anti-oxidant and pro-oxidant effects, which leads to the conflicting regulatory effects of PRDX6 on oxidative stress in respiratory diseases. Moreover, PRDX6 interacts with multiple redox signaling pathways to interfere with cell proliferation and apoptosis. PRDX6 has become a new target in respiratory disease research due to its important regulatory role in oxidative stress. In this paper, the role of PRDX6 in oxidative stress in respiratory diseases and the research progress in targeting PRDX6 are reviewed.
ESTHER : Jia_2023_Cells_12_
PubMedSearch : Jia_2023_Cells_12_
PubMedID: 36611974

Title : Characteristics of CXE family of Salvia miltiorrhiza and identification of interactions between SmGID1s and SmDELLAs - Li_2023_Plant.Physiol.Biochem_206_108140
Author(s) : Li Y , Pang Q , Li B , Fu Y , Guo M , Zhang C , Tian Q , Hu S , Niu J , Wang S , Wang D , Wang Z
Ref : Plant Physiol Biochem , 206 :108140 , 2023
Abstract : Carboxylesterase (CXE) is a class of hydrolases that contain an alpha/beta folding domain, which plays critical roles in plant growth, development, and stress responses. Based on the genomic and transcriptomic data of Salvia miltiorrhiza, the SmCXE family was systematically analyzed using bioinformatics. The results revealed 34 SmCXE family members in S. miltiorrhiza, and the SmCXE family could be divided into five groups (Group I, Group II, Group III, Group IV, and Group V). Cis-regulatory elements indicated that the SmCXE promoter region contained tissue-specific and development-related, hormone-related, stress-related, and photoresponsive elements. Transcriptome analysis revealed that the expression levels of SmCXE2 were highest in roots and flowers (SmCXE8 was highest in stems and SmCXE19 was highest in leaves). Further, two GA receptors SmCXE1 (SmGID1A) and SmCXE2 (SmGID1B) were isolated from the SmCXE family, which are homologous to other plants. SmGID1A and SmGID1B have conserved HGGSF motifs and active amino acid sites (Ser-Asp-Val/IIe), which are required to maintain their GA-binding activities. SmGID1A and SmGID1B were significantly responsive to gibberellic acid (GA(3)) and methyl jasmonate (MeJA) treatment. A subcellular assay revealed that SmCXE1 and SmCXE2 resided within the nucleus. SmGID1B can interact with SmDELLAs regardless of whether GA(3) exists, whereas SmGID1A can only interact with SmDELLAs in the presence of GA(3). A Further assay showed that the GRAS domain mediated the interactions between SmGID1s and SmDELLAs. This study lays a foundation for further elucidating the role of SmCXE in the growth and development of S. miltiorrhiza.
ESTHER : Li_2023_Plant.Physiol.Biochem_206_108140
PubMedSearch : Li_2023_Plant.Physiol.Biochem_206_108140
PubMedID: 38134738
Gene_locus related to this paper: salmi-SmCXE1 , salmi-SmCXE2 , salmi-SmCXE3 , salmi-SmCXE4 , salmi-SmCXE5 , salmi-SmCXE6 , salmi-SmCXE7 , salmi-SmCXE8 , salmi-SmCXE9 , salmi-SmCXE10 , salmi-SmCXE11 , salmi-SmCXE12 , salmi-SmCXE13 , salmi-SmCXE14 , salmi-SmCXE15 , salmi-SmCXE16 , salmi-SmCXE17 , salmi-SmCXE18 , salmi-SmCXE19 , salmi-SmCXE20 , salmi-SmCXE21 , salmi-SmCXE22 , salmi-SmCXE23 , salmi-SmCXE24 , salmi-SmCXE25 , salmi-SmCXE26 , salmi-SmCXE27 , salmi-SmCXE28 , salmi-SmCXE29 , salmi-SmCXE30 , salmi-SmCXE31 , salmi-SmCXE32 , salmi-SmCXE33 , salmi-SmCXE34

Title : Water in liquid crystal emulsion-based sensing platform for colorimetric detection of organophosphorus pesticide - Li_2023_Food.Chem_436_137732
Author(s) : Li B , Wu W , Lin JM , Wang T , Hu Conceptuation Q , Yu L
Ref : Food Chem , 436 :137732 , 2023
Abstract : Development of a simple and convenient method for the rapid detection of organophosphorus pesticides (OPs) is particular important for the safety of environmental water and agriculture products. In this work, the water/liquid crystal (W/LC) emulsion is obtained via dispersing an aqueous solution of sodium dodecyl sulfate (SDS) and peroxidase from horseradish (HRP) into a water-immiscible nematic LC and employed as a sensing platform for the detection of dichlorvos (2, 2-dichlorovinyl dimethyl phosphate, DDVP) that is a typical OP with acute toxicity. Remarkably, the stepwise release of the encapsulated cargo HRP from the W/LC emulsion can be triggered upon the addition of the cationic surfactant myristoylcholine chloride (Myr) due to the strong interfacial charge interactions with the anionic surfactant SDS. The released HRP induces an obvious color change of the overlaying bulk aqueous solution via the H(2)O(2)-HRP-TMB reaction system. As Myr can be enzymatically cleaved by AChE, the detection of AChE is fulfilled successfully. This approach is also employed to detect DDVP that can irreversibly inhibit the activity of AChE. This assay shows a linear response between the absorbance of the oxidized TMB solution and the DDVP concentration in the range of 0.001-10 microg/mL (R(2) = 0.99). The limit of detection (LOD) and the limit of quantity (LOQ) of DDVP are determined to be 1.9 ng/mL and 6.3 ng/mL, respectively. In addition, this strategy also demonstrates excellent performance for the DDVP detection in real samples, the detection recovery rate of DDVP in water samples (lake water and tap water) and vegetables (tomatoes and cole) by this method is 88.0 % -112.6 %, the relative standard deviation (RSD) >= 7.5 %. These results suggest the W/LC emulsion-based sensing platform shows great potential for visual detection of DDVP in real samples. In conclusion, the proposed approach is scalable for practical application in food safety as well as environmental monitoring fields, and will provide promising solutions for the assay of pesticide residues.
ESTHER : Li_2023_Food.Chem_436_137732
PubMedSearch : Li_2023_Food.Chem_436_137732
PubMedID: 37857198

Title : Sclerotinia sclerotiorum SsCut1 Modulates Virulence and Cutinase Activity - Gong_2022_J.Fungi.(Basel)_8_
Author(s) : Gong Y , Fu Y , Xie J , Li B , Chen T , Lin Y , Chen W , Jiang D , Cheng J
Ref : J Fungi (Basel) , 8 : , 2022
Abstract : The plant cuticle is one of the protective layers of the external surface of plant tissues. Plants use the cuticle layer to reduce water loss and resist pathogen infection. Fungi release cell wall-degrading enzymes to destroy the epidermis of plants to achieve the purpose of infection. Sclerotinia sclerotiorum secretes a large amount of cutinase to disrupt the cuticle layer of plants during the infection process. In order to further understand the role of cutinase in the pathogenic process of S. sclerotiorum, the S. sclerotiorum cutinsae 1 (SsCut1) gene was cloned and analyzed. The protein SsCut1 contains the conserved cutinase domain and a fungal cellulose-binding domain. RT-qPCR results showed that the expression of SsCut1 was significantly upregulated during infection. Split-Marker recombination was utilized for the deletion of the SsCut1 gene, deltaSsCut1 mutants showed reduced cutinase activity and virulence, but the deletion of the SsCut1 gene had no effect on the growth rate, colony morphology, oxalic acid production, infection cushion formation and sclerotial development. Complementation with the wild-type SsCut1 allele restored the cutinase activity and virulence to the wild-type level. Interestingly, expression of SsCut1 in plants can trigger defense responses, but it also enhanced plant susceptibility to SsCut1 gene knock-out mutants. Taken together, our finding demonstrated that the SsCut1 gene promotes the virulence of S. sclerotiorum by enhancing its cutinase activity.
ESTHER : Gong_2022_J.Fungi.(Basel)_8_
PubMedSearch : Gong_2022_J.Fungi.(Basel)_8_
PubMedID: 35628781
Gene_locus related to this paper: scls1-a7erz9

Title : Bisphenol AF induces multiple behavioral and biochemical changes in zebrafish (Danio rerio) at different life stages - Rao_2022_Aquat.Toxicol_253_106345
Author(s) : Rao C , Cao X , Li L , Zhou J , Sun D , Li B , Guo S , Yuan R , Cui H , Chen J
Ref : Aquat Toxicol , 253 :106345 , 2022
Abstract : As common environmental endocrine-disrupting chemicals (EDCs), bisphenol AF (BPAF) raises potential concerns for aquatic organisms due to its widespread presence and continued release in the aquatic environment. This research aimed to use zebrafish embryos and adult fish to explore the effects of environmentally relevant concentrations (5 g/L), 50 g/L and 500 g/L of BPAF on zebrafish embryonic development, behavioral alterations, and the potential mechanisms driving these effects. The results showed that 500 g/L of BPAF severely affected the growth and development of embryos. In behavioral experiments, all concentrations of BPAF significantly inhibited the locomotor activity of larvae, 50 and 500 g/L BPAF significantly altered the anxiety-like and aggressive behavior of adult zebrafish. Furthermore, environmentally relevant concentrations and higher concentrations of BPAF induced varying degrees of oxidative stress in both embryonic and adult fish. The most significant histopathological changes and decreased acetylcholinesterase (AChE) activity were observed in the brain at 50 and 500 g/L of BPAF. We hypothesized that oxidative stress is an important cause of behavioral disturbances in larvae and adult fish. To our best knowledge, the present experiment is a pioneer in studying the effects of BPAF on a variety of complex behaviors (swimming performance, anxiety-like, social behavior, aggression) in zebrafish, which emphasizes the potential health risk of higher concentrations of BPAF in terms of induced neurotoxicity.
ESTHER : Rao_2022_Aquat.Toxicol_253_106345
PubMedSearch : Rao_2022_Aquat.Toxicol_253_106345
PubMedID: 36351319

Title : Calcium-dependent cytosolic phospholipase A(2) activation is implicated in neuroinflammation and oxidative stress associated with ApoE4 - Wang_2022_Mol.Neurodegener_17_42
Author(s) : Wang S , Li B , Solomon V , Fonteh A , Rapoport SI , Bennett DA , Arvanitakis Z , Chui HC , Sullivan PM , Yassine HN
Ref : Mol Neurodegener , 17 :42 , 2022
Abstract : BACKGROUND: Apolipoprotein E4 (APOE4) is associated with a greater response to neuroinflammation and the risk of developing late-onset Alzheimer's disease (AD), but the mechanisms for this association are not clear. The activation of calcium-dependent cytosolic phospholipase A(2) (cPLA2) is involved in inflammatory signaling and is elevated within the plaques of AD brains. The relation between APOE4 genotype and cPLA2 activity is not known. METHODS: Mouse primary astrocytes, mouse and human brain samples differing by APOE genotypes were collected for measuring cPLA2 expression, phosphorylation, and activity in relation to measures of inflammation and oxidative stress. RESULTS: Greater cPLA2 phosphorylation, cPLA2 activity and leukotriene B4 (LTB4) levels were identified in ApoE4 compared to ApoE3 in primary astrocytes, brains of ApoE-targeted replacement (ApoE-TR) mice, and in human brain homogenates from the inferior frontal cortex of persons with AD dementia carrying APOE3/4 compared to APOE3/3. Higher phosphorylated p38 MAPK but not ERK1/2 was found in ApoE4 primary astrocytes and mouse brains than that in ApoE3. Greater cPLA2 translocation to cytosol was observed in human postmortem frontal cortical synaptosomes with recombinant ApoE4 than ApoE3 ex vivo. In ApoE4 astrocytes, the greater levels of LTB4, reactive oxygen species (ROS), and inducible nitric oxide synthase (iNOS) were reduced after cPLA2 inhibition. CONCLUSIONS: Our findings implicate greater activation of cPLA2 signaling system with APOE4, which could represent a potential drug target for mitigating the increased neuroinflammation with APOE4 and AD.
ESTHER : Wang_2022_Mol.Neurodegener_17_42
PubMedSearch : Wang_2022_Mol.Neurodegener_17_42
PubMedID: 35705959

Title : Genome-wide analysis of the strigolactone biosynthetic and signaling genes in grapevine and their response to salt and drought stresses - Yu_2022_PeerJ_10_e13551
Author(s) : Yu Y , Xu J , Wang C , Pang Y , Li L , Tang X , Li B , Sun Q
Ref : PeerJ , 10 :e13551 , 2022
Abstract : Strigolactones (SLs) are a novel class of plant hormones that play critical roles in regulating various developmental processes and stress tolerance. Although the SL biosynthetic and signaling genes were already determined in some plants such as Arabidopsis and rice, the information of SL-related genes in grapevine (Vitis vinifera L.) remains largely unknown. In this study, the SL-related genes were identified from the whole grapevine genome, and their expression patterns under salt and drought stresses were determined. The results indicated that the five genes that involved in the SL biosynthesis included one each of the D27, CCD7, CCD8, MAX1 and LBO genes, as well as the three genes that involved in the SL signaling included one each of the D14, MAX2, D53 genes. Phylogenetic analysis suggested that these SL-related proteins are highly conserved among different plant species. Promoter analysis showed that the prevalence of a variety of cis-acting elements associated with hormones and abiotic stress existed in the promoter regions of these SL-related genes. Furthermore, the transcription expression analysis demonstrated that most SL-related genes are involved in the salt and drought stresses response in grapevine. These findings provided valuable information for further investigation and functional analysis of SL biosynthetic and signaling genes in response to salt and drought stresses in grapevine.
ESTHER : Yu_2022_PeerJ_10_e13551
PubMedSearch : Yu_2022_PeerJ_10_e13551
PubMedID: 35712547

Title : Replacement of Pregastric Lipases in Cheese Production: Identification and Heterologous Expression of a Lipase from Pleurotus citrinopileatus - Sowa_2022_J.Agric.Food.Chem__
Author(s) : Sowa MA , Kreuter N , Sella N , Albuquerque W , Manhard J , Siegl A , Ghezellou P , Li B , Spengler B , Weichhard E , Ruhl M , Zorn H , Gand M
Ref : Journal of Agricultural and Food Chemistry , : , 2022
Abstract : Traditionally produced piquant cheeses such as Feta or Provolone rely on pregastric lipolytic enzymes of animal origin to intensify flavor formation during ripening. Herein, we report a novel fungal lipase, derived from the phylum Basidiomycota to replace animal-derived products. A screening of 31 strains for the desired hydrolytic activities was performed, which revealed a promising fungal species. The secretome of an edible golden oyster mushroom, Pleurotus citrinopileatus, provided suitable enzymatic activity, and the coding sequence of the corresponding enzyme was identified by combining transcriptome and liquid chromatography high-resolution electrospray tandem mass spectroscopy (LC-HR-ESI-MS/MS) data. Recombinant expression in Escherichia coli BL21 (DE3) using chaperones GroES-GroEL and DnaK-DnaJ-GrpE was established. The recombinant lipolytic enzyme was purified and biochemically characterized in terms of thermal and pH stability, optimal reaction conditions, and kinetic data toward p-nitrophenyl esters. An application in the microscale production of Feta-type brine cheese revealed promising sensory properties, which were confirmed by headspace solid-phase microextraction gas chromatography mass spectrometry (HS-SPME-GC-MS) analyses in comparison with the reference enzyme opti-zym z10uc from goat origin. Supplementation with 2.3 U of the heterologously expressed fungal lipase produced the most comparable free fatty acid profile after 30 days of ripening. The flavor and texture formed during the application of the new lipase from P. citrinopileatus proved to be competitive to the use of pregastric lipases and could therefore replace the products of animal origin.
ESTHER : Sowa_2022_J.Agric.Food.Chem__
PubMedSearch : Sowa_2022_J.Agric.Food.Chem__
PubMedID: 35213163

Title : Neuroprotective Effect and Possible Mechanisms of Berberine in Diabetes-Related Cognitive Impairment: A Systematic Review and Meta-Analysis of Animal Studies - Hao_2022_Front.Pharmacol_13_917375
Author(s) : Hao Y , Li J , Yue S , Wang S , Hu S , Li B
Ref : Front Pharmacol , 13 :917375 , 2022
Abstract : Berberine, the main bioactive component of Coptis chinensis Franch., is widely used in the treatment of diabetes. Previous studies have reported that berberine supplementation may play a multitarget therapeutic role in diabetes-related cognitive impairment (DCI). This systematic review and meta-analysis evaluated the effect and possible mechanisms of berberine in animal models of DCI. Relevant studies were searched through PubMed, Web of Science, Embase, and three Chinese databases (CNKI, Wanfang, and VIP) until March 2022. Twenty studies involving 442 animals were included, and SYRCLE's risk of bias tool was used to assess methodological quality. The statistical analysis was performed using STATA 15.0 to calculate the weighted standard mean difference (SMD) with a 95% confidence interval (CI). The fasting blood glucose (FBG) and Morris water maze test (MWM) were the main outcomes to be analyzed. The overall results showed that berberine could significantly improve FBG, escape latency, the times of crossing the platform, the time spent in the target quadrant, serum insulin, 2hBG of oral glucose tolerance test (OGTT), amyloid beta (Abeta), acetylcholinesterase (AChE), oxidative stress, and inflammation levels. The present meta-analysis demonstrated that berberine could not only lower blood glucose levels but also improve learning and memory in DCI animal models, which might involve regulating glucose and lipid metabolism, improving insulin resistance, anti-oxidation, anti-neuroinflammation, inhibiting endoplasmic reticulum (ER) stress; and improving the cholinergic system. However, additional attention should be paid to these outcomes due to the significant heterogeneity.
ESTHER : Hao_2022_Front.Pharmacol_13_917375
PubMedSearch : Hao_2022_Front.Pharmacol_13_917375
PubMedID: 35734409

Title : Fine mapping of powdery mildew resistance gene MlWE74 derived from wild emmer wheat (Triticum turgidum ssp. dicoccoides) in an NBS-LRR gene cluster - Zhu_2022_Theor.Appl.Genet__
Author(s) : Zhu K , Li M , Wu H , Zhang D , Dong L , Wu Q , Chen Y , Xie J , Lu P , Guo G , Zhang H , Zhang P , Li B , Li W , Wang Q , Zhu J , Hu W , Guo L , Wang R , Yuan C , Li H , Liu Z , Hua W
Ref : Theor Appl Genet , : , 2022
Abstract : Powdery mildew resistance gene MlWE74, originated from wild emmer wheat accession G-748-M, was mapped in an NBS-LRR gene cluster of chromosome 2BS. Wheat powdery mildew, caused by Blumeria graminis f. sp. tritici (Bgt), is a globally devastating disease. Wild emmer wheat (Triticum turgidum var. dicoccoides) is a valuable genetic resource for improving disease resistance in common wheat. A powdery mildew resistance gene was transferred to hexaploid wheat line WE74 from wild emmer accession G-748-M. Genetic analysis revealed that the powdery mildew resistance in WE74 is controlled by a single dominant gene, herein temporarily designated MlWE74. Bulked segregant analysis (BSA) and molecular mapping delimited MlWE74 to the terminal region of chromosome 2BS flanking by markers WGGBD412 and WGGBH346 within a genetic interval of 0.25 cM and corresponding to 799.9 kb genomic region in the Zavitan reference sequence. Sequence annotation revealed two phosphoglycerate mutase-like genes, an alpha/beta-hydrolases gene, and five NBS-LRR disease resistance genes that could serve as candidates for map-based cloning of MlWE74. The geographical location analysis indicated that MlWE74 is mainly distributed in Rosh Pinna and Amirim regions, in the northern part of Israel, where environmental conditions are favorable to the occurrence of powdery mildew. Moreover, the co-segregated marker WGGBD425 is helpful in marker-assisted transfer of MlWE74 into elite cultivars.
ESTHER : Zhu_2022_Theor.Appl.Genet__
PubMedSearch : Zhu_2022_Theor.Appl.Genet__
PubMedID: 35006335

Title : Response of xenobiotic biodegradation and metabolic genes in Tribolium castaneum following eugenol exposure - Zhang_2022_Mol.Genet.Genomics__
Author(s) : Zhang Y , Gao S , Zhang P , Sun H , Lu R , Yu R , Li Y , Zhang K , Li B
Ref : Mol Genet Genomics , : , 2022
Abstract : Eugenol, a plant-derived component possessing small side effects, has an insecticidal activity to Tribolium castaneum; however, the underlying molecular mechanisms of eugenol acting on T. castaneum are currently unclear. Here, a nerve conduction carboxylesterase and a detoxifying glutathione S-transferase were significantly inhibited after eugenol exposure, resulting in the paralysis or death of beetles. Then, RNA-sequencing of eugenol-exposed and control samples identified 362 differentially expressed genes (DEGs), containing 206 up-regulated and 156 down-regulated genes. RNA-seq data were validated further by qRT-PCR. GO analysis revealed that DEGs were associated with 1308 GO terms of which the most enriched GO terms were catalytic activity, and integral component of membrane; KEGG pathway analysis showed that these DEGs were distributed in 151 different pathways, of which some pathways associated with metabolism of xenobiotics or drug were significantly enriched, which indicated that eugenol most likely disturbed the processes of metabolism, and detoxication. Moreover, several DEGs including Hexokinase type 2, Isocitrate dehydrogenase, and Cytochrome b-related protein, might participate in the respiratory metabolism of eugenol-exposed beetles. Some DEGs encoding CYP, UGT, GST, OBP, CSP, and ABC transporter were involved in the xenobiotic or drug metabolism pathway, which suggested that these genes of T. castaneum participated in the response to eugenol exposure. Additionally, TcOBPC11/ TcGSTs7, detected by qRT-PCR and RNA-interference against these genes, significantly increased the mortality of eugenol-treated T. castaneum, providing further evidence for the involvement of OBP/GST in eugenol metabolic detoxification in T. castaneum. These results aid eugenol insecticidal mechanisms and provide the basis of insect control.
ESTHER : Zhang_2022_Mol.Genet.Genomics__
PubMedSearch : Zhang_2022_Mol.Genet.Genomics__
PubMedID: 35419714

Title : Predictive value of serum cholinesterase in the mortality of acute pancreatitis: A retrospective cohort study - Wei_2022_Eur.J.Clin.Invest__e13741
Author(s) : Wei M , Xie X , Yu X , Lu Y , Ke L , Ye B , Zhou J , Li G , Li B , Tong Z , Lu G , Li W , Li J
Ref : European Journal of Clinical Investigation , :e13741 , 2022
Abstract : BACKGROUND: Severe acute pancreatitis has a high mortality of 20-40%, but there is lack of optimal prognostic biomarker for the severity of acute pancreatitis (AP) or mortality. This study is designed to investigate the relationship between serum cholinesterase (ChE) level and poor outcomes of AP. METHODS: A total of 1904 AP patients were screened in the study, and we finally got 692 patients eligible for analysis. Patients were divided into 2 groups based on serum ChE. The primary outcome was mortality, and multivariable logistic regression analysis for mortality was completed. Additionally, we used receiver operator characteristic (ROC) curve analysis to clarify the predictive value of serum ChE for mortality and organ failure. RESULTS: 378 patients and 314 patients were included in ChE low and normal group, respectively. Patients in ChE low group were older (46.68+/-12.70 vs 43.56+/-12.13 years old, p=0.001) and had a lower percentage of male (62.4% vs 71.0%, p=0.017) when compared with the ChE normal group. Mortality was significantly different in two groups (10.3% vs 0.0%, p<0.001). Moreover, organ failure also differed significantly in two groups (46.6% vs 8.6%, p<0.001). Decreased ChE level was independently associated with mortality in acute pancreatitis (odds ratio: 0.440; 95% confidence interval, 0.231, 0.838, p=0.013). The area under the curve of serum ChE was 0.875 and 0.803 for mortality and organ failure, respectively. CONCLUSIONS: Lower level of serum ChE was independently associated with the severity and mortality of AP.
ESTHER : Wei_2022_Eur.J.Clin.Invest__e13741
PubMedSearch : Wei_2022_Eur.J.Clin.Invest__e13741
PubMedID: 34981831

Title : GPIHBP1 autoantibody is an independent risk factor for the recurrence of hypertriglyceridemia-induced acute pancreatitis - Zhang_2022_J.Clin.Lipidol__
Author(s) : Zhang G , Yang Q , Mao W , Hu Y , Pu N , Deng H , Yu X , Zhang J , Zhou J , Ye B , Li G , Li B , Ke L , Tong Z , Murakami M , Kimura T , Nakajima K , Cao W , Liu Y , Li W
Ref : J Clin Lipidol , : , 2022
Abstract : BACKGROUND: GPIHBP1, a glycolipid-anchored protein of capillary endothelial cells, is a crucial partner for lipoprotein lipase (LPL) in plasma triglyceride metabolism. GPIHBP1 autoantibodies block LPL binding to GPIHBP1 and lead to severe hypertriglyceridemia (HTG) and HTG-induced acute pancreatitis (HTG-AP). We sought to define the incidence of GPIHBP1 autoantibodies in patients with HTG-AP. OBJECTIVE: We determined the incidence of GPIHBP1 autoantibody in HTG-AP patients, and compared the clinical features and long-term outcomes between GPIHBP1 autoantibody-positive and negative groups. METHODS: An enzyme-linked immunosorbent assay was used to screen for GPIHBP1 autoantibody in 116 HTG-AP patients hospitalized from Jan 1, 2015 to Aug 31, 2019. All patients were followed up for 24 months. The primary outcome was the recurrence rate of HTG-AP during the two-year follow-up period. The incidence of recurrent episodes was analyzed by the Kaplan-Meier method and multivariable Cox regression was used to identify risk factors. RESULTS: GPIHBP1 autoantibodies were present in 17 of 116 study patients (14.66%). The 2-year recurrence rate of HTG-AP was much higher in the GPIHBP1 autoantibody-positive group (35%, 6 in 17) than in the negative group (4%, 4 in 99). The multivariable Cox regression analysis showed that GPIHBP1 autoantibody was an independent risk factor for HTG-AP recurrence in two years. CONCLUSIONS: The presence of GPIHBP1 autoantibody is common in patients with HTG-AP, and is an independent risk factor for two-year recurrence of HTG-AP.
ESTHER : Zhang_2022_J.Clin.Lipidol__
PubMedSearch : Zhang_2022_J.Clin.Lipidol__
PubMedID: 36064883

Title : Detection of Carboxylesterase 1 and Chlorpyrifos with ZIF-8 Metal-Organic Frameworks Using a Red Emission BODIPY-Based Probe - Shen_2021_ACS.Appl.Mater.Interfaces__
Author(s) : Shen B , Ma C , Ji Y , Dai J , Li B , Zhang X , Huang H
Ref : ACS Appl Mater Interfaces , : , 2021
Abstract : In this work, a red emission fluorescent probe CBZ-BOD@zeolitic imidazolate framework-8 (ZIF-8) was fabricated based on metal-organic frameworks (MOFs) for detecting carboxylesterase 1 (CES1). The small molecule probe CBZ-BOD was first synthesized and then used to prepare the functionalized MOF material. ZIF-8 was chosen as an encapsulation shell to improve the detection properties of CBZ-BOD. Using this unique porous materials, ultrasensitive quantification of CES1 and chlorpyrifos was successfully realized. The low detection limit and high fluorescence quantum yield were calculated as 1.15 ng/mL and 0.65 for CBZ-BOD@ZIF-8, respectively. CBZ-BOD@ZIF-8 has good biocompatibility and was successfully applied to monitor the activity of CES1 in living cells. A molecular docking study was used to explore the binding of CES1 and CBZ-BOD, finding that CES1 can bind with the probe before and after hydrolysis. This type of materialized probe can inspire the development of fluorescent tools for further exploration of many pathological processes.
ESTHER : Shen_2021_ACS.Appl.Mater.Interfaces__
PubMedSearch : Shen_2021_ACS.Appl.Mater.Interfaces__
PubMedID: 33569946

Title : Acetylcholinesterase target sites for developing environmentally friendly insecticides against Tetranychus urticae (Acari: Tetranychidae) - Li_2021_Exp.Appl.Acarol__
Author(s) : Li C , Cao Y , Yang J , Li M , Li B , Bu C
Ref : Exp Appl Acarol , : , 2021
Abstract : The non-target toxicity and resistance problems of acetylcholinesterase (AChE) insecticides, such as organophosphates and carbamates, are of growing concern. To explore the potential targets for achieving inhibitor selectivity, the AChE structures at or near the catalytic pocket of Tetranychus urticae (TuAChE), honey bees, and humans were compared. The entrances to the AChE catalytic pocket differ significantly because of their different peripheral sites. The role of these potential mite-specific sites in AChE function was further elucidated by site-directed mutagenesis of these sites and then examining the catalytic activities of TuAChE mutants. The spider mite E(316), H(369), and V(105) active sites are important for AChE function. By further analyzing their physostigmine inhibitory properties and the detailed interaction between physostigmine and TuAChE, the peripheral site H(369) locating near the gorge entrance, and S(154) at the oxyanion hole, affects substrate and inhibitor trafficking. The discovery of conserved mite-specific residues in Tetranychus will enable the development of safer, effective pesticides that target residues present only in mite AChEs, potentially offering effective control against this important agricultural pest.
ESTHER : Li_2021_Exp.Appl.Acarol__
PubMedSearch : Li_2021_Exp.Appl.Acarol__
PubMedID: 33914192

Title : Curcumin relieves mice gastric emptying dysfunction induced by L-arginine and atropine through interstitial cells of Cajal - Lin_2021_Exp.Ther.Med_21_548
Author(s) : Lin P , Li B , Ye J , Shang F , Zhao H , Xie J , Yu X
Ref : Exp Ther Med , 21 :548 , 2021
Abstract : Curcumin is natural polyphenol from Curcuma longa rhizomes with several biological properties. Our previous studies demonstrated that curcumin inhibited functional gastric emptying disorders induced by L-arginine, the precursor of nitric oxide (NO), and atropine, an acetylcholine receptor (AChR) blocker. However, the mechanism of action of curcumin remains unclear. In the present study, mouse models of functional gastric emptying disorders induced by L-arginine and atropine were used to examine changes in interstitial cells of Cajal (ICC) and NO- and ACh-mediated regulation of gastrointestinal motility. Curcumin pre-treatment ameliorated the gastric emptying rate in mice treated with L-arginine or atropine (P<0.01). NO content and NO synthase activity significantly increased in the stomachs of L-arginine-treated mice, compared with controls (P<0.01). Acetylcholinesterase activity (P<0.01) and mRNA expression (P<0.01), as well as AChR mRNA levels (P<0.05) significantly decreased following atropine treatment. Moreover, in both models, the levels of c-kit, anoctamin 1 and connexin 43 significantly decreased in the stomach (P<0.01). Conversely, curcumin pre-treatment inhibited the changes induced by L-arginine and atropine (P<0.01 or P<0.05). By affecting the production of exogenous NO, the effects of Ach-AchR and the biomarkers of ICC, curcumin relieves the gastric emptying dysfunction in mice.
ESTHER : Lin_2021_Exp.Ther.Med_21_548
PubMedSearch : Lin_2021_Exp.Ther.Med_21_548
PubMedID: 33850520

Title : Evaluation of PET Degradation Using Artificial Microbial Consortia - Qi_2021_Front.Microbiol_12_778828
Author(s) : Qi X , Ma Y , Chang H , Li B , Ding M , Yuan Y
Ref : Front Microbiol , 12 :778828 , 2021
Abstract : Polyethylene terephthalate (PET) biodegradation is regarded as an environmentally friendly degradation method. In this study, an artificial microbial consortium composed of Rhodococcus jostii, Pseudomonas putida and two metabolically engineered Bacillus subtilis was constructed to degrade PET. First, a two-species microbial consortium was constructed with two engineered B. subtilis that could secrete PET hydrolase (PETase) and monohydroxyethyl terephthalate hydrolase (MHETase), respectively; it could degrade 13.6% (weight loss) of the PET film within 7 days. A three-species microbial consortium was further obtained by adding R. jostii to reduce the inhibition caused by terephthalic acid (TPA), a breakdown product of PET. The weight of PET film was reduced by 31.2% within 3 days, achieving about 17.6% improvement compared with the two-species microbial consortium. Finally, P. putida was introduced to reduce the inhibition caused by ethylene glycol (EG), another breakdown product of PET, obtaining a four-species microbial consortium. With the four-species consortium, the weight loss of PET film reached 23.2% under ambient temperature. This study constructed and evaluated the artificial microbial consortia in PET degradation, which demonstrated the great potential of artificial microbial consortia in the utilization of complex substrates, providing new insights for biodegradation of complex polymers.
ESTHER : Qi_2021_Front.Microbiol_12_778828
PubMedSearch : Qi_2021_Front.Microbiol_12_778828
PubMedID: 35003008

Title : A pendant droplet-based sensor for the detection of acetylcholinesterase and its inhibitors - Li_2021_Chem.Commun.(Camb)_57_8909
Author(s) : Li B , Guo Y , Jiang Y , Lin JM , Hu Q , Yu L
Ref : Chem Commun (Camb) , 57 :8909 , 2021
Abstract : In this work, a pendant droplet-based sensor is developed for the rapid and label-free detection of acetylcholinesterase (AChE) and its inhibitors. The detection limit of AChE reaches 0.17 mU mL(-1). The pIC(50) values of AChE inhibitors such as neostigmine, rivastigmine and galantamine are determined to be 0.45 microM, 0.64 microM and 4.93 microM, respectively.
ESTHER : Li_2021_Chem.Commun.(Camb)_57_8909
PubMedSearch : Li_2021_Chem.Commun.(Camb)_57_8909
PubMedID: 35225993

Title : Integrating target-responsive CD-CdTe QD-based ratiometric fluorescence hydrogel with smartphone for visual and on-site determination of dichlorvos - Huang_2021_Mikrochim.Acta_188_318
Author(s) : Huang S , Yao J , Li B , Ning G , Xiao Q
Ref : Mikrochim Acta , 188 :318 , 2021
Abstract : A facile, economic, and portable test kit based on target-responsive hydrogel with smartphone detection was fabricated for the accurate determination of dichlorvos in tap water and food samples. Carbon dots (CDs) and CdTe quantum dots (QDs) embedded hydrogel were employed as indicator, and fluorescence of CdTe QDs (645 nm) was dynamically quenched by Cu(2+) while that of CDs (490 nm) were non-response for Cu(2+), em erging a typical ratiometric fluorescence signal. Acetylcholinesterase hydrolyzed acetylthiocholine to generate thiocholine that bound with Cu(2+) strongly via S-Cu-S bond. Dichlorvos as competitive inhibitor for acetylcholinesterase prevented the generation of thiocholine, which blocked the formation of Cu-thiocholine complex and changed the ratiometric fluorescence signal. The signal of the test kit, which was recorded by smartphone's camera, was transduced by ImageJ software into the color parameter that was linearly proportional to the logarithm of dichlorvos concentration. This portable test kit showed wide linear range of 1 to 40 ppb and low detection limit of 0.38 ppb for dichlorvos. This test kit exhibited rapid sample-to-answer detection time (50 min) of dichlorvos in tap water and food samples, and the recoveries were in the range 81.3 to 111% with relative standard deviations of less than 9.1%. A facile and economic portable test kit based on CD-CdTe QD target-responsive hydrogel with smartphone was innovatively fabricated for the accurate determination of organophosphorus pesticides. This portable test kit showed low detection limit of 0.38 ppb for dichlorvos and rapid sample-to-answer detection time (50 min) in tap water and food samples, which offered a new sight for portable monitoring of environmental pollution and food safety.
ESTHER : Huang_2021_Mikrochim.Acta_188_318
PubMedSearch : Huang_2021_Mikrochim.Acta_188_318
PubMedID: 34476614

Title : Complexation of caffeine and theophylline with epigallocatechin gallate in aqueous solution: Nuclear magnetic resonance, molecular docking and thermodynamics studies - Guo_2021_Food.Res.Int_148_110587
Author(s) : Guo C , Li J , Chen Y , Geng F , Li B
Ref : Food Res Int , 148 :110587 , 2021
Abstract : Epigallocatechin gallate (EGCg) and methylxanthines are representative bioactive compounds in tea leaves, the strong affinity between them will elicit destruction of tea quality. In order to elucidate the mechanism of complexation between EGCg and methylxanthines, we compared the bindings of theophylline and caffeine to EGCg by nuclear magnetic resonance (NMR), molecular docking and isothermal titration calorimetry (ITC). The results revealed that the stoichiometries of caffeine to EGCg and theophylline to EGCg were both 1:1. Caffeine and theophylline were captured in the hydrophobic space formed by aromatic rings of EGCg. The affinity between EGCg and caffeine was stronger than that between EGCg and theophylline, which could be partially attributed to the two extra CH-Pi interactions between N(7)-Me of caffeine and aromatic rings of EGCg. Furthermore, the results of ITC were agreed well with NMR and molecular docking, indicating that ITC was possible to accurately evaluate the complexation.
ESTHER : Guo_2021_Food.Res.Int_148_110587
PubMedSearch : Guo_2021_Food.Res.Int_148_110587
PubMedID: 34507732

Title : Biochemical and Structural Characterization of a Novel Bacterial Tannase From Lachnospiraceae bacterium in Ruminant Gastrointestinal Tract - Guan_2021_Front.Bioeng.Biotechnol_9_806788
Author(s) : Guan L , Wang K , Gao Y , Li J , Yan S , Ji N , Ren C , Wang J , Zhou Y , Li B , Lu S
Ref : Front Bioeng Biotechnol , 9 :806788 , 2021
Abstract : Tannases are a family of esterases that catalyze the hydrolysis of ester and depside bonds present in hydrolyzable tannins to release gallic acid. Here, a novel tannase from Lachnospiraceae bacterium (TanA(Lb)) was characterized. The recombinant TanA(Lb) exhibited maximal activity at pH 7.0 and 50 degreesC, and it maintained more than 70% relative activity from 30 degreesC to 55 degreesC. The activity of TanA(Lb) was enhanced by Mg(2+) and Ca(2+), and was dramatically reduced by Cu(2+) and Mn(2+). TanA(Lb) is capable of degrading esters of phenolic acids with long-chain alcohols, such as lauryl gallate as well as tannic acid. The Km value and catalytic efficiency (k (cat) /Km) of TanA(Lb) toward five substrates showed that tannic acid (TA) was the favorite substrate. Homology modeling and structural analysis indicated that TanA(Lb) contains an insertion loop (residues 341-450). Based on the moleculer docking and molecular dynamics (MD) simulation, this loop was observed as a flap-like lid to interact with bulk substrates such as tannic acid. TanA(Lb) is a novel bacterial tannase, and the characteristics of this enzyme make it potentially interesting for industrial use.
ESTHER : Guan_2021_Front.Bioeng.Biotechnol_9_806788
PubMedSearch : Guan_2021_Front.Bioeng.Biotechnol_9_806788
PubMedID: 34976993
Gene_locus related to this paper: 9firm-TanALb

Title : Inhibition of Soluble Epoxide Hydrolase Attenuates Bosutinib-Induced Blood Pressure Elevation -
Author(s) : Cui Z , Li B , Zhang Y , He J , Shi X , Wang H , Zhao Y , Yao L , Ai D , Zhang X , Zhu Y
Ref : Hypertension , 78 :1527 , 2021
PubMedID: 34601968

Title : Synthesis and Structure-Activity Relationships of 3-Arylisoquinolone Analogues as Highly Specific hCES2A Inhibitors - Zhao_2021_ChemMedChem_16_388
Author(s) : Zhao Y , Xiong Y , Dong S , Guan X , Song Y , Yang Y , Zou K , Li Z , Zhang Y , Fang S , Li B , Zhu W , Chen K , Jia Q , Ge G
Ref : ChemMedChem , 16 :388 , 2021
Abstract : Mammalian carboxylesterases (CES) are key enzymes that participate in the hydrolytic metabolism of various endogenous and exogenous substrates. Human carboxylesterase 2A (hCES2A), mainly distributed in the small intestine and colon, plays a significant role in the hydrolysis of many drugs. In this study, 3-arylisoquinolones 3h [3-(4-(benzyloxy)-3-methoxyphenyl)-7,8-dimethoxyisoquinolin-1(2H)-one] and 4a [3-(4-(benzyloxy)-3-methoxyphenyl)-4-bromo-7,8-dimethoxyisoquinolin-1(2H)-one] were found to have potent inhibitory effects on hCES2A (IC(50) =0.68microM, K(i) =0.36microM) and excellent specificity (more than 147.05-fold over hCES1A). Moreover, 4a exhibited threefold improved inhibition on intracellular hCES2A in living HepG2 cells relative to 3h, with an IC(50) value of 0.41microM. Results of inhibition kinetics studies and molecular docking simulations demonstrate that both 3h and 4a can bind to multiple sites on hCES2A, functioning as mixed inhibitors. Structure-activity relationship analysis revealed that the lactam moiety on the B ring is crucial for specificity towards hCES2A, while a benzyloxy group is optimal for hCES2A inhibitory potency; the introduction of a bromine atom may enhance cell permeability, thereby increasing the intracellular hCES2A inhibitory activity.
ESTHER : Zhao_2021_ChemMedChem_16_388
PubMedSearch : Zhao_2021_ChemMedChem_16_388
PubMedID: 32935462

Title : Nutritional Status and Body Composition in Wilson Disease: A Cross-Sectional Study From China - Geng_2021_Front.Nutr_8_790520
Author(s) : Geng H , Wang S , Jin Y , Cheng N , Song B , Shu S , Li B , Han Y , Gao L , Ding Z , Xu Y , Wang X , Ma Z , Sun Y
Ref : Front Nutr , 8 :790520 , 2021
Abstract : Background: Abnormal nutritional status is frequently seen in patients with chronic diseases. To date, no study has investigated the detailed characteristics of abnormal nutritional status among Wilson's disease (WD) patients in the Chinese cohort. This study aimed to describe the nutritional status of WD patients, with a particular focus on the differences between patients with different phenotypes. Methods: The study subjects comprised 119 healthy controls, 129 inpatients (hepatic subtype, n = 34; neurological subtype, n = 95) who were being treated at the affiliated hospital of the Institute of Neurology, Anhui University of Chinese Medicine. All of the subjects were assessed for body composition by using bioelectrical impedance analysis. All WD patients received anthropometry, nutritional risk screening 2002 (NRS2002), and laboratory test (hemocyte and serum biomarkers) additionally. Results: Compared with healthy controls, the fat mass and rate of total body and trunk were significantly higher in WD patients (P < 0.001), the muscle and skeletal muscle mass of total body and trunk were significantly lower in WD patients (P < 0.001). Compared with hepatic subtype patients, the fat mass and rate of total body, trunk, and limbs were significantly lower in neurological subtype patients (P<0.01); while there were no significant differences in muscle and skeletal muscle between these two subtypes. The overall prevalence of abnormal nutritional status in WD patients was 43.41% (56/129). The prevalence of high-nutritional risk and overweight in WD patients was 17.83% (23 of 129) and 25.58% (33 of 129), respectively. Compare with patients with high nutritional risk, macro platelet ratio, alkaline phosphatase, the basal metabolic rate (p < 0.05), creatinine, trunk fat rate (p < 0.01) and appendicular skeletal muscle mass (p < 0.001) were significantly higher in patients without nutritional risk (p < 0.001). Patients with a high nutritional risk tend to have a lower cholinesterase concentration (x (2) = 4.227, p < 0.05). Conclusion: Both patients with H-subtype and N-subtype are prone to have an abnormal nutritional status. Longitudinal studies are required to investigate if nutritional status and body composition could reflect prognosis in WD patients, and which of these body composition indexes contribute to malnutrition and worse prognosis.
ESTHER : Geng_2021_Front.Nutr_8_790520
PubMedSearch : Geng_2021_Front.Nutr_8_790520
PubMedID: 35036410

Title : Insecticidal Activity of Artemisia vulgaris Essential Oil and Transcriptome Analysis of Tribolium castaneum in Response to Oil Exposure - Gao_2020_Front.Genet_11_589
Author(s) : Gao S , Zhang K , Wei L , Wei G , Xiong W , Lu Y , Zhang Y , Gao A , Li B
Ref : Front Genet , 11 :589 , 2020
Abstract : Red flour beetle (Tribolium castaneum) is one of the most destructive pests of stored cereals worldwide. The essential oil (EO) of Artemisia vulgaris (mugwort) is known to be a strong toxicant that inhibits the growth, development, and reproduction of T. castaneum. However, the molecular mechanisms underlying the toxic effects of A. vulgaris EO on T. castaneum remain unclear. Here, two detoxifying enzymes, carboxylesterase (CarEs) and cytochrome oxidase P450 (CYPs), were dramatically increased in red flour beetle larvae when they were exposed to A. vulgaris EO. Further, 758 genes were differentially expressed between EO treated and control samples. Based on Gene Ontology (GO) analysis, numerous differentially expressed genes (DEGs) were enriched for terms related to the regulation of biological processes, response to stimulus, and antigen processing and presentation. Our results indicated that A. vulgaris EO disturbed the antioxidant activity in larvae and partially inhibited serine protease (SP), cathepsin (CAT), and lipase signaling pathways, thus disrupting larval development and reproduction as well as down-regulating the stress response. Moreover, these DEGs showed that A. vulgaris indirectly affected the development and reproduction of beetles by inducing the expression of genes encoding copper-zinc-superoxide dismutase (CuZnSOD), heme peroxidase (HPX), antioxidant enzymes, and transcription factors. Moreover, the majority of DEGs were mapped to the drug metabolism pathway in the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Notably, the following genes were detected: 6 odorant binding proteins (OBPs), 5 chemosensory proteins (CSPs), 14 CYPs, 3 esterases (ESTs), 5 glutathione S-transferases (GSTs), 6 UDP-glucuronosyltransferases (UGTs), and 2 multidrug resistance proteins (MRPs), of which 8 CYPs, 2 ESTs, 2 GSTs, and 3 UGTs were up-regulated dramatically after exposure to A. vulgaris EO. The residual DEGs were significantly down-regulated in EO exposed larvae, implying that partial compensation of metabolism detoxification existed in treated beetles. Furthermore, A. vulgaris EO induced overexpression of OBP/CYP, and RNAi against these genes significantly increased mortality of larvae exposed to EO, providing further evidence for the involvement of OBP/CYP in EO metabolic detoxification in T. castaneum. Our results provide an overview of the transcriptomic changes in T. castaneum in response to A. vulgaris EO.
ESTHER : Gao_2020_Front.Genet_11_589
PubMedSearch : Gao_2020_Front.Genet_11_589
PubMedID: 32670352

Title : Supplementation with gamma-glutamylcysteine (gamma-GC) lessens oxidative stress, brain inflammation and amyloid pathology and improves spatial memory in a murine model of AD - Liu_2020_Neurochem.Int__104931
Author(s) : Liu Y , Chen Z , Li B , Yao H , Zarka M , Welch J , Sachdev P , Bridge W , Braidy N
Ref : Neurochem Int , :104931 , 2020
Abstract : INTRODUCTION: The accumulation of oxidative stress, neuroinflammation and abnormal aggregation of amyloid beta-peptide (Abeta) have been shown to induce synaptic dysfunction and memory deficits in Alzheimer's disease (AD). Cellular depletion of the major endogenous antioxidant Glutathione (GSH) has been linked to cognitive decline and the development of AD pathology. Supplementation with gamma-glutamylcysteine (gamma-GC), the immediate precursor and the limiting substrate for GSH biosynthesis, can transiently augment cellular GSH levels by bypassing the regulation of GSH homeostasis. METHODS: In the present study, we investigated the effect of dietary supplementation of gamma-GC on oxidative stress and Abeta pathology in the brains of APP/PS1 mice. The APP/PS1 mice were fed gamma-GC from 3 months of age with biomarkers of apoptosis and cell death, oxidative stress, neuroinflammation and Abeta load being assessed at 6 months of age. RESULTS: Our data showed that supplementation with gamma-GC lowered the levels of brain lipid peroxidation, protein carbonyls and apoptosis, increased both total GSH and the glutathione/glutathione disulphide (GSH/GSSG) ratio and replenished ATP and the activities of the antioxidant enzymes (superoxide dismutase (SOD), catalase, glutamine synthetase and glutathione peroxidase (GPX)), the latter being a key regulator of ferroptosis. Brain Abeta load was lower and acetylcholinesterase (AChE) activity was markedly improved compared to APP/PS1 mice fed a standard chow diet. Alteration in brain cytokine levels and matrix metalloproteinase enzymes MMP-2 and MMP-9 suggested that gamma-GC may lower inflammation and enhance Abeta plaque clearance in vivo. Spatial memory was also improved by gamma-GC as determined using the Morris water maze. CONCLUSION: Our data collectively suggested that supplementation with gamma-GC may represent a novel strategy for the treatment and/or prevention of cognitive impairment and neurodegeneration.
ESTHER : Liu_2020_Neurochem.Int__104931
PubMedSearch : Liu_2020_Neurochem.Int__104931
PubMedID: 33276023

Title : Discovery of nitazoxanide-based derivatives as autophagy activators for the treatment of Alzheimer's disease - Li_2020_Acta.Pharm.Sin.B_10_646
Author(s) : Li X , Lu J , Xu Y , Wang J , Qiu X , Fan L , Li B , Liu W , Mao F , Zhu J , Shen X , Li J
Ref : Acta Pharm Sin B , 10 :646 , 2020
Abstract : Drug repurposing is an efficient strategy for new drug discovery. Our latest study found that nitazoxanide (NTZ), an approved anti-parasite drug, was an autophagy activator and could alleviate the symptom of Alzheimer's disease (AD). In order to further improve the efficacy and discover new chemical entities, a series of NTZ-based derivatives were designed, synthesized, and evaluated as autophagy activator against AD. All compounds were screened by the inhibition of phosphorylation of p70S6K, which was the direct substrate of mammalian target of rapamycin (mTOR) and its phosphorylation level could reflect the mTOR-dependent autophagy level. Among these analogs, compound 22 exhibited excellent potency in promoting beta-amyloid (Abeta) clearance, inhibiting tau phosphorylation, as well as stimulating autophagy both in vitro and in vivo. What's more, 22 could effectively improve the memory and cognitive impairments in APP/PS1 transgenic AD model mice. These results demonstrated that 22 was a potential candidate for the treatment of AD.
ESTHER : Li_2020_Acta.Pharm.Sin.B_10_646
PubMedSearch : Li_2020_Acta.Pharm.Sin.B_10_646
PubMedID: 32322468

Title : Genome sequencing of the Australian wild diploid species Gossypium australe highlights disease resistance and delayed gland morphogenesis - Cai_2020_Plant.Biotechnol.J_18_814
Author(s) : Cai Y , Cai X , Wang Q , Wang P , Zhang Y , Cai C , Xu Y , Wang K , Zhou Z , Wang C , Geng S , Li B , Dong Q , Hou Y , Wang H , Ai P , Liu Z , Yi F , Sun M , An G , Cheng J , Shi Q , Xie Y , Shi X , Chang Y , Huang F , Chen Y , Hong S , Mi L , Sun Q , Zhang L , Zhou B , Peng R , Zhang X , Liu F
Ref : Plant Biotechnol J , 18 :814 , 2020
Abstract : The diploid wild cotton species Gossypium australe possesses excellent traits including resistance to disease and delayed gland morphogenesis, and has been successfully used for distant breeding programmes to incorporate disease resistance traits into domesticated cotton. Here, we sequenced the G. australe genome by integrating PacBio, Illumina short read, BioNano (DLS) and Hi-C technologies, and acquired a high-quality reference genome with a contig N50 of 1.83 Mb and a scaffold N50 of 143.60 Mb. We found that 73.5% of the G. australe genome is composed of various repeat sequences, differing from those of G. arboreum (85.39%), G. hirsutum (69.86%) and G. barbadense (69.83%). The G. australe genome showed closer collinear relationships with the genome of G. arboreum than G. raimondii and has undergone less extensive genome reorganization than the G. arboreum genome. Selection signature and transcriptomics analyses implicated multiple genes in disease resistance responses, including GauCCD7 and GauCBP1, and experiments revealed induction of both genes by Verticillium dahliae and by the plant hormones strigolactone (GR24), salicylic acid (SA) and methyl jasmonate (MeJA). Experiments using a Verticillium-resistant domesticated G. barbadense cultivar confirmed that knockdown of the homologues of these genes caused a significant reduction in resistance against Verticillium dahliae. Moreover, knockdown of a newly identified gland-associated gene GauGRAS1 caused a glandless phenotype in partial tissues using G. australe. The G. australe genome represents a valuable resource for cotton research and distant relative breeding as well as for understanding the evolutionary history of crop genomes.
ESTHER : Cai_2020_Plant.Biotechnol.J_18_814
PubMedSearch : Cai_2020_Plant.Biotechnol.J_18_814
PubMedID: 31479566
Gene_locus related to this paper: gosra-a0a0d2pzd7

Title : Chronic trichlorfon stress induces differential transcriptome expression and interferes with multifunctional pathways in the brain of Rana chensinensis - Ma_2020_J.Environ.Sci.Health.B__1
Author(s) : Ma Y , Li B , Ke Y , Zhu HY , Zhang YH
Ref : J Environ Sci Health B , :1 , 2020
Abstract : Trichlorfon is widely used to control pest insects and various parasitic infestations in agriculture, aquaculture and human medicine. However, the long-term widespread use and overuse of trichlorfon poses risks to public and environmental health. Thus, the aim of this study was to evaluate the interference of trichlorfon on gene transcription patterns in the brain of Rana chensinensis with 4 weeks treatment under control conditions and 0.1 mg/L exposure. In total, 102,013 unigenes were obtained from the brain tissue of R. chensinensis, and 874 differentially expressed genes (DEGs) were identified. Functional annotation indicated that out of 118,643 unigenes, 45,600 (44.7%) were annotated in the Nr, Nt, the Swiss-Prot, KEGG, COG, and GO databases. The differential expression patterns of 4 genes associated with neural activity were selected and validated by quantitative polymerase chain reaction (qPCR). The results revealed that except for the canonical cholinesterase-based mechanism, trichlorfon could act on other receptors and alter certain types of neuronal ion channels as the major target sites. All of these effects ultimately cause disorders of multifunctional pathways and other neurotransmitter pathways in the host. The results further our understanding of the mechanisms underlying nontarget effects of organophosphate insecticides (OPs) through multitargets studies.
ESTHER : Ma_2020_J.Environ.Sci.Health.B__1
PubMedSearch : Ma_2020_J.Environ.Sci.Health.B__1
PubMedID: 33030406

Title : CA10 and CA11 negatively regulate neuronal activity-dependent growth of gliomas - Tao_2019_Mol.Oncol_13_1018
Author(s) : Tao B , Ling Y , Zhang Y , Li S , Zhou P , Wang X , Li B , Jun Z , Zhang W , Xu C , Shi J , Wang L
Ref : Mol Oncol , 13 :1018 , 2019
Abstract : Recent studies have revealed that neurons can promote glioma growth through activity-dependent secretion of neurotrophins, especially neuroligin-3. It has therefore been suggested that blocking neuron-derived neurotrophins may serve as a therapeutic intervention for gliomas. Carbonic anhydrase-related proteins 11 and 10 (CA11 and CA10) are secreted synaptic proteins which function as neurexin ligands, and the gene-encoding CA11 is part of a gene signature associated with radiotherapy and prognosis in gliomas. We therefore hypothesized that CA11/CA10 might participate in the neuronal activity-dependent regulation of glioma growth. In this study, we report that CA11 secreted by depolarized cultured neurons within conditioned medium (CM) inhibited the growth of glioma cell lines. CM from depolarized neurons inhibited CA11 expression in glioma cell lines via the Akt signaling pathway. Consistently, CA11 expression was also reduced in clinical glioma samples and negatively associated with high histological grade. Low CA11 expression of gliomas was associated with short survival in four independent datasets [repository of brain neoplasia data (REMBRANDT), The Cancer Genome Atlas (TCGA) lower grade glioma (LGG), GSE4271, and GSE42669]. CA11 knockdown promoted cell growth, clone formation, and migration; inhibited apoptosis; and increased tumor size in xenografted nude mice. Similarly, CA10 and CA10 secreted by depolarized cultured neurons also inhibited the growth of glioma cell lines. Low CA10 expression was associated with short survival in REMBRANDT, TCGA LGG, and GEO GSE4271 datasets. Our results suggest that CA11 and CA10 negatively regulate neuronal activity-dependent glioma growth and inhibit glioma aggression. Thus, CA11/CA10 may represent a potential therapeutic target for the treatment of gliomas.
ESTHER : Tao_2019_Mol.Oncol_13_1018
PubMedSearch : Tao_2019_Mol.Oncol_13_1018
PubMedID: 30636076

Title : Antioxidant Profile of 1-Monocaffeoyl Glycerol in Lipophobic\/Lipophilic Media - Weng_2019_J.Food.Sci_84_2091
Author(s) : Weng L , Li L , Ji L , Zhao D , Xu Z , Su J , Li B , Zhang X
Ref : J Food Sci , 84 :2091 , 2019
Abstract : Oxidative stress has been generally considered as one trigger of organism imbalance, resulting in lipid peroxidation, DNA damage and protein oxidation, which could be relieved by antioxidant supplement or endogenous antioxidant system. In present study, 1-monocaffeoyl glycerol (1-MCG), an amphipathic caffeic acid natural derivative, was enzymatically synthesized by Lipozyme 435, and its antioxidant profile in both lipophilic and lipophobic media was evaluated. The 1-MCG was identified by HPLC-UV, HPLC-ESI-MS, and (1) H/(13) C-NMR. Subsequently, antioxidant assays in lipophilic (DPPH assay) and lipophobic (ABTS, ORAC, erythrocyte hemolysis, ROS, MDA, and GPx assays) systems were explored. The better and lasting DPPH. and ABTS(+.) inhibitions of 1-MCG than caffeic acid (CA) were related to its better solubilities in ethanol/water media and electron transfer ability. ORAC results suggested the radical scavenging activities of 1-MCG (5 to 40 microM) were higher than Trolox. Furthermore, the effectiveness of 1-MCG against AAPH-induced erythrocytes oxidation indicated that 1-MCG can effectively inhibit hemolysis. ESEM was also applied to verify the hemolysis inhibition and morphology preservation abilities of 1-MCG. Besides, results showed 1-MCG was able to prevent ROS from invasion, reduce production of MDA, up-regulated GPx activity, terminate lipid peroxidation, and maintain the integrity of the structure and function of erythrocytes. PRACTICAL APPLICATION: As an amphiphilic caffeic acid derivative, 1-monocaffeoyl glycerol was synthesized, purified, and identified. 1-Monocaffeoyl glycerol could significantly eliminate radicals including DPPH., ABTS(+.) , and AAPH in ethanol, water, and PBS system, respectively. 1-Monocaffeoyl glycerol could protect erythrocyte from AAPH induced hemolysis.
ESTHER : Weng_2019_J.Food.Sci_84_2091
PubMedSearch : Weng_2019_J.Food.Sci_84_2091
PubMedID: 31313325

Title : Insecticidal effect of aconitine on the rice brown planthoppers - Wei_2019_PLoS.One_14_e0221090
Author(s) : Wei S , Zhang H , Li B , Ji J , Shao X
Ref : PLoS ONE , 14 :e0221090 , 2019
Abstract : The brown planthopper, Nilaparvata lugens (Stal), severely damages rice production and develops high level resistance to several classes of insecticides. To find potential insecticidal resources is always important. As an environmentally friendly compound, aconitine exhibits potential pesticide features. In the present study, the pesticide and knockdown effects of aconitine were first tested on the brown planthopper. The results showed that the knockdown rates for an aconitine concentration of 200 ppm was 83.6%. The insecticidal LD50 was 22.68 ng/pest (95% CI, 17.75-28.99). The molecular mechanisms responding to aconitine application were analyzed through transcriptional sequencing. Compared to that of the knockdown nymphs of the brown planthoppers, the enzymes CYP3A4, UDP-glucuronosyltransferase (UGT), GST, carboxylesterase (EC3.1.1.1), and GABAergic synapse were up-regulated. We inferred that aconitine might be neurotoxic to the brown planthoppers, and the conscious nymphs resist the drug neurotoxicity through the upregulation of CYP3A4, UGT, and GABA receptor mutation. Although aconitine is not safe for mammals, it may be a leading compound to develop novel insecticides.
ESTHER : Wei_2019_PLoS.One_14_e0221090
PubMedSearch : Wei_2019_PLoS.One_14_e0221090
PubMedID: 31426056

Title : First Genome-wide Association Analysis for Growth Traits in the Largest Coral Reef-Dwelling Bony Fishes, the Giant Grouper (Epinephelus lanceolatus) - Wu_2019_Mar.Biotechnol.(NY)_21_707
Author(s) : Wu L , Yang Y , Li B , Huang W , Wang X , Liu X , Meng Z , Xia J
Ref : Mar Biotechnol (NY) , 21 :707 , 2019
Abstract : The giant grouper, Epinephelus lanceolatus, is the largest coral reef-dwelling bony fish species. However, despite extremely fast growth performance and the considerable economic importance in this species, its genetic regulation of growth remains unknown. Here, we performed the first genome-wide association study (GWAS) for five growth traits in 289 giant groupers using 42,323 single nucleotide polymorphisms (SNPs) obtained by genotyping-by-sequencing (GBS). We identified a total of 36 growth-related SNPs, of which 11 SNPs reached a genome-wide significance level. The phenotypic variance explained by these SNPs varied from 7.09% for body height to 18.42% for body length. Moreover, 22 quantitative trait loci (QTLs) for growth traits, including nine significant QTLs and 13 suggestive QTLs, were found on multiple chromosomes. Interestingly, the QTL (LG17: 6934451) was shared between body weight and body height, while two significant QTLs (LG7: 22596399 and LG15: 11877836) for body length were consistent with the associated regions of total length at the genome-wide suggestive level. Eight potential candidate genes close to the associated SNPs were selected for expression analysis, of which four genes (phosphatidylinositol transfer protein cytoplasmic 1, protein tyrosine phosphatase receptor type E, alpha/beta hydrolase domain-containing protein 17C, and vascular endothelial growth factor A-A) were differentially expressed and involved in metabolism, development, response stress, etc. This study improves our understanding of the complex genetic architecture of growth in the giant grouper. The results contribute to the selective breeding of grouper species and the conservation of coral reef fishes.
ESTHER : Wu_2019_Mar.Biotechnol.(NY)_21_707
PubMedSearch : Wu_2019_Mar.Biotechnol.(NY)_21_707
PubMedID: 31392592

Title : Latrophilin mediates insecticides susceptibility and fecundity through two carboxylesterases, esterase4 and esterase6, in Tribolium castaneum - Wei_2019_Bull.Entomol.Res__1
Author(s) : Wei L , Gao S , Xiong W , Liu J , Mao J , Lu Y , Song X , Li B
Ref : Bull Entomol Res , :1 , 2019
Abstract : Latrophilin (LPH) is known as an adhesion G-protein-coupled receptor which involved in multiple physiological processes in organisms. Previous studies showed that lph not only involved the susceptibility to anticholinesterase insecticides but also affected fecundity in Tribolium castaneum. However, its regulatory mechanisms in these biological processes are still not clear. Here, we identified two potential downstream carboxylesterase (cce) genes of Tclph, esterase4 and esterase6, and further characterized their interactions with Tclph. After treatment of T. castaneum larvae with carbofuran or dichlorvos insecticides, the transcript levels of Tcest4 and Tcest6 were significantly induced from 12 to 72 h. RNAi against Tcest4 or Tcest6 led to the higher mortality compared with the controls after the insecticides treatment, suggesting that these two genes play a vital role in detoxification of insecticides in T. castaneum. Furthermore, with insecticides exposure to Tclph knockdown beetles, the expression of Tcest4 was upregulated but Tcest6 was downregulated, indicating that beetles existed a compensatory response against the insecticides. Additionally, RNAi of Tcest6 resulted in 43% reductions in female egg laying and completely inhibited egg hatching, which showed the similar phenotype as that of Tclph knockdown. These results indicated that Tclph affected fecundity by positively regulating Tcest6 expression. Our findings will provide a new insight into the molecular mechanisms of Tclph involved in physiological functions in T. castaneum.
ESTHER : Wei_2019_Bull.Entomol.Res__1
PubMedSearch : Wei_2019_Bull.Entomol.Res__1
PubMedID: 30789108

Title : Inhibition of soluble epoxide hydrolase ameliorates hyperhomocysteinemia-induced hepatic steatosis by enhancing beta-oxidation of fatty acid in mice - Yao_2019_Am.J.Physiol.Gastrointest.Liver.Physiol_316_G527
Author(s) : Yao L , Cao B , Cheng Q , Cai W , Ye C , Liang J , Liu W , Tan L , Yan M , Li B , He J , Hwang SH , Zhang X , Wang C , Ai D , Hammock BD , Zhu Y
Ref : American Journal of Physiology Gastrointest Liver Physiol , 316 :G527 , 2019
Abstract : Hepatic steatosis is the beginning phase of nonalcoholic fatty liver disease, and hyperhomocysteinemia (HHcy) is a significant risk factor. Soluble epoxide hydrolase (sEH) hydrolyzes epoxyeicosatrienoic acids (EETs) and other epoxy fatty acids, attenuating their cardiovascular protective effects. However, the involvement of sEH in HHcy-induced hepatic steatosis is unknown. The current study aimed to explore the role of sEH in HHcy-induced lipid disorder. We fed 6-wk-old male mice a chow diet or 2% (wt/wt) high-metnionine diet for 8 wk to establish the HHcy model. A high level of homocysteine induced lipid accumulation in vivo and in vitro, which was concomitant with the increased activity and expression of sEH. Treatment with a highly selective specific sEH inhibitor (0.8 for the animal model and 1 muM for cells) prevented HHcy-induced lipid accumulation in vivo and in vitro. Inhibition of sEH activated the peroxisome proliferator-activated receptor-alpha (PPAR-alpha), as evidenced by elevated beta-oxidation of fatty acids and the expression of PPAR-alpha target genes in HHcy-induced hepatic steatosis. In primary cultured hepatocytes, the effect of sEH inhibition on PPAR-alpha activation was further confirmed by a marked increase in PPAR-response element luciferase activity, which was reversed by knock down of PPAR-alpha. Of note, 11,12-EET ligand dependently activated PPAR-alpha. Thus increased sEH activity is a key determinant in the pathogenesis of HHcy-induced hepatic steatosis, and sEH inhibition could be an effective treatment for HHcy-induced hepatic steatosis. NEW & NOTEWORTHY In the current study, we demonstrated that upregulation of soluble epoxide hydrolase (sEH) is involved in the hyperhomocysteinemia (HHcy)-caused hepatic steatosis in an HHcy mouse model and in murine primary hepatocytes. Improving hepatic steatosis in HHcy mice by pharmacological inhibition of sEH to activate peroxisome proliferator-activated receptor-alpha was ligand dependent, and sEH could be a potential therapeutic target for the treatment of nonalcoholic fatty liver disease.
ESTHER : Yao_2019_Am.J.Physiol.Gastrointest.Liver.Physiol_316_G527
PubMedSearch : Yao_2019_Am.J.Physiol.Gastrointest.Liver.Physiol_316_G527
PubMedID: 30789748

Title : Genetic Data from Nearly 63,000 Women of European Descent Predicts DNA Methylation Biomarkers and Epithelial Ovarian Cancer Risk - Yang_2019_Cancer.Res_79_505
Author(s) : Yang Y , Wu L , Shu X , Lu Y , Shu XO , Cai Q , Beeghly-Fadiel A , Li B , Ye F , Berchuck A , Anton-Culver H , Banerjee S , Benitez J , Bjorge L , Brenton JD , Butzow R , Campbell IG , Chang-Claude J , Chen K , Cook LS , Cramer DW , deFazio A , Dennis J , Doherty JA , Dork T , Eccles DM , Edwards DV , Fasching PA , Fortner RT , Gayther SA , Giles GG , Glasspool RM , Goode EL , Goodman MT , Gronwald J , Harris HR , Heitz F , Hildebrandt MA , Hogdall E , Hogdall CK , Huntsman DG , Kar SP , Karlan BY , Kelemen LE , Kiemeney LA , Kjaer SK , Koushik A , Lambrechts D , Le ND , Levine DA , Massuger LF , Matsuo K , May T , McNeish IA , Menon U , Modugno F , Monteiro AN , Moorman PG , Moysich KB , Ness RB , Nevanlinna H , Olsson H , Onland-Moret NC , Park SK , Paul J , Pearce CL , Pejovic T , Phelan CM , Pike MC , Ramus SJ , Riboli E , Rodriguez-Antona C , Romieu I , Sandler DP , Schildkraut JM , Setiawan VW , Shan K , Siddiqui N , Sieh W , Stampfer MJ , Sutphen R , Swerdlow AJ , Szafron LM , Teo SH , Tworoger SS , Tyrer JP , Webb PM , Wentzensen N , White E , Willett WC , Wolk A , Woo YL , Wu AH , Yan L , Yannoukakos D , Chenevix-Trench G , Sellers TA , Pharoah PDP , Zheng W , Long J
Ref : Cancer Research , 79 :505 , 2019
Abstract : DNA methylation is instrumental for gene regulation. Global changes in the epigenetic landscape have been recognized as a hallmark of cancer. However, the role of DNA methylation in epithelial ovarian cancer (EOC) remains unclear. In this study, high-density genetic and DNA methylation data in white blood cells from the Framingham Heart Study (N = 1,595) were used to build genetic models to predict DNA methylation levels. These prediction models were then applied to the summary statistics of a genome-wide association study (GWAS) of ovarian cancer including 22,406 EOC cases and 40,941 controls to investigate genetically predicted DNA methylation levels in association with EOC risk. Among 62,938 CpG sites investigated, genetically predicted methylation levels at 89 CpG were significantly associated with EOC risk at a Bonferroni-corrected threshold of P < 7.94 x 10(-7). Of them, 87 were located at GWAS-identified EOC susceptibility regions and two resided in a genomic region not previously reported to be associated with EOC risk. Integrative analyses of genetic, methylation, and gene expression data identified consistent directions of associations across 12 CpG, five genes, and EOC risk, suggesting that methylation at these 12 CpG may influence EOC risk by regulating expression of these five genes, namely MAPT, HOXB3, ABHD8, ARHGAP27, and SKAP1. We identified novel DNA methylation markers associated with EOC risk and propose that methylation at multiple CpG may affect EOC risk via regulation of gene expression. SIGNIFICANCE: Identification of novel DNA methylation markers associated with EOC risk suggests that methylation at multiple CpG may affect EOC risk through regulation of gene expression.
ESTHER : Yang_2019_Cancer.Res_79_505
PubMedSearch : Yang_2019_Cancer.Res_79_505
PubMedID: 30559148

Title : Enhanced Poly(ethylene terephthalate) Hydrolase Activity by Protein Engineering - Ma_2018_Engineering.(Beijing)_4_888
Author(s) : Ma Y , Yao M , Li B , Ding M , He B , Chen S , Zhou X , Yuan Y
Ref : Engineering (Beijing) , 4 :888 , 2018
Abstract : Poly(ethylene terephthalate) hydrolase (PETase) from Ideonella sakaiensis exhibits a strong ability to degrade poly(ethylene terephthalate) (PET) at room temperature, and is thus regarded as a potential tool to solve the issue of polyester plastic pollution. Therefore, we explored the interaction between PETase and the substrate (a dimer of the PET monomer ethylene terephthalate, 2PET), using a model of PETase and its substrate. In this study, we focused on six key residues around the substrate-binding groove in order to create novel high-efficiency PETase mutants through protein engineering. These PETase mutants were designed and tested. The enzymatic activities of the R61A, L88F, and I179F mutants, which were obtained with a rapid cell-free screening system, exhibited 1.4 fold, 2.1 fold, and 2.5 fold increases, respectively, in comparison with wild-type PETase. The I179F mutant showed the highest activity, with the degradation rate of a PET film reaching 22.5 mg per micromol/L PETase per day. Thus, this study has created enhanced artificial PETase enzymes through the rational protein engineering of key hydrophobic sites, and has further illustrated the potential of biodegradable plastics.
ESTHER : Ma_2018_Engineering.(Beijing)_4_888
PubMedSearch : Ma_2018_Engineering.(Beijing)_4_888
Gene_locus related to this paper: idesa-peth

Title : Chinese Medicine for Alzheimer's Disease: A Meta-Analysis of Randomized Controlled Trials - Ma_2018_Chin.J.Integr.Med_24_938
Author(s) : Ma HK , Liu Y , Li B , Zhang Y , Sun LJ , Xu FQ
Ref : Chin J Integr Med , 24 :938 , 2018
Abstract : OBJECTIVE: To evaluate the effificacy of oral Chinese medicine (CM) in comparison with donepezil, a cholinesterase inhibitor (ChEI), for the treatment of Alzheimer's disease (AD). METHODS: Randomized controlled trials (RCTs) have been searched, and the effect of CM compared with donepezil in AD has been investigated. An electronic search of MEDLINE, Excerpta Medica Database (EMBASE), Cochrane Library, Chinese Biological Medicine Database (CBMdisc), and China National Knowledge Infrastructure (CNKI) to identify articles in English and Chinese from the inception of the database until October 18, 2015. A modifified Jadad score (7-points) to judge the methodological quality of studies, comprehensive meta-analysis was performed with Cochrane Collaboration Revman 5.3. Dichotomous data were analyzed by relative risk (RR) with a 95% confifidence interval (CI), while continuous variables were analyzed by using mean differences (MD) with 95% CI for effect size. RESULTS: Six studies involving 596 AD patients through Jadad assessment with low bias were included in the meta-analysis. No signifificant difference was observed in cognitive improvement and daily abilities of patients using the Mini Mental State Examination (MMSE) (MD: 0.69, 95% CI:-0.17 to 1.56) and Activities of Daily Living (ADL) scale (MD: 0.94, 95% CI:-1.54 to 3.43). There were no signifificant differences in status of illness or MD for mild-moderate AD patients at 24 weeks (MD: 0.62, 95% CI:-2.99 to 4.23) and 48 weeks (MD:-0.73, 95% CI:-5.02 to 3.56). Severe AD patients were also assessed at 24 weeks (MD: 3.13, 95% CI:-6.92 to 13.18) and 48 weeks (MD: 4.23, 95% CI:-6.38 to 14.84). Furthermore, compared with donepezil, Xin (Heart)-regulating CM and Shen (Kidney)-tonifying groups were observed (MD:-1.50, 95% CI:-3.08 to 0.08; MD:-1.92, 95% CI:-3.50 to-0.33; respectively). CM had fewer side effects in AD patients. CONCLUSION: Compared with donepezil, oral CM showed no signifificant difference in effectiveness in AD patients, and more evidence is needed to verify the fifindings.
ESTHER : Ma_2018_Chin.J.Integr.Med_24_938
PubMedSearch : Ma_2018_Chin.J.Integr.Med_24_938
PubMedID: 30242591

Title : Mechanistic insight into the relationship between triacylglycerol and crystallization of lipase-catalyzed interesterified blend of palm stearin and vegetable oil - Zhu_2018_Food.Chem_260_306
Author(s) : Zhu TW , Weng HT , Zhang X , Wu H , Li B
Ref : Food Chem , 260 :306 , 2018
Abstract : To give a deep insight into the relationship between triacylglycerol and crystallization of interesterified fat, the blends of palm stearin and various vegetable oil were catalyzed by two different immobilized lipases in this study. After interesterification, the blends had wider plastic range indicated by the SFC results and more beta' crystal. The improved physicochemical characteristics of interesterified blends were attributed to their changed TAG profiles. The statistical analysis showed that the interesterified blends were more likely to form beta' crystal with the increase of SU2-type TAG content and the decrease of SSS-type TAG content (p<0.01). In addition, the decrease of ECN 42- and ECN 48-type TAGs and the increase of ECN 50-type TAGs also significantly enhanced the formation of beta' crystal (p<0.05). Furthermore, the sn-1,3-specific Lipozyme TL IM-catalyzed interesterified blends were favorable for the formation of beta' crystal than the non-specific Novozym 435-catalyzed interesterified blends.
ESTHER : Zhu_2018_Food.Chem_260_306
PubMedSearch : Zhu_2018_Food.Chem_260_306
PubMedID: 29699674

Title : Expression of soluble epoxide hydrolase in renal tubular epithelial cells regulates macrophage infiltration and polarization in IgA nephropathy - Wang_2018_Am.J.Physiol.Renal.Physiol_315_F915
Author(s) : Wang Q , Liang Y , Qiao Y , Zhao X , Yang Y , Yang S , Li B , Zhao Q , Dong L , Quan S , Tian R , Liu Z
Ref : American Journal of Physiology Renal Physiol , 315 :F915 , 2018
Abstract : Tubulointerstitial inflammatory cell infiltration and activation contribute to kidney inflammation and fibrosis. Epoxyeicosatrienoic acids (EETs), which are rapidly metabolized to dihydroxyeicosatrienoic acids by the soluble epoxide hydrolase (sEH), have multiple biological functions, including vasodilation, anti-inflammatory action, and others. Inhibition of sEH has been demonstrated to attenuate inflammation in many renal disease models. However, the relationship between sEH expression and macrophage polarization in the kidney remains unknown. In this study, we investigated the relationships between the level of sEH and clinical and pathological parameters in IgA nephropathy. The level of sEH expression positively correlated with proteinuria and infiltration of macrophages. sEH-positive tubules were found to be surrounded by macrophages. Furthermore, we found that incubation of immortalized human proximal tubular HK-2 cells with total urinary protein and overexpression of sEH promoted inflammatory factor production, which was associated with M1 polarization. We also exposed RAW264.7 mouse leukemic monocytes/macrophages to different HK-2 cell culture media conditioned by incubation with various substances affecting sEH amount or activity. We found that the upregulation of sEH promoted M1 polarization. However, pharmacological inhibition of sEH and supplementation with EETs reversed the conditioning effects of urinary proteins by inhibiting M1 polarization through the NF-kappaB pathway and stimulating M2 polarization through the phosphatidylinositol 3-kinase pathway. These data suggest that inhibition of sEH could be a new strategy to prevent the progression of inflammation and to attenuate renal tubulointerstitial fibrosis.
ESTHER : Wang_2018_Am.J.Physiol.Renal.Physiol_315_F915
PubMedSearch : Wang_2018_Am.J.Physiol.Renal.Physiol_315_F915
PubMedID: 29717935

Title : Identification of the Biosynthetic Pathway for the Antibiotic Bicyclomycin - Patteson_2018_Biochemistry_57_61
Author(s) : Patteson JB , Cai W , Johnson RA , Santa Maria KC , Li B
Ref : Biochemistry , 57 :61 , 2018
Abstract : Diketopiperazines (DKPs) make up a large group of natural products with diverse structures and biological activities. Bicyclomycin is a broad-spectrum DKP antibiotic with unique structure and function: it contains a highly oxidized bicyclic [4.2.2] ring and is the only known selective inhibitor of the bacterial transcription termination factor, Rho. Here, we identify the biosynthetic gene cluster for bicyclomycin containing six iron-dependent oxidases. We demonstrate that the DKP core is made by a tRNA-dependent cyclodipeptide synthase, and hydroxylations on two unactivated sp(3) carbons are performed by two mononuclear iron, alpha-ketoglutarate-dependent hydroxylases. Using bioinformatics, we also identify a homologous gene cluster prevalent in a human pathogen Pseudomonas aeruginosa. We detect bicyclomycin by overexpressing this gene cluster and establish P. aeruginosa as a new producer of bicyclomycin. Our work uncovers the biosynthetic pathway for bicyclomycin and sheds light on the intriguing oxidation chemistry that converts a simple DKP into a powerful antibiotic.
ESTHER : Patteson_2018_Biochemistry_57_61
PubMedSearch : Patteson_2018_Biochemistry_57_61
PubMedID: 29053243
Gene_locus related to this paper: strcj-a0a2g1xfc8 , strcj-a0a2g1xp02

Title : Design, synthesis and biological evaluation of tricyclic pyrazolo[1,5-c][1,3]benzoxazin-5(5H)-one scaffolds as selective BuChE inhibitors - Qiu_2018_J.Enzyme.Inhib.Med.Chem_33_1506
Author(s) : Qiu GL , He SS , Chen SC , Li B , Wu HH , Zhang J , Tang WJ
Ref : J Enzyme Inhib Med Chem , 33 :1506 , 2018
Abstract : Based on the structural analysis of tricyclic scaffolds as butyrylcholinesterase (BuChE) inhibitors, a series of pyrazolo[1,5-c][1,3]benzoxazin-5(5H)-one derivatives were designed, synthesized and evaluated for their acetylcholinesterase (AChE) and BuChE inhibitory activity. Compounds with 5-carbonyl and 7- or/and 9-halogen substitutions showed potential BuChE inhibitory activity, among which compounds 6a, 6c and 6g showed the best BuChE inhibition (IC50 = 1.06, 1.63 and 1.63 microM, respectively). The structure-activity relationship showed that the 5-carbonyl and halogen substituents significantly influenced BuChE activity. Compounds 6a and 6g were found nontoxic, lipophilic and exhibited remarkable neuroprotective activity and mixed-type inhibition against BuChE (Ki = 7.46 and 3.09 microM, respectively). Docking studies revealed that compound 6a can be accommodated into BuChE via five hydrogen bonds, one Pi-Sigma interaction and three Pi-Alkyl interactions.
ESTHER : Qiu_2018_J.Enzyme.Inhib.Med.Chem_33_1506
PubMedSearch : Qiu_2018_J.Enzyme.Inhib.Med.Chem_33_1506
PubMedID: 30284486

Title : Extensive intraspecific gene order and gene structural variations between Mo17 and other maize genomes - Sun_2018_Nat.Genet_50_1289
Author(s) : Sun S , Zhou Y , Chen J , Shi J , Zhao H , Song W , Zhang M , Cui Y , Dong X , Liu H , Ma X , Jiao Y , Wang B , Wei X , Stein JC , Glaubitz JC , Lu F , Yu G , Liang C , Fengler K , Li B , Rafalski A , Schnable PS , Ware DH , Buckler ES , Lai J
Ref : Nat Genet , 50 :1289 , 2018
Abstract : Maize is an important crop with a high level of genome diversity and heterosis. The genome sequence of a typical female line, B73, was previously released. Here, we report a de novo genome assembly of a corresponding male representative line, Mo17. More than 96.4% of the 2,183 Mb assembled genome can be accounted for by 362 scaffolds in ten pseudochromosomes with 38,620 annotated protein-coding genes. Comparative analysis revealed large gene-order and gene structural variations: approximately 10% of the annotated genes were mutually nonsyntenic, and more than 20% of the predicted genes had either large-effect mutations or large structural variations, which might cause considerable protein divergence between the two inbred lines. Our study provides a high-quality reference-genome sequence of an important maize germplasm, and the intraspecific gene order and gene structural variations identified should have implications for heterosis and genome evolution.
ESTHER : Sun_2018_Nat.Genet_50_1289
PubMedSearch : Sun_2018_Nat.Genet_50_1289
PubMedID: 30061735
Gene_locus related to this paper: maize-a0a1d6kqc9 , maize-k7v3i9 , maize-b6u9v9 , maize-a0a3l6e780 , maize-b4fv80 , maize-a0a3l6d913

Title : Discovery of Novel Bat Coronaviruses in South China That Use the Same Receptor as Middle East Respiratory Syndrome Coronavirus - Luo_2018_J.Virol_92_
Author(s) : Luo CM , Wang N , Yang XL , Liu HZ , Zhang W , Li B , Hu B , Peng C , Geng QB , Zhu GJ , Li F , Shi ZL
Ref : J Virol , 92 : , 2018
Abstract : Middle East respiratory syndrome coronavirus (MERS-CoV) has represented a human health threat since 2012. Although several MERS-related CoVs that belong to the same species as MERS-CoV have been identified from bats, they do not use the MERS-CoV receptor, dipeptidyl peptidase 4 (DPP4). Here, we screened 1,059 bat samples from at least 30 bat species collected in different regions in south China and identified 89 strains of lineage C betacoronaviruses, including Tylonycteris pachypus coronavirus HKU4, Pipistrellus pipistrelluscoronavirus HKU5, and MERS-related CoVs. We sequenced the full-length genomes of two positive samples collected from the great evening bat, Ia io, from Guangdong Province. The two genomes were highly similar and exhibited genomic structures identical to those of other lineage C betacoronaviruses. While they exhibited genome-wide nucleotide identities of only 75.3 to 81.2% with other MERS-related CoVs, their gene-coding regions were highly similar to their counterparts, except in the case of the spike proteins. Further protein-protein interaction assays demonstrated that the spike proteins of these MERS-related CoVs bind to the receptor DPP4. Recombination analysis suggested that the newly discovered MERS-related CoVs have acquired their spike genes from a DPP4-recognizing bat coronavirus HKU4. Our study provides further evidence that bats represent the evolutionary origins of MERS-CoV.IMPORTANCE Previous studies suggested that MERS-CoV originated in bats. However, its evolutionary path from bats to humans remains unclear. In this study, we discovered 89 novel lineage C betacoronaviruses in eight bat species. We provide evidence of a MERS-related CoV derived from the great evening bat that uses the same host receptor as human MERS-CoV. This virus also provides evidence for a natural recombination event between the bat MERS-related CoV and another bat coronavirus, HKU4. Our study expands the host ranges of MERS-related CoV and represents an important step toward establishing bats as the natural reservoir of MERS-CoV. These findings may lead to improved epidemiological surveillance of MERS-CoV and the prevention and control of the spread of MERS-CoV to humans.
ESTHER : Luo_2018_J.Virol_92_
PubMedSearch : Luo_2018_J.Virol_92_
PubMedID: 29669833

Title : Tricyclic pyrazolo[1,5-d][1,4]benzoxazepin-5(6H)-one scaffold derivatives: Synthesis and biological evaluation as selective BuChE inhibitors - Chen_2018_Eur.J.Med.Chem_147_194
Author(s) : Chen SC , Qiu GL , Li B , Shi JB , Liu XH , Tang WJ
Ref : Eur Journal of Medicinal Chemistry , 147 :194 , 2018
Abstract : BuChE inhibitors play important roles in treatment of patients with advanced Alzheimer's disease (AD). A series of tricyclic pyrazolo[1,5-d][1,4]benzoxazepin-5(6H)-one derivatives were synthesized and evaluated as acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitors. Some derivatives showed selective BuChE inhibitory activity, which was influenced by the volumes of the substituted groups at the C6 position and halogen substituents at the benzene ring of tricyclic scaffold. Among them, compounds 3f and 3o with dihalogen and 6-ethyl substituent showed the most potent activity (IC50=2.95, 2.04muM, and mixed-type, non-competitive inhibition against BuChE, respectively). Eutomer (6R)-3o exhibited better BuChE inhibitory activity than (6S)-3o. Compound 3o exhibited nontoxic, good ADMET properties, and remarkable neuroprotective activity. Docking studies revealed the same binding orientation within the active site of target enzyme. Compound 3o was nicely bound to BuChE via three hydrogen bonds, one Alkyl interaction and three Pi-Alkyl interactions. The selective BuChE inhibitors had a potential use in progressive neurodegenerative disorder.
ESTHER : Chen_2018_Eur.J.Med.Chem_147_194
PubMedSearch : Chen_2018_Eur.J.Med.Chem_147_194
PubMedID: 29438888

Title : The toxicity and the acaricidal mechanism against Psoroptes cuniculi of the methanol extract of Adonis coerulea Maxim - Shang_2017_Vet.Parasitol_240_17
Author(s) : Shang X , Guo X , Yang F , Li B , Pan H , Miao X , Zhang J
Ref : Vet Parasitol , 240 :17 , 2017
Abstract : SCOPE: Adonis coerulea Maxim. is a perennial herbaceous plant that grows in scrub, grassy slope areas, and as traditional medicine it has been used to treat animal acariasis for thousands of years. In this paper, we aimed to study the acute toxicity and cytotoxicity of the methanol extract of A. coerulea (MEAC) in vivo and in vitro for supporting the clinic uses. The acaricidal activity and the mechanism of action against Psoroptes cuniculi were investigated.
RESULTS: The results showed that isoorientin, luteolin and apigenin were the primary compounds in MEAC. The toxicity test showed that median lethal dose (LD50) and the 50% inhibitory concentration (IC50) of MEAC were estimated to be more than 5000mg/kg in mice in vivo and more than 50mg/ml against RAW 264.7 and GM00637 cells in the 3-(4, 5-dimethylthiazol-2- yl)-2,5-diphenyltetrazolium bromide (MTT) test. After culturing with MEAC, the activities of superoxide dismutase (SOD), catalase (CAT), malonyldialdehyde (MDA), glutathione-S-transferase (GST), acetylcholinesterase (AChE) and Na+-K+-ATPase of mites were evaluated. Compared with the control group, SOD activity of MEAC-treated group of mites was inhibited, and CAT activity was activated at the preliminary phase but was gradually inhibited over the period of incubation. MDA content reached a peak at 6h and then gradually decreased. However, GST activity in the mites was activated in a dose- and time-dependent manner. AChE and Na+-K+-ATPase activities related to neural conduction, vital functions and the transmembrane ion gradient of the mites were inhibited. CONCLUSION: MEAC is safe in the given doses in both the in vitro and the in vivo tests, can be applied in the clinic and it had good acaricidal activity. The extension of the incubation time in the mites led to dynamic disequilibrium between the production and clearing of superoxide anions, a disruption of the energy metabolism and the transmembrane ion gradient, and the inhibition of motor function. These factors may have resulted in mite death.
ESTHER : Shang_2017_Vet.Parasitol_240_17
PubMedSearch : Shang_2017_Vet.Parasitol_240_17
PubMedID: 28576339

Title : Design, Synthesis and Evaluation of Hesperetin Derivatives as Potential Multifunctional Anti-Alzheimer Agents - Li_2017_Molecules_22_
Author(s) : Li B , Huang AL , Zhang YL , Li Z , Ding HW , Huang C , Meng XM , Li J
Ref : Molecules , 22 : , 2017
Abstract : In this study we designed and synthesized a series of new hesperetin derivatives on the basis of the structural characteristics of acetylcholinesterase (AChE) dual-site inhibitors. The activity of the novel derivatives was also evaluated. Results showed that the synthesized hesperetin derivatives displayed stronger inhibitory activity against AChE and higher selectivity than butyrylcholine esterase (BuChE) (selectivity index values from 68 to 305). The Lineweaver-Burk plot and molecular docking study showed that these compounds targeted both the peripheral anionic site (PAS) and catalytic active site (CAS) of AChE. The derivatives also showed a potent self-induced beta-amyloid (Abeta) aggregation inhibition and a peroxyl radical absorbance activity. Moreover, compound 4f significantly protected PC12 neurons against H(2)O(2)-induced cell death at low concentrations. Cytotoxicity assay showed that the low concentration of the derivatives does not affect the viability of the SH-SY5Y neurons. Thus, these hesperetin derivatives are potential multifunctional agents for further development for the treatment of Alzheimer's disease.
ESTHER : Li_2017_Molecules_22_
PubMedSearch : Li_2017_Molecules_22_
PubMedID: 28672874

Title : Comammox in drinking water systems - Wang_2017_Water.Res_116_332
Author(s) : Wang Y , Ma L , Mao Y , Jiang X , Xia Y , Yu K , Li B , Zhang T
Ref : Water Res , 116 :332 , 2017
Abstract : The discovery of complete ammonia oxidizer (comammox) has fundamentally upended our perception of the global nitrogen cycle. Here, we reported four metagenome assembled genomes (MAGs) of comammox Nitrospira that were retrieved from metagenome datasets of tap water in Singapore (SG-bin1 and SG-bin2), Hainan province, China (HN-bin3) and Stanford, CA, USA (ST-bin4). Genes of phylogenetically distinct ammonia monooxygenase subunit A (amoA) and hydroxylamine dehydrogenase (hao) were identified in these four MAGs. Phylogenetic analysis based on ribosomal proteins, AmoA, hao and nitrite oxidoreductase (subunits nxrA and nxrB) sequences indicated their close relationships with published comammox Nitrospira. Canonical ammonia-oxidizing microbes (AOM) were also identified in the three tap water samples, ammonia-oxidizing bacteria (AOB) in Singapore's and Stanford's samples and ammonia-oxidizing archaea (AOA) in Hainan's sample. The comammox amoA-like sequences were also detected from some other drinking water systems, and even outnumbered the AOA and AOB amoA-like sequences. The findings of MAGs and the occurrences of AOM in different drinking water systems provided a significant clue that comammox are widely distributed in drinking water systems.
ESTHER : Wang_2017_Water.Res_116_332
PubMedSearch : Wang_2017_Water.Res_116_332
PubMedID: 28390307
Gene_locus related to this paper: 9bact-a0a1w9j1f6 , 9prot-a0a1w9iez0 , 9prot-a0a1w9i2z8 , 9prot-a0a1w9hbq4 , 9prot-a0a1w9jph2

Title : Disease spectrum of alcoholic liver disease in Beijing 302 Hospital from 2002 to 2013: A large tertiary referral hospital experience from 7422 patients - Huang_2017_Medicine.(Baltimore)_96_e6163
Author(s) : Huang A , Chang B , Sun Y , Lin H , Li B , Teng G , Zou ZS
Ref : Medicine (Baltimore) , 96 :e6163 , 2017
Abstract : Alcohol consumption in China has substantially increased over the last 3 decades and the number of patients with alcoholic liver disease (ALD) is rising at an alarming rate. However, accurate and representative data on time trends in its hospitalization rates are not available. The aim of this study is to assess the current status and burden of ALD in China by analyzing the data from a large tertiary referral hospital, Beijing 302 Hospital.Data were retrospectively recorded from patients diagnosed as ALD in Beijing 302 Hospital from 2002 to 2013. The disease spectrum and biochemical parameters of each patient were collected.The patients with ALD accounted for 3.93% (7422) of all patients (188,902) with liver diseases between 2002 and 2013. The number of patients hospitalized with ALD increased from 110 in 2002 to 1672 in 2013. The ratio of patients hospitalized with ALD to all patients hospitalized with liver diseases was rising almost continuously and increased from 1.68% in 2002 to 4.59% in 2013. Most patients with ALD were male. Age distribution of ALD hospitalization showed that the highest rate was in 40- to 49-year-old group in subjects. Notably, the annual proportion of severe alcoholic hepatitis (SAH) increased 2.43 times from 2002 to 2013. We found the highest levels of mean corpuscular volume, the aspartate aminotransferase/alanine aminotransferase ratio, total bilirubin, international normalized ratio, and alkaline phosphatase in SAH patients, while serum levels of hemoglobin, albumin, and cholinesterase were significantly decreased in SAH group. Among these ALD, the SAH patient population has the worst prognosis. Alcoholic cirrhosis (ALC) is the most common ALD, and annual admissions for ALC increased significantly during the analyzed period.The number of hospitalized patients with ALD and the annual hospitalization rate of ALD were increasing continuously in Beijing 302 Hospital from 2002 to 2013. More attention should be paid to develop population-based effective strategy to control ALD.
ESTHER : Huang_2017_Medicine.(Baltimore)_96_e6163
PubMedSearch : Huang_2017_Medicine.(Baltimore)_96_e6163
PubMedID: 28207552

Title : Expression and effects of mutant Bombyx mori acetylcholinesterase 1 in BmN Cells - Wang_2016_Arch.Insect.Biochem.Physiol_93_110
Author(s) : Wang BB , Xie Y , Li FC , Ni M , Xu KZ , Tian JH , Hu JS , Xue B , Shen WD , Li B
Ref : Archives of Insect Biochemistry & Physiology , 93 :110 , 2016
Abstract : The main mechanism of toxicity of organophosphate (OP) and carbamate (CB) insecticides is their irreversible binding and inhibition of acetylcholinestrase (AChE), encoded by ace1 (acetylcholinestrase gene 1), leading to eventual death of insects. Mutations in AChE may significantly reduce insects susceptibility to these pesticides. Bombyx mori is an important beneficial insect, and no OP- or CB-resistant strains have been generated. In this study, wild-type ace1 (wace1) and mutant ace1 (mace1) were introduced into BmN cells, confirmed by screening and identification. The expression of wace1 and mace1 in the cells was confirmed by Western blot and their expression levels were about 21-fold higher than the endogenous ace1 level. The activities of AChE in wace1 and mace1 transgenic cells were 10.6 and 20.2% higher compared to control cells, respectively. mace1 transgenic cells had higher remaining activity than wace1 transgenic cells under the treatment of physostigmine (a reversible cholinesterase inhibitor) and phoxim (an OP acaricide). The results showed that ace1 transgene can significantly improve ace1 expression, and ace1 mutation at a specific site can reduce the sensitivity to AChE inhibitors. Our study provides a new direction for the exploration of the relationship between AChE mutations and drug resistance.
ESTHER : Wang_2016_Arch.Insect.Biochem.Physiol_93_110
PubMedSearch : Wang_2016_Arch.Insect.Biochem.Physiol_93_110
PubMedID: 27402326
Gene_locus related to this paper: bommo-ACHE1

Title : Effects of mutations on the structure and function of silkworm type 1 acetylcholinesterase - Wang_2016_Pestic.Biochem.Physiol_129_1
Author(s) : Wang BB , Li FC , Xu KZ , Ni M , Hu JS , Tian JH , Li YY , Shen WD , Li B
Ref : Pestic Biochem Physiol , 129 :1 , 2016
Abstract : AChE is the target of organophosphate (OP) and carbamate (CB) pesticides, and mutations in the gene can significantly reduce insects' sensitivity to these pesticides. Bombyx mori is highly sensitive to pesticides. To investigate the effects of mutations on AChE1 structure and function, we used a prokaryotic system to express B.mori wild type AChE1 (wAChE1) and mutant AChE1 (mAChE1) in this study. Active AChE1 proteins were obtained after refolding and purification, and wAChE1 and mAChE1 had similar activities. After incubation with 10(-6)M physostigmine and 10(-3)mg/mL phoxim, the remaining enzyme activity of mAChE1 was 4.42% and 8.86% higher than that of wAChE1's, respectively. Three-dimensional analysis of mutation AChE1 (mAChE1) revealed that the Ser and Ala side chains extended toward the central part of S285 with distances of just 2.80A and 3.68A, respectively, which changed the spatial structure of the active center and reduced its sensitivity to pesticides. These results indicated that the mutations altered the 3D structure of AChE1, which may affect the binding of physostigmine and phoxim to the serine residue at the active center, leading to reduced sensitivity. Our study helps understand the relationship between AChE1 mutations and pesticide resistance and provides a new direction for the cultivation of new pesticide-resistant varieties of B.mori.
ESTHER : Wang_2016_Pestic.Biochem.Physiol_129_1
PubMedSearch : Wang_2016_Pestic.Biochem.Physiol_129_1
PubMedID: 27017875
Gene_locus related to this paper: bommo-ACHE1

Title : A Three-Dimensional Origami Paper-Based Device for Potentiometric Biosensing - Ding_2016_Angew.Chem.Int.Ed.Engl_55_13033
Author(s) : Ding J , Li B , Chen L , Qin W
Ref : Angew Chem Int Ed Engl , 55 :13033 , 2016
Abstract : Current paper-based potentiometric ion-sensing platforms are planar devices used for clinically relevant ions. These devices, however, have not been designed for the potentiometric biosensing of proteins or small molecule analytes. A three-dimensional origami paper-based device, in which a solid-contact ion-selective electrode is integrated with an all-solid-state reference electrode, is described for the first time. The device is made by impregnation of paper with appropriate bioreceptors and reporting reagents on different zones. By folding and unfolding the paper structures, versatile potentiometric bioassays can be performed. A USB-controlled miniaturized electrochemical detector can be used for simple and in situ measurements. Using butyrylcholinesterase as a model enzyme, the device has been successfully applied to the detection of enzyme activities and organophosphate pesticides involved in the enzymatic system as inhibitors. The proposed 3D origami paper device allows the potentiometric biosensing of proteins and small molecules in a simple, portable, and cost-effective way.
ESTHER : Ding_2016_Angew.Chem.Int.Ed.Engl_55_13033
PubMedSearch : Ding_2016_Angew.Chem.Int.Ed.Engl_55_13033
PubMedID: 27634584

Title : Design of hyperthermophilic lipase chimeras by key motif-directed recombination - Zhou_2015_Chembiochem_16_455
Author(s) : Zhou X , Gao L , Yang G , Liu D , Bai A , Li B , Deng Z , Feng Y
Ref : Chembiochem , 16 :455 , 2015
Abstract : Recombination of diverse natural evolved domains within a superfamily offers greater opportunity for enzyme function leaps. How to recombine protein modules from distant parents with less disruption in cross-interfaces is a challenging issue. Here, we identified the existence of a key motif, the sequence VVSVN(D)YR, within a structural motif psi loop in the alpha/beta-hydrolase fold superfamily, by using a MEME server and the PROMOTIF program. To obtain thermostable lipase-like enzymes, two chimeras were engineered at the key motif regions through recombination of domains from a mesophilic lipase and a hyperthermophilic esterase/peptidase with amino acid identity less than 21 %. The chimeras retained the desirable substrate preference of their mesophilic parent and exhibited more than 100-fold increased thermostability at 50 degrees C. Through site-directed mutation, we further improved activity of the chimera by 4.6-fold. The recombination strategy presented here enables the creation of novel catalysts.
ESTHER : Zhou_2015_Chembiochem_16_455
PubMedSearch : Zhou_2015_Chembiochem_16_455
PubMedID: 25530200

Title : Identification of Pathogenicity-Related Genes in Biofilm-Defective Acidovorax citrulli by Transposon Tn5 Mutagenesis - Luo_2015_Int.J.Mol.Sci_16_28050
Author(s) : Luo J , Qiu W , Chen L , Anjum SI , Yu M , Shan C , Ilyas M , Li B , Wang Y , Sun G
Ref : Int J Mol Sci , 16 :28050 , 2015
Abstract : Biofilm formation is important for virulence of a large number of plant pathogenic bacteria. Indeed, some virulence genes have been found to be involved in the formation of biofilm in bacterial fruit blotch pathogen Acidovorax citrulli. However, some virulent strains of A. citrulli were unable to format biofilm, indicating the complexity between biofilm formation and virulence. In this study, virulence-related genes were identified in the biofilm-defective strain A1 of A. citrulli by using Tn5 insertion, pathogenicity test, and high-efficiency thermal asymmetric interlaced PCR (hiTAIL-PCR). Results from this study indicated that 22 out of the obtained 301 mutants significantly decreased the virulence of strain A1 compared to the wild-type. Furthermore, sequence analysis indicated that the obtained 22 mutants were due to the insertion of Tn5 into eight genes, including Aave 4244 (cation diffusion facilitator family transporter), Aave 4286 (hypothetical protein), Aave 4189 (alpha/beta hydrolase fold), Aave 1911 (IMP dehydrogenase/GMP reductase domain), Aave 4383 (bacterial export proteins, family 1), Aave 4256 (Hsp70 protein), Aave 0003 (histidine kinase, DNA gyrase B, and HSP90-like ATPase), and Aave 2428 (pyridoxal-phosphate dependent enzyme). Furthermore, the growth of mutant Aave 2428 was unaffected and even increased by the change in incubation temperature, NaCl concentration and the pH of the LB broth, indicating that this gene may be directly involved in the bacterial virulence. Overall, the determination of the eight pathogenicity-related genes in strain A1 will be helpful to elucidate the pathogenesis of biofilm-defective A. citrulli.
ESTHER : Luo_2015_Int.J.Mol.Sci_16_28050
PubMedSearch : Luo_2015_Int.J.Mol.Sci_16_28050
PubMedID: 26602922

Title : The adverse effects of phoxim exposure in the midgut of silkworm, Bombyx mori - Gu_2014_Chemosphere_96_33
Author(s) : Gu Z , Zhou Y , Xie Y , Li F , Ma L , Sun S , Wu Y , Wang B , Wang J , Hong F , Shen W , Li B
Ref : Chemosphere , 96 :33 , 2014
Abstract : The silkworm is an important economic insect. Poisoning of silkworms by organophosphate pesticides causes tremendous loss to the sericulture. In this study, Solexa sequencing technology was performed to profile the gene expression changes in the midgut of silkworms in response to 24h of phoxim exposure and the impact on detoxification, apoptosis and immune defense were addressed. The results showed that 254 genes displayed at least 2.0-fold changes in expression levels, with 148 genes up-regulated and 106 genes down-regulated. Cytochrome P450 played an important role in detoxification. Histopathology examination and transmission electron microscope revealed swollen mitochondria and disappearance of the cristae of mitochondria, which are the important features in insect apoptotic cells. Cytochrome C release from mitochondria into the cytoplasm was confirmed. In addition, the Toll and immune deficiency (IMD) signal pathways were all inhibited using qRT-PCR. Our results could help better understand the impact of phoxim exposure on silkworm.
ESTHER : Gu_2014_Chemosphere_96_33
PubMedSearch : Gu_2014_Chemosphere_96_33
PubMedID: 23899924

Title : Paper-based chromatographic chemiluminescence chip for the detection of dichlorvos in vegetables - Liu_2014_Biosens.Bioelectron_52_76
Author(s) : Liu W , Kou J , Xing H , Li B
Ref : Biosensors & Bioelectronics , 52 :76 , 2014
Abstract : Paper chromatography was a big breakthrough in the early of 20th century but it is rarely used due to the long separation time and the diffusion on the sample spots. In this work, for the first time, a paper-based chemiluminescence (CL) analytical device combined with paper chromatography was developed for the determination of dichlorvos (DDV) in vegetables without complicated sample pretreatment. The paper chromatography separation procedure can be accomplished in 12 min on a paper support (0.8 x 7.0 cm(2)) by using 5 microL sample spotted on it. After sample developing, the detection area (0.8 x 1.0 cm(2)) was cut and inserted between two layers of water-impermeable single-sided adhesive tapes. The paper-based chip was made by attaching the middle layer of paper onto the bottom layer. Then it was covered by another tape layer, which was patterned by the cutting method to form a square hole (0.8 x 1.0 cm(2)) in it. 10 muL mixed solution of luminol and H2O2 was dropped on the detection area to produce CL. A linear relationship was obtained between the CL intensity and the concentrations of DDV in the range between 10.0 ng mL(-1) and 1.0 mug mL(-1)and the detection limit was 3.6 ng mL(-1). Water-soluble metal ions and vitamins can be developed at different spatial locations relative to DDV, eliminating interference with DDV during detection. The paper-based chromatographic chip can be successfully used for the determination of DDV without complicated sample preparation in vegetables. This study should, therefore, be suitable for rapid and sensitive detection of trace levels of organophosphate pesticides in environmental and food samples.
ESTHER : Liu_2014_Biosens.Bioelectron_52_76
PubMedSearch : Liu_2014_Biosens.Bioelectron_52_76
PubMedID: 24021659

Title : Functional study on the mutations in the silkworm (Bombyx mori) acetylcholinesterase type 1 gene (ace1) and its recombinant proteins - Wang_2014_Mol.Biol.Rep_41_429
Author(s) : Wang JM , Wang BB , Xie Y , Sun SS , Gu ZY , Ma L , Li FC , Zhao YF , Yang B , Shen WD , Li B
Ref : Mol Biol Rep , 41 :429 , 2014
Abstract : The acetylcholinesterase of Lepidoptera insects is encoded by two genes, ace1 and ace2. The expression of the ace1 gene is significantly higher than that of the ace2 gene, and mutations in ace1 are one of the major reasons for pesticide resistance in insects. In order to investigate the effects of the mutations in ace1's characteristic sites on pesticide resistance, we generated mutations for three amino acids using site-directed mutagenesis, which were Ala(GCG)303Ser(TCG), Gly(GGA)329Ala(GCA) and Leu (TCT)554Ser(TTC). The Baculovirus expression system was used for the eukaryotic expression of the wild type ace1 (wace1) and the mutant ace1 (mace1). SDS-PAGE and Western blotting were used to detect the targeting proteins with expected sizeof about 76 kDa. The expression products were purified for the determination of AChE activity and the inhibitory effects of physostigmine and phoxim. We observed no significant differences in the overall activity of the wild type and mutant AChEs. However, with 10 min of physostigmine (10 muM) inhibition, the remaining activity of the wild type AChE was significantly lower than that of the mutant AChE. Ten min inhibition with 33.4 muM phoxim also resulted in significantly lower remaining activity of the wild type AChE than that of the mutant AChE. These results indicated that mutations for the three amino acids reduced the sensitivity of AChE to physostigmine and phoxim, which laid the foundation for future in vivo studies on AChE's roles in pesticide resistance.
ESTHER : Wang_2014_Mol.Biol.Rep_41_429
PubMedSearch : Wang_2014_Mol.Biol.Rep_41_429
PubMedID: 24323194
Gene_locus related to this paper: bommo-ACHE1

Title : Expression analysis and RNA interference of BmCarE-10 gene from Bombyx mori - Zhao_2014_Mol.Biol.Rep_41_1607
Author(s) : Zhao GD , Huang MX , Zhang YL , Wang XC , Du J , Li B , Chen YH , Xu YX , Shen WD , Wei ZG
Ref : Mol Biol Rep , 41 :1607 , 2014
Abstract : Carboxylesterase (CarE) is a multifunctional superfamily, and it plays important roles in xenobiotic detoxification, pheromone degradation, neurogenesis and regulating development. In this research, firstly, we measured the rutin-induced transcriptional level of BmCarE-10 gene by using real-time quantitative RT-PCR method, and dual spike-in strategy. Several possible physiological functions were certified preliminarily by RNAi experiments in silkworm. Promoter truncation analysis using a dual-luciferase reporter assay in Bombyx mori ovary cells (BmN) showed that the region -705 to -625 for BmCarE-10 gene was essential for basal and rutin-induced transcriptional activity. Sequence analysis of this region revealed several potential transcriptional regulatory elements such as Croc and Dfd. The activities of the BmCarE-10 promoter in various tissues of silkworm were also measured by firefly luciferase activity and normalized by the Renilla luciferase activity. Results showed that the activity of the BmCarE-10 promoter were highest in the Malpighian tubule, followed by fat body, silk gland, midgut, epidermis, and hemocyte. The essential region for basal and rutin-induced transcriptional activity was also -894 to -502 in Malpighian tubule and fat body of silkworm. The potential core promoters of BmCarE-10 gene in B. mori are reported for the first time in this research. Further identification of cis- and trans-elements and their role in upregulation of BmCarE-10 gene may be useful for elucidating the contribution of CarE protein to the response mechanism to rutin.
ESTHER : Zhao_2014_Mol.Biol.Rep_41_1607
PubMedSearch : Zhao_2014_Mol.Biol.Rep_41_1607
PubMedID: 24415296
Gene_locus related to this paper: bommo-b1q140

Title : Whole-genome sequencing of the snub-nosed monkey provides insights into folivory and evolutionary history - Zhou_2014_Nat.Genet_46_1303
Author(s) : Zhou X , Wang B , Pan Q , Zhang J , Kumar S , Sun X , Liu Z , Pan H , Lin Y , Liu G , Zhan W , Li M , Ren B , Ma X , Ruan H , Cheng C , Wang D , Shi F , Hui Y , Tao Y , Zhang C , Zhu P , Xiang Z , Jiang W , Chang J , Wang H , Cao Z , Jiang Z , Li B , Yang G , Roos C , Garber PA , Bruford MW , Li R
Ref : Nat Genet , 46 :1303 , 2014
Abstract : Colobines are a unique group of Old World monkeys that principally eat leaves and seeds rather than fruits and insects. We report the sequencing at 146x coverage, de novo assembly and analyses of the genome of a male golden snub-nosed monkey (Rhinopithecus roxellana) and resequencing at 30x coverage of three related species (Rhinopithecus bieti, Rhinopithecus brelichi and Rhinopithecus strykeri). Comparative analyses showed that Asian colobines have an enhanced ability to derive energy from fatty acids and to degrade xenobiotics. We found evidence for functional evolution in the colobine RNASE1 gene, encoding a key secretory RNase that digests the high concentrations of bacterial RNA derived from symbiotic microflora. Demographic reconstructions indicated that the profile of ancient effective population sizes for R. roxellana more closely resembles that of giant panda rather than its congeners. These findings offer new insights into the dietary adaptations and evolutionary history of colobine primates.
ESTHER : Zhou_2014_Nat.Genet_46_1303
PubMedSearch : Zhou_2014_Nat.Genet_46_1303
PubMedID: 25362486
Gene_locus related to this paper: rhibe-a0a2k6jtl7 , rhibe-ACHE , rhibe-a0a2k6k3y7 , rhibe-a0a2k6k493 , rhibe-a0a2k6lev4 , rhibe-a0a2k6lfa5 , rhibe-a0a2k6m6k8 , rhiro-a0a2k6p1u8 , rhiro-a0a2k6q1t8 , rhiro-a0a2k6q1w3 , rhibe-a0a2k6n5t9 , rhibe-a0a2k6ju46 , rhibe-a0a2k6kt48 , rhibe-a0a2k6llm5 , rhibe-a0a2k6lnt5 , rhiro-a0a2k6qzp6 , rhiro-a0a2k6q4a6 , rhibe-a0a2k6kn93 , rhibe-a0a2k6lm22 , rhibe-a0a2k6jwp8 , rhiro-a0a2k6qun2 , rhiro-a0a2k6nj56 , rhiro-a0a2k6n885 , rhiro-a0a2k6nnj4 , rhiro-a0a2k6n7n5 , rhibe-a0a2k6jvz4 , rhiro-a0a2k6nfk9 , rhiro-a0a2k6qjv0 , rhibe-a0a2k6jn19 , rhibe-a0a2k6k333 , rhibe-a0a2k6mff5

Title : Population genomics reveal recent speciation and rapid evolutionary adaptation in polar bears - Liu_2014_Cell_157_785
Author(s) : Liu S , Lorenzen ED , Fumagalli M , Li B , Harris K , Xiong Z , Zhou L , Korneliussen TS , Somel M , Babbitt C , Wray G , Li J , He W , Wang Z , Fu W , Xiang X , Morgan CC , Doherty A , O'Connell MJ , McInerney JO , Born EW , Dalen L , Dietz R , Orlando L , Sonne C , Zhang G , Nielsen R , Willerslev E , Wang J
Ref : Cell , 157 :785 , 2014
Abstract : Polar bears are uniquely adapted to life in the High Arctic and have undergone drastic physiological changes in response to Arctic climates and a hyper-lipid diet of primarily marine mammal prey. We analyzed 89 complete genomes of polar bear and brown bear using population genomic modeling and show that the species diverged only 479-343 thousand years BP. We find that genes on the polar bear lineage have been under stronger positive selection than in brown bears; nine of the top 16 genes under strong positive selection are associated with cardiomyopathy and vascular disease, implying important reorganization of the cardiovascular system. One of the genes showing the strongest evidence of selection, APOB, encodes the primary lipoprotein component of low-density lipoprotein (LDL); functional mutations in APOB may explain how polar bears are able to cope with life-long elevated LDL levels that are associated with high risk of heart disease in humans.
ESTHER : Liu_2014_Cell_157_785
PubMedSearch : Liu_2014_Cell_157_785
PubMedID: 24813606
Gene_locus related to this paper: ursma-a0a384cw87 , ursma-a0a384cqm7 , ursma-a0a452vbh6 , ursma-a0a384cyu0

Title : Exoproteome analysis of Starmerella bombicola results in the discovery of an esterase required for lactonization of sophorolipids - Ciesielska_2014_J.Proteomics_98_159
Author(s) : Ciesielska K , Van Bogaert IN , Chevineau S , Li B , Groeneboer S , Soetaert W , Van de Peer Y , Devreese B
Ref : J Proteomics , 98 :159 , 2014
Abstract : The yeast Starmerella bombicola secretes sophorolipids, a family of biosurfactants that find applications in green household products and cosmetics. Over the past years, a gene cluster was discovered that is responsible for the entire synthesis of the open (acidic) form of these molecules from glucose, fatty acids and acetyl-CoA building blocks. However, a significant fraction of the natural product is obtained as a ring closed form (lactonic). Both genetic and proteomic approaches hitherto failed to discover an enzyme responsible for the esterification reaction required for the ring closure step. We hypothesized that this enzyme is extracellularly secreted. Therefore, we characterized the composition of the S. bombicola exoproteome at different time points of the growth and compared it with known yeast exoproteomes. We identified 44 proteins, many of them commonly found in other fungi. Curiously, we discovered an enzyme with homology to Pseudozyma antarctica lipase A. A deletion mutation of its gene resulted in complete abolishment of the sophorolipid lactonization providing evidence that this might be the missing enzyme in the sophorolipid biosynthetic pathway. BIOLOGICAL SIGNIFICANCE: Growing concern about the impact of chemical processes on the environment increases consumers' demand for bio-based products. Lately, the household care and personal care sectors show increasing interest in naturally occurring biosurfactants, which constitute environment-friendly alternatives for chemical surfactants, typically derived from mineral oils. A particular group of biosurfactants, sophorolipids, already found their way to the market, being used in a range of household detergent products and in cosmetics. This work describes how proteomic approaches have led to the completion of our knowledge on the biosynthetic pathway of sophorolipids as performed by Starmerella bombicola, a fungus used in the industrial production of these biosurfactants. Moreover, we proved that by creating a deletion mutant in the lactone esterase discovered in this study, we can shape the biosynthesis towards custom-made sophorolipids with desired functions. Herewith, we demonstrate the potential of proteomics in industrial biotechnology.
ESTHER : Ciesielska_2014_J.Proteomics_98_159
PubMedSearch : Ciesielska_2014_J.Proteomics_98_159
PubMedID: 24418522
Gene_locus related to this paper: stabo-sble

Title : Paraoxonase activity and genetic polymorphisms in northern Han Chinese workers exposed to organophosphate pesticides - Zhang_2014_Exp.Biol.Med.(Maywood)_239_232
Author(s) : Zhang X , Sui H , Li H , Zheng J , Wang F , Li B , Zhang Y
Ref : Exp Biol Med (Maywood) , 239 :232 , 2014
Abstract : Paraoxonase (PON1) is one of the major players in the detoxification of organophosphates (OPs). This study presents our investigation into the effect of OPs on serum PON1 activity and the distribution of common PON1 polymorphisms in Han Chinese workers with repeated high exposure to OP pesticides, and the factors modulating PON1 activity. In all, 400 participants, including 180 workers exposed to OP pesticides occupationally, and 220 controls were investigated. Serum PON1 and cholinesterase (ChE) activity were measured, and genotyping was done using polymerase chain reaction-restriction fragment length polymorphism. The association between PON1 activity and PON1 polymorphisms, and the influencing factors of PON1 activity, were analyzed. The results revealed that repeated OP exposures significantly decreased serum PON1 and ChE activity (P < 0.05), although the exposed workers did not complain of health problems. Higher L and R allele frequencies for the L55M and Q192R polymorphisms of PON1 were observed. PON1 polymorphisms (especially the Q192R polymorphism) and pesticide exposures significantly affected serum PON1 activity in the study population. Therefore, the results of this investigation indicate PON1 polymorphisms and pesticide exposures may be important risk predictors for OP poisoning in the Han Chinese population, who display very high frequencies of the M allele and R allele for PON1 polymorphisms at the positions 55 and 192, respectively.
ESTHER : Zhang_2014_Exp.Biol.Med.(Maywood)_239_232
PubMedSearch : Zhang_2014_Exp.Biol.Med.(Maywood)_239_232
PubMedID: 24326413

Title : Molecular Mechanisms of Reduced Nerve Toxicity by Titanium Dioxide Nanoparticles in the Phoxim-Exposed Brain of Bombyx mori - Xie_2014_PLoS.One_9_e101062
Author(s) : Xie Y , Wang B , Li F , Ma L , Ni M , Shen W , Hong F , Li B
Ref : PLoS ONE , 9 :e101062 , 2014
Abstract : Bombyx mori (B. mori), silkworm, is one of the most important economic insects in the world, while phoxim, an organophosphorus (OP) pesticide, impact its economic benefits seriously. Phoxim exposure can damage the brain, fatbody, midgut and haemolymph of B. mori. However the metabolism of proteins and carbohydrates in phoxim-exposed B. mori can be improved by Titanium dioxide nanoparticles (TiO2 NPs). In this study, we explored whether TiO2 NPs treatment can reduce the phoxim-induced brain damage of the 5th larval instar of B. mori. We observed that TiO2 NPs pretreatments significantly reduced the mortality of phoxim-exposed larva and relieved severe brain damage and oxidative stress under phoxim exposure in the brain. The treatments also relieved the phoxim-induced increases in the contents of acetylcholine (Ach), glutamate (Glu) and nitric oxide (NO) and the phoxim-induced decreases in the contents of norepinephrine (NE), Dopamine (DA), and 5-hydroxytryptamine (5-HT), and reduced the inhibition of acetylcholinesterase (AChE), Na+/K+-ATPase, Ca2+-ATPase, and Ca2+/Mg2+-ATPase activities and the activation of total nitric oxide synthase (TNOS) in the brain. Furthermore, digital gene expression profile (DGE) analysis and real time quantitative PCR (qRT-PCR) assay revealed that TiO2 NPs pretreatment inhibited the up-regulated expression of ace1, cytochrome c, caspase-9, caspase-3, Bm109 and down-regulated expression of BmIap caused by phoxim; these genes are involved in nerve conduction, oxidative stress and apoptosis. TiO2 NPs pretreatment also inhibited the down-regulated expression of H+ transporting ATP synthase and vacuolar ATP synthase under phoxim exposure, which are involved in ion transport and energy metabolism. These results indicate that TiO2 NPs pretreatment reduced the phoxim-induced nerve toxicity in the brain of B. mori.
ESTHER : Xie_2014_PLoS.One_9_e101062
PubMedSearch : Xie_2014_PLoS.One_9_e101062
PubMedID: 24971466

Title : Design, synthesis, and biological evaluation of acetophenone derivatives as dual binding acetylcholinesterase inhibitors - Shen_2013_Pharmazie_68_307
Author(s) : Shen Y , Li B , Xu H , Zhang G
Ref : Pharmazie , 68 :307 , 2013
Abstract : As part of a project aimed at developing new agents for potential application in Alzheimer's disease, a new series of acetophenone derivatives which possess alkylamine side chains were designed, synthesized and assayed as acetylcholinesterase (AChE) inhibitors that could simultaneously bind to the peripheral and catalytic sites of the enzyme. The compounds were synthesized, and the inhibitory activities toward AChE and butyrylcholinesterase (BCHE) in vitro were determined using a modified Ellman method. Of the compounds tested, 6 derivatives were found to inhibit AChE in the micromolar range. The best compound, 2e, had an 1C50 of 0.13 microM. A detailed molecular modeling study was performed to explore the interaction of 2e with AChE.
ESTHER : Shen_2013_Pharmazie_68_307
PubMedSearch : Shen_2013_Pharmazie_68_307
PubMedID: 23802426

Title : Transcriptional characteristics of gene expression in the midgut of domestic silkworms (Bombyx mori) exposed to phoxim - Gu_2013_Pestic.Biochem.Physiol_105_36
Author(s) : Gu ZY , Sun SS , Wang YH , Wang BB , Xie Y , Ma L , Wang JM , Shen WD , Li B
Ref : Pesticide Biochemistry and Physiology , 105 :36 , 2013
Abstract : Silkworm (Bombyx mori) is not only an economically important insect but also a model system for lepidoptera. As a vital organ of digestion and nutrient absorption, the midgut of insects also serves as the first physiological barrier to chemical pesticides. In this study, microarray was performed to profile the gene expression changes in the midgut of silkworms exposed to phoxim. After 24h of phoxim exposure (4.0mug/mL), 266 genes displayed at least 2.0-fold changes in expression levels. Among them, 192 genes were up-regulated, and 74 genes were down-regulated. The most significant changes were 14.88-fold up-regulation and 23.36-fold down-regulation. According to gene ontology annotation and pathway analysis, differentially expressed genes were mainly classified into different groups based on their potential involvements in detoxification, immunne response, stress response, energy metabolism and transport. Particularly, the transcription levels of detoxification-related genes were up-regulated, such as cytochrome P450s, esterases and glutathione-S-transferase (GST), indicating increased detoxification activity in the midgut. Our study provides new insights into the molecular mechanism of pesticide metabolism in the midgut of insects, which may promote the development of highly efficient insecticides.
ESTHER : Gu_2013_Pestic.Biochem.Physiol_105_36
PubMedSearch : Gu_2013_Pestic.Biochem.Physiol_105_36
PubMedID: 24238288

Title : Identification of new dystroglycan complexes in skeletal muscle - Johnson_2013_PLoS.One_8_e73224
Author(s) : Johnson EK , Li B , Yoon JH , Flanigan KM , Martin PT , Ervasti J , Montanaro F
Ref : PLoS ONE , 8 :e73224 , 2013
Abstract : The dystroglycan complex contains the transmembrane protein beta-dystroglycan and its interacting extracellular mucin-like protein alpha-dystroglycan. In skeletal muscle fibers, the dystroglycan complex plays an important structural role by linking the cytoskeletal protein dystrophin to laminin in the extracellular matrix. Mutations that affect any of the proteins involved in this structural axis lead to myofiber degeneration and are associated with muscular dystrophies and congenital myopathies. Because loss of dystrophin in Duchenne muscular dystrophy (DMD) leads to an almost complete loss of dystroglycan complexes at the myofiber membrane, it is generally assumed that the vast majority of dystroglycan complexes within skeletal muscle fibers interact with dystrophin. The residual dystroglycan present in dystrophin-deficient muscle is thought to be preserved by utrophin, a structural homolog of dystrophin that is up-regulated in dystrophic muscles. However, we found that dystroglycan complexes are still present at the myofiber membrane in the absence of both dystrophin and utrophin. Our data show that only a minority of dystroglycan complexes associate with dystrophin in wild type muscle. Furthermore, we provide evidence for at least three separate pools of dystroglycan complexes within myofibers that differ in composition and are differentially affected by loss of dystrophin. Our findings indicate a more complex role of dystroglycan in muscle than currently recognized and may help explain differences in disease pathology and severity among myopathies linked to mutations in DAPC members.
ESTHER : Johnson_2013_PLoS.One_8_e73224
PubMedSearch : Johnson_2013_PLoS.One_8_e73224
PubMedID: 23951345

Title : Solvent-free enzymatic synthesis of 1, 3-diacylglycerols by direct esterification of glycerol with saturated fatty acids - Zhong_2013_Lipids.Health.Dis_12_65
Author(s) : Zhong N , Gui Z , Xu L , Huang J , Hu K , Gao Y , Zhang X , Xu Z , Su J , Li B
Ref : Lipids Health Dis , 12 :65 , 2013
Abstract : BACKGROUND: Pure 1, 3-diacylglycerols (1, 3-DAG) have been considered to be significant surfactants in food, cosmetics and pharmaceutical industries, as well as the effect on obesity prevention. METHODS: In this study, a vacuum-driven air bubbling operation mode was developed and evaluated for the enzymatic synthesis of 1, 3-DAG of saturated fatty acids, by direct esterification of glycerol with fatty acids in a solvent-free system. The employed vacuum-driven air bubbling operation mode was comparable to vacuum-driven N2 bubbling protocol, in terms of lauric acid conversion and 1, 3-dilaurin content. RESULTS: Some operation parameters were optimized, and 95.3% of lauric acid conversion and 80.3% of 1, 3-dilaurin content was obtained after 3-h reaction at 50 degC, with 5 wt% of Lipozyme RM IM (based on reactants) amount. Of the lipases studied, both Lipozyme RM IM and Novozym 435 exhibited good performance in terms of lauric acid conversion. Lipozyme TL IM, however, showed low activity. Lipozyme RM IM showed good operational stability in this operation protocol, 80.2% of the original catalytic activity remained after 10 consecutive batch applications. Some other 1, 3-DAG were prepared and high content was obtained after purification: 98.5% for 1, 3-dicaprylin, 99.2% for 1, 3-dicaprin, 99.1% for 1, 3-dilaurin, 99.5 for 1, 3-dipalmitin and 99.4% for 1, 3-disterin. CONCLUSION: The established vacuum-driven air bubbling operation protocol had been demonstrated to be a simple-operating, cost-effective, application practical and efficient methodology for 1, 3-DAG preparation.
ESTHER : Zhong_2013_Lipids.Health.Dis_12_65
PubMedSearch : Zhong_2013_Lipids.Health.Dis_12_65
PubMedID: 23656739

Title : Polyclonal antibody to soman-tyrosine - Li_2013_Chem.Res.Toxicol_26_584
Author(s) : Li B , Duysen EG , Froment MT , Masson P , Nachon F , Jiang W , Schopfer LM , Thiele GM , Klassen LW , Cashman JR , Williams GR , Lockridge O
Ref : Chemical Research in Toxicology , 26 :584 , 2013
Abstract : Soman forms a stable, covalent bond with tyrosine 411 of human albumin, with tyrosines 257 and 593 in human transferrin, and with tyrosine in many other proteins. The pinacolyl group of soman is retained, suggesting that pinacolyl methylphosphonate bound to tyrosine could generate specific antibodies. Tyrosine in the pentapeptide RYGRK was covalently modified with soman simply by adding soman to the peptide. The phosphonylated-peptide was linked to keyhole limpet hemocyanin, and the conjugate was injected into rabbits. The polyclonal antiserum recognized soman-labeled human albumin, soman-mouse albumin, and soman human transferrin but not nonphosphonylated control proteins. The soman-labeled tyrosines in these proteins are surrounded by different amino acid sequences, suggesting that the polyclonal recognizes soman-tyrosine independent of the amino acid sequence. Antiserum obtained after 4 antigen injections over a period of 18 weeks was tested in a competition ELISA where it had an IC50 of 10(-11) M. The limit of detection on Western blots was 0.01 mug (15 picomoles) of soman-labeled albumin. In conclusion, a high-affinity, polyclonal antibody that specifically recognizes soman adducts on tyrosine in a variety of proteins has been produced. Such an antibody could be useful for identifying secondary targets of soman toxicity.
ESTHER : Li_2013_Chem.Res.Toxicol_26_584
PubMedSearch : Li_2013_Chem.Res.Toxicol_26_584
PubMedID: 23469927

Title : The duck genome and transcriptome provide insight into an avian influenza virus reservoir species - Huang_2013_Nat.Genet_45_776
Author(s) : Huang Y , Li Y , Burt DW , Chen H , Zhang Y , Qian W , Kim H , Gan S , Zhao Y , Li J , Yi K , Feng H , Zhu P , Li B , Liu Q , Fairley S , Magor KE , Du Z , Hu X , Goodman L , Tafer H , Vignal A , Lee T , Kim KW , Sheng Z , An Y , Searle S , Herrero J , Groenen MA , Crooijmans RP , Faraut T , Cai Q , Webster RG , Aldridge JR , Warren WC , Bartschat S , Kehr S , Marz M , Stadler PF , Smith J , Kraus RH , Ren L , Fei J , Morisson M , Kaiser P , Griffin DK , Rao M , Pitel F , Wang J , Li N
Ref : Nat Genet , 45 :776 , 2013
Abstract : The duck (Anas platyrhynchos) is one of the principal natural hosts of influenza A viruses. We present the duck genome sequence and perform deep transcriptome analyses to investigate immune-related genes. Our data indicate that the duck possesses a contractive immune gene repertoire, as in chicken and zebra finch, and this repertoire has been shaped through lineage-specific duplications. We identify genes that are responsive to influenza A viruses using the lung transcriptomes of control ducks and ones that were infected with either a highly pathogenic (A/duck/Hubei/49/05) or a weakly pathogenic (A/goose/Hubei/65/05) H5N1 virus. Further, we show how the duck's defense mechanisms against influenza infection have been optimized through the diversification of its beta-defensin and butyrophilin-like repertoires. These analyses, in combination with the genomic and transcriptomic data, provide a resource for characterizing the interaction between host and influenza viruses.
ESTHER : Huang_2013_Nat.Genet_45_776
PubMedSearch : Huang_2013_Nat.Genet_45_776
PubMedID: 23749191
Gene_locus related to this paper: anapl-BCHE , anapl-r0lw36 , anapl-r0m5n4 , anapl-thioe , anapl-u3iqr9 , anapl-r0l4n7 , anapl-u3j4v8 , anapl-u3icy5 , anapl-u3ivv9 , anapl-u3j4g1 , anapl-u3j4i2 , anapl-u3j4v5 , anapl-r0kv25 , anapl-u3ild2 , anapl-u3imh5 , anapl-b6dzk9 , anapl-u3imp7 , anapl-u3i5h5 , anapl-u3id17 , anapl-r0m1y3 , anapl-r0lhc4 , anapl-r0ktn0 , anapl-r0l8l1 , anapl-r0lin6 , anapl-r0jhf3

Title : Changes in the activity and the expression of detoxification enzymes in silkworms (Bombyx mori) after phoxim feeding - Wang_2013_Pestic.Biochem.Physiol_105_13
Author(s) : Wang YH , Gu ZY , Wang JM , Sun SS , Wang BB , Jin YQ , Shen WD , Li B
Ref : Pesticide Biochemistry and Physiology , 105 :13 , 2013
Abstract : Silkworm (Bombyx mori) is an economically important insect. However, non-cocoon caused by chemical insecticide poisoning has largely hindered the development of sericulture. To explore the roles of detoxification enzymes in B. mori after insecticide poisoning, we monitored the activity changes of cytochrome P450 monooxygenase, glutathione-S-transferase, and carboxylesterase in B. mori midgut and fatbody after phoxim feeding. At the same time, the expression levels of detoxification enzyme-related genes were also determined by real-time quantitative PCR. Compare to the control levels, the activity of P450 in the midgut and fatbody was increased to 1.72 and 6.72 folds; the activity of GST was no change in midgut, and in fatbody increased to 1.11 folds; the activity of carboxylesterase in the midgut was decreased to 0.69 folds, and in fatbody increased to 1.13 folds. Correspondingly, the expression levels of detoxifying enzyme genes CYP6ae22, CYP9a21, GSTo1 and Bmcce were increased to 15.99, 3.32, 1.86 and 2.30 folds in the midgut and to 3.58, 1.84, 2.14 and 4.21 folds in the fatbody after phoxim treatment. These results demonstrated the important roles of detoxification enzymes in phoxim metabolism. In addition, the detected activities of such enzymes were generally lower than those in cotton bollworms (Helicoverpa armigera), which may contribute to the high susceptibility of B. mori to insecticides. Our findings laid the foundation for further investigations of the molecular mechanisms of organophosphorus pesticide metabolism in B. mori.
ESTHER : Wang_2013_Pestic.Biochem.Physiol_105_13
PubMedSearch : Wang_2013_Pestic.Biochem.Physiol_105_13
PubMedID: 24238284

Title : Whole-genome sequencing of Oryza brachyantha reveals mechanisms underlying Oryza genome evolution - Chen_2013_Nat.Commun_4_1595
Author(s) : Chen J , Huang Q , Gao D , Wang J , Lang Y , Liu T , Li B , Bai Z , Luis Goicoechea J , Liang C , Chen C , Zhang W , Sun S , Liao Y , Zhang X , Yang L , Song C , Wang M , Shi J , Liu G , Liu J , Zhou H , Zhou W , Yu Q , An N , Chen Y , Cai Q , Wang B , Liu B , Min J , Huang Y , Wu H , Li Z , Zhang Y , Yin Y , Song W , Jiang J , Jackson SA , Wing RA , Chen M
Ref : Nat Commun , 4 :1595 , 2013
Abstract : The wild species of the genus Oryza contain a largely untapped reservoir of agronomically important genes for rice improvement. Here we report the 261-Mb de novo assembled genome sequence of Oryza brachyantha. Low activity of long-terminal repeat retrotransposons and massive internal deletions of ancient long-terminal repeat elements lead to the compact genome of Oryza brachyantha. We model 32,038 protein-coding genes in the Oryza brachyantha genome, of which only 70% are located in collinear positions in comparison with the rice genome. Analysing breakpoints of non-collinear genes suggests that double-strand break repair through non-homologous end joining has an important role in gene movement and erosion of collinearity in the Oryza genomes. Transition of euchromatin to heterochromatin in the rice genome is accompanied by segmental and tandem duplications, further expanded by transposable element insertions. The high-quality reference genome sequence of Oryza brachyantha provides an important resource for functional and evolutionary studies in the genus Oryza.
ESTHER : Chen_2013_Nat.Commun_4_1595
PubMedSearch : Chen_2013_Nat.Commun_4_1595
PubMedID: 23481403
Gene_locus related to this paper: orysa-Q6ZDG3 , orysa-q6h415 , orysj-q6yse8 , orysa-q33aq0 , orybr-j3l7k2 , orybr-j3m138 , orybr-j3l6m8 , orybr-j3m3b3 , orybr-j3l8d1 , orybr-j3kza5 , orybr-j3mnb5 , orybr-j3n4p4 , orybr-j3lg73 , orybr-j3l342 , orybr-j3msi2 , orybr-j3nb83 , orybr-j3mpc5

Title : Jujube promotes learning and memory in a rat model by increasing estrogen levels in the blood and nitric oxide and acetylcholine levels in the brain - Li_2013_Exp.Ther.Med_5_1755
Author(s) : Li B , Wang L , Liu Y , Chen Y , Zhang Z , Zhang J
Ref : Exp Ther Med , 5 :1755 , 2013
Abstract : The aim of this study was to observe the effects of jujube on learning and memory in ovariectomized rats. The effects of jujube on learning and memory in ovariectomized rats were observed using the Morris water maze method. The serum follicle-stimulating hormone (FSH), estrogen and luteinizing hormone (LH) levels, and the brain nitric oxide synthase (NOS) and acetylcholinesterase (AChE) levels of the rats were determined. The results indicated that jujube reduced the latency period and increased the number of crossings made by the ovariectomized rats in the Morris water maze test. Jujube also increased the serum estrogen level, reduced the serum FSH and corpus luteum LH levels, increased brain NOS activity and reduced AChE activity. The results indicate that jujube promoted the learning and memory of the ovariectomized rats. This effect may be correlated with the increase in the estrogen level in the blood, and the changes in the nitric oxide and acetylcholine levels in the brain.
ESTHER : Li_2013_Exp.Ther.Med_5_1755
PubMedSearch : Li_2013_Exp.Ther.Med_5_1755
PubMedID: 23837068

Title : Resistance of human butyrylcholinesterase to methylene blue-catalyzed photoinactivation\; mass spectrometry analysis of oxidation products - Tacal_2013_Photochem.Photobiol_89_336
Author(s) : Tacal O , Li B , Lockridge O , Schopfer LM
Ref : Photochem Photobiol , 89 :336 , 2013
Abstract : Methylene blue, 3, 7-bis(dimethylamino)-phenothiazin-5-ium chloride, is a reversible inhibitor of human butyrylcholinesterase (BChE) in the absence of light. In the presence of light and oxygen, methylene blue promotes irreversible inhibition of human BChE as a function of time, requiring 3 h irradiation to inhibit 95% activity. Inactivation was accompanied by a progressive loss of Coomassie-stained protein bands on native and denaturing polyacrylamide gels, suggesting backbone fragmentation. Aggregation was not detected. MALDI-TOF/TOF mass spectrometry identified oxidized tryptophan (W52, 56, 231, 376, 412, 490, 522), oxidized methionine (M81, 144, 302, 532, 554, 555), oxidized histidine (H214), oxidized proline (P230), oxidized cysteine (C519) and oxidized serine (S215). A 20 min irradiation in the presence of methylene blue resulted in 17% loss of BChE activity, suggesting that BChE is relatively resistant to methylene blue-catalyzed photoinactivation and that therefore this process could be used to sterilize BChE preparations.
ESTHER : Tacal_2013_Photochem.Photobiol_89_336
PubMedSearch : Tacal_2013_Photochem.Photobiol_89_336
PubMedID: 23136924

Title : Molecular cloning of a novel bioH gene from an environmental metagenome encoding a carboxylesterase with exceptional tolerance to organic solvents - Shi_2013_BMC.Biotechnol_13_13
Author(s) : Shi Y , Pan Y , Li B , He W , She Q , Chen L
Ref : BMC Biotechnol , 13 :13 , 2013
Abstract : ABSTRACT: BACKGROUND: BioH is one of the key enzymes to produce the precursor pimeloyl-ACP to initiate biotin biosynthesis de novo in bacteria. To date, very few bioH genes have been characterized. In this study, we cloned and identified a novel bioH gene, bioHx, from an environmental metagenome by a functional metagenomic approach. The bioHx gene, encoding an enzyme that is capable of hydrolysis of p-nitrophenyl esters of fatty acids, was expressed in Escherichia coli BL21 using the pET expression system. The biochemical property of the purified BioHx protein was also investigated.
RESULTS: Screening of an unamplified metagenomic library with a tributyrin-containing medium led to the isolation of a clone exhibiting lipolytic activity. This clone carried a 4,570-bp DNA fragment encoding for six genes, designated bioF, bioHx, fabG, bioC, orf5 and sdh, four of which were implicated in the de novo biotin biosynthesis. The bioHx gene encodes a protein of 259 aa with a calculated molecular mass of 28.60 kDa, displaying 24-39% amino acid sequence identity to a few characterized bacterial BioH enzymes. It contains a pentapeptide motif (Gly76-Trp77-Ser78-Met79-Gly80) and a catalytic triad (Ser78-His230-Asp202), both of which are characteristic for lipolytic enzymes. BioHx was expressed as a recombinant protein and characterized. The purified BioHx protein displayed carboxylesterase activity, and it was most active on p-nitrophenyl esters of fatty acids substrate with a short acyl chain (C4). Comparing BioHx with other known BioH proteins revealed interesting diversity in their sensitivity to ionic and nonionic detergents and organic solvents, and BioHx exhibited exceptional resistance to organic solvents, being the most tolerant one amongst all known BioH enzymes. This ascribed BioHx as a novel carboxylesterase with a strong potential in industrial applications.
CONCLUSIONS: This study constituted the first investigation of a novel bioHx gene in a biotin biosynthetic gene cluster cloned from an environmental metagenome. The bioHx gene was successfully cloned, expressed and characterized. The results demonstrated that BioHx is a novel carboxylesterase, displaying distinct biochemical properties with strong application potential in industry. Our results also provided the evidence for the effectiveness of functional metagenomic approach for identifying novel bioH genes from complex ecosystem.
ESTHER : Shi_2013_BMC.Biotechnol_13_13
PubMedSearch : Shi_2013_BMC.Biotechnol_13_13
PubMedID: 23413993

Title : BmNPV Resistance of Silkworm Larvae Resulting from the Ingestion of TiO(2) Nanoparticles - Li_2012_Biol.Trace.Elem.Res_150_221
Author(s) : Li B , Xie Y , Cheng Z , Cheng J , Hu R , Gui S , Sang X , Sun Q , Zhao X , Sheng L , Shen W , Hong F
Ref : Biol Trace Elem Res , 150 :221 , 2012
Abstract : Bombyx mori nucleopolyhedrovirus (BmNPV) causes infection in the silkworm that is often lethal. The infection is hard to prevent, partly because of the nature of the virus particles and partly because of the different strains of B. mori. Titanium dioxide nanoparticles (TiO(2) NPs) have been demonstrated to have antimicrobial properties. The present study investigated whether TiO(2) NPs added to an artificial diet can increase the resistance of B. mori larvae to BmNPV and examined the molecular mechanism behind any resistance shown. The results indicated that ingested TiO(2) NPs decreased reactive oxygen species and NO accumulation in B. mori larvae under BmNPV infection, which in turn led to a decrease in their growth inhibition and mortality. In addition, the TiO(2) NPs significantly promoted the expression of resistance-related genes, including those encoding superoxide dismutase, catalase, glutathione peroxidase, acetylcholine esterase, carboxylesterase, heat shock protein 21, glutathione S transferase o1, P53, and transferring and of genes encoding cytochrome p302 and nitric oxide synthase. These findings are a useful addition to the understanding of the mechanism of BmNPV resistance of B. mori larvae in response to TiO(2) NPs addition. Such information also provides a theoretical basis for the use of TiO(2) NPs in sericulture.
ESTHER : Li_2012_Biol.Trace.Elem.Res_150_221
PubMedSearch : Li_2012_Biol.Trace.Elem.Res_150_221
PubMedID: 23054861

Title : Systematic review and meta-analysis of the relationship between EPHX1 polymorphisms and colorectal cancer risk - Liu_2012_PLoS.One_7_e43821
Author(s) : Liu F , Yuan D , Wei Y , Wang W , Yan L , Wen T , Xu M , Yang J , Li B
Ref : PLoS ONE , 7 :e43821 , 2012
Abstract : BACKGROUND: Microsomal epoxide hydrolase (EPHX1) plays an important role in both the activation and detoxification of PAHs, which are carcinogens found in cooked meat and tobacco smoking. Polymorphisms at exons 3 and 4 of the EPHX1 gene have been reported to be associated with variations in EPHX1 activity. The aim of this study is to quantitatively summarize the relationship between EPHX1 polymorphisms and colorectal cancer (CRC) risk.
METHODS: Two investigators independently searched the Medline, Embase, CNKI, and Chinese Biomedicine Databases for studies published before June 2012. Summary odds ratios (ORs) and 95% confidence intervals (CIs) for EPHX1 Tyr113His (rs1051740) and His139Arg (rs2234922) polymorphisms and CRC were calculated in a fixed-effects model and a random-effects model when appropriate.
RESULTS: This meta-analysis yielded 14 case-control studies, which included 13 studies for Tyr113His (6395 cases and 7893 controls) and 13 studies for His139Arg polymorphisms (5375 cases and 6962 controls). Overall, the pooled results indicated that EPHX1 Tyr113His polymorphism was not associated with CRC risk; while the His139Arg polymorphism was significantly associated with decreased CRC risk (Arg/His vs. His/His, OR = 0.90, 95%CI = 0.83-0.98; dominant model, OR = 0.92, 95%CI = 0.85-0.99). The statistically significant association between EPHX1 His139Arg polymorphism and CRC was observed among Caucasians and population-based case-control studies. This association showed little heterogeneity and remained consistently strong when analyses were limited to studies in which genotype frequencies were in Hardy-Weinberg equilibrium, or limited to studies with matched controls. When cumulative meta-analyses of the two associations were conducted by studies' publication time, the results were persistent and robust. CONCLUSION: This meta-analysis suggests that EPHX1 Tyr113His polymorphism may be not associated with CRC development; while the EPHX1 His139Arg polymorphism may have a potential protective effect on CRC.
ESTHER : Liu_2012_PLoS.One_7_e43821
PubMedSearch : Liu_2012_PLoS.One_7_e43821
PubMedID: 22928041

Title : Interkingdom gene transfer may contribute to the evolution of phytopathogenicity in botrytis cinerea - Zhu_2012_Evol.Bioinform.Online_8_105
Author(s) : Zhu B , Zhou Q , Xie G , Zhang G , Zhang X , Wang Y , Sun G , Li B , Jin G
Ref : Evol Bioinform Online , 8 :105 , 2012
Abstract : The ascomycete Botrytis cinerea is a phytopathogenic fungus infecting and causing significant yield losses in a number of crops. The genome of B. cinerea has been fully sequenced while the importance of horizontal gene transfer (HGT) to extend the host range in plant pathogenic fungi has been recently appreciated. However, recent data confirm that the B. cinerea fungus shares conserved virulence factors with other fungal plant pathogens with narrow host range. Therefore, interkingdom HGT may contribute to the evolution of phytopathogenicity in B. cinerea. In this study, a stringent genome comparison pipeline was used to identify potential genes that have been obtained by B. cinerea but not by other fungi through interkingdom HGT. This search led to the identification of four genes: a UDP-glucosyltransferase (UGT), a lipoprotein and two alpha/beta hydrolase fold proteins. Phylogenetic analysis of the four genes suggests that B. cinerea acquired UGT from plants and the other 3 genes from bacteria. Based on the known gene functions and literature searching, a correlation between gene acquision and the evolution of pathogenicity in B. cinerea can be postulated.
ESTHER : Zhu_2012_Evol.Bioinform.Online_8_105
PubMedSearch : Zhu_2012_Evol.Bioinform.Online_8_105
PubMedID: 22346340

Title : Role of the NC-loop in catalytic activity and stability in lipase from Fervidobacterium changbaicum - Li_2012_PLoS.One_7_e46881
Author(s) : Li B , Yang G , Wu L , Feng Y
Ref : PLoS ONE , 7 :e46881 , 2012
Abstract : Flexible NC-loops between the catalytic domain and the cap domain of the alpha/beta hydrolase fold enzymes show remarkable diversity in length, sequence, and configuration. Recent investigations have suggested that the NC-loop might be involved in catalysis and substrate recognition in many enzymes from the alpha/beta hydrolase fold superfamily. To foster a deep understanding of its role in catalysis, stability, and divergent evolution, we here systemically investigated the function of the NC-loop (residues 131-151) in a lipase (FClip1) from thermophilic bacterium Fervidobacterium changbaicum by loop deletion, alanine-scanning mutagenesis and site-directed mutagenesis. We found that the upper part of the NC-loop (residues 131-138) was of great importance to enzyme catalysis. Single substitutions in this region could fine-tune the activity of FClip1 as much as 41-fold, and any deletions from this region rendered the enzyme completely inactive. The lower part of the NC-loop (residues 139-151) was capable of enduring extensive deletions without loss of activity. The shortened mutants in this region were found to show both improved activity and increased stability simultaneously. We therefore speculated that the NC-loop, especially the lower part, would be a perfect target for enzyme engineering to optimize the enzymatic properties, and might present a hot zone for the divergent evolution of alpha/beta hydrolases. Our findings may provide an opportunity for better understanding of the mechanism of divergent evolution in the alpha/beta hydrolase fold superfamily, and may also guide the design of novel biocatalysts for industrial applications.
ESTHER : Li_2012_PLoS.One_7_e46881
PubMedSearch : Li_2012_PLoS.One_7_e46881
PubMedID: 23056508
Gene_locus related to this paper: 9them-a1yv97

Title : New Alkaloids from Lycopodium japonicum - Li_2012_Chem.Pharm.Bull.(Tokyo)_60_1448
Author(s) : Li B , Zhang WD , He YR , Lu L , Kong DY , Shen YH
Ref : Chem Pharm Bull (Tokyo) , 60 :1448 , 2012
Abstract : Three new alkaloids (1-3), together with ten known alkaloids, were isolated from the ethanolic extract of the whole plants of Lycopodium japonicum THUNB. Their structures were elucidated on the basis of spectroscopic analysis, including MS and NMR methods. All alkaloids isolated were assayed for cytotoxic activity against four human cancer cell lines and acetylcholinesterase (AChE) inhibitory activity. No alkaloid showed either cytotoxic activity against four human cancer cell lines or AChE inhibitory activity.
ESTHER : Li_2012_Chem.Pharm.Bull.(Tokyo)_60_1448
PubMedSearch : Li_2012_Chem.Pharm.Bull.(Tokyo)_60_1448
PubMedID: 22971777

Title : Whole-genome sequence of Schistosoma haematobium - Young_2012_Nat.Genet_44_221
Author(s) : Young ND , Jex AR , Li B , Liu S , Yang L , Xiong Z , Li Y , Cantacessi C , Hall RS , Xu X , Chen F , Wu X , Zerlotini A , Oliveira G , Hofmann A , Zhang G , Fang X , Kang Y , Campbell BE , Loukas A , Ranganathan S , Rollinson D , Rinaldi G , Brindley PJ , Yang H , Wang J , Gasser RB
Ref : Nat Genet , 44 :221 , 2012
Abstract : Schistosomiasis is a neglected tropical disease caused by blood flukes (genus Schistosoma; schistosomes) and affecting 200 million people worldwide. No vaccines are available, and treatment relies on one drug, praziquantel. Schistosoma haematobium has come into the spotlight as a major cause of urogenital disease, as an agent linked to bladder cancer and as a predisposing factor for HIV/AIDS. The parasite is transmitted to humans from freshwater snails. Worms dwell in blood vessels and release eggs that become embedded in the bladder wall to elicit chronic immune-mediated disease and induce squamous cell carcinoma. Here we sequenced the 385-Mb genome of S. haematobium using Illumina-based technology at 74-fold coverage and compared it to sequences from related parasites. We included genome annotation based on function, gene ontology, networking and pathway mapping. This genome now provides an unprecedented resource for many fundamental research areas and shows great promise for the design of new disease interventions.
ESTHER : Young_2012_Nat.Genet_44_221
PubMedSearch : Young_2012_Nat.Genet_44_221
PubMedID: 22246508
Gene_locus related to this paper: schha-ACHE , schha-a0a094zs51 , schha-a0a095agr4 , schha-a0a095ai61 , schha-a0a095ayl3 , schha-a0a095c2i3 , schha-a0a095ce64

Title : Cloning of Xuhuai goat lipoprotein lipase gene and the preparation of transgenic sheep - Qin_2012_Mol.Biol.Rep_39_8439
Author(s) : Qin Y , Zhang Y , Yin Y , Xu F , Gao B , Shi Q , Zhu C , Li W , Li B
Ref : Mol Biol Rep , 39 :8439 , 2012
Abstract : This paper presents cloning of cDNA of lipoprotein lipase (LPL) gene from Xuhuai goat, and the sub-cellular localization analysis through enhanced green fluorescent (EGFP) fusion protein. cDNA was cloned by reverse transcription polymerase chain reaction (RT-PCR). Fusion expression vector named pEGFP-LPL was constructed successfully. Then NIH-3T3 cells were transfected with pEGFP-LPL through polyethylene imine and observed under inverted microscope after 48 h transfection. The RT-PCR was performed to analysis the level of expression of mRNA. The complete coding sequence (1,530 bp) of LPL was acquired, and the open reading frame size was 1,437 bp with a capacity to encode 478 amino acids. The prediction of signal peptide region showed that LPL protein contained a short signal peptide with a probability of 100 %, and the signal peptidase cleavage site located between the 23rd and the 24th amino acid with a probability of 65.9 %. RT-PCR results showed the LPL mRNA expressed successfully in vitro. Sub-cellullar localization analysis showed that pEGFP-LPL fusion protein located at the cytoplasm. LPL gene of Xuhuai goat was transfer into sheep by testicular injection. According to detection from different level, the LPL gene was expressed successfully in F(1) generation.
ESTHER : Qin_2012_Mol.Biol.Rep_39_8439
PubMedSearch : Qin_2012_Mol.Biol.Rep_39_8439
PubMedID: 22711304
Gene_locus related to this paper: caphi-a0fi82

Title : Complete genome analysis of Sulfobacillus acidophilus strain TPY, isolated from a hydrothermal vent in the Pacific Ocean - Li_2011_J.Bacteriol_193_5555
Author(s) : Li B , Chen Y , Liu Q , Hu S , Chen X
Ref : Journal of Bacteriology , 193 :5555 , 2011
Abstract : Sulfobacillus acidophilus strain TPY is a moderately thermoacidophilic bacterium originally isolated from a hydrothermal vent in the Pacific Ocean. Ferrous iron and sulfur oxidation in acidic environments in strain TPY have been confirmed. Here we report the genome sequence and annotation of the strain TPY, which is the first complete genome of Sulfobacillus acidophilus.
ESTHER : Li_2011_J.Bacteriol_193_5555
PubMedSearch : Li_2011_J.Bacteriol_193_5555
PubMedID: 21914875
Gene_locus related to this paper: sulat-f8ic83

Title : Genome sequencing and comparison of two nonhuman primate animal models, the cynomolgus and Chinese rhesus macaques - Yan_2011_Nat.Biotechnol_29_1019
Author(s) : Yan G , Zhang G , Fang X , Zhang Y , Li C , Ling F , Cooper DN , Li Q , Li Y , van Gool AJ , Du H , Chen J , Chen R , Zhang P , Huang Z , Thompson JR , Meng Y , Bai Y , Wang J , Zhuo M , Wang T , Huang Y , Wei L , Li J , Wang Z , Hu H , Yang P , Le L , Stenson PD , Li B , Liu X , Ball EV , An N , Huang Q , Fan W , Zhang X , Wang W , Katze MG , Su B , Nielsen R , Yang H , Wang X
Ref : Nat Biotechnol , 29 :1019 , 2011
Abstract : The nonhuman primates most commonly used in medical research are from the genus Macaca. To better understand the genetic differences between these animal models, we present high-quality draft genome sequences from two macaque species, the cynomolgus/crab-eating macaque and the Chinese rhesus macaque. Comparison with the previously sequenced Indian rhesus macaque reveals that all three macaques maintain abundant genetic heterogeneity, including millions of single-nucleotide substitutions and many insertions, deletions and gross chromosomal rearrangements. By assessing genetic regions with reduced variability, we identify genes in each macaque species that may have experienced positive selection. Genetic divergence patterns suggest that the cynomolgus macaque genome has been shaped by introgression after hybridization with the Chinese rhesus macaque. Macaque genes display a high degree of sequence similarity with human disease gene orthologs and drug targets. However, we identify several putatively dysfunctional genetic differences between the three macaque species, which may explain functional differences between them previously observed in clinical studies.
ESTHER : Yan_2011_Nat.Biotechnol_29_1019
PubMedSearch : Yan_2011_Nat.Biotechnol_29_1019
PubMedID: 22002653
Gene_locus related to this paper: macfa-BCHE , macfa-g7nzc0 , macfa-g7nze2 , macfa-g7p4b9 , macfa-g7pa87 , macfa-g7pd01 , macfa-g7q259 , macfa-3neur , macfa-g8f585 , macfa-KANSL3 , macfa-q4r8p0 , macfa-SPG21 , macfa-TEX30 , macmu-3neur , macmu-ACHE , macmu-BCHE , macmu-f6sz31 , macmu-f6the6 , macmu-f6zkq5 , macmu-f7buk8 , macmu-f7cfi8 , macmu-f7flv1 , macmu-f7ggk1 , macmu-f7hir7 , macmu-g7n054 , macmu-g7npb8 , macmu-g7nq39 , macmu-KANSL3 , macmu-TEX30 , macfa-g7pgg6 , macmu-g7n4x3 , macfa-g7nzx2 , macfa-g8f4f7 , macmu-f7ba84 , macfa-g7psx7 , macmu-h9er02 , macfa-g8f3k0 , macfa-a0a2k5w1n7 , macmu-g7mxj6 , macfa-g7pbk1 , macfa-a0a2k5urk5 , macfa-a0a2k5wye4 , macfa-g7pe14 , macmu-f7hkw9 , macmu-f7hm08 , macmu-g7mke4 , macfa-g7nxn9 , macmu-a0a1d5rh04 , macmu-h9fud6 , macfa-g8f3e1 , macfa-i7gcw6 , macmu-f6qwx1 , macmu-f7h4t2 , macfa-a0a2k5wkd0 , macfa-a0a2k5v7v4 , macfa-g7p7y3 , macfa-a0a2k5uqq3 , macmu-i2cu80 , macfa-g8f5i1 , macmu-f7h550 , macmu-f7gkb9 , macfa-a0a2k5tui1

Title : Complete genome of Pseudomonas mendocina NK-01, which synthesizes medium-chain-length polyhydroxyalkanoates and alginate oligosaccharides - Guo_2011_J.Bacteriol_193_3413
Author(s) : Guo W , Wang Y , Song C , Yang C , Li Q , Li B , Su W , Sun X , Song D , Yang X , Wang S
Ref : Journal of Bacteriology , 193 :3413 , 2011
Abstract : Pseudomonas mendocina NK-01 can synthesize medium-chain-length polyhydroxyalkanoate (PHA(MCL)) and alginate oligosaccharides (AO) simultaneously from glucose under conditions of limited nitrogen. Here, we report the complete sequence of the 5.4-Mbp genome of Pseudomonas mendocina NK-01, which was isolated from farmland soil in Tianjin, China.
ESTHER : Guo_2011_J.Bacteriol_193_3413
PubMedSearch : Guo_2011_J.Bacteriol_193_3413
PubMedID: 21551299
Gene_locus related to this paper: pseme-PHAZ , psemn-f4dpi6 , psemn-f4dyl0 , psemn-f4dqg5 , pseme-a0a081x852 , psemn-f4dv64

Title : The genome of the mesopolyploid crop species Brassica rapa - Wang_2011_Nat.Genet_43_1035
Author(s) : Wang X , Wang H , Wang J , Sun R , Wu J , Liu S , Bai Y , Mun JH , Bancroft I , Cheng F , Huang S , Li X , Hua W , Freeling M , Pires JC , Paterson AH , Chalhoub B , Wang B , Hayward A , Sharpe AG , Park BS , Weisshaar B , Liu B , Li B , Tong C , Song C , Duran C , Peng C , Geng C , Koh C , Lin C , Edwards D , Mu D , Shen D , Soumpourou E , Li F , Fraser F , Conant G , Lassalle G , King GJ , Bonnema G , Tang H , Belcram H , Zhou H , Hirakawa H , Abe H , Guo H , Jin H , Parkin IA , Batley J , Kim JS , Just J , Li J , Xu J , Deng J , Kim JA , Yu J , Meng J , Min J , Poulain J , Hatakeyama K , Wu K , Wang L , Fang L , Trick M , Links MG , Zhao M , Jin M , Ramchiary N , Drou N , Berkman PJ , Cai Q , Huang Q , Li R , Tabata S , Cheng S , Zhang S , Sato S , Sun S , Kwon SJ , Choi SR , Lee TH , Fan W , Zhao X , Tan X , Xu X , Wang Y , Qiu Y , Yin Y , Li Y , Du Y , Liao Y , Lim Y , Narusaka Y , Wang Z , Li Z , Xiong Z , Zhang Z
Ref : Nat Genet , 43 :1035 , 2011
Abstract : We report the annotation and analysis of the draft genome sequence of Brassica rapa accession Chiifu-401-42, a Chinese cabbage. We modeled 41,174 protein coding genes in the B. rapa genome, which has undergone genome triplication. We used Arabidopsis thaliana as an outgroup for investigating the consequences of genome triplication, such as structural and functional evolution. The extent of gene loss (fractionation) among triplicated genome segments varies, with one of the three copies consistently retaining a disproportionately large fraction of the genes expected to have been present in its ancestor. Variation in the number of members of gene families present in the genome may contribute to the remarkable morphological plasticity of Brassica species. The B. rapa genome sequence provides an important resource for studying the evolution of polyploid genomes and underpins the genetic improvement of Brassica oil and vegetable crops.
ESTHER : Wang_2011_Nat.Genet_43_1035
PubMedSearch : Wang_2011_Nat.Genet_43_1035
PubMedID: 21873998
Gene_locus related to this paper: braol-Q8GTM3 , braol-Q8GTM4 , brarp-m4ei94 , brarp-m4c988 , brana-a0a078j4a9 , brana-a0a078e1m0 , brana-a0a078cd75 , brarp-m4dwa6 , brana-a0a078j4f0 , brana-a0a078cus4 , brana-a0a078f8c2 , brana-a0a078jql1 , brana-a0a078dgj3 , brana-a0a078hw50 , brana-a0a078cuu0 , brana-a0a078dfa9 , brana-a0a078ic91 , brarp-m4ctw3 , brana-a0a078ca65 , brana-a0a078ctc8 , brana-a0a078h021 , brana-a0a078jx23 , brarp-m4da84 , brarp-m4dwr7 , brana-a0a078dh94 , brana-a0a078h612 , brana-a0a078j2t3 , braol-a0a0d3dpb2 , braol-a0a0d3dx76 , brana-a0a078jxa8 , brana-a0a078i2k3 , brarp-m4cwq4 , brarp-m4dcj8 , brarp-m4eh17 , brarp-m4eey4 , brarp-m4dnj8 , brarp-m4ey83 , brarp-m4ey84

Title : Exposure to tri-o-cresyl phosphate detected in jet airplane passengers - Liyasova_2011_Toxicol.Appl.Pharmacol_256_337
Author(s) : Liyasova M , Li B , Schopfer LM , Nachon F , Masson P , Furlong CE , Lockridge O
Ref : Toxicol Appl Pharmacol , 256 :337 , 2011
Abstract : The aircraft cabin and flight deck ventilation are supplied from partially compressed unfiltered bleed air directly from the engine. Worn or defective engine seals can result in the release of engine oil into the cabin air supply. Aircrew and passengers have complained of illness following such "fume events". Adverse health effects are hypothesized to result from exposure to tricresyl phosphate mixed esters, a chemical added to jet engine oil and hydraulic fluid for its anti-wear properties. Our goal was to develop a laboratory test for exposure to tricresyl phosphate. The assay was based on the fact that the active-site serine of butyrylcholinesterase reacts with the active metabolite of tri-o-cresyl phosphate, cresyl saligenin phosphate, to make a stable phosphorylated adduct with an added mass of 80 Da. No other organophosphorus agent makes this adduct in vivo on butyrylcholinesterase. Blood samples from jet airplane passengers were obtained 24-48 h after completing a flight. Butyrylcholinesterase was partially purified from 25 ml serum or plasma, digested with pepsin, enriched for phosphorylated peptides by binding to titanium oxide, and analyzed by mass spectrometry. Of 12 jet airplane passengers tested, 6 were positive for exposure to tri-o-cresyl phosphate that is, they had detectable amounts of the phosphorylated peptide FGEpSAGAAS. The level of exposure was very low. No more than 0.05 to 3% of plasma butyrylcholinesterase was modified. None of the subjects had toxic symptoms. Four of the positive subjects were retested 3 to 7 months following their last airplane trip and were found to be negative for phosphorylated butyrylcholinesterase. In conclusion, this is the first report of an assay that detects exposure to tri-o-cresyl phosphate in jet airplane travelers.
ESTHER : Liyasova_2011_Toxicol.Appl.Pharmacol_256_337
PubMedSearch : Liyasova_2011_Toxicol.Appl.Pharmacol_256_337
PubMedID: 21723309

Title : Deregulation of sphingolipid metabolism in Alzheimer's disease - He_2010_Neurobiol.Aging_31_398
Author(s) : He X , Huang Y , Li B , Gong CX , Schuchman EH
Ref : Neurobiology of Aging , 31 :398 , 2010
Abstract : Abnormal sphingolipid metabolism has been previously reported in Alzheimer's disease (AD). To extend these findings, several sphingolipids and sphingolipid hydrolases were analyzed in brain samples from AD patients and age-matched normal individuals. We found a pattern of elevated acid sphingomyelinase (ASM) and acid ceramidase (AC) expression in AD, leading to a reduction in sphingomyelin and elevation of ceramide. More sphingosine also was found in the AD brains, although sphingosine-1-phosphate (S1P) levels were reduced. Notably, significant correlations were observed between the brain ASM and S1P levels and the levels of amyloid beta (Abeta) peptide and hyperphosphorylated tau protein. Based on these findings, neuronal cell cultures were treated with Abeta oligomers, which were found to activate ASM, increase ceramide, and induce apoptosis. Pre-treatment of the neurons with purified, recombinant AC prevented the cells from undergoing Abeta-induced apoptosis. We propose that ASM activation is an important pathological event leading to AD, perhaps due to Abeta deposition. The downstream consequences of ASM activation are elevated ceramide, activation of ceramidases, and production of sphingosine. The reduced levels of S1P in the AD brain, together with elevated ceramide, likely contribute to the disease pathogenesis.
ESTHER : He_2010_Neurobiol.Aging_31_398
PubMedSearch : He_2010_Neurobiol.Aging_31_398
PubMedID: 18547682

Title : Mass spectral characterization of organophosphate-labeled, tyrosine-containing peptides: characteristic mass fragments and a new binding motif for organophosphates - Schopfer_2010_J.Chromatogr.B.Analyt.Technol.Biomed.Life.Sci_878_1297
Author(s) : Schopfer LM , Grigoryan H , Li B , Nachon F , Masson P , Lockridge O
Ref : Journal of Chromatography B Analyt Technol Biomed Life Sciences , 878 :1297 , 2010
Abstract : We have identified organophosphorus agent (OP)-tyrosine adducts on 12 different proteins labeled with six different OP. Labeling was achieved by treating pure proteins with up to 40-fold molar excess of OP at pH 8-8.6. OP-treated proteins were digested with trypsin, and peptides were separated by HPLC. Fragmentation patterns for 100 OP-peptides labeled on tyrosine were determined in the mass spectrometer. The goals of the present work were (1) to determine the common features of the OP-reactive tyrosines, and (2) to describe non-sequence MSMS fragments characteristic of OP-tyrosine peptides. Characteristic ions at 272 and 244 amu for tyrosine-OP immonium ions were nearly always present in the MSMS spectrum of peptides labeled on tyrosine by chlorpyrifos-oxon. Characteristic fragments also appeared from the parent ions that had been labeled with diisopropylfluorophosphate (216 amu), sarin (214 amu), soman (214 amu) or FP-biotin (227, 312, 329, 691 and 708 amu). In contrast to OP-reactive serines, which lie in the consensus sequence GXSXG, the OP-reactive tyrosines have no consensus sequence. Their common feature is the presence of nearby positively charged residues that activate the phenolic hydroxyl group. The significance of these findings is the recognition of a new binding motif for OP to proteins that have no active site serine. Modified peptides are difficult to find when the OP bears no radiolabel and no tag. The characteristic MSMS fragment ions are valuable because they are identifiers for OP-tyrosine, independent of the peptide.
ESTHER : Schopfer_2010_J.Chromatogr.B.Analyt.Technol.Biomed.Life.Sci_878_1297
PubMedSearch : Schopfer_2010_J.Chromatogr.B.Analyt.Technol.Biomed.Life.Sci_878_1297
PubMedID: 19762289

Title : Genome-wide association study of advanced age-related macular degeneration identifies a role of the hepatic lipase gene (LIPC) - Neale_2010_Proc.Natl.Acad.Sci.U.S.A_107_7395
Author(s) : Neale BM , Fagerness J , Reynolds R , Sobrin L , Parker M , Raychaudhuri S , Tan PL , Oh EC , Merriam JE , Souied E , Bernstein PS , Li B , Frederick JM , Zhang K , Brantley MA, Jr. , Lee AY , Zack DJ , Campochiaro B , Campochiaro P , Ripke S , Smith RT , Barile GR , Katsanis N , Allikmets R , Daly MJ , Seddon JM
Ref : Proc Natl Acad Sci U S A , 107 :7395 , 2010
Abstract : Advanced age-related macular degeneration (AMD) is the leading cause of late onset blindness. We present results of a genome-wide association study of 979 advanced AMD cases and 1,709 controls using the Affymetrix 6.0 platform with replication in seven additional cohorts (totaling 5,789 unrelated cases and 4,234 unrelated controls). We also present a comprehensive analysis of copy-number variations and polymorphisms for AMD. Our discovery data implicated the association between AMD and a variant in the hepatic lipase gene (LIPC) in the high-density lipoprotein cholesterol (HDL) pathway (discovery P = 4.53e-05 for rs493258). Our LIPC association was strongest for a functional promoter variant, rs10468017, (P = 1.34e-08), that influences LIPC expression and serum HDL levels with a protective effect of the minor T allele (HDL increasing) for advanced wet and dry AMD. The association we found with LIPC was corroborated by the Michigan/Penn/Mayo genome-wide association study; the locus near the tissue inhibitor of metalloproteinase 3 was corroborated by our replication cohort for rs9621532 with P = 3.71e-09. We observed weaker associations with other HDL loci (ABCA1, P = 9.73e-04; cholesterylester transfer protein, P = 1.41e-03; FADS1-3, P = 2.69e-02). Based on a lack of consistent association between HDL increasing alleles and AMD risk, the LIPC association may not be the result of an effect on HDL levels, but it could represent a pleiotropic effect of the same functional component. Results implicate different biologic pathways than previously reported and provide new avenues for prevention and treatment of AMD.
ESTHER : Neale_2010_Proc.Natl.Acad.Sci.U.S.A_107_7395
PubMedSearch : Neale_2010_Proc.Natl.Acad.Sci.U.S.A_107_7395
PubMedID: 20385826

Title : Genotyping of acetylcholinesterase in insects - Li_2010_Pestic.Biochem.Physiol_98_19
Author(s) : Li B , Wang YH , Liu HT , Xu YX , Wei ZG , Chen YH , Shen WD
Ref : Pesticide Biochemistry and Physiology , 98 :19 , 2010
Abstract : To investigate the genotyping criteria for the insect acetylcholinesterase gene (ace), we cloned two types of ace genes in domestic (Bombyx mori) and wild silkworm (Bombyx mandarina) through RT-PCR. The cloned genes were named Bm-ace1, Bm-ace2, Bmm-ace1 and Bmm-ace2, respectively. The ORFs of Bm-ace1 and Bmm-ace1 contained 2025 base pairs, encoding 683 amino acid residues (AAs). The predicted protein has a molecular weight (MW) of 76.955 kDa and an isoelectric point (pI) of 6.36. The Bm-ace2 and Bm-ace2 genes contained 1917 bp nucleotides, encoding 638 AAs. The predicted protein has a MW of 71.675 kDa and a pI of 5.49. Both ace1 and ace2 contain signature domains of acetylcholinesterases. Homology analysis of 18 NCBI downloaded insect AChEs peptide sequences and the 4 AChEs deducted in this study revealed that type 1 and type 2 insect AChEs had significant differences. Type 2 sequence is more conserved than type 1. Near the active centers of both types of AChEs, 48 strictly conserved AA's (336-384) are present, and homology of these two peptide fragments was only 54.16%. Meanwhile, at AA positions 280-297, type 1 and type 2 AChEs both have conserved sequences with the similarity of the two being 52.94%. In type 2 AChEs, a uniquely conserved peptide sequence is found at positions 226-239 (QHLRVRHHQDKPL). We propose to use the above mentioned three conserved regions as criteria for insect acetylcholinesterases gene genotyping. This will benefit the genotyping of other acetylcholinesterase genes and the study of their functions.
ESTHER : Li_2010_Pestic.Biochem.Physiol_98_19
PubMedSearch : Li_2010_Pestic.Biochem.Physiol_98_19

Title : Dichlorvos, chlorpyrifos oxon and Aldicarb adducts of butyrylcholinesterase, detected by mass spectrometry in human plasma following deliberate overdose - Li_2010_J.Appl.Toxicol_30_559
Author(s) : Li B , Ricordel I , Schopfer LM , Baud F , Megarbane B , Masson P , Lockridge O
Ref : J Appl Toxicol , 30 :559 , 2010
Abstract : The goal of this study was to develop a method to detect pesticide adducts in tryptic digests of butyrylcholinesterase in human plasma from patients poisoned by pesticides. Adducts to butyrylcholinesterase in human serum may serve as biomarkers of pesticide exposure because organophosphorus and carbamate pesticides make a covalent bond with the active site serine of butyrylcholinesterase. Serum samples from five attempted suicides (with dichlorvos, Aldicarb, Baygon and an unknown pesticide) and from one patient who accidentally inhaled dichlorvos were analyzed. Butyrylcholinesterase was purified from 2 ml serum by ion exchange chromatography at pH 4, followed by procainamide affinity chromatography at pH 7. The purified butyrylcholinesterase was denatured, digested with trypsin and the modified peptide isolated by HPLC. The purified peptide was analyzed by multiple reaction monitoring in a QTRAP 4000 mass spectrometer. This method successfully identified the pesticide-adducted butyrylcholinesterase peptide in four patients whose butyrylcholinesterase was inhibited 60-84%, but not in two patients whose inhibition levels were 8 and 22%. It is expected that low inhibition levels will require analysis of larger serum plasma volumes. In conclusion, a mass spectrometry method for identification of exposure to live toxic pesticides has been developed, based on identification of pesticide adducts on the active site serine of human butyrylcholinesterase.
ESTHER : Li_2010_J.Appl.Toxicol_30_559
PubMedSearch : Li_2010_J.Appl.Toxicol_30_559
PubMedID: 20809544

Title : Detection of adduct on tyrosine 411 of albumin in humans poisoned by dichlorvos - Li_2010_Toxicol.Sci_116_23
Author(s) : Li B , Ricordel I , Schopfer LM , Baud F , Megarbane B , Nachon F , Masson P , Lockridge O
Ref : Toxicol Sci , 116 :23 , 2010
Abstract : Studies in mice and guinea pigs have shown that albumin is a new biomarker of organophosphorus toxicant (OP) and nerve agent exposure. Our goal was to determine whether OP-labeled albumin could be detected in the blood of humans exposed to OP. Blood from four OP-exposed patients was prepared for mass spectrometry analysis by digesting 0.010 ml of serum with pepsin and purifying the labeled albumin peptide by offline high performance liquid chromatography. Dimethoxyphosphate-labeled tyrosine 411 was identified in albumin peptides VRY(411)TKKVPQVSTPTL and LVRY(411)TKKVPQVSTPTL from two patients who had attempted suicide with dichlorvos. The butyrylcholinesterase activity in these serum samples was inhibited 80%. A third patient whose serum BChE activity was inhibited 8% by accidental inhalation of dichlorvos had undetectable levels of adduct on albumin. A fourth patient whose BChE activity was inhibited 60% by exposure to chlorpyrifos had no detectable adduct on albumin. This is the first report to demonstrate the presence of OP-labeled albumin in human patients. It is concluded that tyrosine 411 of human albumin is covalently modified in the serum of humans poisoned by dichlorvos and that the modification is detectable by mass spectrometry. The special reactivity of tyrosine 411 with OP suggests that other proteins may also be modified on tyrosine. Identification of other OP-modified proteins may lead to an understanding of neurotoxic symptoms that appear long after the initial OP exposure.
ESTHER : Li_2010_Toxicol.Sci_116_23
PubMedSearch : Li_2010_Toxicol.Sci_116_23
PubMedID: 20395308

Title : The sequence and de novo assembly of the giant panda genome - Li_2010_Nature_463_311
Author(s) : Li R , Fan W , Tian G , Zhu H , He L , Cai J , Huang Q , Cai Q , Li B , Bai Y , Zhang Z , Zhang Y , Wang W , Li J , Wei F , Li H , Jian M , Nielsen R , Li D , Gu W , Yang Z , Xuan Z , Ryder OA , Leung FC , Zhou Y , Cao J , Sun X , Fu Y , Fang X , Guo X , Wang B , Hou R , Shen F , Mu B , Ni P , Lin R , Qian W , Wang G , Yu C , Nie W , Wang J , Wu Z , Liang H , Min J , Wu Q , Cheng S , Ruan J , Wang M , Shi Z , Wen M , Liu B , Ren X , Zheng H , Dong D , Cook K , Shan G , Zhang H , Kosiol C , Xie X , Lu Z , Li Y , Steiner CC , Lam TT , Lin S , Zhang Q , Li G , Tian J , Gong T , Liu H , Zhang D , Fang L , Ye C , Zhang J , Hu W , Xu A , Ren Y , Zhang G , Bruford MW , Li Q , Ma L , Guo Y , An N , Hu Y , Zheng Y , Shi Y , Li Z , Liu Q , Chen Y , Zhao J , Qu N , Zhao S , Tian F , Wang X , Wang H , Xu L , Liu X , Vinar T , Wang Y , Lam TW , Yiu SM , Liu S , Huang Y , Yang G , Jiang Z , Qin N , Li L , Bolund L , Kristiansen K , Wong GK , Olson M , Zhang X , Li S , Yang H
Ref : Nature , 463 :311 , 2010
Abstract : Using next-generation sequencing technology alone, we have successfully generated and assembled a draft sequence of the giant panda genome. The assembled contigs (2.25 gigabases (Gb)) cover approximately 94% of the whole genome, and the remaining gaps (0.05 Gb) seem to contain carnivore-specific repeats and tandem repeats. Comparisons with the dog and human showed that the panda genome has a lower divergence rate. The assessment of panda genes potentially underlying some of its unique traits indicated that its bamboo diet might be more dependent on its gut microbiome than its own genetic composition. We also identified more than 2.7 million heterozygous single nucleotide polymorphisms in the diploid genome. Our data and analyses provide a foundation for promoting mammalian genetic research, and demonstrate the feasibility for using next-generation sequencing technologies for accurate, cost-effective and rapid de novo assembly of large eukaryotic genomes.
ESTHER : Li_2010_Nature_463_311
PubMedSearch : Li_2010_Nature_463_311
PubMedID: 20010809
Gene_locus related to this paper: ailme-ABH15 , ailme-ACHE , ailme-BCHE , ailme-d2gtv3 , ailme-d2gty9 , ailme-d2gu87 , ailme-d2gu97 , ailme-d2gve7 , ailme-d2gwu1 , ailme-d2gx08 , ailme-d2gyt0 , ailme-d2gz36 , ailme-d2gz37 , ailme-d2gz38 , ailme-d2gz39 , ailme-d2gz40 , ailme-d2h5r9 , ailme-d2h7b7 , ailme-d2h9c9 , ailme-d2h794 , ailme-d2hau7 , ailme-d2hau8 , ailme-d2hcd9 , ailme-d2hdi6 , ailme-d2heu6 , ailme-d2hga4 , ailme-d2hqw5 , ailme-d2hs98 , ailme-d2hsx4 , ailme-d2hti6 , ailme-d2htv3 , ailme-d2htz6 , ailme-d2huc7 , ailme-d2hwj8 , ailme-d2hwy7 , ailme-d2hxm1 , ailme-d2hyc8 , ailme-d2hyv2 , ailme-d2hz11 , ailme-d2hza3 , ailme-d2hzr4 , ailme-d2i1l4 , ailme-d2i2g8 , ailme-g1l7m3 , ailme-g1lu36 , ailme-g1m769 , ailme-g1mc29 , ailme-g1mdj8 , ailme-g1mdr5 , ailme-g1mfp4 , ailme-g1mfx5 , ailme-g1lj41 , ailme-g1lm28 , ailme-g1l3u1 , ailme-g1l7l1 , ailme-g1m5i3 , ailme-g1l2f6 , ailme-g1lji5 , ailme-g1lqk3 , ailme-g1l8s9 , ailme-d2h717 , ailme-d2h718 , ailme-d2h719 , ailme-d2h720 , ailme-g1m5v0 , ailme-g1m5y7 , ailme-g1lkt7 , ailme-g1l2a1 , ailme-g1lsc8 , ailme-g1lrp4 , ailme-d2gv02 , ailme-g1mik5 , ailme-g1ljr1 , ailme-g1lxw7 , ailme-d2h8b5 , ailme-d2h2r2 , ailme-d2h9w7 , ailme-g1meh3 , ailme-g1m719

Title : Mass spectral characterization of organophosphate-labeled lysine in peptides. - Grigoryan_2009_Anal.Biochem_394_92
Author(s) : Grigoryan H , Li B , Xue W , Grigoryan M , Schopfer LM , Lockridge O
Ref : Analytical Biochemistry , 394 :92 , 2009
Abstract : Organophosphate (OP) esters bind covalently to the active site serine of enzymes in the serine hydrolase family. Recently, mass spectrometry identified covalent binding of OPs to tyrosine in a wide variety of proteins when purified proteins were incubated with OPs. In the current work, manual inspection of tandem mass spectrometry (MS/MS) data led to the realization that lysines also make a covalent bond with OPs. OP-labeled lysine residues were found in seven proteins that had been treated with either chlorpyrifos oxon (CPO) or diisopropylfluorophosphate (DFP): human serum albumin (K212, K414, K199, and K351), human keratin 1 (K211 and K355), human keratin 10 (K163), bovine tubulin alpha (K60, K336, K163, K394, and K401), bovine tubulin beta (K58), bovine actin (K113, K291, K326, K315, and K328), and mouse transferrin (K296 and K626). These results suggest that OP binding to lysine is a general phenomenon. Characteristic fragments specific for CPO-labeled lysine appeared at 237.1, 220.0, 192.0, 163.9, 128.9, and 83.9amu. Characteristic fragments specific for DFP-labeled lysine appeared at 164.0, 181.2, and 83.8amu. This new OP-binding motif to lysine suggests new directions to search for mechanisms of long-term effects of OP exposure and in the search for biomarkers of OP exposure.
ESTHER : Grigoryan_2009_Anal.Biochem_394_92
PubMedSearch : Grigoryan_2009_Anal.Biochem_394_92
PubMedID: 19596251

Title : Covalent binding of the organophosphorus agent FP-biotin to tyrosine in eight proteins that have no active site serine - Grigoryan_2009_Chem.Biol.Interact_180_492
Author(s) : Grigoryan H , Li B , Anderson EK , Xue W , Nachon F , Lockridge O , Schopfer LM
Ref : Chemico-Biological Interactions , 180 :492 , 2009
Abstract : Organophosphorus (OP) esters are known to bind covalently to the active site serine of enzymes in the serine hydrolase family. It was a surprise to find that proteins with no active site serine are also covalently modified by OP. The binding site in albumin, transferrin, and tubulin was identified as tyrosine. The goal of the present work was to determine whether binding to tyrosine is a general phenomenon. Fourteen proteins were treated with a biotin-tagged organophosphorus agent called FP-biotin. The proteins were digested with trypsin and the labeled peptides enriched by binding to monomeric avidin. Peptides were purified by HPLC and fragmented by collision induced dissociation in a tandem ion trap mass spectrometer. Eight proteins were labeled and six were not. Tyrosine was labeled in human alpha-2-glycoprotein 1 zinc-binding protein (Tyr 138, Tyr 174 and Tyr 181), human kinesin 3C motor domain (Tyr 145), human keratin 1 (Tyr 230), bovine actin (Tyr 55 and Tyr 200), murine ATP synthase beta (Tyr 431), murine adenine nucleotide translocase 1 (Tyr 81), bovine chymotrypsinogen (Tyr 201) and porcine pepsin (Tyr 310). Only 1-3 tyrosines per protein were modified, suggesting that the reactive tyrosine was activated by nearby residues that facilitated ionization of the hydroxyl group of tyrosine. These results suggest that OP binding to tyrosine is a general phenomenon. It is concluded that organophosphorus-reactive proteins include not only enzymes in the serine hydrolase family, but also proteins that have no active site serine. The recognition of a new OP-binding motif to tyrosine suggests new directions to search for mechanisms of long-term effects of OP exposure. Another application is in the search for biomarkers of organophosphorus agent exposure. Previous searches have been limited to serine hydrolases. Now proteins such as albumin and keratin can be considered.
ESTHER : Grigoryan_2009_Chem.Biol.Interact_180_492
PubMedSearch : Grigoryan_2009_Chem.Biol.Interact_180_492
PubMedID: 19539807

Title : Tyrosines of human and mouse transferrin covalently labeled by organophosphorus agents: a new motif for binding to proteins that have no active site serine - Li_2009_Toxicol.Sci_107_144
Author(s) : Li B , Schopfer LM , Grigoryan H , Thompson CM , Hinrichs SH , Masson P , Lockridge O
Ref : Toxicol Sci , 107 :144 , 2009
Abstract : The expectation from the literature is that organophosphorus (OP) agents bind to proteins that have an active site serine. However, transferrin, a protein with no active site serine, was covalently modified in vitro by 0.5mM 10-fluoroethoxyphosphinyl-N-biotinamido pentyldecanamide, chlorpyrifos oxon, diisopropylfluorophosphate, dichlorvos, sarin, and soman. The site of covalent attachment was identified by analyzing tryptic peptides in the mass spectrometer. Tyr 238 and Tyr 574 in human transferrin and Tyr 238, Tyr 319, Tyr 429, Tyr 491, and Tyr 518 in mouse transferrin were labeled by OP. Tyrosine in the small synthetic peptide ArgTyrThrArg made a covalent bond with diisopropylfluorophosphate, chlorpyrifos oxon, and dichlorvos at pH 8.3. These results, together with our previous demonstration that albumin and tubulin bind OP on tyrosine, lead to the conclusion that OP bind covalently to tyrosine, and that OP binding to tyrosine is a new OP-binding residue. The OP-reactive tyrosines are activated by interaction with Arg or Lys. It is suggested that many proteins in addition to those already identified may be modified by OP on tyrosine. The extent to which tyrosine modification by OP can occur in vivo and the toxicological implications of such modifications require further investigation.
ESTHER : Li_2009_Toxicol.Sci_107_144
PubMedSearch : Li_2009_Toxicol.Sci_107_144
PubMedID: 18930948

Title : The genome of the cucumber, Cucumis sativus L - Huang_2009_Nat.Genet_41_1275
Author(s) : Huang S , Li R , Zhang Z , Li L , Gu X , Fan W , Lucas WJ , Wang X , Xie B , Ni P , Ren Y , Zhu H , Li J , Lin K , Jin W , Fei Z , Li G , Staub J , Kilian A , van der Vossen EA , Wu Y , Guo J , He J , Jia Z , Tian G , Lu Y , Ruan J , Qian W , Wang M , Huang Q , Li B , Xuan Z , Cao J , Asan , Wu Z , Zhang J , Cai Q , Bai Y , Zhao B , Han Y , Li Y , Li X , Wang S , Shi Q , Liu S , Cho WK , Kim JY , Xu Y , Heller-Uszynska K , Miao H , Cheng Z , Zhang S , Wu J , Yang Y , Kang H , Li M , Liang H , Ren X , Shi Z , Wen M , Jian M , Yang H , Zhang G , Yang Z , Chen R , Ma L , Liu H , Zhou Y , Zhao J , Fang X , Fang L , Liu D , Zheng H , Zhang Y , Qin N , Li Z , Yang G , Yang S , Bolund L , Kristiansen K , Li S , Zhang X , Wang J , Sun R , Zhang B , Jiang S , Du Y
Ref : Nat Genet , 41 :1275 , 2009
Abstract : Cucumber is an economically important crop as well as a model system for sex determination studies and plant vascular biology. Here we report the draft genome sequence of Cucumis sativus var. sativus L., assembled using a novel combination of traditional Sanger and next-generation Illumina GA sequencing technologies to obtain 72.2-fold genome coverage. The absence of recent whole-genome duplication, along with the presence of few tandem duplications, explains the small number of genes in the cucumber. Our study establishes that five of the cucumber's seven chromosomes arose from fusions of ten ancestral chromosomes after divergence from Cucumis melo. The sequenced cucumber genome affords insight into traits such as its sex expression, disease resistance, biosynthesis of cucurbitacin and 'fresh green' odor. We also identify 686 gene clusters related to phloem function. The cucumber genome provides a valuable resource for developing elite cultivars and for studying the evolution and function of the plant vascular system.
ESTHER : Huang_2009_Nat.Genet_41_1275
PubMedSearch : Huang_2009_Nat.Genet_41_1275
PubMedID: 19881527
Gene_locus related to this paper: cucsa-a0a0a0ktw5 , cucsa-a0a0a0lnt6 , cucsa-a0a0a0kpn7 , cucsa-a0a0a0lvt9 , cucsa-a0a0a0kdx8 , cucsa-a0a0a0m228 , cucsa-a0a0a0kz31 , cucsa-a0a0a0k5t5 , cucsa-a0a0a0kfs7 , cucsa-a0a0a0kjj7 , cucsa-a0a0a0kzs7 , cucsa-a0a0a0l0a6 , cucsa-a0a0a0l4w4 , cucsa-a0a0a0lpz0 , cucsa-a0a0a0ls66

Title : The butyrylcholinesterase knockout mouse a research tool in the study of drug sensitivity, bio-distribution, obesity and Alzheimer's disease - Duysen_2009_Expert.Opin.Drug.Metab.Toxicol_5_523
Author(s) : Duysen EG , Li B , Lockridge O
Ref : Expert Opin Drug Metab Toxicol , 5 :523 , 2009
Abstract : Butyrylcholinesterase (BChE) mutations common in the human population may result in complete or partial BChE deficiency, making the BChE knockout (KO) mouse a model for human deficiencies. The BChE KO mouse cannot tolerate standard doses of the muscle relaxant succinylcholine or the Alzheimer's disease drugs huperzine A and donepezil. It is resistant to the asthma drug bambuterol. The importance of BChE in detoxication of cocaine has been demonstrated by hepatotoxicity and cardiotoxicity in cocaine-challenged BChE KO mice. The BChE KO mouse becomes obese on a high-fat diet, suggesting a role for BChE in fat metabolism. BChE serves as a backup for acetylcholinesterase by hydrolyzing the neurotransmitter acetylcholine in acetylcholinesterase knockout mice. Imaging studies show that BChE injected intrathecally crosses the blood-brain barrier. Mice, but not humans, have carboxylesterase in their blood. Carboxylesterase obscures the role of BChE in detoxication of organophosphorus pesticides. Future studies will make a double knockout that has neither BChE nor carboxylesterase. The double knockout is expected to be unusually sensitive to the toxicity of organophosphorus pesticides. Knowledge of drug sensitivities in the mouse model of human BChE deficiency will aid in understanding adverse drug effects in humans.
ESTHER : Duysen_2009_Expert.Opin.Drug.Metab.Toxicol_5_523
PubMedSearch : Duysen_2009_Expert.Opin.Drug.Metab.Toxicol_5_523
PubMedID: 19416087

Title : Synthesis and in vitro activity of 1-(2,3-dichlorophenyl)-N-(pyridin-3-ylmethyl)-1H-1,2,4-triazol-5-amine and 4-(2,3-dichlorophenyl)-N-(pyridin-3-ylmethyl)-4H-1,2,4-triazol-3-amine P2X7 antagonists - Florjancic_2008_Bioorg.Med.Chem.Lett_18_2089
Author(s) : Florjancic AS , Peddi S , Perez-Medrano A , Li B , Namovic MT , Grayson G , Donnelly-Roberts D , Jarvis MF , Carroll WA
Ref : Bioorganic & Medicinal Chemistry Lett , 18 :2089 , 2008
Abstract : A novel series of aminotriazole-based P2X(7) antagonists was synthesized, and their structure-activity relationships (SAR) were investigated for activity at both human and rat P2X(7) receptors. Most compounds showed greater potency at the human receptor although several analogs were discovered with potent activity (pIC(50) > or = 7.5) at both human and rat P2X(7).
ESTHER : Florjancic_2008_Bioorg.Med.Chem.Lett_18_2089
PubMedSearch : Florjancic_2008_Bioorg.Med.Chem.Lett_18_2089
PubMedID: 18272366

Title : Binding and hydrolysis of soman by human serum albumin - Li_2008_Chem.Res.Toxicol_21_421
Author(s) : Li B , Nachon F , Froment MT , Verdier L , Debouzy JC , Brasme B , Gillon E , Schopfer LM , Lockridge O , Masson P
Ref : Chemical Research in Toxicology , 21 :421 , 2008
Abstract : Human plasma and fatty acid free human albumin were incubated with soman at pH 8.0 and 25 degrees C. Four methods were used to monitor the reaction of albumin with soman: progressive inhibition of the aryl acylamidase activity of albumin, the release of fluoride ion from soman, 31P NMR, and mass spectrometry. Inhibition (phosphonylation) was slow with a bimolecular rate constant of 15 +/- 3 M(-1) min (-1). MALDI-TOF and tandem mass spectrometry of the soman-albumin adduct showed that albumin was phosphonylated on tyrosine 411. No secondary dealkylation of the adduct (aging) occurred. Covalent docking simulations and 31P NMR experiments showed that albumin has no enantiomeric preference for the four stereoisomers of soman. Spontaneous reactivation at pH 8.0 and 25 degrees C, measured as regaining of aryl acylamidase activity and decrease of covalent adduct (pinacolyl methylphosphonylated albumin) by NMR, occurred at a rate of 0.0044 h (-1), indicating that the adduct is quite stable ( t1/2 = 6.5 days). At pH 7.4 and 22 degrees C, the covalent soman-albumin adduct, measured by MALDI-TOF mass spectrometry, was more stable ( t1/2 = 20 days). Though the concentration of albumin in plasma is very high (about 0.6 mM), its reactivity with soman (phosphonylation and phosphotriesterase activity) is too slow to play a major role in detoxification of the highly toxic organophosphorus compound soman. Increasing the bimolecular rate constant of albumin for organophosphates is a protein engineering challenge that could lead to a new class of bioscavengers to be used against poisoning by nerve agents. Soman-albumin adducts detected by mass spectrometry could be useful for the diagnosis of soman exposure.
ESTHER : Li_2008_Chem.Res.Toxicol_21_421
PubMedSearch : Li_2008_Chem.Res.Toxicol_21_421
PubMedID: 18163544

Title : Increased hepatotoxicity and cardiac fibrosis in cocaine-treated butyrylcholinesterase knockout mice - Duysen_2008_Basic.Clin.Pharmacol.Toxicol_103_514
Author(s) : Duysen EG , Li B , Carlson M , Li YF , Wieseler S , Hinrichs SH , Lockridge O
Ref : Basic Clin Pharmacol Toxicol , 103 :514 , 2008
Abstract : In mice, cocaine is detoxified to inactive products by butyrylcholinesterase (BChE) and carboxylesterase. In human beings, cocaine detoxification is primarily by BChE. The focus of this investigation was to elucidate the importance of BChE in reducing pathophysiological effects following cocaine exposure. Previous studies examining the effects of cocaine on BChE deficient animals relied on chemical inhibition of BChE with tetraisopropyl pyrophosphoramide (iso-OMPA). The creation of the BChE knockout mouse has provided a model for studying pathological effects of cocaine in mice free of chemical confounders. We hypothesized that mice with low or no BChE activity would have reduced cocaine metabolism, leading to hepatotoxicity and cardiomyopathy. A high-resolution in vivo imaging system recorded cardiac and respiratory function following treatment with a carboxylesterase inhibitor and a high dose of cocaine (100 mg/kg, intraperitoneally). The BChE-/- mice demonstrated depressed respiration through 12 hr after dosing and abnormal respiratory patterns consisting of a pause at full inspiration (apneusis), whereas BChE+/+ mice had recovered normal respiration rates by 30 min. after dosing and exhibited no apneusis. Liver and cardiac histology sections were analysed following a 20 mg/kg intraperitoneally dose of cocaine administered daily for 7 days. BChE-/- mice treated for 7 days with the chronic low dose showed significant hepatotoxicity and cardiac perivascular fibrosis compared to BChE+/+ mice. The observed functional changes following acute high-dose and chronic low-dose cocaine in BChE-/- and +/- mice warrants further investigation into the possibility of increased cocaine toxicity in human beings with BChE deficiency.
ESTHER : Duysen_2008_Basic.Clin.Pharmacol.Toxicol_103_514
PubMedSearch : Duysen_2008_Basic.Clin.Pharmacol.Toxicol_103_514
PubMedID: 19067679

Title : Five tyrosines and two serines in human albumin are labeled by the organophosphorus agent FP-biotin - Ding_2008_Chem.Res.Toxicol_21_1787
Author(s) : Ding SJ , Carr J , Carlson JE , Tong L , Xue W , Li Y , Schopfer LM , Li B , Nachon F , Asojo OA , Thompson CM , Hinrichs SH , Masson P , Lockridge O
Ref : Chemical Research in Toxicology , 21 :1787 , 2008
Abstract : Tyrosine 411 of human albumin is an established site for covalent attachment of 10-fluoroethoxyphosphinyl- N-biotinamidopentyldecanamide (FP-biotin), diisopropylfluorophosphate, chlorpyrifos oxon, soman, sarin, and dichlorvos. This work investigated the hypothesis that other residues in albumin could be modified by organophosphorus agents (OP). Human plasma was aggressively treated with FP-biotin; plasma proteins were separated into high and low abundant portions using a proteome partitioning antibody kit, and the proteins were digested with trypsin. The FP-biotinylated tryptic peptides were isolated by binding to monomeric avidin beads. The major sites of covalent attachment identified by mass spectrometry were Y138, Y148, Y401, Y411, Y452, S232, and S287 of human albumin. Prolonged treatment of pure human albumin with chlorpyrifos oxon labeled Y138, Y150, Y161, Y401, Y411, and Y452. To identify the most reactive residue, albumin was treated for 2 h with DFP, FP-biotin, chlorpyrifos oxon, or soman, digested with trypsin or pepsin, and analyzed by mass spectrometry. The most reactive residue was always Tyr 411. Diethoxyphosphate-labeled Tyr 411 was stable for months at pH 7.4. These results will be useful in the development of specific antibodies to detect OP exposure and to engineer albumin for use as an OP scavenger.
ESTHER : Ding_2008_Chem.Res.Toxicol_21_1787
PubMedSearch : Ding_2008_Chem.Res.Toxicol_21_1787
PubMedID: 18707141

Title : Defective protein folding and intracellular retention of thyroglobulin-R19K mutant as a cause of human congenital goiter - Kim_2008_Mol.Endocrinol_22_477
Author(s) : Kim PS , Lee J , Jongsamak P , Menon S , Li B , Hossain SA , Bae JH , Panijpan B , Arvan P
Ref : Mol Endocrinol , 22 :477 , 2008
Abstract : It has been suggested that a thyroglobulin (Tg)-R19K missense mutation may be a newly identified cause of human congenital goiter, which is surprising for this seemingly conservative substitution. Here, we have examined the intracellular fate of recombinant mutant Tg expressed in COS-7 cells. Incorporation of the R19K mutation largely blocked Tg secretion, and this mutant was approximately 90% degraded intracellularly over a 24-h period after synthesis. Before its degradation, the Tg-R19K mutant exhibited abnormally increased association with molecular chaperones BiP, calnexin, and protein disulfide isomerase, and was unable to undergo anterograde advance from the endoplasmic reticulum (ER) through the Golgi complex. Inhibitors of proteasomal proteolysis and ER mannosidase-I both prevented ER-associated degradation of the Tg-R19K mutant and increased its association with ER molecular chaperones. ER quality control around Tg residue 19 is not dependent upon charge but upon side-chain packing, because Tg-R19Q was efficiently secreted. Whereas a Tg mutant truncated after residue 174 folds sufficiently well to escape ER quality control, introduction of the R19K point mutation blocked its secretion. The data indicate that the R19K mutation induces local misfolding in the amino-terminal domain of Tg that has global effects on Tg transport and thyroid hormonogenesis.
ESTHER : Kim_2008_Mol.Endocrinol_22_477
PubMedSearch : Kim_2008_Mol.Endocrinol_22_477
PubMedID: 17916655
Gene_locus related to this paper: human-TG

Title : Effect of polysaccharide from Auricularia auricula on blood lipid metabolism and lipoprotein lipase activity of ICR mice fed a cholesterol-enriched diet - Chen_2008_J.Food.Sci_73_H103
Author(s) : Chen G , Luo YC , Li BP , Li B , Guo Y , Li Y , Su W , Xiao ZL
Ref : J Food Sci , 73 :H103 , 2008
Abstract : Polysaccharides from Auricularia auricula (AAP) extracted in hot water and precipitated by ethanol were chemically well defined, including 42.5% total carbohydrate, 19.6% uronic acids, 15.8% sulfate groups, 1.7% N, and 20.3% ash. Gas chromatography analysis demonstrated that the neutral sugars were mainly composed of rhamnose, xylose, and glucose and smaller amounts of mannose, galactose, and arabinose. The present study was designed to investigate the antioxidant capacity of AAP on blood lipid metabolism and lipoprotein lipase (LPL) activity in ICR mice fed cholesterol-enriched diet (CED) for the 1st time. Furthermore, the relationship between the atherosclerotic index (AI) and LPL activity to total antioxidant capacity (TAC) was studied. Thirty-six ICR mice were randomly assigned to 3 groups (n=12). The mice in control group (NG) received regular diet and the mice in model group (MG) received CED; these 2 groups were provided with distilled water by oral gavage. The experimental group (EG) was fed CED with oral gavage of AAP (120 mg/kg/d body weight) for an 8-wk period. After 2, 4, 6, and 8 wk, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglyceride (TG) levels of the serum were determined by enzymatic methods. The results indicated that the polysaccharides significantly lowered the concentrations of serum TC and LDL-C compared with the CED control group (P<0.05). Moreover, oral administration of polysaccharides significantly improved TAC, LPL activity, and decreased MDA level, as well as AI. These conclusions revealed the beneficial effects ofAAP on the preventive actions against hypercholesterolemia.
ESTHER : Chen_2008_J.Food.Sci_73_H103
PubMedSearch : Chen_2008_J.Food.Sci_73_H103
PubMedID: 19241585

Title : Synthesis and activity of N-cyanoguanidine-piperazine P2X7 antagonists - Betschmann_2008_Bioorg.Med.Chem.Lett_18_3848
Author(s) : Betschmann P , Bettencourt B , Donnelly-Roberts D , Friedman M , George J , Hirst G , Josephsohn N , Konopacki D , Li B , Maull J , Morytko MJ , Moore NS , Namovic M , Rafferty P , Salmeron-Garcia JA , Tarcsa E , Wang L , Woller K
Ref : Bioorganic & Medicinal Chemistry Lett , 18 :3848 , 2008
Abstract : A novel series of cyanoguanidine-piperazine P2X(7) antagonists were identified and structure-activity relationship (SAR) studies described. Compounds were assayed for activity at human and rat P2X(7) receptors in addition to their ability to inhibit IL-1 beta release from stimulated human whole blood cultures. Compound 27 possesses potent activity (0.12 microM) in this latter assay and demonstrates moderate clearance in-vivo.
ESTHER : Betschmann_2008_Bioorg.Med.Chem.Lett_18_3848
PubMedSearch : Betschmann_2008_Bioorg.Med.Chem.Lett_18_3848
PubMedID: 18595695

Title : The butyrylcholinesterase knockout mouse as a model for human butyrylcholinesterase deficiency - Li_2008_J.Pharmacol.Exp.Ther_324_1146
Author(s) : Li B , Duysen EG , Carlson M , Lockridge O
Ref : Journal of Pharmacology & Experimental Therapeutics , 324 :1146 , 2008
Abstract : Butyrylcholinesterase (BChE) is an important enzyme for metabolism of ester drugs. Many humans have partial or complete BChE deficiency due to genetic variation. Our goal was to create a mouse model of BChE deficiency to allow testing of drug toxicity. For this purpose, we created the BChE knockout mouse by gene-targeted deletion of a portion of the BCHE gene (accession number M99492). The BChE(-/-) mouse had no BChE activity in plasma, but it had low residual butyrylthiocholine hydrolase activity in all other tissues attributed to carboxylesterase ES-10. The BChE(-/-) mouse had a normal phenotype except when challenged with drugs. Nicotinic receptor function as indicated by response to nicotine seemed to be normal in BChE(-/-) mice, but muscarinic receptor function as measured by response to oxotremorine and pilocarpine was altered. Heart rate, blood pressure, and respiration, measured in a Vevo imager, were similar in BChE(+/+) and BChE(-/-) mice. Like BChE(-/-) humans, the BChE(-/-) mouse responded to succinylcholine with prolonged respiratory arrest. Bambuterol was not toxic to BChE(-/-) mice, suggesting it is safe in BChE(-/-) humans. Challenge with 150 mg/kg pilocarpine i.p., a muscarinic agonist, or with 50 mg/kg butyrylcholine i.p., induced tonicclonic convulsions and death in BChE(-/-) mice. This suggests that butyrylcholine, like pilocarpine, binds to muscarinic receptors. In conclusion, the BChE(-/-) mouse is a suitable model for human BChE deficiency.
ESTHER : Li_2008_J.Pharmacol.Exp.Ther_324_1146
PubMedSearch : Li_2008_J.Pharmacol.Exp.Ther_324_1146
PubMedID: 18056867

Title : The butyrylcholinesterase knockout mouse is obese on a high-fat diet - Li_2008_Chem.Biol.Interact_175_88
Author(s) : Li B , Duysen EG , Lockridge O
Ref : Chemico-Biological Interactions , 175 :88 , 2008
Abstract : Butyrylcholinesterase (BChE) inactivates the appetite stimulating hormone octanoyl-ghrelin. The hypothesis was tested that BChE-/- mice would have abnormally high body weight and high levels of octanoyl-ghrelin. It was found that BChE-/- mice fed a standard 5% fat diet had normal body weight. However, BChE-/- mice fed a diet containing 11% fat became obese. Their obesity was not explained by increased levels of octanoyl-ghrelin, or by increased caloric intake, or by decreased exercise. Instead, a role for BChE in fat utilization was suggested.
ESTHER : Li_2008_Chem.Biol.Interact_175_88
PubMedSearch : Li_2008_Chem.Biol.Interact_175_88
PubMedID: 18452903

Title : The genome of the model beetle and pest Tribolium castaneum - Richards_2008_Nature_452_949
Author(s) : Richards S , Gibbs RA , Weinstock GM , Brown SJ , Denell R , Beeman RW , Gibbs R , Bucher G , Friedrich M , Grimmelikhuijzen CJ , Klingler M , Lorenzen M , Roth S , Schroder R , Tautz D , Zdobnov EM , Muzny D , Attaway T , Bell S , Buhay CJ , Chandrabose MN , Chavez D , Clerk-Blankenburg KP , Cree A , Dao M , Davis C , Chacko J , Dinh H , Dugan-Rocha S , Fowler G , Garner TT , Garnes J , Gnirke A , Hawes A , Hernandez J , Hines S , Holder M , Hume J , Jhangiani SN , Joshi V , Khan ZM , Jackson L , Kovar C , Kowis A , Lee S , Lewis LR , Margolis J , Morgan M , Nazareth LV , Nguyen N , Okwuonu G , Parker D , Ruiz SJ , Santibanez J , Savard J , Scherer SE , Schneider B , Sodergren E , Vattahil S , Villasana D , White CS , Wright R , Park Y , Lord J , Oppert B , Brown S , Wang L , Weinstock G , Liu Y , Worley K , Elsik CG , Reese JT , Elhaik E , Landan G , Graur D , Arensburger P , Atkinson P , Beidler J , Demuth JP , Drury DW , Du YZ , Fujiwara H , Maselli V , Osanai M , Robertson HM , Tu Z , Wang JJ , Wang S , Song H , Zhang L , Werner D , Stanke M , Morgenstern B , Solovyev V , Kosarev P , Brown G , Chen HC , Ermolaeva O , Hlavina W , Kapustin Y , Kiryutin B , Kitts P , Maglott D , Pruitt K , Sapojnikov V , Souvorov A , Mackey AJ , Waterhouse RM , Wyder S , Kriventseva EV , Kadowaki T , Bork P , Aranda M , Bao R , Beermann A , Berns N , Bolognesi R , Bonneton F , Bopp D , Butts T , Chaumot A , Denell RE , Ferrier DE , Gordon CM , Jindra M , Lan Q , Lattorff HM , Laudet V , von Levetsow C , Liu Z , Lutz R , Lynch JA , da Fonseca RN , Posnien N , Reuter R , Schinko JB , Schmitt C , Schoppmeier M , Shippy TD , Simonnet F , Marques-Souza H , Tomoyasu Y , Trauner J , Van der Zee M , Vervoort M , Wittkopp N , Wimmer EA , Yang X , Jones AK , Sattelle DB , Ebert PR , Nelson D , Scott JG , Muthukrishnan S , Kramer KJ , Arakane Y , Zhu Q , Hogenkamp D , Dixit R , Jiang H , Zou Z , Marshall J , Elpidina E , Vinokurov K , Oppert C , Evans J , Lu Z , Zhao P , Sumathipala N , Altincicek B , Vilcinskas A , Williams M , Hultmark D , Hetru C , Hauser F , Cazzamali G , Williamson M , Li B , Tanaka Y , Predel R , Neupert S , Schachtner J , Verleyen P , Raible F , Walden KK , Angeli S , Foret S , Schuetz S , Maleszka R , Miller SC , Grossmann D
Ref : Nature , 452 :949 , 2008
Abstract : Tribolium castaneum is a member of the most species-rich eukaryotic order, a powerful model organism for the study of generalized insect development, and an important pest of stored agricultural products. We describe its genome sequence here. This omnivorous beetle has evolved the ability to interact with a diverse chemical environment, as shown by large expansions in odorant and gustatory receptors, as well as P450 and other detoxification enzymes. Development in Tribolium is more representative of other insects than is Drosophila, a fact reflected in gene content and function. For example, Tribolium has retained more ancestral genes involved in cell-cell communication than Drosophila, some being expressed in the growth zone crucial for axial elongation in short-germ development. Systemic RNA interference in T. castaneum functions differently from that in Caenorhabditis elegans, but nevertheless offers similar power for the elucidation of gene function and identification of targets for selective insect control.
ESTHER : Richards_2008_Nature_452_949
PubMedSearch : Richards_2008_Nature_452_949
PubMedID: 18362917
Gene_locus related to this paper: trica-ACHE1 , trica-ACHE2 , trica-d2a0g9 , trica-d2a0h0 , trica-d2a0w9 , trica-d2a0x0 , trica-d2a0x1 , trica-d2a0x3 , trica-d2a0x4.1 , trica-d2a0x4.2 , trica-d2a0x6 , trica-d2a2b8 , trica-d2a2h1 , trica-d2a3c3 , trica-d2a3g9 , trica-d2a5y5 , trica-d2a309 , trica-d2a514 , trica-d2a515 , trica-d2a516 , trica-d2a577 , trica-d2a578 , trica-d6w6x8 , trica-d6w7f9 , trica-d6w7h2 , trica-d6w8e7 , trica-d6w9c0 , trica-d6w855 , trica-d6wac8 , trica-d6wan4 , trica-d6wd50 , trica-d6wd73 , trica-d6wd74 , trica-A0A139WM97 , trica-d6wfu3 , trica-d6wgl2 , trica-d6wj57 , trica-d6wj59 , trica-d6wjs3 , trica-d6wl31 , trica-d6wnv1 , trica-d6wpl0 , trica-d6wqd6 , trica-d6wqr4 , trica-d6ws52 , trica-d6wsm0 , trica-d6wu38 , trica-d6wu39 , trica-d6wu40 , trica-d6wu41 , trica-d6wu44 , trica-d6wvk5 , trica-d6wvz7 , trica-d6wwu9 , trica-d6wwv0 , trica-d6wxz0 , trica-d6wyy1 , trica-d6wyy2 , trica-d6x0z2 , trica-d6x0z5 , trica-d6x0z6 , trica-d6x4b2 , trica-d6x4e8 , trica-d6x4e9 , trica-d6x197 , trica-d7eip7 , trica-d7eld3 , trica-d7us45 , trica-q5wm43 , trica-q5zex9 , trica-d6wie5 , trica-d6w7t0 , trica-d6x4h0 , trica-d6x4h1 , trica-a0a139wae8 , trica-a0a139wc96 , trica-d6x325 , trica-d2a4s2 , trica-d6wvw8

Title : Aging of cholinesterases phosphylated by tabun proceeds through O-dealkylation - Carletti_2008_J.Am.Chem.Soc_130_16011
Author(s) : Carletti E , Li H , Li B , Ekstrom F , Nicolet Y , Loiodice M , Gillon E , Froment MT , Lockridge O , Schopfer LM , Masson P , Nachon F
Ref : Journal of the American Chemical Society , 130 :16011 , 2008
Abstract : Human butyrylcholinesterase (hBChE) hydrolyzes or scavenges a wide range of toxic esters, including heroin, cocaine, carbamate pesticides, organophosphorus pesticides, and nerve agents. Organophosphates (OPs) exert their acute toxicity through inhibition of acetylcholinesterase (AChE) by phosphorylation of the catalytic serine. Phosphylated cholinesterase (ChE) can undergo a spontaneous, time-dependent process called "aging", during which the OP-ChE conjugate is dealkylated. This leads to irreversible inhibition of the enzyme. The inhibition of ChEs by tabun and the subsequent aging reaction are of particular interest, because tabun-ChE conjugates display an extraordinary resistance toward most current oxime reactivators. We investigated the structural basis of oxime resistance for phosphoramidated ChE conjugates by determining the crystal structures of the non-aged and aged forms of hBChE inhibited by tabun, and by updating the refinement of non-aged and aged tabun-inhibited mouse AChE (mAChE). Structures for non-aged and aged tabun-hBChE were refined to 2.3 and 2.1 A, respectively. The refined structures of aged ChE conjugates clearly show that the aging reaction proceeds through O-dealkylation of the P(R) enantiomer of tabun. After dealkylation, the negatively charged oxygen forms a strong salt bridge with protonated His438N epsilon2 that prevents reactivation. Mass spectrometric analysis of the aged tabun-inhibited hBChE showed that both the dimethylamine and ethoxy side chains were missing from the phosphorus. Loss of the ethoxy is consistent with the crystallography results. Loss of the dimethylamine is consistent with acid-catalyzed deamidation during the preparation of the aged adduct for mass spectrometry. The reported 3D data will help in the design of new oximes capable of reactivating tabun-ChE conjugates.
ESTHER : Carletti_2008_J.Am.Chem.Soc_130_16011
PubMedSearch : Carletti_2008_J.Am.Chem.Soc_130_16011
PubMedID: 18975951
Gene_locus related to this paper: human-BCHE , mouse-ACHE

Title : Matrix-assisted laser desorption\/ionization time-of-flight mass spectrometry assay for organophosphorus toxicants bound to human albumin at Tyr411 - Li_2007_Anal.Biochem_361_263
Author(s) : Li B , Schopfer LM , Hinrichs SH , Masson P , Lockridge O
Ref : Analytical Biochemistry , 361 :263 , 2007
Abstract : Our goal was to determine whether chlorpyrifos oxon, dichlorvos, diisopropylfluorophosphate (DFP), and sarin covalently bind to human albumin. Human albumin or plasma was treated with organophosphorus (OP) agent at alkaline pH, digested with pepsin at pH 2.3, and analyzed by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry. Two singly charged peaks m/z 1718 and 1831, corresponding to the unlabeled peptide fragments containing the active site Tyr411 residue, were detected in all samples. The sequences of the two peptides were VRYTKKVPQVSTPTL and LVRYTKKVPQVSTPTL. The peptide-OP adducts of these peptides were also found. They had masses of 1854 and 1967 for chlorpyrifos oxon, 1825 and 1938 for dichlorvos, 1881 and 1994 for DFP, and 1838 and 1938 for sarin; these masses fit a mechanism whereby OP bound covalently to Tyr411. The binding of DFP to Tyr411 of human albumin was confirmed by electrospray tandem mass spectrometry and analysis of product ions. None of the OP-albumin adducts lost an alkoxy group, leading to the conclusion that aging did not occur. Our results show that OP pesticides and nerve agents bind covalently to human albumin at Tyr411. The presence of Tyr411 on an exposed surface of albumin suggests that an antibody response could be generated against OP-albumin adducts.
ESTHER : Li_2007_Anal.Biochem_361_263
PubMedSearch : Li_2007_Anal.Biochem_361_263
PubMedID: 17188226

Title : Sensitivity of butyrylcholinesterase knockout mice to (--)-huperzine A and donepezil suggests humans with butyrylcholinesterase deficiency may not tolerate these Alzheimer's disease drugs and indicates butyrylcholinesterase function in neurotransmission - Duysen_2007_Toxicology_233_60
Author(s) : Duysen EG , Li B , Darvesh S , Lockridge O
Ref : Toxicology , 233 :60 , 2007
Abstract : Butyrylcholinesterase (EC BChE) is present in all human and mouse tissues, and is more abundant than acetylcholinesterase (EC AChE) in all tissues except brain. People who have no BChE activity due to a genetic variation are healthy. This has led to the hypothesis that BChE has no physiological function. We tested this hypothesis by challenging BChE and AChE knockout mice, as well as wild-type mice, with the AChE specific inhibitors, (--)-huperzine A and donepezil, and with serine hydrolase inhibitors, echothiophate and chlorpyrifos oxon. (--)-Huperzine A and donepezil caused mortality and significant toxicity in the BChE-/- animals. The BChE heterozygote (BCHE+/-) mice with approximately one-half the BChE activity of the BChE wild type (BChE+/+) exhibited intermediate toxic symptoms, and survived a longer period. The BChE+/+ animals displayed comparatively minor toxic symptoms and recovered by 24h post-dosing. Plasma AChE activity was inhibited to the same extent in BChE-/-, +/-, and +/+ mice, whereas BChE activity was not inhibited. This indicated that the protective effect of BChE was not due to scavenging (--)-huperzine A. AChE-/- mice were unaffected by (--)-huperzine A and donepezil, demonstrating the specificity of these inhibitors for AChE. AChE-/- mice treated with chlorpyrifos oxon lost all BChE activity, had severe cholinergic symptoms and died of convulsions. This showed that BChE activity was essential for survival of AChE-/- mice. In conclusion, we propose that the protective effect of BChE is explained by hydrolysis of excess acetylcholine in physiologically relevant regions such as diaphragm, cardiac muscle, and brain. Thus, BChE has a function in neurotransmission. People with BChE deficiency are expected to be intolerant of standard doses of the anti-Alzheimer's drugs, (--)-huperzine A and donepezil.
ESTHER : Duysen_2007_Toxicology_233_60
PubMedSearch : Duysen_2007_Toxicology_233_60
PubMedID: 17194517

Title : Gene transfer of acetylcholinesterase protects the knockout mouse from the toxicity of DFP - Li_2006_J.Mol.Neurosci_30_79
Author(s) : Li B , Duysen EG , Lockridge O
Ref : Journal of Molecular Neuroscience , 30 :79 , 2006
Abstract : Acetylcholinesterase (AChE) has a clear role in nerve impulse transmission. Organophosphorus esters are highly toxic chemicals used as pesticides, fire retardants, plasticizers, and chemical warfare agents. The acute toxicity of organophosphorus poisons is attributed to inhibition of AChE in nerve synapses. This leads to seizures, respiratory arrest, and death. Our goal was to find a new therapeutic for protection against the toxicity of organophosphates (OPs). We investigated the feasibility of using a gene therapy vector to deliver AChE over long time periods and in quantities sufficiently high to provide protection against diisopropylfluorophosphate (DFP) toxicity. We used the AChE-/- mouse for these studies because this mouse has no endogenous AChE activity (Xie et al., 2000). Any AChE activity found in tissues could only come from the viral vector.
ESTHER : Li_2006_J.Mol.Neurosci_30_79
PubMedSearch : Li_2006_J.Mol.Neurosci_30_79
PubMedID: 17192637

Title : Production of the butyrylcholinesterase knockout mouse - Li_2006_J.Mol.Neurosci_30_193
Author(s) : Li B , Duysen EG , Saunders TL , Lockridge O
Ref : Journal of Molecular Neuroscience , 30 :193 , 2006
Abstract : The butyrylcholinesterase (BChE [EC]) knockout mouse is a model for BChE deficiency in humans. The existence of genetic variants of human BChE was discovered after a new muscle relaxant, succinylcholine, was introduced into the practice of medicine in the late 1950s. People with the atypical variant were unable to breathe for 2 h after receiving a dose intended to paralyze for 3-5 min (Kalow and Gunn, 1957, 1959). The atypical variant was later found to have a single-amino-acid mutation at Asp-70 (McGuire et al., 1989), which decreased the affinity of BChE for all positively charged compounds. Though the atypical BChE mutant is the one most commonly encountered in cases of succinylcholine apnea, an additional 58 mutations in the BChE coding sequence have been reported. The frequency of BChE mutations in the American population is known (Lockridge, 1990). One person out of 25 carries one atypical allele (D70G), whereas 1 out of 2500 is homozygous for D70G. The most frequent mutation, A539T, is carried by 1 person out of every 4 and is found in homozygous form in 1 person out of 69 (Bartels et al., 1992). The homozygous A539T form is associated with a 33% decrease in plasma BChE activity. Some people have no detectable BChE activity in plasma, owing to a mutation that truncates the protein, or inactivates it. The frequency of silent BChE is 1 out of 160 for carriers, and 1 out of 110,000 for homozygotes. The BChE knockout mice are models for silent BChE in humans. The literature contains no documentation of the health of people with silent BChE, other than to say they are healthy. We know nothing about their life expectancy, fertility, risk of cognitive impairment, risk of heart disease, or susceptibility to toxins. The BChE knockout mouse will allow us to test the hypothesis that the function of BChE is to detoxify poisons and will allow us to test the role of BChE in other physiological functions.
ESTHER : Li_2006_J.Mol.Neurosci_30_193
PubMedSearch : Li_2006_J.Mol.Neurosci_30_193
PubMedID: 17192674

Title : Protection from the toxicity of diisopropylfluorophosphate by adeno-associated virus expressing acetylcholinesterase - Li_2006_Toxicol.Appl.Pharmacol_214_152
Author(s) : Li B , Duysen EG , Poluektova LY , Murrin LC , Lockridge O
Ref : Toxicol Appl Pharmacol , 214 :152 , 2006
Abstract : Organophosphorus esters (OP) are highly toxic chemicals used as pesticides and nerve agents. Their acute toxicity is attributed to inhibition of acetylcholinesterase (AChE, EC in nerve synapses. Our goal was to find a new therapeutic for protection against OP toxicity. We used a gene therapy vector, adeno-associated virus serotype 2 (AAV-2), to deliver murine AChE to AChE-/- mice that have no endogenous AChE activity. The vector encoded the most abundant form of AChE: exons 2, 3, 4, and 6. Two-day old animals, with an immature immune system, were injected. AChE delivered intravenously was expressed up to 5 months in plasma, liver, heart, and lung, at 5-15% of the level in untreated wild-type mice. A few mice formed antibodies, but antibodies did not block AChE activity. The plasma AChE was a mixture of dimers and tetramers. AChE delivered intramuscularly had 40-fold higher activity levels than in wild-type muscle. None of the AChE was collagen-tailed. No retrograde transport through the motor neurons to the central nervous system was detected. AChE delivered intrastriatally assembled into tetramers. In brain, the AAV-2 vector transduced neurons, but not astrocytes and microglia. Vector-treated AChE-/- mice lived longer than saline-treated controls. AChE-/- mice were protected from diisopropylfluorophosphate-induced respiratory failure when the vector was delivered intravenously, but not intrastriatally. Since vector-treated animals had no AChE activity in diaphragm muscle, protection from respiratory failure came from AChE in other tissues. We conclude that AChE scavenged OP and in this way protected the activity of butyrylcholinesterase (BChE, EC in motor endplates.
ESTHER : Li_2006_Toxicol.Appl.Pharmacol_214_152
PubMedSearch : Li_2006_Toxicol.Appl.Pharmacol_214_152
PubMedID: 16443250

Title : Butyrylcholinesterase, paraoxonase, and albumin esterase, but not carboxylesterase, are present in human plasma - Li_2005_Biochem.Pharmacol_70_1673
Author(s) : Li B , Sedlacek M , Manoharan I , Boopathy R , Duysen EG , Masson P , Lockridge O
Ref : Biochemical Pharmacology , 70 :1673 , 2005
Abstract : The goal of this work was to identify the esterases in human plasma and to clarify common misconceptions. The method for identifying esterases was nondenaturing gradient gel electrophoresis stained for esterase activity. We report that human plasma contains four esterases: butyrylcholinesterase (EC, paraoxonase (EC, acetylcholinesterase (EC, and albumin. Butyrylcholinesterase (BChE), paraoxonase (PON1), and albumin are in high enough concentrations to contribute significantly to ester hydrolysis. However, only trace amounts of acetylcholinesterase (AChE) are present. Monomeric AChE is seen in wild-type as well as in silent BChE plasma. Albumin has esterase activity with alpha- and beta-naphthylacetate as well as with p-nitrophenyl acetate. Misconception #1 is that human plasma contains carboxylesterase. We demonstrate that human plasma contains no carboxylesterase (EC, in contrast to mouse, rat, rabbit, horse, cat, and tiger that have high amounts of plasma carboxylesterase. Misconception #2 is that lab animals have BChE but no AChE in their plasma. We demonstrate that mice, unlike humans, have substantial amounts of soluble AChE as well as BChE in their plasma. Plasma from AChE and BChE knockout mice allowed identification of AChE and BChE bands without the use of inhibitors. Human BChE is irreversibly inhibited by diisopropylfluorophosphate, echothiophate, and paraoxon, but mouse BChE spontaneously reactivates. Since human plasma contains no carboxylesterase, only BChE, PON1, and albumin esterases need to be considered when evaluating hydrolysis of an ester drug in human plasma.
ESTHER : Li_2005_Biochem.Pharmacol_70_1673
PubMedSearch : Li_2005_Biochem.Pharmacol_70_1673
PubMedID: 16213467

Title : Poster (55) Life without acetylcholinesterase -
Author(s) : Lockridge O , Duysen EG , Li B , Hrabovska A
Ref : In: Cholinesterases in the Second Millennium: Biomolecular and Pathological Aspects , (Inestrosa NC, Campos EO) P. Universidad Catolica de Chile-FONDAP Biomedicina :350 , 2004

Title : Poster (90) Acetylcholinesterase knockout mice are resistant oxotremorine-induced hypothermia and pilocarpine-induced seizures -
Author(s) : Li B , Duysen EG , Lockridge O
Ref : In: Cholinesterases in the Second Millennium: Biomolecular and Pathological Aspects , (Inestrosa NC, Campos EO) P. Universidad Catolica de Chile-FONDAP Biomedicina :368 , 2004

Title : Genome sequence of the Brown Norway rat yields insights into mammalian evolution - Gibbs_2004_Nature_428_493
Author(s) : Gibbs RA , Weinstock GM , Metzker ML , Muzny DM , Sodergren EJ , Scherer S , Scott G , Steffen D , Worley KC , Burch PE , Okwuonu G , Hines S , Lewis L , DeRamo C , Delgado O , Dugan-Rocha S , Miner G , Morgan M , Hawes A , Gill R , Celera , Holt RA , Adams MD , Amanatides PG , Baden-Tillson H , Barnstead M , Chin S , Evans CA , Ferriera S , Fosler C , Glodek A , Gu Z , Jennings D , Kraft CL , Nguyen T , Pfannkoch CM , Sitter C , Sutton GG , Venter JC , Woodage T , Smith D , Lee HM , Gustafson E , Cahill P , Kana A , Doucette-Stamm L , Weinstock K , Fechtel K , Weiss RB , Dunn DM , Green ED , Blakesley RW , Bouffard GG , de Jong PJ , Osoegawa K , Zhu B , Marra M , Schein J , Bosdet I , Fjell C , Jones S , Krzywinski M , Mathewson C , Siddiqui A , Wye N , McPherson J , Zhao S , Fraser CM , Shetty J , Shatsman S , Geer K , Chen Y , Abramzon S , Nierman WC , Havlak PH , Chen R , Durbin KJ , Egan A , Ren Y , Song XZ , Li B , Liu Y , Qin X , Cawley S , Cooney AJ , D'Souza LM , Martin K , Wu JQ , Gonzalez-Garay ML , Jackson AR , Kalafus KJ , McLeod MP , Milosavljevic A , Virk D , Volkov A , Wheeler DA , Zhang Z , Bailey JA , Eichler EE , Tuzun E , Birney E , Mongin E , Ureta-Vidal A , Woodwark C , Zdobnov E , Bork P , Suyama M , Torrents D , Alexandersson M , Trask BJ , Young JM , Huang H , Wang H , Xing H , Daniels S , Gietzen D , Schmidt J , Stevens K , Vitt U , Wingrove J , Camara F , Mar Alba M , Abril JF , Guigo R , Smit A , Dubchak I , Rubin EM , Couronne O , Poliakov A , Hubner N , Ganten D , Goesele C , Hummel O , Kreitler T , Lee YA , Monti J , Schulz H , Zimdahl H , Himmelbauer H , Lehrach H , Jacob HJ , Bromberg S , Gullings-Handley J , Jensen-Seaman MI , Kwitek AE , Lazar J , Pasko D , Tonellato PJ , Twigger S , Ponting CP , Duarte JM , Rice S , Goodstadt L , Beatson SA , Emes RD , Winter EE , Webber C , Brandt P , Nyakatura G , Adetobi M , Chiaromonte F , Elnitski L , Eswara P , Hardison RC , Hou M , Kolbe D , Makova K , Miller W , Nekrutenko A , Riemer C , Schwartz S , Taylor J , Yang S , Zhang Y , Lindpaintner K , Andrews TD , Caccamo M , Clamp M , Clarke L , Curwen V , Durbin R , Eyras E , Searle SM , Cooper GM , Batzoglou S , Brudno M , Sidow A , Stone EA , Payseur BA , Bourque G , Lopez-Otin C , Puente XS , Chakrabarti K , Chatterji S , Dewey C , Pachter L , Bray N , Yap VB , Caspi A , Tesler G , Pevzner PA , Haussler D , Roskin KM , Baertsch R , Clawson H , Furey TS , Hinrichs AS , Karolchik D , Kent WJ , Rosenbloom KR , Trumbower H , Weirauch M , Cooper DN , Stenson PD , Ma B , Brent M , Arumugam M , Shteynberg D , Copley RR , Taylor MS , Riethman H , Mudunuri U , Peterson J , Guyer M , Felsenfeld A , Old S , Mockrin S , Collins F
Ref : Nature , 428 :493 , 2004
Abstract : The laboratory rat (Rattus norvegicus) is an indispensable tool in experimental medicine and drug development, having made inestimable contributions to human health. We report here the genome sequence of the Brown Norway (BN) rat strain. The sequence represents a high-quality 'draft' covering over 90% of the genome. The BN rat sequence is the third complete mammalian genome to be deciphered, and three-way comparisons with the human and mouse genomes resolve details of mammalian evolution. This first comprehensive analysis includes genes and proteins and their relation to human disease, repeated sequences, comparative genome-wide studies of mammalian orthologous chromosomal regions and rearrangement breakpoints, reconstruction of ancestral karyotypes and the events leading to existing species, rates of variation, and lineage-specific and lineage-independent evolutionary events such as expansion of gene families, orthology relations and protein evolution.
ESTHER : Gibbs_2004_Nature_428_493
PubMedSearch : Gibbs_2004_Nature_428_493
PubMedID: 15057822
Gene_locus related to this paper: rat-abhea , rat-abheb , rat-cd029 , rat-d3zaw4 , rat-dpp9 , rat-d3zhq1 , rat-d3zkp8 , rat-d3zuq1 , rat-d3zxw8 , rat-d4a4w4 , rat-d4a7w1 , rat-d4a9l7 , rat-d4a071 , rat-d4aa31 , rat-d4aa33 , rat-d4aa61 , rat-dglb , rat-f1lz91 , rat-Kansl3 , rat-nceh1 , rat-Tex30 , ratno-1hlip , ratno-1neur , ratno-1plip , ratno-2neur , ratno-3neur , ratno-3plip , ratno-ABH15 , ratno-ACHE , ratno-balip , ratno-BCHE , ratno-cauxin , ratno-Ces1d , ratno-Ces1e , ratno-Ces2f , ratno-d3ze31 , ratno-d3zp14 , ratno-d3zxi3 , ratno-d3zxq0 , ratno-d3zxq1 , ratno-d4a3d4 , ratno-d4aa05 , ratno-dpp4 , ratno-dpp6 , ratno-est8 , ratno-FAP , ratno-hyep , ratno-hyes , ratno-kmcxe , ratno-lmcxe , ratno-LOC246252 , ratno-MGLL , ratno-pbcxe , ratno-phebest , ratno-Ppgb , ratno-q4qr68 , ratno-q6ayr2 , ratno-q6q629 , ratno-SPG21 , ratno-thyro , rat-m0rc77 , rat-a0a0g2k9y7 , rat-a0a0g2kb83 , rat-d3zba8 , rat-d3zbj1 , rat-d3zcr8 , rat-d3zxw5 , rat-d4a340 , rat-f1lvg7 , rat-m0r509 , rat-m0r5d4 , rat-b5den3 , rat-d3zxk4 , rat-d4a1b6 , rat-d3zmg4 , rat-ab17c

Title : Muscarinic acetylcholine receptors are down-regulated in acetylcholinesterase knockout mice. -
Author(s) : Li B , Duysen EG , Lockridge O
Ref : Cholinergic Mechanisms, CRC Press :619 , 2004

Title : Regulation of muscarinic acetylcholine receptor function in acetylcholinesterase knockout mice - Li_2003_Pharmacol.Biochem.Behav_74_977
Author(s) : Li B , Duysen EG , Volpicelli-Daley LA , Levey AI , Lockridge O
Ref : Pharmacol Biochem Behav , 74 :977 , 2003
Abstract : Acetylcholinesterase (AChE) hydrolyzes acetylcholine to terminate cholinergic neurotransmission. Overstimulation of cholinergic receptors by excess acetylcholine is known to be lethal. However, AChE knockout mice live to adulthood, although they have weak muscles, do not eat solid food, and die early from seizures. We wanted to know what compensatory factors allowed these mice to survive. We had previously shown that their butyrylcholinesterase activity was normal and had not increased. In this report, we tested the hypothesis that AChE-/- mice adapted to the absence of AChE by downregulating cholinergic receptors. Receptor downregulation is expected to reduce sensitivity to agonists and to increase sensitivity to antagonists. Physiological response to the muscarinic agonists, oxotremorine (OXO) and pilocarpine, showed that AChE-/- mice were resistant to OXO-induced hypothermia, tremor, salivation, and analgesia, and to pilocarpine-induced seizures. AChE+/- mice had an intermediate response. The muscarinic receptor binding sites measured with [3H]quinuclinyl benzilate, as well as the protein levels of M1, M2, and M4 receptors measured with specific antibodies on Western blots, were reduced to be approximately 50% in AChE-/- brain. However, mRNA levels for muscarinic receptors were unchanged. These results indicate that one adaptation to the absence of AChE is downregulation of muscarinic receptors, thus reducing response to cholinergic stimulation..
ESTHER : Li_2003_Pharmacol.Biochem.Behav_74_977
PubMedSearch : Li_2003_Pharmacol.Biochem.Behav_74_977
PubMedID: 12667913

Title : Random mutagenesis of the M3 muscarinic acetylcholine receptor expressed in yeast. Identification of point mutations that silence a constitutively active mutant M3 receptor and greatly impair receptor\/G protein coupling - Schmidt_2003_J.Biol.Chem_278_30248
Author(s) : Schmidt C , Li B , Bloodworth L , Erlenbach I , Zeng FY , Wess J
Ref : Journal of Biological Chemistry , 278 :30248 , 2003
Abstract : The M3 muscarinic receptor is a prototypical member of the class I family of G protein-coupled receptors (GPCRs). To facilitate studies on the structural mechanisms governing M3 receptor activation, we generated an M3 receptor-expressing yeast strain (Saccharomyces cerevisiae) that requires agonist-dependent M3 receptor activation for cell growth. By using receptor random mutagenesis followed by a genetic screen in yeast, we initially identified a point mutation at the cytoplasmic end of transmembrane domain (TM) VI (Q490L) that led to robust agonist-independent M3 receptor signaling in both yeast and mammalian cells. To explore further the molecular mechanisms by which point mutations can render GPCRs constitutively active, we subjected a region of the Q490L mutant M3 receptor that included TM V-VII to random mutagenesis. We then applied a yeast genetic screen to identify second-site mutations that could suppress the activating effects of the Q490L mutation and restore wild-type receptor-like function to the Q490L mutant receptor. This analysis led to the identification of 12 point mutations that allowed the Q490L mutant receptor to function in a fashion similar to the wild-type receptor. These amino acid substitutions mapped to two distinct regions of the M3 receptor, the exofacial segments of TM V and VI and the cytoplasmic ends of TM V-VII. Strikingly, in the absence of the activating Q490L mutation, all recovered point mutations severely reduced the efficiency of receptor/G protein coupling, indicating that the targeted residues play important roles in receptor activation and/or receptor/G protein coupling. This strategy should be generally applicable to identify sites in GPCRs that are critically involved in receptor function.
ESTHER : Schmidt_2003_J.Biol.Chem_278_30248
PubMedSearch : Schmidt_2003_J.Biol.Chem_278_30248
PubMedID: 12750375

Title : [Single factor study of prognosis from 520 cases with chronic severe hepatitis] - Zou_2002_Zhonghua.Shi.Yan.He.Lin.Chuang.Bing.Du.Xue.Za.Zhi_16_246
Author(s) : Zou Z , Chen J , Xin S , Xing H , Li B , Li J , Shen H , Liu Y
Ref : Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za Zhi , 16 :246 , 2002
Abstract : OBJECTIVE: To further understand chronic severe hepatitis (CSH) and to improve the level of diagnosis and treatment and to explore the methods to reduce the fatality rate of CSH through analysing the factors related to prognosis of CSH.
METHODS: The factors related to prognosis from 520 cases with CSH were analyzed by SPASS and STATA software.
RESULTS: 1. The fatality rate in cases with age > or = 40 years was higher than that in cases with age <40 years (P<0.001), there was no significant difference (P>0.05) in sex and pathogenic basis of CSH; 2. The fatality rate rose in cases with WBC > or = 10.0 x 10(9) per liter or platelet <100 x 10(9) per liter; 3. The fatality rate increased gradually with the ratio of aspartic aminotransferase to alanine aminotransferase (AST/ALT) and serum total bilirubin (TBil), appearance of deviation of TBil and ALT, decrease in prothrombin activity (PTA), total cholesterol (TC), cholinesterase and albumin (Alb) (P<0.001). 4. The fatality rate increased with appearance of complications such as ascites, electrolyte disturbance, spontaneous peritonitis and so on (P<0.001).
CONCLUSIONS: The important factors related to prognosis were age, > or = 40 years, WBC 10.0 x 10(9) per liter or platelet <100 x 10(9) per liter; the ratio of AST/ALT, TBil, Tc, cholinesterase, Alb and complication, to monitor dynamically laboratory indexes such as TBil, PTA, Tc, cholinesterase and so on and to prevent and cure various complications are important measures to reduce the fatality rate of CSH.
ESTHER : Zou_2002_Zhonghua.Shi.Yan.He.Lin.Chuang.Bing.Du.Xue.Za.Zhi_16_246
PubMedSearch : Zou_2002_Zhonghua.Shi.Yan.He.Lin.Chuang.Bing.Du.Xue.Za.Zhi_16_246
PubMedID: 12665931

Title : Evidence for nonacetylcholinesterase targets of organophosphorus nerve agent: supersensitivity of acetylcholinesterase knockout mouse to vx lethality - Duysen_2001_J.Pharmacol.Exp.Ther_299_528
Author(s) : Duysen EG , Li B , Xie W , Schopfer LM , Anderson RS , Broomfield CA , Lockridge O
Ref : Journal of Pharmacology & Experimental Therapeutics , 299 :528 , 2001
Abstract : The possibility that organophosphate toxicity is due to inhibition of targets other than acetylcholinesterase (AChE, EC was examined in AChE knockout mice. Mice (34-55 days old) were grouped for this study, after it was determined that AChE, butyrylcholinesterase (BChE), and carboxylesterase activities had reached stable values by this age. Mice with 0, 50, or 100% AChE activity were treated subcutaneously with the nerve agent VX. The LD50 for VX was 10 to 12 microg/kg in AChE-/-, 17 microg/kg in AChE+/-, and 24 microg/kg in AChE+/+ mice. The same cholinergic signs of toxicity were present in AChE-/- mice as in wild-type mice, even though AChE-/- mice have no AChE whose inhibition could lead to cholinergic signs. Wild-type mice, but not AChE-/- mice, were protected by pretreatment with atropine. Tissues were extracted from VX-treated and untreated animals and tested for AChE, BChE, and acylpeptide hydrolase activity. VX treatment inhibited 50% of the AChE activity in brain and muscle of AChE+/+ and +/- mice, 50% of the BChE activity in all three AChE genotypes, but did not significantly inhibit acylpeptide hydrolase activity. It was concluded that the toxicity of VX must be attributed to inhibition of nonacetylcholinesterase targets in the AChE-/- mouse. Organophosphorus ester toxicity in wild-type mice is probably due to inhibition or binding to several proteins, only one of which is AChE.
ESTHER : Duysen_2001_J.Pharmacol.Exp.Ther_299_528
PubMedSearch : Duysen_2001_J.Pharmacol.Exp.Ther_299_528
PubMedID: 11602663

Title : [Relationship between cholinesterase, prothrombin activity and albumin and the pathology of the liver] - Zou_2001_Zhonghua.Shi.Yan.He.Lin.Chuang.Bing.Du.Xue.Za.Zhi_15_349
Author(s) : Zou Z , Xin S , Li B
Ref : Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za Zhi , 15 :349 , 2001
Abstract : BACKGROUND: To investigate the relationship between serum cholinesterase, albumin and plasma prothrombin activity and the pathology of the liver in patients with viral hepatitis.
METHODS: Totally 135 patients diagnosed as chronic hepatitis, cirrhosis and/or severe hepatitis with needle biopsy of liver were enrolled in this study. Serum cholinesterase and albumin of the patients were detected with enzyme rate method; meanwhile, their plasma prothrombin activity was detected with turbidimetry test.
RESULTS: The percentage of decrease of the level of serum cholinesterase was higher than that of albumin and plasma prothrombin activity in chronic mild and moderate hepatitis; the level of serum cholinesterase, albumin and plasma prothrombin activity decreased gradually followed by the exacerbation of inflammatory reaction (P<0.001) and by the elevation of degree of fibrosis of the liver (P <0.001) their correlation coefficient was 0.720 to 0.778 (P<0.001). CONCLUSION: The level of serum cholinesterase could better a nd more sensitively reflect the synthetic function and the damage of the pathology of the liver than that of albumin and plasma prothrombin activity could do, they all negatively correlated with the pathology of the liver.
ESTHER : Zou_2001_Zhonghua.Shi.Yan.He.Lin.Chuang.Bing.Du.Xue.Za.Zhi_15_349
PubMedSearch : Zou_2001_Zhonghua.Shi.Yan.He.Lin.Chuang.Bing.Du.Xue.Za.Zhi_15_349
PubMedID: 11986723

Title : Abundant tissue butyrylcholinesterase and its possible function in the acetylcholinesterase knockout mouse - Li_2000_J.Neurochem_75_1320
Author(s) : Li B , Stribley JA , Ticu A , Xie W , Schopfer LM , Hammond P , Brimijoin S , Hinrichs SH , Lockridge O
Ref : Journal of Neurochemistry , 75 :1320 , 2000
Abstract : We have described recently an acetylcholinesterase (AChE) knockout mouse. While comparing the tissue distribution of AChE and butyrylcholinesterase (BChE), we found that extraction buffers containing Triton X-100 strongly inhibited mouse BChE activity. In contrast, buffers with Tween 20 caused no inhibition of BChE. Conventional techniques grossly underestimated BChE activity by up to 15-fold. In Tween 20 buffer, the intestine, serum, lung, liver, and heart had higher BChE than AChE activity. Only brain had higher AChE than BChE activity in AChE +/+ mice. These findings contradict the dogma, based mainly on observations in Triton X-100 extracts, that BChE is a minor cholinesterase in animal tissues. AChE +/- mice had 50% of normal AChE activity and AChE -/- mice had none, but all mice had similar levels of BChE activity. BChE was inhibited by Triton X-100 in all species tested, except rat and chicken. Inhibition was reversible and competitive with substrate binding. The active site of rat BChE was unique, having an arginine in place of leucine at position 286 (human BChE numbering) in the acyl-binding pocket of the active site, thus explaining the lack of inhibition of rat BChE by Triton X-100. The generally high levels of BChE activity in tissues, including the motor endplate, and the observation that mice live without AChE, suggest that BChE has an essential function in nullizygous mice and probably in wild-type mice as well.
ESTHER : Li_2000_J.Neurochem_75_1320
PubMedSearch : Li_2000_J.Neurochem_75_1320
PubMedID: 10936216

Title : A missense mutation G2320R in the thyroglobulin gene causes non-goitrous congenital primary hypothyroidism in the WIC-rdw rat - Kim_2000_Mol.Endocrinol_14_1944
Author(s) : Kim PS , Ding M , Menon S , Jung CG , Cheng JM , Miyamoto T , Li B , Furudate S , Agui T
Ref : Mol Endocrinol , 14 :1944 , 2000
Abstract : A convincing line of evidence is being developed that the congenital nongoitrous hypothyroidism and dwarfism observed in the WIC-rdw rat may indeed be caused by a primary defect in thyroid hormonogenesis. In support of this hypothesis, several recent reports have shown the presence of elevated molecular chaperone levels in the WIC-rdw thyrocytes, the endoplasmic reticulum of which was markedly dilated, suggesting a defect in intracellular protein transport. Here the studies were undertaken to identify the precise molecular defect in the WIC-rdw rat. First, the genetic linkage analysis revealed that the rdw locus was on rat chromosome 7 and was identical to the thyroglobulin (Tg) gene locus. Moreover, the Tg protein level was reduced in the WIC-rdw thyroid despite a similar level of the Tg gene transcripts that were indistinguishable in their size from the normal. Next, the complete sequencing of the rdw and the normal rat Tg cDNAs revealed a single nucleotide change, G6958C, resulting in a G2320R missense mutation in a highly conserved region of the Tg molecule. Finally, transient expression of the intact Tg cDNA containing the rdw mutation in the COS-7 cells showed no detectable Tg in the secreted media, indicating a severe defect in the export of the mutant Tg. Together, our observations suggest that a missense mutation, G2320R, in the Tg gene is responsible for the rdw mutation in the WIC-rdw rat.
ESTHER : Kim_2000_Mol.Endocrinol_14_1944
PubMedSearch : Kim_2000_Mol.Endocrinol_14_1944
PubMedID: 11117525
Gene_locus related to this paper: ratno-thyro