Author Report for: Xu XNo contact information in database for Xu X
Chen Y, Duan M, Xu X, Wu C Ref: Aquat Toxicol, 260:106595, 2023 : PubMed ESTHER: Chen_2023_Aquat.Toxicol_260_106595 PubMedSearch: Chen 2023 Aquat.Toxicol 260 106595 PubMedID: 37269673 Abstract Microplastics as emerging contaminants show various composition features in the environment. However, influence of polymer types on the toxicity of microplastics is still unclear, thus affecting evaluation of their toxicity and ecological risks. In this work, toxic effects of microplastics (fragment, 52-74 microm) with different polymer types including polyethylene (PE), polyethylene terephthalate (PET), polypropylene (PP) and polystyrene (PS) to zebrafish (Danio rerio) were studied using acute embryo test and chronic larvae test. Silicon dioxide (SiO(2)) was used as a control representing natural particles. Results showed microplastics with different polymers had no influence on embryonic development at environmental relevant concentration (10(2) particles/L), but could lead to accelerated heartbeat rate and increased embryonic death when exposed to SiO(2), PE and PS at higher concentrations (10(4) and 10(6) particles/L). Chronic exposure for zebrafish larvae indicated different polymers of microplastics did not affect zebrafish larvae' feeding and growth, nor induce oxidative stress. But larvae' locomotion level and AChE (acetylcholinesterase) activities could be inhibited by SiO(2) and microplastics at 10(4) particles/L. Our study demonstrated negligible toxicity of microplastics at environmental relevant concentration, while different polymers of microplastics have similar toxic effects as SiO(2) at high concentrations. We suggest that microplastic particles may have the same biological toxicity as natural particles. Title: Translating clinical notes into quantitative measures-a real-world observation on the response to cholinesterase inhibitors or selective serotonin reuptake inhibitors prescribed to outpatients with dementia using electronic medical records Chotiyanonta JS, Onda K, Nowrangi MA, Li X, Xu X, Adams R, Lyketsos CG, Zandi P, Oishi K Ref: Front Pharmacol, 14:1177026, 2023 : PubMed ESTHER: Chotiyanonta_2023_Front.Pharmacol_14_1177026 PubMedSearch: Chotiyanonta 2023 Front.Pharmacol 14 1177026 PubMedID: 37234714 Abstract Objective: Cholinesterase inhibitors (CEIs) are prescribed for dementia to maintain or improve memory. Selective serotonin reuptake inhibitors (SSRIs) are also prescribed to manage psychiatric symptoms seen in dementia. What proportion of outpatients actually responds to these drugs is still unclear. Our objective was to investigate the responder rates of these medications in an outpatient setting using the electronic medical record (EMR). Methods: We used the Johns Hopkins EMR system to identify patients with dementia who were prescribed a CEI or SSRI for the first time between 2010 and 2021. Treatment effects were assessed through routinely documented clinical notes and free-text entries in which healthcare providers record clinical findings and impressions of patients. Responses were scored using a three-point Likert scale named the NOte-based evaluation method for Treatment Efficacy (NOTE) in addition to the Clinician's Interview-Based Impression of Change Plus caregiver input (CIBIC-plus), a seven-point Likert scale used in clinical trials. To validate NOTE, the relationships between NOTE and CIBIC-plus and between NOTE and change in MMSE (Mini-Mental State Examination) before and after medication were examined. Inter-rater reliability was evaluated using Krippendorff's alpha. The responder rates were calculated. Results: NOTE showed excellent inter-rater reliability and correlated well with CIBIC-plus and changes in MMSEs. Out of 115 CEI cases, 27.0% reported improvement and 34.8% reported stable symptoms in cognition; out of 225 SSRI cases, 69.3% reported an improvement in neuropsychiatric symptoms. Conclusion: NOTE showed high validity in measuring the pharmacotherapy effects based on unstructured clinical entries. Although our real-world observation included various types of dementia, the results were remarkably similar to what was reported in controlled clinical trials of Alzheimer's disease and its related neuropsychiatric symptoms. Title: Strigolactone regulates adventitious root formation via the MdSMXL7-MdWRKY6-MdBRC1 signaling cascade in apple Fan X, Li Y, Deng CH, Wang S, Wang Z, Wang Y, Qiu C, Xu X, Han Z, Li W Ref: Plant J, 113:772, 2023 : PubMed ESTHER: Fan_2023_Plant.J_113_772 PubMedSearch: Fan 2023 Plant.J 113 772 PubMedID: 36575587 Abstract Propagation through stem cuttings is a popular method worldwide for species such as fruit tree rootstocks and forest trees. Adventitious root (AR) formation from stem cuttings is crucial for effective and successful clonal propagation of apple rootstocks. Strigolactones (SLs) are newly identified hormones involved in AR formation. However, the regulatory mechanisms underpinning this process remain elusive. In the present study, weighted gene co-expression network analysis, as well as rooting assays using stable transgenic apple materials, revealed that MdBRC1 served as a key gene in the inhibition of AR formation by SLs. We have demonstrated that MdSMXL7 and MdWRKY6 synergistically regulated MdBRC1 expression, depending on the interactions of MdSMXL7 and MdWRKY6 at the protein level downstream of SLs as well as the direct promoter binding on MdBRC1 by MdWRKY6. Furthermore, biochemical studies and genetic analysis revealed that MdBRC1 inhibited AR formation by triggering the expression of MdGH3.1 in a transcriptional activation pathway. Finally, the present study not only proposes a component, MdWRKY6, that enables MdSMXL7 to regulate MdBRC1 during the process of SL-controlled AR formation in apple, but also provides prospective target genes to enhance AR formation capacity using CRISPR (i.e. clustered regularly interspaced short palindromic repeats) technology, particularly in woody plants. Title: Neuroligins facilitate the development of bone cancer pain via regulating synaptic transmission: an experimental study Xie X, Li Y, Su S, Li X, Xu X, Gao Y, Peng M, Ke C Ref: Braz J Anesthesiol, :, 2023 : PubMed ESTHER: Xie_2023_Braz.J.Anesthesiol__ PubMedSearch: Xie 2023 Braz.J.Anesthesiol PubMedID: 36841430 Abstract BACKGROUND: The underlying mechanism of chronic pain involves the plasticity in synaptic receptors and neurotransmitters. This study aimed to investigate potential roles of Neuroligins (NLs) within the spinal dorsal horn of rats in a newly established Bone Cancer Pain (BCP) model. The objective was to explore the mechanism of neuroligin involved in the occurrence and development of bone cancer pain. METHODS: Using our rat BCP model, we assessed pain hypersensitivity over time. Quantitative real-time polymerase chain reaction and Western blot analysis were performed to investigate NL expression, and NLs were overexpressed in the rat spinal cord using lentiviral vectors. Immunofluorescence staining and whole-cell patch-clamp recordings were deployed to investigate the role of NLs in the development of BCP. RESULTS: We observed reduced expression levels of NL1 and NL2, but not of NL3, within the rat spinal cord, which were found to be associated with and essential for the development of BCP in our model. Accordingly, NL1 or NL2 overexpression in the spinal cord alleviated mechanical hypersensitivity of rats. Electrophysiological experiments indicated that NL1 and NL2 are involved in BCP via regulating gamma-aminobutyric acid-ergic interneuronal synapses and the activity of glutamatergic interneuronal synapses, respectively. CONCLUSIONS: Our observations unravel the role of NLs in cancer-related chronic pain and further suggest that inhibitory mechanisms are central features of BCP in the spinal dorsal horn. These results provide a new perspective and basis for subsequent studies elucidating the onset and progression of BCP. Title: Novel miR-108 and miR-234 target juvenile hormone esterase to regulate the response of Plutella xylostella to Cry1Ac protoxin Yang J, Chen S, Xu X, Lin S, Wu J, Lin G, Bai J, Song Q, You M, Xie M Ref: Ecotoxicology & Environmental Safety, 254:114761, 2023 : PubMed ESTHER: Yang_2023_Ecotoxicol.Environ.Saf_254_114761 PubMedSearch: Yang 2023 Ecotoxicol.Environ.Saf 254 114761 PubMedID: 36907089 Abstract Insect hormones, such as juvenile hormone (JH), precisely regulate insect life-history traits. The regulation of JH is tightly associated with the tolerance or resistance to Bacillus thuringiensis (Bt). JH esterase (JHE) is a primary JH-specific metabolic enzyme which plays a key role in regulating JH titer. Here, we characterized a JHE gene from Plutella xylostella (PxJHE), and found it was differentially expressed in the Bt Cry1Ac resistant and susceptible strains. Suppression of PxJHE expression with RNAi increased the tolerance of P. xylostella to Cry1Ac protoxin. To investigate the regulatory mechanism of PxJHE, two target site prediction algorithms were applied to predict the putative miRNAs targeting PxJHE, and the resulting putative miRNAs were subsequently verified for their function targeting PxJHE using luciferase reporter assay and RNA immunoprecipitation. MiR-108 or miR-234 agomir delivery dramatically reduced PxJHE expression in vivo, whilst only miR-108 overexpression consequently increased the tolerance of P. xylostella larvae to Cry1Ac protoxin. By contrast, reduction of miR-108 or miR-234 dramatically increased PxJHE expression, accompanied by the decreased tolerance to Cry1Ac protoxin. Furthermore, injection of miR-108 or miR-234 led to developmental defects in P. xylostella, whilst injection of antagomir did not cause any obvious abnormal phenotypes. Our results indicated that miR-108 or miR-234 can be applied as potential molecular targets to combat P. xylostella and perhaps other lepidopteran pests, providing novel insights into miRNA-based integrated pest management. Title: Bioimprinted lipase-catalyzed synthesis of medium- and long-chain structured lipids rich in docosahexaenoic acid for infant formula Zou X, Su H, Zhang F, Zhang H, Yeerbolati Y, Xu X, Chao Z, Zheng L, Jiang B Ref: Food Chem, 424:136450, 2023 : PubMed ESTHER: Zou_2023_Food.Chem_424_136450 PubMedSearch: Zou 2023 Food.Chem 424 136450 PubMedID: 37247604 Abstract Medium- and long-chain structured lipids (MLSLs) rich in docosahexaenoic acid (DHA) were obtained in shorter reaction time by acidolysis of single-cell oil (DHASCO) from Schizochytrium sp. with caprylic acid (CA) using a lipase bioimprinted with fatty acids as a catalyst. The conditions for preparation of the bioimprinted lipase for the acidolysis reaction were firstly optimized and the activity of the obtained lipase was 2.17 times higher than that of the non-bioimprinted. The bioimprinted lipase was then used as a catalyst and the reaction conditions were optimized. Under the optimal conditions, the equilibrium could be achieved in 4 h, and the total and sn-1,3 CA contents in the product were 29.18% and 42.34%, respectively, and the total and sn-2 DHA contents were 46.26% and 70.12%, respectively. Such MLSLs rich in sn-1,3 CA and sn-2 DHA are beneficial for DHA absorption, and thus have potential for use in infant formula. Title: Neuroligin-1 plays an important role in methamphetamine-induced hippocampal synaptic plasticity Cao C, Wang L, Zhang J, Liu Z, Li M, Xie S, Chen G, Xu X Ref: Toxicol Lett, 361:1, 2022 : PubMed ESTHER: Cao_2022_Toxicol.Lett_361_1 PubMedSearch: Cao 2022 Toxicol.Lett 361 1 PubMedID: 35331841 Abstract The neurotoxic effects of methamphetamine (METH) include not only neuronal apoptosis and autophagy, but also lead to substance use disorder and have become increasingly prominent. Studies suggest that synaptic plasticity may be the structural basis of METH-induced neurological impairment. Neuroligins are postsynaptic adhesion molecules involved in the regulation of synaptic organization and function. Animal studies have shown that neuroligin (NLG)- 1 is involved in memory formation; however, its role in METH-induced neurotoxicity is not clear. In the present study, we used 1 mM METH in vitro; mice in the acute and subacute exposure groups received intraperitoneal injections of 30 mg/kg METH (1 injection) or 15 mg/kg METH (8 separate injections at 12-h intervals). We found that the expression of NLG-1, Synapsin-1, and postsynaptic density-95 were increased after METH exposure. We further observed that METH-induced inhibition of long-term potentiation and spatial memory loss could be alleviated when mice were pretreated with NLG-1 small interfering RNA. Therefore, our study provides evidence that NLG-1 is involved in METH-induced hippocampal synaptic plasticity and may be a potential target for the treatment of METH-induced neurotoxicity. Title: The suppression of pancreatic lipase-related protein 2 ameliorates experimental hepatic fibrosis in mice Ding Z, Cheng R, Liu J, Zhao Y, Ge W, Yang Y, Xu X, Wang S, Zhang J Ref: Biochimica & Biophysica Acta Molecular & Cellular Biology Lipids, 1867:159102, 2022 : PubMed ESTHER: Ding_2022_Biochim.Biophys.Acta.Mol.Cell.Biol.Lipids_1867_159102 PubMedSearch: Ding 2022 Biochim.Biophys.Acta.Mol.Cell.Biol.Lipids 1867 159102 PubMedID: 34995790 Gene_locus related to this paper: mouse-LIPR2 Abstract Quiescent hepatic stellate cells (HSCs) store vitamin A as lipid droplets in the cytoplasm. When activated, these cells lose vitamin A and exhibit an increased capacity for proliferation, mobility, contractility, and the synthesis of collagen and other components of the extracellular matrix. Our previous work demonstrated that the lipid hydrolytic gene pancreatic lipase-related protein 2 (mPlrp2) is involved in the hydrolysis of retinyl esters (REs) in the liver. Here, we showed that bile duct ligation (BDL)-induced liver injury triggered the conditional expression of mPlrp2 in livers and describe evidence of a strong relationship between the expression of mPlrp2 and Acta-2, a marker for activated HSCs. RNA interference targeting mPlrp2 inhibited HSC activation and ameliorated hepatic fibrosis induced by BDL in mice. Liver BDL markedly reduced the adenosine level and increased the ratio between S-adenosyl-L-methionine (SAM) and S-adenosyl-L-homocysteine (SAH). Chromatin immunoprecipitation (ChIP) analysis demonstrated an increase in trimethylated histone H3K4 at the mPlrp2 promoter in BDL mice, which was associated with the conditional expression of mPlrp2 in the liver. SAM, a well-known hepatoprotective substance, inhibited mPlrp2 expression and reduced RE hydrolysis in mice with hepatic fibrosis induced by chronic CCl(4) treatment. Liver fibrosis induced by CCl(4) or BDL was improved in Plrp2(-/-) mice. Our results reveal that mPlrp2 suppression is a potential approach for treating hepatic fibrosis. Title: Differences in susceptibility to chlorantraniliprole between Chilo suppressalis (Lepidoptera: Crambidae) and two dominant parasitic wasps collected from Sichuan Province, China Li MY, Gong CW, Zhang YZ, Zhao X, Jia Y, Pu J, Liu XM, Xu X, Wang XG Ref: Pestic Biochem Physiol, 185:105150, 2022 : PubMed ESTHER: Li_2022_Pestic.Biochem.Physiol_185_105150 PubMedSearch: Li 2022 Pestic.Biochem.Physiol 185 105150 PubMedID: 35772843 Abstract Chilo suppressalis Walker (Lepidoptera: Crambidae) is one of the most destructive pests occurring in the rice-growing regions of Asia. Parasitoids, mainly egg parasitoids, have been of interest for several years even with practical used cases. Therefore, the potential impact of insecticides on natural enemies needs great attention. In this study, chlorantraniliprole was evaluated for its impact on C. suppressalis and two dominant parasitic wasps. Bioassays showed that chlorantraniliprole had negligible toxicity to Eriborus terebrans but was significantly toxic to Chelonus munakatae; the mortality exceeded 50% when the concentration reached 46.83 ng/cm(2). Enzyme assays suggested that the significantly different carboxylesterase activity may be involved in the high-level detoxification metabolism of E. terebrans. According to the results of enzyme gene correlation analysis, P450s may be the dominant factor in the detoxification metabolism of C. munakatae. In addition, the ryanodine receptor C-terminus of C. suppressalis (CsRyR), C. munakatae (CmRyR) and E. terebrans (EtRyR) were successfully cloned. Different amino acids at resistance mutation I4758 M between susceptible C. suppressalis (I) and parasitic wasps (M) may be related to susceptibility differences. Simulated docking showed that CsRyR and CmRyR can interact with chlorantraniliprole but not EtRyR. More interaction forces were formed between CsRyR and chlorantraniliprole than CmRyR. Furthermore, a Pi-Pi T-shape formed between 73PHE in CsRyR and the benzene ring in chlorantraniliprole. These results indicated that both detoxification metabolism and the target site could mediate the susceptibility difference between C. suppressalis and its parasitic wasps. Title: Safety, tolerability, and pharmacokinetics of fluoropezil (DC20), a novel AChE inhibitor: a singlecenter, phase I study in healthy young and elderly Chinese subjects Qian H, Yu C, Zhu H, Ding Q, Cai Y, Jing J, Xu X, Guo R, Zhang H and Liu Y <2 more author(s)> Qian H, Yu C, Zhu H, Ding Q, Cai Y, Jing J, Xu X, Guo R, Zhang H, Liu H, Chen X, Liu Y (- 2) Ref: ResearchSquare, :, 2022 : PubMed ESTHER: Qian_2022_ResearchSquare__ PubMedSearch: Qian 2022 ResearchSquare Inhibitor(s) related to this paper: Fluoropezil Abstract https://www.researchsquare.com/article/rs-1744060/latest.pdf Background Acetylcholinesterase (AChE) inhibitors attempt to reduce the breakdown of acetylcholine levels in the brain of patients with Alzheimers disease (AD) by inhibiting the responsible enzyme AChE in the synaptic cleft. This study evaluated the safety, tolerability, and pharmacokinetics of fluoropezil (DC20), a novel AChE inhibitor under development for the treatment of AD in healthy young and elderly Chinese subjects. Methods The study on young subjects were divided into two arms: the multiple ascending-dose (MAD) arm (double-blind, randomized, placebo-controlled, multiple ascending-dose, 2 and 6 mg, N = 24), and the food effect arm (three-period, self-crossover, open-labeled, fasting/standard diet/high-fat diet administration, 4 mg, N = 12). A two-period, self-crossover, open-labeled, single ascending-dose study was designed for elderly subjects (2 and 4 mg, N = 11). Results For young subjects study: In the MAD arm, the accumulation ratios of DC20 in vivo were 2.29 and 2.15, respectively. In the food effect arm, compared with fasting administration, area under the concentrationtime curve from zero to t (AUC0-t) orally after a standard diet and high-fat diet slightly increased by about 19% and 29% and the Tmax were delayed by around 1 hour. For elderly subjects study, Tmax were 1.5 and 1.25 hour, t1/2 were 77.1 and 74.2 hour, respectively. After oral administration of DC20 in healthy young and elderly subjects, no serious adverse events occurred, the most common adverse events associated with the study drug were gastrointestinal reactions. Conclusion We predicted the safety risks of DC20 in the clinical treatment of AD, which were well tolerated by the healthy young and elderly subjects. The elimination of DC20 from the body was slower in elderly subjects than in young subjects. Title: Structurally diverse steroids from an endophyte of Aspergillus tennesseensis 1022LEF attenuates LPS-induced inflammatory response through the cholinergic anti-inflammatory pathway Su JC, Pan Q, Xu X, Wei X, Lei X, Zhang P Ref: Chemico-Biological Interactions, 362:109998, 2022 : PubMed ESTHER: Su_2022_Chem.Biol.Interact_362_109998 PubMedSearch: Su 2022 Chem.Biol.Interact 362 109998 PubMedID: 35649461 Abstract The emerging cholinergic anti-inflammatory pathway plays a key role in regulating inflammation. Steroids are known to possess remarkable anti-inflammatory activity. However, the links between steroids and the cholinergic anti-inflammatory pathway remain unidentified. In this study, eight steroids (1-8) featuring five different structural types were characterized from an endophytic fungus Aspergillus tennesseensis 1022LEF, and were subsequently evaluated for their potential role in regulating the cholinergic anti-inflammatory pathway. As a result, compound 8, with the best potency, showed remarkable anti-inflammatory activity at the nanomolar to low micromolar level. Further pharmacological study indicated that 8 notably increased alpha7nAchR expression and inhibited the activation of its down-stream signaling pathways. Collectively, the present study not only highlighted the potential correlation between steroids and the cholinergic anti-inflammatory pathway, but also identified 8 as a dual-functional modulator via directly inhibition to acetylcholinesterase as well as up-regulation of alpha7nAchR expression. Title: Impact of Imidacloprid Resistance on the Demographic Traits and Expressions of Associated Genes in Aphis gossypii Glover Ullah F, Xu X, GUl H, Gncan A, Hafeez M, Gao X, Song D Ref: Toxics, 10:, 2022 : PubMed ESTHER: Ullah_2022_Toxics_10_ PubMedSearch: Ullah 2022 Toxics 10 PubMedID: 36355949 Abstract Imidacloprid is one of the most widely used neonicotinoid insecticides to control sap-sucking insect pests, including Aphis gossypii. The intensive application of chemical insecticides to A. gossypii led to the development of resistance against several insecticides, including imidacloprid. Therefore, it is crucial to understand the association between imidacloprid resistance and the fitness of A. gossypii to limit the spread of the resistant population under field contexts. In this study, we used the age-stage, two-sex life table method to comprehensively investigate the fitness of imidacloprid resistant (ImR) and susceptible strains (SS) of melon aphids. Results showed that ImR aphids have prolonged developmental stages and decreased longevity, fecundity, and reproductive days. The key demographic parameters (r, , and R(0)) were significantly reduced in ImR strain compared to SS aphids. Additionally, the molecular mechanism for fitness costs was investigated by comparing the expression profile of juvenile hormone-binding protein (JHBP), juvenile hormone epoxide hydrolase (JHEH), juvenile hormone acid O-methyltransferase (JHAMT), Vitellogenin (Vg), ecdysone receptor (EcR), and ultraspiracle protein (USP) supposed to be associated with development and reproduction in insects. The results of RT-qPCR showed that EcR, JHBP, JHAMT, JHEH, and Vg genes were downregulated, while USP was statistically the same in ImR A. gossypii compared to the SS strain. Together, these results provide in-depth information about the occurrence and magnitude of fitness costs against imidacloprid resistance that could help manage the evolution and spread of A. gossypii resistance in field populations. Title: Isoprocarb causes neurotoxicity of zebrafish embryos through oxidative stress-induced apoptosis Wang S, Han X, Yu T, Liu Y, Zhang H, Mao H, Hu C, Xu X Ref: Ecotoxicology & Environmental Safety, 242:113870, 2022 : PubMed ESTHER: Wang_2022_Ecotoxicol.Environ.Saf_242_113870 PubMedSearch: Wang 2022 Ecotoxicol.Environ.Saf 242 113870 PubMedID: 35816841 Abstract Isoprocarb is a widely used carbamate insecticide in agriculture and aquaculture. Overuse of isoprocarb always leaves toxic residues in soil and water, however, the potential ecotoxicity of isoprocarb to organisms is still confusing. In this study, zebrafish embryo was used as a model to evaluate the toxicity of isoprocarb. Zebrafish embryos (96 hpf) were separately exposed at different concentrations of isoprocarb. The mortality rate, hatchability rate, average heart beat of the zebrafish embryo were separately calculated. Our results suggested that exposure to isoprocarb induced developmental toxicity in zebrafish embryos. HE staining showed that exposure to isoprocarb caused developmental defect in the hindbrain of zebrafish embryos. As expected, the behavioral analysis also showed that the motor ability of zebrafish embryos were significantly inhibited following exposure to isoprocarb. In terms of mechanism, The expressions of genes involved in neurodevelopment signaling pathways, such as foxo3a, gfap, syn2a, elavl3 and sox19b, were inhibited in zebrafish embryos after exposure to isoprocarb. The acetylcholinesterase (AChE) activity was also reduced in isoprocarb-treated zebrafish embryos. Moreover, oxidative stress was induced by increasing the reactive oxygen species (ROS) level and decreasing the activity of antioxidant enzyme (SOD) after exposure to isoprocarb. Expectedly, acridine orange (AO) staining and the detection of some apoptosis-related genes revealed that oxidative stress resulted in apoptosis. In short, the expressions of genes associated with the neurodevelopmental signaling pathway are inhibited, and oxidative stress is also induced in zebrafish embryos after exposure to isoprocarb, which may be the molecular basics of isoprocarb-induced neurotoxicity in zebrafish embryos. Title: Development and structure-activity relationship of tacrine derivatives as highly potent CDK2/9 inhibitors for the treatment of cancer Wu L, Liu W, Huang Y, Zhu C, Ma Q, Wu Q, Tian L, Feng X, Liu M and Zhao Q <6 more author(s)> Wu L, Liu W, Huang Y, Zhu C, Ma Q, Wu Q, Tian L, Feng X, Liu M, Wang N, Xu X, Liu X, Xu C, Qiu J, Xu Z, Zhao Q (- 6) Ref: Eur Journal of Medicinal Chemistry, 242:114701, 2022 : PubMed ESTHER: Wu_2022_Eur.J.Med.Chem_242_114701 PubMedSearch: Wu 2022 Eur.J.Med.Chem 242 114701 PubMedID: 36054949 Abstract CDK2/9 are members of the CDKs family, which play key roles in the occurrence and development of many cancers by regulating cell cycle and transcriptional prolongation, respectively. To further optimize and discuss the structure-activity relationships (SARs), a series of tacrine-based compounds were designed and synthesized from the compound ZLWT-37, which was studied by our group previously but no detailed SARs study was conducted on CDK2/9. Among this series, compounds ZLMT-12 (35) exhibited the most potent antiproliferative activity (GI(50) = 0.006 microM for HCT116) and superior CDK2/9 inhibitory properties (CDK2: IC(50) = 0.011 microM, CDK9: IC(50) = 0.002 microM). Meanwhile, ZLMT-12 showed a weak inhibitory effect on acetylcholinesterase (AChE, IC(50) = 19.023 microM) and butyrylcholinesterase (BuChE, IC(50) = 2.768 microM). In addition, ZLMT-12 can suppress colony formation and migration in HCT116 cells, as well as induce the apoptosis and arrest the cell cycle in the S phase and G2/M phase. In vivo investigations revealed that ZLMT-12 inhibits tumor growth in the HCT116 xenograft tumor model at a low dose of 10 mg/kg without causing hepatotoxicity. The acute toxicity test showed low toxicity with a median lethal dosage (LD(50)) of 104.417 mg/kg. These findings showed that ZLMT-12 might be used as a drug candidate by targeting CDK2/9. Title: SARM1 deletion in parvalbumin neurons is associated with autism-like behaviors in mice Xiang L, Wu Q, Sun H, Miao X, Lv Z, Liu H, Chen L, Gu Y, Chen J and Huang Z <13 more author(s)> Xiang L, Wu Q, Sun H, Miao X, Lv Z, Liu H, Chen L, Gu Y, Chen J, Zhou S, Jiang H, Du S, Zhou Y, Dong H, Fan Y, Miao S, Lu Q, Chang L, Wang H, Lu Y, Xu X, Wang W, Huang Z (- 13) Ref: Cell Death Dis, 13:638, 2022 : PubMed ESTHER: Xiang_2022_Cell.Death.Dis_13_638 PubMedSearch: Xiang 2022 Cell.Death.Dis 13 638 PubMedID: 35869039 Abstract Autism spectrum disorder (ASD), a group of neurodevelopmental disorder diseases, is characterized by social deficits, communication difficulties, and repetitive behaviors. Sterile alpha and TIR motif-containing 1 protein (SARM1) is known as an autism-associated protein and is enriched in brain tissue. Moreover, SARM1 knockdown mice exhibit autism-like behaviors. However, its specific mechanism in ASD pathogenesis remains unclear. Here we generated parvalbumin-positive interneurons (PVI)-specific conditional SARM1 knockout (SARM1(PV)-CKO) mice. SARM1(PV)-CKO male mice showed autism-like behaviors, such as mild social interaction deficits and repetitive behaviors. Moreover, we found that the expression level of parvalbumin was reduced in SARM1(PV)-CKO male mice, together with upregulated apoptosis-related proteins and more cleaved-caspase-3-positive PVIs, suggesting that knocking out SARM1 may cause a reduction in the number of PVIs due to apoptosis. Furthermore, the expression of c-fos was shown to increase in SARM1(PV)-CKO male mice, in combination with upregulation of excitatory postsynaptic proteins such as PSD-95 or neuroligin-1, indicating enhanced excitatory synaptic input in mutant mice. This notion was further supported by the partial rescue of autism-like behavior deficits by the administration of GABA receptor agonists in SARM1(PV)-CKO male mice. In conclusion, our findings suggest that SARM1 deficiency in PVIs may be involved in the pathogenesis of ASD. Title: Chlorphoxim induces neurotoxicity in zebrafish embryo through activation of oxidative stress Xiong Y, Wang C, Dong M, Li M, Hu C, Xu X Ref: Environ Toxicol, :, 2022 : PubMed ESTHER: Xiong_2022_Environ.Toxicol__ PubMedSearch: Xiong 2022 Environ.Toxicol PubMedID: 36331003 Abstract It is known that chlorphoxim is a broad-spectrum and high-effective pesticide. With the wide use in agricultural practice, chlorphoxim residue is also frequently detected in water, but its potential toxicity to aquatic life is still unclear. In this study, zebrafish is used as a model to detect the toxicity of chlorphoxim. Our results showed that exposure of high concentration of chlorphoxim at 96 h post-fertilization (hpf) resulted in a high mortality and pericardium edema rate, a low hatchability rate and heart rate. The nervous system damage, swimming behavior alteration and acetylcholinesterase (AChE) inhibition were measured in zebrafish embryos after a 6 days post-fertilization (dpf) of chlorphoxim exposure. The expression of neural-related genes is abnormal in zebrafish embryos. Chlorphoxim exposure significantly increases oxidative stress in zebrafish embryos by inhibiting antioxidant enzyme (SOD and CAT) and activating reactive oxygen species (ROS). As expected, chlorphoxim exposure induces apoptosis by enhancing the expression of apoptotic genes (Bax, Bcl2, and p53). Astaxanthin (ATX), an effective antioxidant, was found to be able to rescue the neurotoxicity of chlorphoxim through relieving oxidative stress and apoptosis. Altogether, the results showed that chlorphoxim exposure led to severe neurotoxicity to zebrafish embryos, which was contributed to a more comprehensive understanding of the safety use of the organophosphorus pesticide. Title: Fenpropathrin exposure induces neurotoxicity in zebrafish embryos Yu T, Xu X, Mao H, Han X, Liu Y, Zhang H, Lai J, Gu J, Xia M and Li D <1 more author(s)> Yu T, Xu X, Mao H, Han X, Liu Y, Zhang H, Lai J, Gu J, Xia M, Hu C, Li D (- 1) Ref: Fish Physiol Biochem, :, 2022 : PubMed ESTHER: Yu_2022_Fish.Physiol.Biochem__ PubMedSearch: Yu 2022 Fish.Physiol.Biochem PubMedID: 36266516 Abstract Fenpropathrin has been a commonly used insecticide to control agricultural and household insects over a few decades. Up to now, fenpropathrin residue in soil and water has been often determined due to its widespread use, which poses serious threat to environment and aquatic organisms. The potential of fenpropathrin to affect aquatic lives is still poorly understood. In this study, we used zebrafish (Danio rerio) embryo as an experimental model system to evaluate the toxicity of fenpropathrin to the development of zebrafish nervous system. Zebrafish embryos were separately exposed to fenpropathrin at the dose of 0.016 mg/L, 0.032 mg/L, 0.064 mg/L, starting at 6 h post-fertilizationhpf (hpf) up to 96 hpf. The results showed that fenpropathrin exposure gives rise to physiological, behavioral, and neurodevelopmental impairments in zebrafish embryos, including enhanced acetylcholinesterase (AChE) activity, abnormal swimming behavior, karyopyknosis in brain cells, increased intercellular space, and uneven migration of neuron in brain area. In addition, the expressions of genes concerning neurodevelopment and neurotransmitter system were inhibited following fenpropathrin exposure. We also found that fenpropathrin exposure distinctly induced oxidative stress by increasing reactive oxygen species (ROS) generation and inhibiting the production of antioxidant enzymes catalase (CAT) and superoxide dismutase (SOD). Expectedly, some apoptosis-associated genes were induced and the apoptosis appeared in the brain and heart cells of zebrafish embryos. Moreover, fenpropathrin exposure also inhibited the expressions of genes in Nrf2 signaling pathway, such as heme oxygenase-1 (HO-1) and SOD. In summary, the results of this study indicate that oxidative stress-triggered apoptosis may be an underlying fundamental of fenpropathrin-induced neurotoxicity in zebrafish embryos. Title: Characterization and functional analysis of two acetylcholinesterase genes in Bradysia odoriphaga Yang et Zhang (Diptera: Sciaridae) Ding Q, Xu X, Wang X, Ullah F, Gao X, Song D Ref: Pestic Biochem Physiol, 174:104807, 2021 : PubMed ESTHER: Ding_2021_Pestic.Biochem.Physiol_174_104807 PubMedSearch: Ding 2021 Pestic.Biochem.Physiol 174 104807 PubMedID: 33838708 Gene_locus related to this paper: 9dipt-MT380203, 9dipt-MT380204 Abstract Two acetylcholinesterase genes (Boace1 and Boace2) were cloned from Bradysia odoriphaga, a devastating soil pest that mainly damages Chinese chives. The Boace1 encodes BoAChE1 protein consisting of 696 amino acid residues, while Boace2 encodes BoAChE2 containing 638 amino acids. Phylogenetic analysis showed that Boace1 and Boace2 are appeared to be distinct clusters. The gene expression patterns at different development stages and various body parts tissues were examined, and their biological functions were characterized by RNA interference and analog docking prediction. The results showed that both Boace genes were expressed in all developmental stages and examined tissues. The transcript level of Boace2 was significantly higher than Boace1 in all tested samples, and Boace1 was found most abundant in the head while Boace2 was highly expressed in the fat body of B. odoriphaga. The silencing of Boace1 and Boace2 significantly decreased the AChE activity of 36.6% and 14.8% separately, and increased the susceptibility of B. odoriphaga to phoxim, with 60.8% and 44.7% mortality. Besides, overexpression and gene duplication of Boace1 were found in two field resistant populations, and two major mutations, A319S and G400V, were detected in Boace1. Moreover, the docking results revealed that BoAChE1 had a higher affinity towards organophosphorus than BoAChE2. It is concluded that Boace2 is the most abundant ace type in B. odoriphaga, while both Boace play vital roles. Boace1 might play a major neurological function and more likely be the prime target for insecticides, while Boace2 might play some important unidentified roles. Title: Characterization of the insecticide detoxification carboxylesterase Boest1 from Bradysia odoriphaga Yang et Zhang (Diptera:Sciaridae) Ding Q, Xu X, Sang Z, Wang R, Ullah F, Gao X, Song D Ref: Pest Manag Sci, :, 2021 : PubMed ESTHER: Ding_2021_Pest.Manag.Sci__ PubMedSearch: Ding 2021 Pest.Manag.Sci PubMedID: 34596943 Gene_locus related to this paper: 9dipt-Boest1, braco-est1 Inhibitor(s) related to this paper: TPHP Abstract BACKGROUND: In insects, carboxylesterases (CarEs) are enzymes involved in the detoxification of insecticides. However, the molecular mechanism of CarE-mediated insecticide metabolism in Bradysia odoriphaga, a serious agricultural pest, remains unclear. The aim of this study is to investigate the detoxification process of malathion, bifenthrin, and imidacloprid by B. odoriphaga carboxylesterase (Boest1). RESULTS: An alpha class CarE gene Boest1 was cloned from B. odoriphaga. The results of real-time quantitative PCR showed that Boest1 is up-regulated with age during the larval stage, and the level of transcription of Boest1 is higher in the midgut and Malpighian tubule than in other tissues. The expression level of Boest1 was significantly increased after exposure to malathion and bifenthrin. Recombinant BoEST1 expressed in vitro showed high catalytic activity toward alpha-naphthyl acetate, which was substantially inhibited by malathion and triphenyl phosphate. The in vitro metabolism assays showed that BoEST1 demonstrates hydrolytic capacity toward malathion and bifenthrin but not imidacloprid. The binding free energy analysis indicates that BoEST1 has a higher affinity for malathion and bifenthrin than imidacloprid. CONCLUSION: These results suggest that BoEST1 plays a role in the breakdown of insecticides and may be involved in the development of resistance in the Chinese chive pest B. odoriphaga; our findings also provide data for better pest management and perspectives for new pesticides development. This article is protected by copyright. All rights reserved. Title: Soluble Epoxide Hydrolase Deletion Attenuated Nicotine-induced Arterial Stiffness via Limiting the Loss of SIRT1 Hu S, Luo J, Fu M, Luo L, Cai Y, Li W, Li Y, Dong R, Yang Y and Xu X <1 more author(s)> Hu S, Luo J, Fu M, Luo L, Cai Y, Li W, Li Y, Dong R, Yang Y, Tu L, Xu X (- 1) Ref: American Journal of Physiology Heart Circ Physiol, :, 2021 : PubMed ESTHER: Hu_2021_Am.J.Physiol.Heart.Circ.Physiol__ PubMedSearch: Hu 2021 Am.J.Physiol.Heart.Circ.Physiol PubMedID: 34142887 Abstract Arterial stiffness, a consequence of smoking, is an underlying risk factor of cardiovascular diseases. Epoxyeicosatrienoic acids (EETs), hydrolyzed by soluble epoxide hydrolase (sEH), have beneficial effects against vascular dysfunction. However, the role of sEH knockout in nicotine-induced arterial stiffness was not characterized. We hypothesized that sEH knockout could prevent nicotine-induced arterial stiffness. In the present study, Ephx2 (the gene encodes sEH enzyme) null (Ephx2(-/-)) mice and wild-type (WT) littermate mice were infused with or without nicotine and administered with or without nicotinamide (NAM, SIRT1 inhibitor) simultaneously for four weeks. Nicotine treatment increased sEH expression and activity in the aortas of WT mice. Nicotine infusion significantly induced vascular remodeling, arterial stiffness, and SIRT1 deactivation in WT mice, which was attenuated in Ephx2(-/-) mice without NAM treatment. However, the arterial protective effects were gone in Ephx2(-/-) mice with NAM treatment. In vitro, 11,12-EET treatment attenuated nicotine-induced MMP2 upregulation via SIRT1-mediated YAP deacetylation. In conclusion, sEH knockout attenuated nicotine-induced arterial stiffness and vascular remodeling via SIRT1-induced YAP deacetylation. Title: Antidiabetic Agent DPP-4i Facilitates Murine Breast Cancer Metastasis by Oncogenic ROS-NRF2-HO-1 Axis via a Positive NRF2-HO-1 Feedback Loop Li R, Zeng X, Yang M, Xu X, Feng J, Bao L, Xue B, Wang X, Huang Y Ref: Front Oncol, 11:679816, 2021 : PubMed ESTHER: Li_2021_Front.Oncol_11_679816 PubMedSearch: Li 2021 Front.Oncol 11 679816 PubMedID: 34123848 Abstract Cancer has been as one of common comorbidities of diabetes. Long-term antidiabetic treatment may potentially exert uncertain impacts on diabetic patients with cancer including breast cancer (BC). Dipeptidyl peptidase-4 inhibitors (DPP-4i) are currently recommended by the AACE as first-line hypoglycemic drugs in type 2 diabetes mellitus (T2DM). Although the safety of DPP-4i has been widely evaluated, the potential side-effects of DPP-4i in cancer metastasis were also reported and remain controversial. Here, we revealed that Saxagliptin (Sax) and Sitagliptin (Sit), two common DPP-4i compounds, potentially promoted murine BC 4T1 metastasis in vitro and in vivo under immune-deficient status. Mechanically, we observed that DPP-4i treatment induced aberrant oxidative stress by triggering ROS overproduction, as well as ROS-dependent NRF2 and HO-1 activations in BC cells, while specific inhibition of ROS, NRF2 or HO-1 activations abrogated DPP-4i-driven BC metastasis and metastasis-associated gene expression in vitro. Furthermore, ALA, a NRF2 activator significantly promoted BC metastasis in vitro and in vivo, which can be abrogated by specific HO-1 inhibition in vitro. Moreover, specific HO-1 inhibition not only reversed DPP-4i-induced NRF2 activation but also abrogated ALA-induced NRF2 activation, resulting in a decrease of metastasis-associated genes, indicating a positive-feedback NRF2-HO-1 loop. Our findings suggest that DPP-4i accelerates murine BC metastasis through an oncogenic ROS-NRF2-HO-1 axis via a positive-feedback NRF2-HO-1 loop. Therefore, this study not only offers novel insights into an oncogenic role of DPP-4i in BC progression but also provides new strategies to alleviate the dark side of DPP-4i by targeting HO-1. Title: Inhibition of soluble epoxide hydrolase alleviates insulin resistance and hypertension via downregulation of SGLT2 in the mouse kidney Luo J, Hu S, Fu M, Luo L, Li Y, Li W, Cai Y, Dong R, Yang Y and Xu X <1 more author(s)> Luo J, Hu S, Fu M, Luo L, Li Y, Li W, Cai Y, Dong R, Yang Y, Tu L, Xu X (- 1) Ref: Journal of Biological Chemistry, :100667, 2021 : PubMed ESTHER: Luo_2021_J.Biol.Chem__100667 PubMedSearch: Luo 2021 J.Biol.Chem 100667 PubMedID: 33864813 Abstract The epoxyeicosatrienoic acid (EET) exerts beneficial effects on insulin resistance and/or hypertension. EETs could be readily converted to less biological active diols by soluble epoxide hydrolase (sEH). However, whether sEH inhibition can ameliorate the comorbidities of insulin resistance and hypertension, and the underlying mechanisms of this relationship, are unclear. In this study, C57BL/6 mice were rendered hypertensive and insulin resistant through a high-fat and high-salt (HF-HS) diet. The sEH inhibitor trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea (TPPU) was used to treat mice (1 mg/kg/d) for 8 weeks, followed by analysis of metabolic parameters. The expression of sEH and the sodium-glucose cotransporter 2 (SGLT2) were markedly upregulated in the kidneys of mice fed a HF-HS diet. We found that TPPU administration increased kidney EET levels, improved insulin resistance, and reduced hypertension. Furthermore, TPPU treatment prevented upregulation of SGLT2, and the associated increased urine volume and the excretion of urine glucose and urine sodium. Importantly, TPPU alleviated renal inflammation. In vitro, human renal proximal tubule epithelial cells (HK-2 cells) were used to further investigate the underlying mechanism. We observed that 14,15-EET or sEH knock-down or inhibition prevented the upregulation of SGLT2 upon treatment with palmitic acid or NaCl by inhibiting the IKKalpha/beta/NF-kappaB signaling pathway. In conclusion, sEH inhibition by TPPU alleviated insulin resistance and hypertension induced by a HF-HS diet in mice. The increased urine excretion of glucose and sodium was mediated by decreased renal SGLT2 expression due to inactivation of the IKKalpha/beta/NF-kappaB-induced inflammatory response. Title: Magnetic covalent organic framework immobilized gold nanoparticles with high-efficiency catalytic performance for chemiluminescent detection of pesticide triazophos Ma Y, Zhao Y, Xu X, Ding S, Li Y Ref: Talanta, 235:122798, 2021 : PubMed ESTHER: Ma_2021_Talanta_235_122798 PubMedSearch: Ma 2021 Talanta 235 122798 PubMedID: 34517656 Abstract Covalent organic frameworks (COFs) are considered to be a promising support material for catalyst due to their highly ordered porous structure. Here, a core-shell structured Fe(3)O(4) magnetic covalent organic framework (Fe(3)O(4)@COF) was synthesized and employed to provide basic sites for immobilization of gold nanoparticles (AuNPs). The AuNPs was in-situ immobilized on the shell of Fe(3)O(4)@COF via a citrate reducing method. The Fe(3)O(4)@COF-AuNP had convenient magnetic separability and exhibited excellent mimicking peroxidase-like activity in catalyzing chemiluminescence (CL) reaction of luminol with hydrogen peroxide (H(2)O(2)). With acetylcholine chloride (ACh) as substrate of acetylcholinesterase (AChE), a CL method was exploited for sensitive detection of organophosphorus pesticide triazophos due to its irreversible inhibiting effect on the AChE activity and subsequently influences the production of H(2)O(2) under the condition of choline oxidase (ChOx). This method gave a good linearity for triazophos in the range of 5.0-300.0 nmol L(-1), and a limit of detection (LOD) of 1 nmol L(-1) was acquired. The applicability of this method was verified by the determination of triazophos in different spiked vegetable samples. Title: Toxic effects of the dinoflagellate Karenia mikimotoi on zebrafish (Danio rerio) larval behavior Niu X, Xu S, Yang Q, Xu X, Zheng M, Li X, Guan W Ref: Harmful Algae, 103:101996, 2021 : PubMed ESTHER: Niu_2021_Harmful.Algae_103_101996 PubMedSearch: Niu 2021 Harmful.Algae 103 101996 PubMedID: 33980436 Abstract Karenia mikimotoi is a toxic dinoflagellate that forms harmful blooms in coastal waters, threatening aquaculture worldwide. However, we do not know whether K. mikimotoi has a neurotoxic effect on aquatic animal behavior. Thus, this study investigated potential K. mikimotoi neurotoxicity in zebrafish larvae. Cells of K. mikimotoi were collected at the mid-exponential phase from a batch culture to prepare ruptured cell solutions (RCS). At 6 h post-fertilization (hpf), zebrafish embryos were exposed to different RCS concentrations (0, 10(2), 10(3), 10(4), and 2.5 x 10(4) cells mL(-1)). After 120 hpf, treated larvae were collected to analyze locomotor behavior; activities of acetylcholinesterase (AChE), superoxide dismutase (SOD), catalase (CAT); and expression of genes related to neurodevelopment. We found that RCS did not affect survival rate, but significantly decreased larval locomotion, as well as their AChE, SOD, and CAT activity. Additionally, the examination of the day-night behavioral experiment revealed RCS decreased locomotion only at night. Zebrafish larvae were also significantly hypoactive in response to light and sound stimulations. Of the neurodevelopment genes, three (th, neurog1, and neurod1) were downregulated, while two (bdnf and manf) were upregulated. Our study suggests that K. mikimotoi neurotoxicity occurs through causing oxidative damage, as well as disorders in the cholinergic system and nervous system development. The results provide new insight that K. mikimotoi in low abundance did not cause significant lethal effect but still exhibited significant neurotoxicity on aquatic animals. Title: Identification, Classification, and Expression Analysis of the Triacylglycerol Lipase (TGL) Gene Family Related to Abiotic Stresses in Tomato Wang Q, Xu X, Cao X, Hu T, Xia D, Zhu J, Zhan X Ref: Int J Mol Sci, 22:1387, 2021 : PubMed ESTHER: Wang_2021_Int.J.Mol.Sci_22_1387 PubMedSearch: Wang 2021 Int.J.Mol.Sci 22 1387 PubMedID: 33573234 Abstract Triacylglycerol Lipases (TGLs) are the major enzymes involved in triacylglycerol catabolism. TGLs hydrolyze long-chain fatty acid triglycerides, which are involved in plant development and abiotic stress responses. Whereas most studies of TGLs have focused on seed oil metabolism and biofuel in plants, limited information is available regarding the genome-wide identification and characterization of the TGL gene family in tomato (Solanum lycopersicum L.). Based on the latest published tomato genome annotation ITAG4.0, 129 SlTGL genes were identified and classified into 5 categories according to their structural characteristics. Most SlTGL genes were distributed on 3 of 12 chromosomes. Segment duplication appeared to be the driving force underlying expansion of the TGL gene family in tomato. The promoter analysis revealed that the promoters of SlTGLs contained many stress responsiveness cis-elements, such as ARE, LTR, MBS, WRE3, and WUN-motifs. Expression of the majority of SlTGL genes was suppressed following exposure to chilling and heat, while it was induced under drought stress, such as SlTGLa9, SlTGLa6, SlTGLa25, SlTGLa26, and SlTGLa13. These results provide valuable insights into the roles of the SlTGL genes family and lay a foundation for further functional studies on the linkage between triacylglycerol catabolism and abiotic stress responses in tomato. Title: Autistic-like behavior, spontaneous seizures, and increased neuronal excitability in a Scn8a mouse model Wong JC, Grieco SF, Dutt K, Chen L, Thelin JT, Inglis GAS, Parvin S, Garraway SM, Xu X and Escayg A <1 more author(s)> Wong JC, Grieco SF, Dutt K, Chen L, Thelin JT, Inglis GAS, Parvin S, Garraway SM, Xu X, Goldin AL, Escayg A (- 1) Ref: Neuropsychopharmacology, :, 2021 : PubMed ESTHER: Wong_2021_Neuropsychopharmacology__ PubMedSearch: Wong 2021 Neuropsychopharmacology PubMedID: 33658654 Abstract Patients with SCN8A epileptic encephalopathy exhibit a range of clinical features, including multiple seizure types, movement disorders, and behavioral abnormalities, such as developmental delay, mild-to-severe intellectual disability, and autism. Recently, the de novo heterozygous SCN8A R1620L mutation was identified in an individual with autism, intellectual disability, and behavioral seizures without accompanying electrographic seizure activity. To date, the effects of SCN8A mutations that are primarily associated with behavioral abnormalities have not been studied in a mouse model. To better understand the phenotypic and functional consequences of the R1620L mutation, we used CRISPR/Cas9 technology to generate mice expressing the corresponding SCN8A amino acid substitution. Homozygous mutants exhibit tremors and a maximum lifespan of 22 days, while heterozygous mutants (RL/+) exhibit autistic-like behaviors, such as hyperactivity and learning and social deficits, increased seizure susceptibility, and spontaneous seizures. Current clamp analyses revealed a reduced threshold for firing action potentials in heterozygous CA3 pyramidal neurons and reduced firing frequency, suggesting that the R1620L mutation has both gain- and loss-of-function effects. In vivo calcium imaging using miniscopes in freely moving RL/+ mutants showed hyperexcitability of cortical excitatory neurons that is likely to increase seizure susceptibility. Finally, we found that oxcarbazepine and Huperzine A, a sodium channel blocker and reversible acetylcholinesterase inhibitor, respectively, were capable of conferring robust protection against induced seizures in RL/+ mutants. This mouse line will provide the opportunity to better understand the range of clinical phenotypes associated with SCN8A mutations and to develop new therapeutic approaches. Title: Celastrol Attenuates Learning and Memory Deficits in an Alzheimer's Disease Rat Model Xiao Y, Wang X, Wang S, Li J, Xu X, Wang M, Li G, Shen W Ref: Biomed Res Int, 2021:5574207, 2021 : PubMed ESTHER: Xiao_2021_Biomed.Res.Int_2021_5574207 PubMedSearch: Xiao 2021 Biomed.Res.Int 2021 5574207 PubMedID: 34350293 Abstract Alzheimer's disease (AD) is a chronic progressive neurodegenerative disorder that is associated with learning, memory, and cognitive deficits. Neuroinflammation and synapse loss are involved in the pathology of AD. Diverse measures have been applied to treat AD, but currently, there is no effective treatment. Celastrol (CEL) is a pentacyclic triterpene isolated from Tripterygium wilfordii Hook F that has been shown to enhance cell viability and inhibit amyloid-beta production induced by lipopolysaccharides in vitro. In the present study, the protective effect of CEL on Abeta (25-35)-induced rat model of AD was assessed. Our results showed that CEL administration at a dose of 2 mg/kg/day improved spatial memory in the Morris water maze. Further biochemical analysis showed that CEL treatment of intrahippocampal Abeta (25-35)-microinjected rats attenuated hippocampal NF-kappaB activity; inhibited proinflammatory markers, namely, IL-1beta, IL-6, and TNF-alpha; and upregulated anti-inflammatory factors, such as IL-4 and IL-10. Furthermore, CEL upregulated hippocampal neurexin-1beta, neuroligin-1, CA1, and PSD95 expression levels, which may improve synaptic function. Simultaneously, CEL also increased glucose metabolism in Abeta (25-35)-microinjected rats. In conclusion, CEL could exert protective effects against learning and memory decline induced by intrahippocampal Abeta (25-35) through anti-inflammation, promote synaptic development, and maintain hippocampal energy metabolism. Title: Genome-wide analysis of the serine carboxypeptidase-like protein family in Triticum aestivum reveals TaSCPL184-6D is involved in abiotic stress response Xu X, Zhang L, Zhao W, Fu L, Han Y, Wang K, Yan L, Li Y, Zhang XH, Min DH Ref: BMC Genomics, 22:350, 2021 : PubMed ESTHER: Xu_2021_BMC.Genomics_22_350 PubMedSearch: Xu 2021 BMC.Genomics 22 350 PubMedID: 33992092 Abstract BACKGROUND: The serine carboxypeptidase-like protein (SCPL) family plays a vital role in stress response, growth, development and pathogen defense. However, the identification and functional analysis of SCPL gene family members have not yet been performed in wheat. RESULTS: In this study, we identified a total of 210 candidate genes encoding SCPL proteins in wheat. According to their structural characteristics, it is possible to divide these members into three subfamilies: CPI, CPII and CPIII. We uncovered a total of 209 TaSCPL genes unevenly distributed across 21 wheat chromosomes, of which 65.7% are present in triads. Gene duplication analysis showed that ~ 10.5% and ~ 64.8% of the TaSCPL genes are derived from tandem and segmental duplication events, respectively. Moreover, the Ka/Ks ratios between duplicated TaSCPL gene pairs were lower than 0.6, which suggests the action of strong purifying selection. Gene structure analysis showed that most of the TaSCPL genes contain multiple introns and that the motifs present in each subfamily are relatively conserved. Our analysis on cis-acting elements showed that the promoter sequences of TaSCPL genes are enriched in drought-, ABA- and MeJA-responsive elements. In addition, we studied the expression profiles of TaSCPL genes in different tissues at different developmental stages. We then evaluated the expression levels of four TaSCPL genes by qRT-PCR, and selected TaSCPL184-6D for further downstream analysis. The results showed an enhanced drought and salt tolerance among TaSCPL184-6D transgenic Arabidopsis plants, and that the overexpression of the gene increased proline and decreased malondialdehyde levels, which might help plants adapting to adverse environments. Our results provide comprehensive analyses of wheat SCPL genes that might work as a reference for future studies aimed at improving drought and salt tolerance in wheat. CONCLUSIONS: We conducte a comprehensive bioinformatic analysis of the TaSCPL gene family in wheat, which revealing the potential roles of TaSCPL genes in abiotic stress. Our analysis also provides useful resources for improving the resistance of wheat. Title: Strigolactones regulate sepal senescence in Arabidopsis Xu X, Jibran R, Wang Y, Dong L, Flokova K, Esfandiari A, McLachlan ARG, Heiser A, Sutherland-Smith AJ and Hunter DA <3 more author(s)> Xu X, Jibran R, Wang Y, Dong L, Flokova K, Esfandiari A, McLachlan ARG, Heiser A, Sutherland-Smith AJ, Brummell DA, Bouwmeester HJ, Dijkwel PP, Hunter DA (- 3) Ref: J Exp Bot, :, 2021 : PubMed ESTHER: Xu_2021_J.Exp.Bot__ PubMedSearch: Xu 2021 J.Exp.Bot PubMedID: 33970249 Abstract Flower sepals are critical for flower development and vary greatly in lifespan depending on their function post-pollination. Very little is known about what controls sepal longevity. Using a sepal senescence mutant screen, we identified two Arabidopsis mutants with delayed senescence directly connecting strigolactones (SL) with senescence regulation in a novel floral context that hitherto has not been explored. The mutations were in the SL biosynthetic gene MORE AXILLARY GROWTH1 (MAX1) and in the SL receptor DWARF14 (AtD14). The mutation in AtD14 changed the catalytic Ser97 to Phe in the enzyme active site, which is the first mutation of its kind in planta. The lesion in MAX1 was in the haem-iron ligand signature of the cytochrome P450 protein, converting the highly conserved Gly469 to Arg, which was shown in a transient expression assay to substantially inhibit activity of MAX1. The two mutations highlighted the importance of SL activity for driving to completion senescence initiated both developmentally and in response to carbon-limiting stress, as has been found for the more well-known senescence-associated regulators ethylene and abscisic acid. Analysis of transcript abundances in excised inflorescences during an extended night suggested an intricate relationship among sugar starvation, senescence and SL biosynthesis and signalling. Title: Bioinformatics analysis of PAE family in Populus trichocarpa and responsiveness to carbon and nitrogen treatment Xu C, Zhang S, Suo J, Chang R, Xu X, Xu Z, Yang C, Qu C, Liu G Ref: 3 Biotech, 11:370, 2021 : PubMed ESTHER: Xu_2021_3.Biotech_11_370 PubMedSearch: Xu 2021 3.Biotech 11 370 PubMedID: 34295610 Abstract Plant Pectin acetylesterase (PAE) belongs to family CE13 of carbohydrate esterases in the CAZy database. The ability of PAE to regulate the degree of acetylation of pectin, an important polysaccharide in the cell wall, affects the structure of plant cell wall. In this study, ten PtPAE genes were identified and characterized in Populus trichocarpa genome using bioinformatics methods, and the physiochemical properties such as molecular weight, isoelectric points, and hydrophilicity, as well as the secondary and tertiary structure of the protein were predicted. According to phylogenetic analysis, ten PtPAEs can be divided into three evolutionary clades, each of which had similar gene structure and motifs. Tissue-specific expression profiles indicated that the PtPAEs had different expression patterns. Real-time quantitative PCR (RT-qPCR) analysis showed that transcription level of PtPAEs was regulated by different CO(2) and nitrogen concentrations. These results provide important information for the study of the phylogenetic relationship and function of PtPAEs in Populus trichocarpa. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13205-021-02918-1. Title: Differential Effects of 17,18-EEQ and 19,20-EDP Combined with Soluble Epoxide Hydrolase Inhibitor t-TUCB on Diet-Induced Obesity in Mice Yang Y, Xu X, Wu H, Yang J, Chen J, Morisseau C, Hammock BD, Bettaieb A, Zhao L Ref: Int J Mol Sci, 22:, 2021 : PubMed ESTHER: Yang_2021_Int.J.Mol.Sci_22_ PubMedSearch: Yang 2021 Int.J.Mol.Sci 22 PubMedID: 34361032 Inhibitor(s) related to this paper: t-TUCB Abstract 17,18-Epoxyeicosatetraenoic acid (17,18-EEQ) and 19,20-epoxydocosapentaenoic acid (19,20-EDP) are bioactive epoxides produced from n-3 polyunsaturated fatty acid eicosapentaenoic acid and docosahexaenoic acid, respectively. However, these epoxides are quickly metabolized into less active diols by soluble epoxide hydrolase (sEH). We have previously demonstrated that an sEH inhibitor, t-TUCB, decreased serum triglycerides (TG) and increased lipid metabolic protein expression in the brown adipose tissue (BAT) of diet-induced obese mice. This study investigates the preventive effects of t-TUCB (T) alone or combined with 19,20-EDP (T + EDP) or 17,18-EEQ (T + EEQ) on BAT activation in the development of diet-induced obesity and metabolic disorders via osmotic minipump delivery in mice. Both T + EDP and T + EEQ groups showed significant improvement in fasting glucose, serum triglycerides, and higher core body temperature, whereas heat production was only significantly increased in the T + EEQ group. Moreover, both the T + EDP and T + EEQ groups showed less lipid accumulation in the BAT. Although UCP1 expression was not changed, PGC1alpha expression was increased in all three treated groups. In contrast, the expression of CPT1A and CPT1B, which are responsible for the rate-limiting step for fatty acid oxidation, was only increased in the T + EDP and T + EEQ groups. Interestingly, as a fatty acid transporter, CD36 expression was only increased in the T + EEQ group. Furthermore, both the T + EDP and T + EEQ groups showed decreased inflammatory NFkappaB signaling in the BAT. Our results suggest that 17,18-EEQ or 19,20-EDP combined with t-TUCB may prevent high-fat diet-induced metabolic disorders, in part through increased thermogenesis, upregulating lipid metabolic protein expression, and decreasing inflammation in the BAT. Title: sEH Inhibitor Tppu Ameliorates Cecal Ligation and Puncture-Induced Sepsis by Regulating Macrophage Functions Chen Z, Tang Y, Yu J, Dong R, Yang Y, Fu M, Luo J, Hu S, Wang DW and Xu X <1 more author(s)> Chen Z, Tang Y, Yu J, Dong R, Yang Y, Fu M, Luo J, Hu S, Wang DW, Tu L, Xu X (- 1) Ref: Shock, 53:761, 2020 : PubMed ESTHER: Chen_2020_Shock_53_761 PubMedSearch: Chen 2020 Shock 53 761 PubMedID: 31318834 Abstract BACKGROUND: Sepsis is a life-threatening organ dysfunction initiated by a dysregulated response to infection, with imbalanced inflammation and immune homeostasis. Macrophages play a pivotal role in sepsis. N-[1-(1-oxopropyl)-4-piperidinyl]-N'-[4-(trifluoromethoxy)phenyl)-urea (TPPU) is an inhibitor of soluble epoxide hydrolase (sEH), which can rapidly hydrolyze epoxyeicosatrienoic acids (EETs) to the bio-inactive dihydroxyeicosatrienoic acids. TPPU was linked with the regulation of macrophages and inflammation. Here, we hypothesized that sEH inhibitor TPPU ameliorates cecal ligation and puncture (CLP)-induced sepsis by regulating macrophage functions. METHODS: A polymicrobial sepsis model induced by CLP was used in our study. C57BL/6 mice were divided into four groups: sham+ phosphate buffer saline (PBS), sham+TPPU, CLP+PBS, CLP+TPPU. Mice were observed 48h after surgery to assess the survival rate. For other histological examinations, mice were sacrificed 6h after surgery. Macrophage cell line RAW264.7 was used for in vitro studies. RESULTS: TPPU treatment, accompanied with increased EETs levels, markedly improved the survival of septic mice induced by CLP surgery, which was associated with alleviated organ damage and dysfunction triggered by systemic inflammatory response. Moreover, TPPU treatment significantly inhibited systemic inflammatory response via EETs-induced inactivation of mitogen-activated protein kinase signaling due to enhanced macrophage phagocytic ability and subsequently reduced bacterial proliferation and dissemination, and decreased inflammatory factors release. CONCLUSION: sEH inhibitor TPPU ameliorates cecal ligation and puncture-induced sepsis by regulating macrophage functions, including improved phagocytosis and reduced inflammatory response. Our data indicate that sEH inhibition has potential therapeutic effects on polymicrobial-induced sepsis. Title: Decreased T-cell mediated hepatic injury in concanavalin A-treated PLRP2-deficient mice Ge W, Gao Y, Zhao Y, Yang Y, Sun Q, Yang X, Xu X, Zhang J Ref: Int Immunopharmacol, 85:106604, 2020 : PubMed ESTHER: Ge_2020_Int.Immunopharmacol_85_106604 PubMedSearch: Ge 2020 Int.Immunopharmacol 85 106604 PubMedID: 32428799 Gene_locus related to this paper: mouse-LIPR2 Abstract Concanavalin A (Con A) activates innate immunity and causes liver damage mediated by cytotoxic T lymphocytes (CTL) in mice. The Pancreatic lipase-related protein 2 (PLRP2) is induced by interleukin (IL)-4 in vitro in CTLs and associated with CTL functions. We examined the role of PLRP2 in a mouse model of Con A-induced T cell-mediated hepatitis. PLRP2-knockout and wild-type (WT) mice were inoculated with 20 mg/kg Con A. Mice lacking PLRP2 reduced Con A-induced hepatitis, which was manifested by a decrease in serum aminotransferase and histopathological assessment. The expression and secretion of cytokines including tumor necrosis factor-alpha (TNF-alpha), interferon (IFN)-gamma, IL-6, and IL-1beta were suppressed in Con A-treated PLRP2-knockout mice. In PLRP2 knockout mice, Con A-induced liver chemokines and adhesion molecules (such as MIP-1alpha, MIP-1beta, ICAM-1 and MCP-1) were also down regulated. In the WT liver treated with Con A, the number of T cells (CD4(+) and CD8(+)) and macrophages (CD11b(+) F4/80(+)) increased significantly, while the lack of PLRP2 reduced the number of T cells in the liver, but had no effect on macrophages. The shift of the metabolic profiles was impaired in Con A-treated PLRP2-knockout mice compared to WT mice. In conclusion, these results indicate that PLRP2 deficiency reduces T-cell mediated Con A-induced hepatitis, and suggest PLRP2 is a potential target of anti-inflammatory and immunomodulatory drugs to treat immune-mediated hepatitis. Title: Multilevel ecotoxicity assessment of environmentally relevant bisphenol F concentrations in Daphnia magna Liu J, Shen J, Lu G, Xu X, Yang H, Yan Z, Chen W Ref: Chemosphere, 240:124917, 2020 : PubMed ESTHER: Liu_2020_Chemosphere_240_124917 PubMedSearch: Liu 2020 Chemosphere 240 124917 PubMedID: 31726617 Abstract With the pressure to ban or limit the use of Bisphenol A (BPA), substitutes such as bisphenol F (BPF) are applied to various commodities and generally detected in aquatic systems worldwide. To understand the potential ecological risk of BPF, the acute toxicity as well as behavioural, physiological and biochemical parameters of the water flea Daphnia magna were assessed. Following BPF exposure at concentrations ranging from 0.1mugL(-1) to 100mugL(-1), phenotypic traits including growth development, fecundity and swimming activity were significantly inhibited in response to exposure to sublethal concentrations (1-100mugL(-1)) of BPF, which had a positive relationship with the activity of antioxidant enzymes. Moreover, the acetylcholinesterase (AChE) activity, which was strictly associated with the behavioural changes, was clearly inhibited, which was also obviously related to the heart rate and thoracic limb activity. Compared to the toxicity of BPA, BPF induces similar toxic effects, and the health concerns regarding the use of these alternatives should be highlighted. Title: Soluble Epoxide Hydrolase Inhibition by t-TUCB Promotes Brown Adipogenesis and Reduces Serum Triglycerides in Diet-Induced Obesity Overby H, Yang Y, Xu X, Graham K, Hildreth K, Choi S, Wan D, Morisseau C, Zeldin DC and Zhao L <3 more author(s)> Overby H, Yang Y, Xu X, Graham K, Hildreth K, Choi S, Wan D, Morisseau C, Zeldin DC, Hammock BD, Wang S, Bettaieb A, Zhao L (- 3) Ref: Int J Mol Sci, 21:, 2020 : PubMed ESTHER: Overby_2020_Int.J.Mol.Sci_21_ PubMedSearch: Overby 2020 Int.J.Mol.Sci 21 PubMedID: 32987880 Inhibitor(s) related to this paper: t-TUCB Abstract Brown adipose tissue (BAT) is an important target for obesity treatment and prevention. Soluble epoxide hydrolase (sEH) converts bioactive epoxy fatty acids (EpFAs) into less active diols. sEH inhibitors (sEHI) are beneficial in many chronic diseases by stabilizing EpFAs. However, roles of sEH and sEHI in brown adipogenesis and BAT activity in treating diet-induced obesity (DIO) have not been reported. sEH expression was studied in in vitro models of brown adipogenesis and the fat tissues of DIO mice. The effects of the sEHI, trans-4-{4-[3-(4-trifluoromethoxy-phenyl)-ureido]-cyclohexyloxy-benzoic acid (t-TUCB), were studied in vitro and in the obese mice via mini osmotic pump delivery. sEH expression was increased in brown adipogenesis and the BAT of the DIO mice. t-TUCB promoted brown adipogenesis in vitro. Although t-TCUB did not change body weight, fat pad weight, or glucose and insulin tolerance in the obese mice, it decreased serum triglycerides and increased protein expression of genes important for lipid metabolism in the BAT. Our results suggest that sEH may play a critical role in brown adipogenesis, and sEHI may be beneficial in improving BAT protein expression involved in lipid metabolism. Further studies using the sEHI combined with EpFA generating diets for obesity treatment and prevention are warranted. Title: Efficacy and safety of DBPR108 monotherapy in patients with type 2 diabetes: a 12-week, randomized, double-blind, placebo-controlled, phase II clinical trial Wang W, Yao J, Guo X, Guo Y, Yan C, Liu K, Zhang Y, Wang X, Li H and Yuan J <22 more author(s)> Wang W, Yao J, Guo X, Guo Y, Yan C, Liu K, Zhang Y, Wang X, Li H, Wen Z, Li S, Xiao X, Liu W, Li Z, Zhang L, Shao S, Ye S, Qin G, Li Y, Li F, Zhang X, Li X, Peng Y, Deng H, Xu X, Zhou L, Huang Y, Cao M, Xia X, Shi M, Dou J, Yuan J (- 22) Ref: Curr Med Res Opin, 36:1107, 2020 : PubMed ESTHER: Wang_2020_Curr.Med.Res.Opin_36_1107 PubMedSearch: Wang 2020 Curr.Med.Res.Opin 36 1107 PubMedID: 32338063 Inhibitor(s) related to this paper: Prusogliptin Abstract Objective: DBPR108, a novel dipeptidyl-peptidase-4 inhibitor, has shown great antihyperglycemic effect in animal models. This study was to evaluate the efficacy and safety of DBPR108 monotherapy in type 2 diabetes mellitus (T2DM).Methods: This was a 12-week, double-blind, placebo-controlled phase II clinical trial. The newly diagnosed or inadequately controlled untreated T2DM patients were randomized to receive 50, 100, 200 mg DBPR108 or placebo in a ratio of 1:1:1:1. The primary efficacy outcome was HbA1c change from baseline to week 12. Relevant secondary efficacy parameters and safety were assessed. The clinical trial registration is NCT04124484.Results: Overall, 271 of the 276 randomized patients, who received 50 mg (n = 68), 100 mg (n = 67), 200 mg (n = 69) DBPR108 or placebo (n = 67), were included in full analysis set. At week 12, HbA1c change from baseline was -0.04 +/- 0.77 in placebo group, -0.51 +/- 0.71, -0.75 +/- 0.73, and -0.57 +/- 0.78 (%, p < .001 vs. placebo) in 50, 100, and 200 mg DBPR108 groups, respectively. Since week 4, DBPR108 monotherapy resulted in significant improvements in secondary efficacy parameters. At end of 12-week treatment, the goal of HbA1c >=7% was achieved in 29.85, 58.82, 55.22, and 47.83% of the patients in placebo, 50, 100, and 200 mg DBPR108 groups, respectively. The incidence of adverse events did not show significant difference between DBPR108 and placebo except mild hypoglycemia in DBPR108 200 mg group.Conclusions: The study results support DBPR108 100 mg once daily as the primary dosing regimen for T2DM patients in phase III development program. Title: Anti-foodborne enteritis effect of galantamine potentially via acetylcholine anti-inflammatory pathway in fish Wu N, Xu X, Wang B, Li XM, Cheng YY, Li M, Xia XQ, Zhang YA Ref: Fish Shellfish Immunol, 97:204, 2020 : PubMed ESTHER: Wu_2020_Fish.Shellfish.Immunol_97_204 PubMedSearch: Wu 2020 Fish.Shellfish.Immunol 97 204 PubMedID: 31843701 Abstract Foodborne enteritis has become a limiting factor in aquaculture. Plant protein sources have already caused enteritic inflammation and inhibition in growth performance. Attempts have been made to find an effective solution to foodborne enteritis. Based on the previously suggested fish cholinergic anti-inflammatory pathway, galantamine, a typical cholinesterase inhibitor, was tested for the repression of pro-inflammatory cytokines for soybean meal induced enteritis by injection into grass carp. Both the phylogenetic analysis of cholinesterase, AchR and bioinformatic prediction, indicated galantamine's potential use as an enteritis drug. The result highlighted galantamine's potential effect for anti-enteritis in fish, especially in carps. Subsequently, a 4-week feeding trail using galantamine as an additive, in a zebrafish soybean meal induced enteritis model, demonstrated the prevention of enteritis. The results demonstrated that galantamine could prevent intestinal pathology, both histologically and molecularly, and also maintain growth performance. Reflected by gene expressional analysis, all mechanical, chemical and immune functions of the intestinal barrier could be protected by galantamine supplementation, which aided molecularly in the control of fish foodborne enteritis, through down-regulating Th17 type proinflammatory factors, meanwhile resuming the level of Treg type anti-inflammatory factors. Therefore, the current results shed light on fish intestinal acetylcholine anti-inflammation, by the dietary addition of galantamine, which could give rise to protection from foodborne enteritis. Title: AGLPM and QMDDQ peptides exert a synergistic action on memory improvement against scopolamine-induced amnesiac mice Wu D, Xu X, Sun N, Li D, Zhu B, Lin S Ref: Food Funct, 11:10925, 2020 : PubMed ESTHER: Wu_2020_Food.Funct_11_10925 PubMedSearch: Wu 2020 Food.Funct 11 10925 PubMedID: 33242042 Abstract This study aimed to explore the synergistic action of pentapeptides Gln-Met-Asp-Asp-Gln (QMDDQ) and Ala-Gly-Leu-Pro-Met (AGLPM) on memory improvement against scopolamine-induced impairment in mice compared to those of either peptide alone. In behavioral tests, the codelivery of QMDDQ and AGLPM was superior to the individual supplements of either peptide alone not only in enhancing the memory ability at training trials but also in recovering the memory impairment in scopolamine-induced amnesiac mice in test trials. Furthermore, combination treatment with QMDDQ and AGLPM could significantly reduce the acetylcholinesterase (AChE) level and increase the acetylcholine (ACh) level in the hippocampus, and noticeably improve the pathological morphology of the neuron cells in hippocampal regions CA1 and CA2 and dentate gyrus (DG). The findings indicated that the combination treatment with QMDDQ and AGLPM could improve the memory function by regulating the cholinergic system. Title: Cell Surface Display of Thermomyces lanuginosus Lipase in Pichia pastoris Yang J, Huang K, Xu X, Miao Y, Lin Y, Han S Ref: Front Bioeng Biotechnol, 8:544058, 2020 : PubMed ESTHER: Yang_2020_Front.Bioeng.Biotechnol_8_544058 PubMedSearch: Yang 2020 Front.Bioeng.Biotechnol 8 544058 PubMedID: 33195113 Abstract A cell surface displayed system in Pichia pastoris GS115 was developed by using GCW61, a glycosylphosphatidylinositol-modified cell wall protein from P. pastoris, as the anchor protein. Thermomyces lanuginosus lipase (TLL) was successfully displayed on the P. pastoris cell wall by fusing GCW61 gene with TLL2 gene (NCBI Accession: O59952) that was optimized with codon bias and synthesized. Cell surface displayed TLL2 was confirmed by the immunofluorescence microscopy. Flask fermentation was performed for 144 h with lipase activity up to 1964.76 U/g. Enzymatic properties of cell surface displayed TLL2 were also investigated. Displayed TLL2 occurred the maximum activity at pH 9 and 55 degC and demonstrated characteristics of wide thermal adaptability and alkaline pH resistance. The optimum substrate was p-nitrophenyl hexanoate. Bivalent metal ions Ca(2+), Mn(2+), and Zn(2+) had the activation effect on displayed TLL2, while Cu(2+), Fe(2+), Fe(3+), K(+), Li(+), Na(+), and Co(2+) ions had the inhibitory effect on it. Since cell surface displayed TLL2 required less purification steps compared with free enzyme and showed high enzyme activities, it would be able to be further applied in various potential applications. Title: A ratiometric fluorescence probe based on carbon dots for discriminative and highly sensitive detection of acetylcholinesterase and butyrylcholinesterase in human whole blood Xu X, Cen Y, Xu G, Wei F, Shi M, Hu Q Ref: Biosensors & Bioelectronics, 131:232, 2019 : PubMed ESTHER: Xu_2019_Biosens.Bioelectron_131_232 PubMedSearch: Xu 2019 Biosens.Bioelectron 131 232 PubMedID: 30849722 Abstract A ratiometric fluorescence probe based on carbon dots (CDs) was developed for discriminative and highly sensitive detection of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activity in human whole blood. When o-phenylenediamine (OPD) was oxidized by Cu(2+), the product 2,3-diaminophenazine (oxOPD) could effectively quench the fluorescence of CDs at 460nm due to the inner filter effect and gave rise to a new emission peak at 570nm. The AChE or BChE catalyzed hydrolysis reaction of acetylthiocholine or butyrylthiocholine to generate thiocholine, whose sulfhydryl group strongly captured Cu(2+) to inhibit the oxidization of OPD, thus effectively preserving the natural fluorescence emission of CDs. The resulting fluorescence intensity ratio served as the signal output of the probe for cholinesterases (ChEs) activity sensing. The activities of AChE and BChE were determined to range from 0.2 to 14.0 U L(-1) and from 0.1 to 5.0 U L(-1), with detection limits of 0.1 U L(-1) and 0.04 U L(-1), respectively. Additionally, the IC50 of tacrine and ethopropazine for the inhibition of AChE and BChE were estimated to be 29.8nM and 132.6nM, respectively. Moreover, the probe was successfully applied to the discriminative determination of AChE and BChE in human whole blood without any pretreatment. These results suggested that the proposed strategy provided a discriminative, sensitive and robust analytical platform for ChEs clinical diagnostics and drug screening. Title: Candidate detoxification-related genes in brown planthopper, Nilaparvata lugens, in response to beta-asarone based on transcriptomic analysis Xu X, Li X, Wang F, Han K, Liu Z, Fan L, Hua H, Cai W, Yao Y Ref: Ecotoxicology & Environmental Safety, 185:109735, 2019 : PubMed ESTHER: Xu_2019_Ecotoxicol.Environ.Saf_185_109735 PubMedSearch: Xu 2019 Ecotoxicol.Environ.Saf 185 109735 PubMedID: 31586846 Abstract Nilaparvata lugens(Stal) is a serious pest of rice and has evolved different levels of resistance against most chemical pesticides. beta-asarone is the main bioactive insecticidal compound of Acorus calamus L. that shows strong insecticidal activity against pests. In this study, we conducted a bioassay experiment to determine the contact toxicity of beta-asarone to N. lugens nymphs. The LD30 sublethal dose was 0.106mug per nymph, with 95% confidence limits of 0.070-0.140mug. We applied the LD30 concentration of beta-asarone to nymphs for 24h or 72h and then performed a transcriptome sequence analysis by referencing the N. lugens genome to characterize the variation. The transcriptomic analysis showed that several GO terms and KEGG pathways presented significant changes. Individually, 126 differentially expressed genes (DEGs), including 72 upregulated and 54 downregulated genes, were identified at 24h, and 1771 DEGs, including 882 upregulated and 889 downregulated genes, were identified at 72h. From the DEGs, we identified a total of 40 detoxification-related genes, including eighteen Cytochrome P450 monooxygenase genes (P450s), three Glutathione S-transferase genes, one Carboxylesterase gene, twelve UDP-glucosyltransferases and six ATP-binding cassette genes. We selected the eighteen P450s for subsequent verification by quantitative PCR. These findings indicated that beta-asarone presented strong contact toxicity to N. lugens nymphs and induced obvious variation of detoxification-related genes that may be involved in the response to beta-asarone. Title: Biomarker Effects in Carassius auratus Exposure to Ofloxacin, Sulfamethoxazole and Ibuprofen Yang X, Xu X, Wei X, Wan J, Zhang Y Ref: Int J Environ Research Public Health, 16:, 2019 : PubMed ESTHER: Yang_2019_Int.J.Environ.Res.Public.Health_16_ PubMedSearch: Yang 2019 Int.J.Environ.Res.Public.Health 16 PubMedID: 31075982 Abstract Ofloxacin, sulfamethoxazole and ibuprofen are three commonly used drugs which can be detected in aquatic environments. To assess their ecotoxicity, the effects of these three pharmaceuticals and their mixture on AChE (acetylcholinesterase) activity in the brain, and EROD (7-ethoxyresorufin-O-deethylase) and SOD (superoxide dismutase) activities in the liver of the freshwater crucian carp Carassius auratus were tested after exposure for 1, 2, 4 and 7 days. The results showed that treatments with 0.002(-)0.01 mg/L ofloxacin and 0.0008(-)0.004 mg/L sulfamethoxazole did not significantly change AChE, EROD and SOD activities. AChE activity was significantly inhibited in response to treatment with 0.05mg/L ofloxacin and 0.02mg/L sulfamethoxazole. All three biomarkers were induced significantly in treatments with ibuprofen and the mixture of the three pharmaceuticals at all the tested concentrations. The combined effects of ofloxacin, sulfamethoxazole and ibuprofen were compared with their isolated effects on the three biomarkers, and the results indicated that exposure to ibuprofen and the mixture at environmentally relevant concentrations could trigger adverse impacts on Carassius auratus. The hazard quotient (HQ) index also demonstrated a high risk for ibuprofen. Moreover, the present study showed that the effects of ofloxacin, sulfamethoxazole and ibuprofen might be additive on the physiological indices of Carassius auratus. Title: MicroRNA-187 Reduces Acute Ischemic Renal Podocyte Injury via Targeting Acetylcholinesterase Yue J, Si Y, Zhu T, Yang J, Xu X, Fang Y, Fu W Ref: J Surg Res, 244:302, 2019 : PubMed ESTHER: Yue_2019_J.Surg.Res_244_302 PubMedSearch: Yue 2019 J.Surg.Res 244 302 PubMedID: 31302329 Abstract BACKGROUND: Podocyte injury was reported to be involved in the major pathogenesis of ischemia/reperfusion (I/R)-induced ischemic acute renal failure. Our purpose was to study the mechanism of miR-187 improving I/R-induced podocytes injury. MATERIALS AND METHODS: The miR-187 mimics and inhibitor were transfected into the immortalized mouse podocyte (MPC-5) cells, and then transfected cells were subjected to hypoxia/reoxygenation (H/R, 3/3 h) to establish an H/R cell model. To investigate the effects of miR-187 on H/R-induced cell injury, cell viability and apoptosis were measured by Cell Counting Kit-8 (CCK-8) assay and flow cytometry. Dual-luciferase report system was used to verify whether miR-187 could directly target acetylcholinesterase (ACHE). The animal ischemia/reperfusion model was established and injected with miR-187 agomir. Kidney tissue sections were subjected to histological examination by hematoxylin and eosin staining to assess the renal injury. Real-time quantitative PCR and western blot were performed to determine gene expressions. RESULTS: The transfection of miR-187 mimics contributed to MPC-cells resistance to H/R-induced cell injury, which was reflected by enhanced cell viability and reduced apoptosis (from 20.05% to 9.43%) in H/R + negative control group. ACHE was confirmed as a target of miR-187, and ACHE siRNA had a similar efficiency to miR-187 mimic. The injection of miR-187 agomir not only effectively protected the kidney from I/R-induced injury, but also reduced the concentrations of serum creatinine. Moreover, nephrin was noticeably increased and desmin was decreased under the effects of agomir. CONCLUSIONS: Our findings indicated that miR-187 improved I/R-induced ischemic acute renal failure through protecting glomerular filtration barrier by blocking the expression of ACHE. Title: Bioaccumulation, behavior changes and physiological disruptions with gender-dependent in lizards (Eremias argus) after exposure to glufosinate-ammonium and l-glufosinate-ammonium Zhang L, Chen L, Meng Z, Zhang W, Xu X, Wang Z, Qin Y, Deng Y, Liu R and Diao J <1 more author(s)> Zhang L, Chen L, Meng Z, Zhang W, Xu X, Wang Z, Qin Y, Deng Y, Liu R, Zhou Z, Diao J (- 1) Ref: Chemosphere, 226:817, 2019 : PubMed ESTHER: Zhang_2019_Chemosphere_226_817 PubMedSearch: Zhang 2019 Chemosphere 226 817 PubMedID: 30965253 Abstract Reptiles, the most diverse taxon of terrestrial vertebrates, might be particularly vulnerable to soil pollution. Reptiles especially lizards have been rarely evaluated in ecotoxicological studies, and there is a very limited report for effects of soil pesticide contaminants on lizards. In this study, male and female lizards (Eremias argus) were exposed to Glufosinate-ammonium (GLA) and l- Glufosinate-ammonium (L-GLA) for 60 days. Slower sprint speed, higher frequency of turning back and reduced brain index were observed in treatment groups. The accumulation of GLA in the brain of lizard was higher than that of L-GLA. Moreover, the activities of neurotoxicity-related enzymes and biomarkers of oxidative stress were also investigated. In summary, the neurotoxic effects of lizards have been observed after exposure to GLA and L-GLA. Based on the result of the Integrated Biomarker Response (IBR), males were more sensitive to contaminants than females. On the other hand, the neurotoxic pathways by GLA and L-GLA triggered were slightly different: GLA mainly acted on glutamine synthetase (GS), acetylcholinesterase (AchE) and Catalase (CAT) and L-GLA aimed at AchE, Na(+)/K(+)-ATPase, Superoxide dismutase (SOD) and Malondialdehyde (MDA). In summary, the accumulation of GLA and L-GLA in lizard's brain induced neurotoxicity by altering the levels of enzymes related to nervous system and antioxidant activity and further resulted in the decrease of brain index and locomotor performance. Title: Dual effects of insect nAChR chaperone RIC-3 on hybrid receptor: Promoting assembly on endoplasmic reticulum but suppressing transport to plasma membrane on Xenopus oocytes Bao H, Xu X, Liu W, Yu N, Liu Z Ref: Neurochem Int, 115:24, 2018 : PubMed ESTHER: Bao_2018_Neurochem.Int_115_24 PubMedSearch: Bao 2018 Neurochem.Int 115 24 PubMedID: 29032010 Abstract Resistance to inhibitors of cholinesterase (RIC) -3 promotes the maturation (folding and assembly) of neuronal nicotinic acetylcholine receptors (nAChRs) as a molecular chaperone. The modulation effects of RIC-3 on homomeric alpha7 nAChRs are always positive, but its effects on heteromeric subtypes are inconsistent among reports. In this study, five RIC-3 isoforms were identified from Locusta migratoria. Four isoforms showed obvious effects on hybrid receptor Localpha1/rbeta2 expressed in Xenopus oocytes. As a representative, the co-expression of RIC-3v4 exhibited the decreased agonist responses (Imax) on oocytes, lower specific [(3)H]epibatidine binding (Bmax) on plasma membrane protein (PMP), and reduced subunit levels in PMP, which showed that the mature Localpha1/rbeta2 on the plasma membrane was decreased by the co-expression of RIC-3. In contrast, the [(3)H]epibatidine binding and mature Localpha1/rbeta2 levels in the endoplasmic reticulum membrane protein (ERMP) were much increased when co-expressing with RIC-3v4. The [(3)H]epibatidine binding and mature Localpha1/rbeta2 levels in total membrane protein (TMP) gave the similar results as that in ERMP. Taking data together, the results showed that the co-expression of RIC-3 increased the mature Localpha1/rbeta2 receptor levels on ER of Xenopus oocytes, but these mature receptors were mostly kept on ER and suppressed to transport to plasma membrane. Title: The molecular basis for lipase stereoselectivity Chen H, Meng X, Xu X, Liu W, Li S Ref: Applied Microbiology & Biotechnology, 102:3487, 2018 : PubMed ESTHER: Chen_2018_Appl.Microbiol.Biotechnol_102_3487 PubMedSearch: Chen 2018 Appl.Microbiol.Biotechnol 102 3487 PubMedID: 29500755 Abstract Lipases are among the most applied biocatalysts in organic synthesis to catalyze the kinetic resolution of a wide range of racemic substrates to yield optically pure compounds. Due to the rapidly increased demands for optically pure compounds, deep understanding of the molecular basis for lipase stereoselectivity and how to obtain lipases with excellent asymmetric selectivity have become one of primary research goals in this field. This review is focused on the molecular factors that have impacts on the stereoselectivity of lipases including the steric complementarity between the lipase topological structure and its substrate, the regional structural flexibility, the hydrogen bonds between the residues around the catalytic site and the tetrahedral intermediates, and the electrostatic interactions between surface residues. Moreover, the synergistic effects of these structural factors on the catalytic properties including stereoselectivity, activity, and stability are also discussed. Title: Screening and Characterization of Novel Polyesterases from Environmental Metagenomes with High Hydrolytic Activity against Synthetic Polyesters Hajighasemi M, Tchigvintsev A, Nocek B, Flick R, Popovic A, Hai T, Khusnutdinova AN, Brown G, Xu X and Yakunin AF <11 more author(s)> Hajighasemi M, Tchigvintsev A, Nocek B, Flick R, Popovic A, Hai T, Khusnutdinova AN, Brown G, Xu X, Cui H, Anstett J, Chernikova TN, Bruls T, Le Paslier D, Yakimov MM, Joachimiak A, Golyshina OV, Savchenko A, Golyshin PN, Edwards EA, Yakunin AF (- 11) Ref: Environ Sci Technol, 52:12388, 2018 : PubMed ESTHER: Hajighasemi_2018_Environ.Sci.Technol_52_12388 PubMedSearch: Hajighasemi 2018 Environ.Sci.Technol 52 12388 PubMedID: 30284819 Gene_locus related to this paper: 9zzzz-a0a0g3fj39, 9zzzz-a0a0g3fj48, 9zzzz-A0A0G3FEJ8, 9bact-a4uz10 Abstract The continuous growth of global plastics production, including polyesters, has resulted in increasing plastic pollution and subsequent negative environmental impacts. Therefore, enzyme-catalyzed depolymerization of synthetic polyesters as a plastics recycling approach has become a focus of research. In this study, we screened over 200 purified uncharacterized hydrolases from environmental metagenomes and sequenced microbial genomes and identified at least 10 proteins with high hydrolytic activity against synthetic polyesters. These include the metagenomic esterases MGS0156 and GEN0105, which hydrolyzed polylactic acid (PLA), polycaprolactone, as well as bis(benzoyloxyethyl)-terephthalate. With solid PLA as a substrate, both enzymes produced a mixture of lactic acid monomers, dimers, and higher oligomers as products. The crystal structure of MGS0156 was determined at 1.95 A resolution and revealed a modified alpha/beta hydrolase fold, with a lid domain and highly hydrophobic active site. Mutational studies of MGS0156 identified the residues critical for hydrolytic activity against both polyester and monoester substrates, with two-times higher polyesterase activity in the MGS0156 L169A mutant protein. Thus, our work identified novel, highly active polyesterases in environmental metagenomes and provided molecular insights into their activity, thereby augmenting our understanding of enzymatic polyester hydrolysis. Title: Determinants and prediction of esterase substrate promiscuity patterns Martinez-Martinez M, Coscolin C, Santiago G, Chow J, Stogios PJ, Bargiela R, Gertler C, Navarro-Fernandez J, Bollinger A and Ferrer M <32 more author(s)> Martinez-Martinez M, Coscolin C, Santiago G, Chow J, Stogios PJ, Bargiela R, Gertler C, Navarro-Fernandez J, Bollinger A, Thies S, Mendez-Garcia C, Popovic A, Brown G, Chernikova TN, Garcia-Moyano A, Bjergah GE, Perez-Garcia P, Hai T, Del Pozo MV, Stokke R, Steen IH, Cui H, Xu X, Nocek BP, Alcaide M, Distaso M, Mesa V, Pelaez AI, Sanchez J, Buchholz PCF, Pleiss J, Fernandez-Guerra A, Glockner FO, Golyshina OV, Yakimov MM, Savchenko A, Jaeger KE, Yakunin AF, Streit WR, Golyshin PN, Guallar V, Ferrer M (- 32) Ref: ACS Chemical Biology, 13:225, 2018 : PubMed ESTHER: Martinez-Martinez_2018_ACS.Chem.Biol_13_225 PubMedSearch: Martinez-Martinez 2018 ACS.Chem.Biol 13 225 PubMedID: 29182315 Gene_locus related to this paper: 9zzzz-a0a2k8jn75, 9zzzz-a0a2k8jt94, 9zzzz-a0a0g3fj44, 9zzzz-a0a0g3fh10, 9zzzz-a0a0g3fh03, 9bact-a0a1s5qkj8, 9zzzz-a0a0g3feh5, 9zzzz-a0a0g3fkz4, 9zzzz-a0a0g3fh07, 9zzzz-a0a0g3fh34, 9zzzz-a0a0g3fh31, 9bact-KY458167, alcbs-q0vqa3, 9bact-a0a1s5qki8, 9zzzz-a0a0g3feq8, 9zzzz-a0a0g3feh8, 9zzzz-a0a0g3fh19, 9bact-KY203037, 9bact-a0a1s5ql22, 9bact-a0a1s5qm34, 9bact-KY203034, 9bact-r9qzg0, 9bact-a0a1s5qly8, 9zzzz-a0a0g3fkz8, 9zzzz-a0a0g3feg9, 9zzzz-KY203033, 9zzzz-a0a0g3fes4, 9zzzz-a0a0g3fh42, 9bact-a0a1s5qlx2, 9zzzz-KY483651, 9bact-a0a1s5qmh4, 9zzzz-KY203032, 9zzzz-EH87, 9zzzz-a0a0g3fei1, 9zzzz-a0a0g3fet2, 9zzzz-KY483647, 9zzzz-EH82, 9zzzz-a0a0g3fe15, 9bact-KY203031, 9bact-t1w006, 9zzzz-a0a0g3fet6, 9bact-KY458164, geoth-g8myf3, 9bact-a0a1s5ql04, 9gamm-a0a1y0ihk7, 9bact-a0a1s5qly6, 9bact-a0a1s5qkg4, 9bact-a0a1s5qkm4, 9gamm-s5tv80, 9gamm-a0a0c4zhg2, 9zzzz-t1b379, 9gamm-KY483646, 9bact-KY458160, 9zzzz-a0a0g3fj57, 9gamm-s5t8349, 9arch-KY203036, 9bact-KY458168, 9zzzz-a0a0g3fes0, 9zzzz-t1be47, 9bact-KY458159, 9zzzz-a0a0g3fh39, 9bact-t1vzd5, 9prot-EH41, 9bact-Lip114, alcbs-q0vt77, 9bact-a0a1s5qke6, 9bact-a0a1s5qkf3, 9prot-SRP030024, 9gamm-s5t532, 9bact-a0a1s5qkl2, 9bact-a0a1s5qkk8, 9zzzz-KY203030, 9zzzz-t1d4I7, 9prot-KY019260, 9bact-a0a1s5qm38, 9arch-KY458161, 9prot-KY010302, 9zzzz-a0a0g3fl25, 9actn-KY010298, 9gamm-s5u059, 9bact-a0a1s5qmi7, 9bact-KY010297, 9bact-KY483642, 9bact-a0a1s5qkj1, 9bact-KY010299, 9bact-KY483648, alcbs-q0vtl7, 9bact-a0a1s5qf1, 9bact-a0a1s5qkg0, 9bact-a0a0h4tgu6, 9bact-MilE3, 9bact-LAE6, 9alte-MGS-MT1, 9bact-r9qzf7, 9gamm-k0c6t6, alcbs-q0vl36, alcbs-q0vlq1, alcbs-q0vq49, bacsu-pnbae, canar-LipB, canan-lipasA, geost-lipas, marav-a1u5n0, pseps-i7k8x5, staep-GEHD, symth-q67mr3, altma-s5cfn7, cycsp-k0c2b8, alcbs-q0vlk5, 9bact-k7qe48, 9bact-MGS-M1, 9bact-MGS-M2, 9bact-a0a0b5kns5, 9zzzz-a0a0g3fej4, 9zzzz-a0a0g3fj60, 9zzzz-a0a0g3fej0, 9zzzz-a0a0g3fj64, 9bact-a0a0b5kc16, 9zzzz-a0a0g3feg6, 9zzzz-a0a0g3feu6 Abstract Esterases receive special attention because their wide distribution in biological systems and environments and their importance for physiology and chemical synthesis. The prediction of esterases substrate promiscuity level from sequence data and the molecular reasons why certain such enzymes are more promiscuous than others, remain to be elucidated. This limits the surveillance of the sequence space for esterases potentially leading to new versatile biocatalysts and new insights into their role in cellular function. Here we performed an extensive analysis of the substrate spectra of 145 phylogenetically and environmentally diverse microbial esterases, when tested with 96 diverse esters. We determined the primary factors shaping their substrate range by analyzing substrate range patterns in combination with structural analysis and protein-ligand simulations. We found a structural parameter that helps ranking (classifying) promiscuity level of esterases from sequence data at 94% accuracy. This parameter, the active site effective volume, exemplifies the topology of the catalytic environment by measuring the active site cavity volume corrected by the relative solvent accessible surface area (SASA) of the catalytic triad. Sequences encoding esterases with active site effective volumes (cavity volume/SASA) above a threshold show greater substrate spectra, which can be further extended in combination with phylogenetic data. This measure provides also a valuable tool for interrogating substrates capable of being converted. This measure, found to be transferred to phosphatases of the haloalkanoic acid dehalogenase superfamily and possibly other enzymatic systems, represents a powerful tool for low-cost bioprospecting for esterases with broad substrate ranges, in large scale sequence datasets. Title: Novel piperidine-derived amide sEH inhibitors as mediators of lipid metabolism with improved stability Pecic S, Zeki AA, Xu X, Jin GY, Zhang S, Kodani S, Halim M, Morisseau C, Hammock BD, Deng SX Ref: Prostaglandins Other Lipid Mediat, 136:90, 2018 : PubMed ESTHER: Pecic_2018_Prostaglandins.Other.Lipid.Mediat_136_90 PubMedSearch: Pecic 2018 Prostaglandins.Other.Lipid.Mediat 136 90 PubMedID: 29567338 Abstract We have previously identified and reported several potent piperidine-derived amide inhibitors of the human soluble epoxide hydrolase (sEH) enzyme. The inhibition of this enzyme leads to elevated levels of epoxyeicosatrienoic acids (EETs), which are known to possess anti-inflammatory, vasodilatory, and anti-fibrotic effects. Herein, we report the synthesis of 9 analogs of the lead sEH inhibitor and the follow-up structure-activity relationship and liver microsome stability studies. Our findings show that isosteric modifications that lead to significant alterations in the steric and electronic properties at a specific position in the molecule can reduce the efficacy by up to 75-fold. On the other hand, substituting hydrogen with deuterium produces a notable increase ( approximately 30%) in the molecules' half-lives in both rat and human microsomes, while maintaining sEH inhibition potency. These data highlight the utility of isosteric replacement for improving bioavailability, and the newly-synthesized inhibitor structures may thus, serve as a starting point for preclinical development. Our docking study reveals that in the catalytic pocket of sEH, these analogs are in proximity of the key amino acids involved in hydrolysis of EETs. Title: Associations of the ABCA1 and LPL Gene Polymorphisms With Lipid Levels in a Hyperlipidemic Population Tao F, Weinstock J, Venners SA, Cheng J, Hsu YH, Zou Y, Pan F, Jiang S, Zha X, Xu X Ref: Clin Appl Thromb Hemost, 24:771, 2018 : PubMed ESTHER: Tao_2018_Clin.Appl.Thromb.Hemost_24_771 PubMedSearch: Tao 2018 Clin.Appl.Thromb.Hemost 24 771 PubMedID: 28891316 Abstract We conducted a cross-sectional study to investigate the effects of the adenosine triphosphate-binding cassette transporter 1 (ABCA1) I883M and lipoprotein lipase (LPL) HindIII polymorphisms on lipid levels in patients with hyperlipidemia. A total of 533 patients were enrolled. Serum lipid parameters were determined by an automatic biochemistry analyzer. Genotyping of the ABCA1 I883M and LPL HindIII was carried out using the polymerase chain reaction-restriction fragment length polymorphism technique. Multiple linear regression analysis was used to estimate the associations between serum lipid levels and the genetic polymorphisms. The frequency distribution of the ABCA1 I883M and LPL HindIII polymorphisms did not deviate from Hardy-Weinberg equilibrium. The major finding of our regression analysis showed that neither the ABCA1 I883M nor the LPL HindIII polymorphism was associated with baseline serum lipid levels in the total population. However, among patients with elevated alanine aminotransferase (ALT) levels (ALT >/= 40 U/L), carriers of the M allele of the ABCA1 gene had lower levels of high-density lipoprotein cholesterol (HDL-C) and higher levels of low-density lipoprotein cholesterol (LDL-C) after adjusting for age, sex, smoking status, alcohol consumption, education level, occupation, and work intensity ( P < .05 for both). A test on interaction terms between the ABCA1 I833M polymorphism and ALT on HDL-C and LDL-C levels also remained significant ( P = .001 and P = .014, respectively). Our data suggest that there are significant interactive effects between ABCA1 I883M and ALT levels on HDL-C and LDL-C levels. However, the LPL HindIII polymorphism did not influence lipid levels. Title: Responses of Antioxidant Defense and Immune Gene Expression in Early Life Stages of Large Yellow Croaker (Pseudosciaena crocea) Under Methyl Mercury Exposure Wu F, Huang W, Liu Q, Xu X, Zeng J, Cao L, Hu J, Gao Y, Jia S Ref: Front Physiol, 9:1436, 2018 : PubMed ESTHER: Wu_2018_Front.Physiol_9_1436 PubMedSearch: Wu 2018 Front.Physiol 9 1436 PubMedID: 30364149 Abstract Early life stages of marine organisms are the most sensitive stages to environment stressors including pollutants. In order to understand the toxicological effects induced by MeHg exposure on juveniles of large yellow croaker (Pseudosciaena crocea), a toxicity test was performed wherein fish were exposed to sub-lethal concentrations of MeHg under laboratory conditions (18 +/- 1 degrees C; 26 +/- 1 in salinity). After 30 days of 0-4.0 mug L(-1) MeHg exposure, SOD activity was significantly decreased in the 0.25, 1.0, and 4.0 mug L(-1) treatments; while CAT activity was significantly increased in the 4.0 mug L(-1) treatments; GSH level, GPx activity were significantly elevated in the 4.0 mug L(-1) treatments, respectively. Meanwhile, malondialdehyde content was also significantly increased in the 1.0 and 4.0 mug L(-1) treatments with respect to the control. Acetylcholinesterase activity was significantly decreased by 18.3, 25.2, and 21.7% in the 0.25, 1.0, and 4.0 mug L(-1) treatments, respectively. The expression of TCTP, GST3, Hsp70, Hsp27 mRNA were all up-regulated in juveniles with a dose-dependent manner exposed to MeHg. These results suggest that large yellow croaker juveniles have the potential to regulate the levels of antioxidant enzymes and initiate immune response in order to protect fish to some extent from oxidative stress induced by MeHg. Title: TRPA1 channel mediates organophosphate-induced delayed neuropathy Ding Q, Fang S, Chen X, Wang Y, Li J, Tian F, Xu X, Attali B, Xie X, Gao Z Ref: Cell Discov, 3:17024, 2017 : PubMed ESTHER: Ding_2017_Cell.Discov_3_17024 PubMedSearch: Ding 2017 Cell.Discov 3 17024 PubMedID: 28894590 Abstract The organophosphate-induced delayed neuropathy (OPIDN), often leads to paresthesias, ataxia and paralysis, occurs in the late-stage of acute poisoning or after repeated exposures to organophosphate (OP) insecticides or nerve agents, and may contribute to the Gulf War Syndrome. The acute phase of OP poisoning is often attributed to acetylcholinesterase inhibition. However, the underlying mechanism for the delayed neuropathy remains unknown and no treatment is available. Here we demonstrate that TRPA1 channel (Transient receptor potential cation channel, member A1) mediates OPIDN. A variety of OPs, exemplified by malathion, activates TRPA1 but not other neuronal TRP channels. Malathion increases the intracellular calcium levels and upregulates the excitability of mouse dorsal root ganglion neurons in vitro. Mice with repeated exposures to malathion also develop local tissue nerve injuries and pain-related behaviors, which resembles OPIDN. Both the neuropathological changes and the nocifensive behaviors can be attenuated by treatment of TRPA1 antagonist HC030031 or abolished by knockout of Trpa1 gene. In the classic hens OPIDN model, malathion causes nerve injuries and ataxia to a similar level as the positive inducer tri-ortho-cresyl phosphate (TOCP), which also activates TRPA1 channel. Treatment with HC030031 reduces the damages caused by malathion or tri-ortho-cresyl phosphate. Duloxetine and Ketotifen, two commercially available drugs exhibiting TRPA1 inhibitory activity, show neuroprotective effects against OPIDN and might be used in emergency situations. The current study suggests TRPA1 is the major mediator of OPIDN and targeting TRPA1 is an effective way for the treatment of OPIDN. Title: MicroRNA31-NDRG3 regulation axes are essential for hepatocellular carcinoma survival and drug resistance Du Z, Niu S, Xu X, Xu Q Ref: Cancer Biomark, 19:221, 2017 : PubMed ESTHER: Du_2017_Cancer.Biomark_19_221 PubMedSearch: Du 2017 Cancer.Biomark 19 221 PubMedID: 28269758 Abstract BACKGROUNDS: Hepatocellular carcinoma (HCC) is an epithelial cancer that originates from hepatocytes and it is the most common primary malignant tumor of the liver. Till now the prognosis of HCC patients is generally poor. The molecular mechanism giving rise to HCC development and recurrence is still largely unknown. MicroRNA-31 (miR-31) is among the most commonly altered microRNAs in human cancers, and alternations of miR-31 expression were reported to play pivotal roles in tumorigenesis and tumor progression. METHODS: In this work, the primary biological function of miR-31 in HCC tumorigenesis was investigated. RESULTS: Our data showed that overexpression of miR-31 induced markedly inhibition of HCC cell proliferation, migration in vitro and inhibited xenograft tumor growth in vivo. One target gene of miR-31, NDRG3, was also demonstrated indispensable for HCC cell survival. Furthermore, miR-31 and NDRG3 were both essential for HCC cell drug resistance in adriamycin. CONCLUSIONS: We conclude that miR-31 is a crucial regulator in hepatocellular carcinoma, miR-31 and its target gene NDRG3 may be potential therapeutic targets for HCC treatment in the future. Title: The asparagus genome sheds light on the origin and evolution of a young Y chromosome Harkess A, Zhou J, Xu C, Bowers JE, Van der Hulst R, Ayyampalayam S, Mercati F, Riccardi P, McKain MR and Chen G <31 more author(s)> Harkess A, Zhou J, Xu C, Bowers JE, Van der Hulst R, Ayyampalayam S, Mercati F, Riccardi P, McKain MR, Kakrana A, Tang H, Ray J, Groenendijk J, Arikit S, Mathioni SM, Nakano M, Shan H, Telgmann-Rauber A, Kanno A, Yue Z, Chen H, Li W, Chen Y, Xu X, Zhang Y, Luo S, Gao J, Mao Z, Pires JC, Luo M, Kudrna D, Wing RA, Meyers BC, Yi K, Kong H, Lavrijsen P, Sunseri F, Falavigna A, Ye Y, Leebens-Mack JH, Chen G (- 31) Ref: Nat Commun, 8:1279, 2017 : PubMed ESTHER: Harkess_2017_Nat.Commun_8_1279 PubMedSearch: Harkess 2017 Nat.Commun 8 1279 PubMedID: 29093472 Gene_locus related to this paper: aspof-a0a5p1ew48 Abstract Sex chromosomes evolved from autosomes many times across the eukaryote phylogeny. Several models have been proposed to explain this transition, some involving male and female sterility mutations linked in a region of suppressed recombination between X and Y (or Z/W, U/V) chromosomes. Comparative and experimental analysis of a reference genome assembly for a double haploid YY male garden asparagus (Asparagus officinalis L.) individual implicates separate but linked genes as responsible for sex determination. Dioecy has evolved recently within Asparagus and sex chromosomes are cytogenetically identical with the Y, harboring a megabase segment that is missing from the X. We show that deletion of this entire region results in a male-to-female conversion, whereas loss of a single suppressor of female development drives male-to-hermaphrodite conversion. A single copy anther-specific gene with a male sterile Arabidopsis knockout phenotype is also in the Y-specific region, supporting a two-gene model for sex chromosome evolution. Title: Characterization of the Fifth Putative Acetylcholinesterase in the Wolf Spider, Pardosa pseudoannulata Meng X, Xu X, Bao H, Wang J, Liu Z Ref: Molecules, 22:, 2017 : PubMed ESTHER: Meng_2017_Molecules_22_ PubMedSearch: Meng 2017 Molecules 22 PubMedID: 28696352 Gene_locus related to this paper: 9arac-KU501289 Abstract Background: Acetylcholinesterase (AChE) is an important neurotransmitter hydrolase in invertebrate and vertebrate nervous systems. The number of AChEs is various among invertebrate species, with different functions including the 'classical' role in terminating synaptic transmission and other 'non-classical' roles. Methods: Using rapid amplification of cDNA ends (RACE) technology, a new putative AChE-encoding gene was cloned from Pardosa pseudoannulata, an important predatory natural enemy. Sequence analysis and in vitro expression were employed to determine the structural features and biochemical properties of this putative AChE. Results: The cloned AChE contained the most conserved motifs of AChEs family and was clearly clustered with Arachnida AChEs. Determination of biochemical properties revealed that the recombinant enzyme had the obvious preference for the substrate ATC (acetylthiocholine iodide) versus BTC (butyrylthiocholine iodide). The AChE was highly sensitive to AChE-specific inhibitor BW284C51, but not butyrylcholinesterase-specific inhibitor tetraisopropyl pyrophosphoramide (ISO-OMPA). Based on these results, we concluded that a new AChE was identified from P. pseudoannulata and denoted as PpAChE5. Conclusion: Here we report the identification of a new AChE from P. pseudoannulata and increased the AChE number to five in this species. Although PpAChE5 had the biggest Vmax value among five identified AChEs, it showed relatively low affinity with ATC. Similar sensitivity to test insecticides indicated that this AChE might serve as the target for both organophosphorus and carbamate insecticides. Title: The pomegranate (Punica granatum L.) genome and the genomics of punicalagin biosynthesis Qin G, Xu C, Ming R, Tang H, Guyot R, Kramer EM, Hu Y, Yi X, Qi Y and Xu Y <6 more author(s)> Qin G, Xu C, Ming R, Tang H, Guyot R, Kramer EM, Hu Y, Yi X, Qi Y, Xu X, Gao Z, Pan H, Jian J, Tian Y, Yue Z, Xu Y (- 6) Ref: Plant J, 91:1108, 2017 : PubMed ESTHER: Qin_2017_Plant.J_91_1108 PubMedSearch: Qin 2017 Plant.J 91 1108 PubMedID: 28654223 Gene_locus related to this paper: prupe-a0a251r634, pungr-a0a218xv87, pungr-a0a218xi98, pungr-a0a218wma5, pungr-a0a218w0a8, pungr-a0a218w138, pungr-a0a218w7t6, pungr-a0a218weu3, pungr-a0a218xzu6 Abstract Pomegranate (Punica granatum L.) is a perennial fruit crop grown since ancient times that has been planted worldwide and is known for its functional metabolites, particularly punicalagins. We have sequenced and assembled the pomegranate genome with 328 Mb anchored into nine pseudo-chromosomes and annotated 29 229 gene models. A Myrtales lineage-specific whole-genome duplication event was detected that occurred in the common ancestor before the divergence of pomegranate and Eucalyptus. Repetitive sequences accounted for 46.1% of the assembled genome. We found that the integument development gene INNER NO OUTER (INO) was under positive selection and potentially contributed to the development of the fleshy outer layer of the seed coat, an edible part of pomegranate fruit. The genes encoding the enzymes for synthesis and degradation of lignin, hemicelluloses and cellulose were also differentially expressed between soft- and hard-seeded varieties, reflecting differences in their accumulation in cultivars differing in seed hardness. Candidate genes for punicalagin biosynthesis were identified and their expression patterns indicated that gallic acid synthesis in tissues could follow different biochemical pathways. The genome sequence of pomegranate provides a valuable resource for the dissection of many biological and biochemical traits and also provides important insights for the acceleration of breeding. Elucidation of the biochemical pathway(s) involved in punicalagin biosynthesis could assist breeding efforts to increase production of this bioactive compound. Title: Genome assembly with in vitro proximity ligation data and whole-genome triplication in lettuce Reyes-Chin-Wo S, Wang Z, Yang X, Kozik A, Arikit S, Song C, Xia L, Froenicke L, Lavelle DO and Michelmore RW <9 more author(s)> Reyes-Chin-Wo S, Wang Z, Yang X, Kozik A, Arikit S, Song C, Xia L, Froenicke L, Lavelle DO, Truco MJ, Xia R, Zhu S, Xu C, Xu H, Xu X, Cox K, Korf I, Meyers BC, Michelmore RW (- 9) Ref: Nat Commun, 8:14953, 2017 : PubMed ESTHER: Reyes-Chin-Wo_2017_Nat.Commun_8_14953 PubMedSearch: Reyes-Chin-Wo 2017 Nat.Commun 8 14953 PubMedID: 28401891 Gene_locus related to this paper: lacsa-a0a2j6jnd3, lacsa-a0a2j6l6y4, lacsa-a0a2j6mjs5, lacsa-a0a2j6mk82, lacsa-a0a2j6k5z4, lacsa-a0a2j6mk08, lacsa-a0a2j6mhc5, lacsa-a0a2j6m8d0, lacsa-a0a2j6mdb6, lacsa-a0a2j6mdh6, lacsa-a0a2j6jnf0, lacsa-a0a2j6mji4, lacsa-a0a2j6ke81, lacsa-a0a2j6jip3, lacsa-a0a2j6jir5, lacsa-a0a2j6ksa7, lacsa-a0a2j6l4a3 Abstract Lettuce (Lactuca sativa) is a major crop and a member of the large, highly successful Compositae family of flowering plants. Here we present a reference assembly for the species and family. This was generated using whole-genome shotgun Illumina reads plus in vitro proximity ligation data to create large superscaffolds; it was validated genetically and superscaffolds were oriented in genetic bins ordered along nine chromosomal pseudomolecules. We identify several genomic features that may have contributed to the success of the family, including genes encoding Cycloidea-like transcription factors, kinases, enzymes involved in rubber biosynthesis and disease resistance proteins that are expanded in the genome. We characterize 21 novel microRNAs, one of which may trigger phasiRNAs from numerous kinase transcripts. We provide evidence for a whole-genome triplication event specific but basal to the Compositae. We detect 26% of the genome in triplicated regions containing 30% of all genes that are enriched for regulatory sequences and depleted for genes involved in defence. Title: N-myc downstream regulated gene 1(NDRG1) promotes the stem-like properties of lung cancer cells through stabilized c-Myc Wang Y, Zhou Y, Tao F, Chai S, Xu X, Yang Y, Xu H, Wang K Ref: Cancer Letters, 401:53, 2017 : PubMed ESTHER: Wang_2017_Cancer.Lett_401_53 PubMedSearch: Wang 2017 Cancer.Lett 401 53 PubMedID: 28456659 Gene_locus related to this paper: human-NDRG1 Abstract Tumor-initiating cells (TICs) play an important role in tumorigenesis and development for many various tissue origin cancers including non-small cell lung cancer (NSCLC). However, the mechanism to maintain TICs in NSCLC is still largely unknown. Here, we evaluated differences of mRNA expression between parental and oncosphere cells that enriched TICs. We found that N-myc downstream regulated gene 1(NDRG1) was upregulated in oncosphere cells derived from human NSCLC cell lines and primary NSCLC cells. NDRG1 promoted stem-like properties of LTICs in NSCLC including iPSC (induced pluripotent stem cell) factors (OCT4, SOX2, KLF4, and C-MYC), the spheres-forming ability and the tumorigenicity of NSCLC. NDRG1 prevented the degradation of c-Myc through Skp2-mediated ubiquitination. NDRG1 directly interacted with Skp2, and decreased phosphorylation of Skp2 through inactivation of CDK2. Finally, we confirmed that NDRG1 was negatively correlated with survival and prognosis. Thus, our findings indicate that NDRG1 is a potential target for eradicating TICs in NSCLC. Title: Not all neuroligin 3 and 4X missense variants lead to significant functional inactivation Xu X, Hu Z, Zhang L, Liu H, Cheng Y, Xia K, Zhang X Ref: Brain Behav, 7:e00793, 2017 : PubMed ESTHER: Xu_2017_Brain.Behav_7_e00793 PubMedSearch: Xu 2017 Brain.Behav 7 e00793 PubMedID: 28948087 Gene_locus related to this paper: human-NLGN4X Abstract INTRODUCTION: Neuroligins are postsynaptic cell adhesion molecules that interact with neurexins to regulate the fine balance between excitation and inhibition of synapses. Recently, accumulating evidence, involving mutation analysis, cellular assays, and mouse models, has suggested that neuroligin (NLGN) mutations affect synapse maturation and function. Previously, four missense variations [p.G426S (NLGN3), p.G84R (NLGN4X), p.Q162K (NLGN4X), and p.A283T (NLGN4X)] in four different unrelated patients have been identified by PCR and direct sequencing. Title: Synergistic toxicity of zno nanoparticles and dimethoate in mice: Enhancing their biodistribution by synergistic binding of serum albumin and dimethoate to zno nanoparticles Yan X, Xu X, Guo M, Wang S, Gao S, Zhu S, Rong R Ref: Environ Toxicol, 32:1202, 2017 : PubMed ESTHER: Yan_2017_Environ.Toxicol_32_1202 PubMedSearch: Yan 2017 Environ.Toxicol 32 1202 PubMedID: 27441385 Abstract The extensive applications of ZnO nanoparticles (nano ZnO) and dimethoate (DM) have increased the risk of humans' co-exposure to nano ZnO and DM. Here, we report the synergistic effect of nano ZnO and DM on their biodistribution and subacute toxicity in mice. Nano ZnO and DM had a synergistic toxicity in mice. In contrast, bulk ZnO and DM did not cause an obvious synergistic toxicity in mice. Although nano ZnO was low toxic to mice, coexposure to nano ZnO and DM significantly enhanced DM-induced oxidative damage in the liver. Coadministration of nano ZnO with DM significantly increased Zn accumulation by 30.9 +/- 1.9% and DM accumulation by 45.6 +/- 2.2% in the liver, respectively. The increased accumulations of DM and Zn in the liver reduced its cholinesterase activity from 5.65 +/- 0.32 to 4.37 +/- 0.49 U/mg protein and induced hepatic oxidative stress. Nano ZnO had 3-fold or 2.4-fold higher binding capability for serum albumin or DM, respectively, than bulk ZnO. In addition, serum albumin significantly increased the binding capability of nano ZnO for DM by approximately four times via the interaction of serum albumin and DM. The uptake of serum albumin- and DM-bound nano ZnO by the macrophages significantly increased DM accumulation in mice. Serum albumins play an important role in the synergistic toxicity of nano ZnO and DM. (c) 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1202-1212, 2017. Title: Altered methylations of H19, Snrpn, Mest and Peg3 are reversible by developmental reprogramming in kidney tissue of ICSI-derived mice Zhan Q, Qi X, Wang N, Le F, Mao L, Yang X, Yuan M, Lou H, Xu X and Jin F <1 more author(s)> Zhan Q, Qi X, Wang N, Le F, Mao L, Yang X, Yuan M, Lou H, Xu X, Chen X, Jin F (- 1) Ref: Sci Rep, 7:11936, 2017 : PubMed ESTHER: Zhan_2017_Sci.Rep_7_11936 PubMedSearch: Zhan 2017 Sci.Rep 7 11936 PubMedID: 28931827 Abstract Although the prevalence of Intracytoplasmic sperm injection (ICSI) has increased year by year, there remains concern about the safety of these procedures because of reports of the increased risk for imprinting disorders. Previous research has demonstrated that gonadotropin stimulation contributes to an increased incidence of epimutations in ICSI-derived mice. However, the epimutations in ICSI offspring after removing the effect of gonadotropin stimulation and the possibility that epimutations are reversible by developmental reprogramming has not been investigated. Our study is the first to investigate the effect of ICSI itself on methylation and exclude the effect of superovulation using the kidney tissues from the adult and old mice. We found reduced methylation and up-regulated expression of the imprinted genes, H19, Mest and Peg3, in adult ICSI mice, but the above alterations observed in adult mice were not detected in old ICSI mice. At the Snrpn DMR, methylation status was not altered in adult ICSI-derived mice, but hypermethylation and correlated down-regulated expression of Snrpn were observed in old mice. In conclusion, ICSI manipulation and early embryo culture resulted in alterations of methylation in differentially methylated region of H19, Mest, Peg3 and Snrpn, and the alterations were reprogrammed by developmental reprogramming. Title: Depletion of juvenile hormone esterase extends larval growth in Bombyx mori Zhang Z, Liu X, Shiotsuki T, Wang Z, Xu X, Huang Y, Li M, Li K, Tan A Ref: Insect Biochemistry & Molecular Biology, 81:72, 2017 : PubMed ESTHER: Zhang_2017_Insect.Biochem.Mol.Biol_81_72 PubMedSearch: Zhang 2017 Insect.Biochem.Mol.Biol 81 72 PubMedID: 28057597 Abstract Two major hormones, juvenile hormone (JH) and 20-hydroxyecdysone (20E), regulate insect growth and development according to their precisely coordinated titres, which are controlled by both biosynthesis and degradation pathways. Juvenile hormone esterase (JHE) is the primary JH-specific degradation enzyme that plays a key role in regulating JH titers, along with JH epoxide hydrolase (JHEH) and JH diol kinase (JHDK). In the current study, a loss-of-function analysis of JHE in the silkworm, Bombyx mori, was performed by targeted gene disruption using the transgenic CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/RNA-guided Cas9 nucleases) system. Depletion of B. mori JHE (BmJHE) resulted in the extension of larval stages, especially the penultimate and ultimate larval stages, without deleterious effects to silkworm physiology. The expression of JHEH and JHDK was upregulated in mutant animals, indicating the existence of complementary routes in the JH metabolism pathway in which inactivation of one enzyme will activate other enzymes. RNA-Seq analysis of mutant animals revealed that genes involved in protein processing in the endoplasmic reticulum and in amino acid metabolism were affected by BmJHE depletion. Depletion of JHE and subsequent delayed JH metabolism activated genes in the TOR pathway, which are ultimately responsible for extending larval growth. The transgenic Cas9 system used in the current study provides a promising approach for analysing the actions of JH, especially in nondrosophilid insects. Furthermore, prolonging larval stages produced larger larvae and cocoons, which is greatly beneficial to silk production. Title: NDRG1 Controls Gastric Cancer Migration and Invasion through Regulating MMP-9 Chang X, Xu X, Xue X, Ma J, Li Z, Deng P, Chen J, Zhang S, Zhi Y, Dai D Ref: Pathol Oncol Res, 22:789, 2016 : PubMed ESTHER: Chang_2016_Pathol.Oncol.Res_22_789 PubMedSearch: Chang 2016 Pathol.Oncol.Res 22 789 PubMedID: 27154576 Abstract The purpose of this study is to detect the clinical significance of NDRG1 and its relationship with MMP-9 in gastric cancer metastatic progression. 101 cases of gastric cancer specimens were utilized to identify the protein expression of NDRG1 and MMP-9 by immunohistochemistry, their clinical significance was also analyzed. The suppression by siRNA-NDRG1 was employed to detect the role of NDRG1 in gastric cancer progression and its relationship with MMP-9. NDRG1 expression was correlated inversely with the degree of tumor cell differentiation (p < 0.01), invasion depth (p < 0.05), lymph node metastasis (p < 0.05) and TNM stage (p < 0.05), whereas MMP-9 was positive correlated with the degree of tumor cell differentiation (p < 0.01), lymph node metastasis (p < 0.05) and TNM stage (p < 0.05), but not correlated with invasion depth (p>0.05). Furthermore, cell proliferation and invasion effect were remarkably enhanced when NDRG1 was silencing, but MMP-9 expression was increased. NDRG1 silencing enhances gastric cancer cells progression through upregulating MMP-9. It suggests that NDRG1 may inhibit the metastasis of gastric cancer via regulating MMP-9. Title: Biochemical and Structural Insights into Enzymatic Depolymerization of Polylactic Acid and Other Polyesters by Microbial Carboxylesterases Hajighasemi M, Nocek BP, Tchigvintsev A, Brown G, Flick R, Xu X, Cui H, Hai T, Joachimiak A and Yakunin AF <3 more author(s)> Hajighasemi M, Nocek BP, Tchigvintsev A, Brown G, Flick R, Xu X, Cui H, Hai T, Joachimiak A, Golyshin PN, Savchenko A, Edwards EA, Yakunin AF (- 3) Ref: Biomacromolecules, 17:2027, 2016 : PubMed ESTHER: Hajighasemi_2016_Biomacromolecules_17_2027 PubMedSearch: Hajighasemi 2016 Biomacromolecules 17 2027 PubMedID: 27087107 Gene_locus related to this paper: marav-a1u5n0, rhopa-q6n9m9, alcbs-q0vlq1 Abstract Polylactic acid (PLA) is a biodegradable polyester derived from renewable resources, which is a leading candidate for the replacement of traditional petroleum-based polymers. Since the global production of PLA is quickly growing, there is an urgent need for the development of efficient recycling technologies, which will produce lactic acid instead of CO2 as the final product. After screening 90 purified microbial alpha/beta-hydrolases, we identified hydrolytic activity against emulsified PLA in two uncharacterized proteins, ABO2449 from Alcanivorax borkumensis and RPA1511 from Rhodopseudomonas palustris. Both enzymes were also active against emulsified polycaprolactone and other polyesters as well as against soluble alpha-naphthyl and p-nitrophenyl monoesters. In addition, both ABO2449 and RPA1511 catalyzed complete or extensive hydrolysis of solid PLA with the production of lactic acid monomers, dimers, and larger oligomers as products. The crystal structure of RPA1511 was determined at 2.2 A resolution and revealed a classical alpha/beta-hydrolase fold with a wide-open active site containing a molecule of polyethylene glycol bound near the catalytic triad Ser114-His270-Asp242. Site-directed mutagenesis of both proteins demonstrated that the catalytic triad residues are important for the hydrolysis of both monoester and polyester substrates. We also identified several residues in RPA1511 (Gln172, Leu212, Met215, Trp218, and Leu220) and ABO2449 (Phe38 and Leu152), which were not essential for activity against soluble monoesters but were found to be critical for the hydrolysis of PLA. Our results indicate that microbial carboxyl esterases can efficiently hydrolyze various polyesters making them attractive biocatalysts for plastics depolymerization and recycling. Title: 4H-Thieno[3,2-c]chromene based inhibitors of Notum Pectinacetylesterase Han Q, Pabba PK, Barbosa J, Mabon R, Healy JP, Gardyan MW, Terranova KM, Brommage R, Thompson AY and Carson KG <4 more author(s)> Han Q, Pabba PK, Barbosa J, Mabon R, Healy JP, Gardyan MW, Terranova KM, Brommage R, Thompson AY, Schmidt JM, Wilson AG, Xu X, Tarver JE, Jr., Carson KG (- 4) Ref: Bioorganic & Medicinal Chemistry Lett, 26:1184, 2016 : PubMed ESTHER: Han_2016_Bioorg.Med.Chem.Lett_26_1184 PubMedSearch: Han 2016 Bioorg.Med.Chem.Lett 26 1184 PubMedID: 26821819 Inhibitor(s) related to this paper: LP-935001 Abstract A group of small molecule thienochromenes inhibitors of Notum Pectinacetylesterase are described. We developed SAR on three series based on carbon, oxygen and sulfur replacement of the 5-position. In each series, highly potent Notum Pectinacetylesterase inhibitors were identified. Title: Preparation of Diacylglycerol-enriched Rice Bran Oil by Lipase-catalyzed Deacidification in Packed-bed Reactors by Continuous Dehydration Lu Y, Zou X, Han W, Jiang Y, Jin Q, Li L, Xu X, Wang X Ref: J Oleo Sci, 65:151, 2016 : PubMed ESTHER: Lu_2016_J.Oleo.Sci_65_151 PubMedSearch: Lu 2016 J.Oleo.Sci 65 151 PubMedID: 26833284 Abstract Diacylglycerol-enriched rice bran oil (RBO-DAG) was produced by deacidification of high-acid rice bran oil (RBO) with glycerol (Gly) using Lipozyme RM IM by continuous dehydration by combination of two enzyme columns (column 1 and 3, used for deacidification) with one molecular sieves column (column 2, used for dehydration). The conditions for three columns were respectively optimized. Response surface methodology (RSM) was used to optimize the conditions of column 1. The content of DAG and conversion of free fatty acid (FFA) were used as indicators and the effects of the enzyme load (8-12 g), flow rate (0.3-0.6 mL/min), substrate molar ratio (4-6) and reaction temperature (55-75 degC) were investigated. The content of DAG and conversion of FFA were significantly correlated to the flow rate and substrate molar ratio. Most desirable conditions of the reaction with respect to the maximal DAG content and FFA conversion was attained under the residence time of 40 min, substrate molar ratio of 5.52 (Gly: RBO) and temperature of 66 degC. The conditions for column 2 were investigated by varying molecular sieves load and flow rate, and the maximal dehydration rate of 85.22% was obtained under the optimal conditions. For column 3, the optimum conditions were obtained as: flow rate, 0.2mL/min; temperature, 65 degC, and the content of DAG and FFA were 38.99% and 3.04%, respectively under these conditions. The catalytic activity of the lipase was stable in twelve continuous operations with 83.22% of its original ability, demonstrating its potential in the continuous packed-bed reactors (PBRs) system. These results showed that packed-bed reactors combined with continuous deacidification and dehydration in one system had great value in industrial production for high-acid RBO with the improved conversion rate. Title: Subcellular Compartmentalization and Trafficking of the Biosynthetic Machinery for Fungal Melanin Upadhyay S, Xu X, Lowry D, Jackson JC, Roberson RW, Lin X Ref: Cell Rep, 14:2511, 2016 : PubMed ESTHER: Upadhyay_2016_Cell.Rep_14_2511 PubMedSearch: Upadhyay 2016 Cell.Rep 14 2511 PubMedID: 26972005 Gene_locus related to this paper: aspfu-AYG1 Abstract Protection by melanin depends on its subcellular location. Although most filamentous fungi synthesize melanin via a polyketide synthase pathway, where and how melanin biosynthesis occurs and how it is deposited as extracellular granules remain elusive. Using a forward genetic screen in the pathogen Aspergillus fumigatus, we find that mutations in an endosomal sorting nexin abolish melanin cell-wall deposition. We find that all enzymes involved in the early steps of melanin biosynthesis are recruited to endosomes through a non-conventional secretory pathway. In contrast, late melanin enzymes accumulate in the cell wall. Such subcellular compartmentalization of the melanin biosynthetic machinery occurs in both A. fumigatus and A. nidulans. Thus, fungal melanin biosynthesis appears to be initiated in endosomes with exocytosis leading to melanin extracellular deposition, much like the synthesis and trafficking of mammalian melanin in endosomally derived melanosomes. Title: The Role of Cytochrome P450 Epoxygenases, Soluble Epoxide Hydrolase, and Epoxyeicosatrienoic Acids in Metabolic Diseases Xu X, Li R, Chen G, Hoopes SL, Zeldin DC, Wang DW Ref: Adv Nutr, 7:1122, 2016 : PubMed ESTHER: Xu_2016_Adv.Nutr_7_1122 PubMedSearch: Xu 2016 Adv.Nutr 7 1122 PubMedID: 28140329 Abstract Metabolic diseases are associated with an increased risk of developing cardiovascular disease. The features comprising metabolic diseases include obesity, insulin resistance, hyperglycemia, hyperlipidemia, and hypertension. Recent evidence has emerged showcasing a role for cytochrome P450 epoxygenases, soluble epoxide hydrolase, and epoxyeicosatrienoic acids (EETs) in the development and progression of metabolic diseases. This review discusses the current knowledge related to the modulation of cytochrome P450 epoxygenases and soluble epoxide hydrolase to alter concentrations of biologically active EETs, resulting in effects on insulin resistance, lipid metabolism, obesity, and diabetes. Future areas of research to address current deficiencies in the understanding of these enzymes and their eicosanoid metabolites in various aspects of metabolic diseases are also discussed. Title: Delayed diagnosis of congenital myasthenia due to associated mitochondrial enzyme defect Guo Y, Menezes MJ, Menezes MP, Liang J, Li D, Riley LG, Clarke NF, Andrews PI, Tian L and Xu X <9 more author(s)> Guo Y, Menezes MJ, Menezes MP, Liang J, Li D, Riley LG, Clarke NF, Andrews PI, Tian L, Webster R, Wang F, Liu X, Shen Y, Thorburn DR, Keating BJ, Engel A, Hakonarson H, Christodoulou J, Xu X (- 9) Ref: Neuromuscular Disorders, 25:257, 2015 : PubMed ESTHER: Guo_2015_Neuromuscul.Disord_25_257 PubMedSearch: Guo 2015 Neuromuscul.Disord 25 257 PubMedID: 25557462 Abstract Clinical phenotypes of congenital myasthenic syndromes and primary mitochondrial disorders share significant overlap in their clinical presentations, leading to challenges in making the correct diagnosis. Next generation sequencing is transforming molecular diagnosis of inherited neuromuscular disorders by identifying novel disease genes and by identifying previously known genes in undiagnosed patients. This is evident in two patients who were initially suspected to have a mitochondrial myopathy, but in whom a clear diagnosis of congenital myasthenic syndromes was made through whole exome sequencing. In patient 1, whole exome sequencing revealed compound heterozygous mutations c.1228C > T (p.Arg410Trp) and c.679C > T (p.Arg227*) in collagen-like tail subunit (single strand of homotrimer) of asymmetric acetylcholinesterase (COLQ). In patient 2, in whom a deletion of exon 52 in Dystrophin gene was previously detected by multiplex ligation-dependent probe amplification, Sanger sequencing revealed an additional homozygous mutation c.1511_1513delCTT (p.Pro504Argfs*183) in docking protein7 (DOK7). These case reports highlight the need for careful diagnosis of clinically heterogeneous syndromes like congenital myasthenic syndromes, which are treatable, and for which delayed diagnosis is likely to have implications for patient health. The report also demonstrates that whole exome sequencing is an effective diagnostic tool in providing molecular diagnosis in patients with complex phenotypes. Title: Complete Genome Sequence of Paenibacillus polymyxa CF05, a Strain of Plant Growth-Promoting Rhizobacterium with Elicitation of Induced Systemic Resistance Lei M, Lu P, Jin L, Wang Y, Qin J, Xu X, Zhang L Ref: Genome Announc, 3:, 2015 : PubMed ESTHER: Lei_2015_Genome.Announc_3_e00198 PubMedSearch: Lei 2015 Genome.Announc 3 e00198 PubMedID: 25883277 Gene_locus related to this paper: paepo-a0a0f6ex20, paepo-a0a0f6em71, paepo-a0a0f6ezz0 Abstract Paenibacillus polymyxa CF05 is a Gram-positive rod-shaped bacterium isolated from the interior of an ancient tree, Cryptomeria fortunei, in China. This bacterium displays potent biocontrol effects against certain soil-borne diseases and the elicitation of induced systemic resistance in tomatoes. Here, we report the complete genome sequence of P. polymyxa CF05. Title: Genome sequence of cultivated Upland cotton (Gossypium hirsutum TM-1) provides insights into genome evolution Li F, Fan G, Lu C, Xiao G, Zou C, Kohel RJ, Ma Z, Shang H, Ma X and Yu S <30 more author(s)> Li F, Fan G, Lu C, Xiao G, Zou C, Kohel RJ, Ma Z, Shang H, Ma X, Wu J, Liang X, Huang G, Percy RG, Liu K, Yang W, Chen W, Du X, Shi C, Yuan Y, Ye W, Liu X, Zhang X, Liu W, Wei H, Wei S, Zhu S, Zhang H, Sun F, Wang X, Liang J, Wang J, He Q, Huang L, Cui J, Song G, Wang K, Xu X, Yu JZ, Zhu Y, Yu S (- 30) Ref: Nat Biotechnol, 33:524, 2015 : PubMed ESTHER: Li_2015_Nat.Biotechnol_33_524 PubMedSearch: Li 2015 Nat.Biotechnol 33 524 PubMedID: 25893780 Gene_locus related to this paper: gosra-a0a0d2rxs2, gosra-a0a0d2tng2, gosra-a0a0d2twz7, goshi-a0a1u8hr03, gosra-a0a0d2vdc5, goshi-a0a1u8ljh5, gosra-a0a0d2vj24, goshi-a0a1u8pxd3, gosra-a0a0d2sr31, goshi-a0a1u8knd1, goshi-a0a1u8nhw9, goshi-a0a1u8mt09, goshi-a0a1u8kis4, goshi-a0a1u8ibk3, goshi-a0a1u8ieg2, goshi-a0a1u8iki6, goshi-a0a1u8jvp4, goshi-a0a1u8jw35, gosra-a0a0d2pzd7 Abstract Gossypium hirsutum has proven difficult to sequence owing to its complex allotetraploid (AtDt) genome. Here we produce a draft genome using 181-fold paired-end sequences assisted by fivefold BAC-to-BAC sequences and a high-resolution genetic map. In our assembly 88.5% of the 2,173-Mb scaffolds, which cover 89.6% approximately 96.7% of the AtDt genome, are anchored and oriented to 26 pseudochromosomes. Comparison of this G. hirsutum AtDt genome with the already sequenced diploid Gossypium arboreum (AA) and Gossypium raimondii (DD) genomes revealed conserved gene order. Repeated sequences account for 67.2% of the AtDt genome, and transposable elements (TEs) originating from Dt seem more active than from At. Reduction in the AtDt genome size occurred after allopolyploidization. The A or At genome may have undergone positive selection for fiber traits. Concerted evolution of different regulatory mechanisms for Cellulose synthase (CesA) and 1-Aminocyclopropane-1-carboxylic acid oxidase1 and 3 (ACO1,3) may be important for enhanced fiber production in G. hirsutum. Title: Schisandrin C Ameliorates Learning and Memory Deficits by Abeta(1-42) -induced Oxidative Stress and Neurotoxicity in Mice Mao X, Liao Z, Guo L, Xu X, Wu B, Xu M, Zhao X, Bi K, Jia Y Ref: Phytother Res, 29:1373, 2015 : PubMed ESTHER: Mao_2015_Phytother.Res_29_1373 PubMedSearch: Mao 2015 Phytother.Res 29 1373 PubMedID: 26074330 Abstract Schisandrin C (SCH-C) is a main and typical antioxidative lignan isolated from the fruits of Schisandra chinensis (Trucz.) Baill (a widely used traditional Chinese medicine). The present study aimed to characterize the effect of SCH-C on memory impairment and further research on pathological changes in Abeta(1-42) -induced Alzheimer's disease mice. Mice were administration with SCH-C daily for 5 days in the lateral cerebral ventricles using sterotaxically implanted cannula. Cognitive functions were assessed by Y-maze test, active avoidance test and Morris water maze test in all groups, and the level of Abeta(1-42) and neuronal injury induced by Abeta(1-42) were reversed remarkably following SCH-C treatment compared with sham group; meanwhile the impairment of short-term or working memory was dramatically improved. In addition, SCH-C significantly inhibited total cholinesterase (ChEtotal), and increased superoxide dismutase (SOD) and glutathione peroxidase (GSH-px) activity glutathione (GSH) levels in the hippocampus and cerebral cortex. It can be speculated that SCH-C offers protection against Abeta(1-42) -induced dysfunction in learning and memory by inhibiting ChEtotal and its antioxidant action. Copyright 2015 John Wiley & Sons, Ltd. Title: Role of Neurexin-1beta and Neuroligin-1 in Cognitive Dysfunction After Subarachnoid Hemorrhage in Rats Shen H, Chen Z, Wang Y, Gao A, Li H, Cui Y, Zhang L, Xu X, Wang Z, Chen G Ref: Stroke, 46:2607, 2015 : PubMed ESTHER: Shen_2015_Stroke_46_2607 PubMedSearch: Shen 2015 Stroke 46 2607 PubMedID: 26219651 Abstract BACKGROUND AND PURPOSE: Neurexin-1beta and neuroligin-1 play an important role in the formation, maintenance, and regulation of synaptic structures. This study is to estimate the potential role of neurexin-1beta and neuroligin-1 in subarachnoid hemorrhage (SAH)-induced cognitive dysfunction. Title: Effects of ZnO Nanoparticles on Dimethoate-Induced Toxicity in Mice Yan X, Rong R, Zhu S, Guo M, Gao S, Wang S, Xu X Ref: Journal of Agricultural and Food Chemistry, 63:8292, 2015 : PubMed ESTHER: Yan_2015_J.Agric.Food.Chem_63_8292 PubMedSearch: Yan 2015 J.Agric.Food.Chem 63 8292 PubMedID: 26335275 Abstract The extensive applications of ZnO nanoparticles (nano ZnO) and dimethoate have increased the risk of people's coexposure to nano ZnO and dimethoate. Therefore, we evaluated in this study the effects of nano or bulk ZnO on dimethoate-induced toxicity in mice. The serum biochemical parameters, biodistributions, oxidative stress responses, and histopathological changes in mice were measured after intragastric administration of nano or bulk ZnO and/or dimethoate for 14 days. Oral administration of nano or bulk ZnO at a dose of 50 mg/kg did not cause obvious injury in mice. In contrast, oral administration of dimethoate at a dose of 15 mg/kg induced observable oxidative damage in mice. Co-administration of nano or bulk ZnO with dimethoate significantly increased Zn accumulation by 30.7 +/- 1.7% or 29.7 +/- 2.4% and dimethoate accumulation by 42.8 +/- 2.1% or 46.6 +/- 2.9% in the liver, respectively. The increased accumulations of dimethoate and Zn in the liver reduced its cholinesterase activity from 5.64 +/- 0.45 U/mg protein to 4.67 +/- 0.42 U/mg protein or 4.76 +/- 0.45 U/mg protein for nano or bulk ZnO, respectively. Furthermore, the accumulations of dimethoate and Zn in liver also increased hepatic oxidative stress, resulting in severe liver damage. Both nano and bulk ZnO dissolved quickly in acidic gastric fluid, regardless of particle size; therefore, they had nearly identical enhanced effects on dimethoate-induced toxicity in mice. Title: NDRG1 expression is related to the progression and prognosis of gastric cancer patients through modulating proliferation, invasion and cell cycle of gastric cancer cells Chang X, Xu X, Ma J, Xue X, Li Z, Deng P, Zhang S, Zhi Y, Chen J, Dai D Ref: Mol Biol Rep, 41:6215, 2014 : PubMed ESTHER: Chang_2014_Mol.Biol.Rep_41_6215 PubMedSearch: Chang 2014 Mol.Biol.Rep 41 6215 PubMedID: 24985974 Abstract N-myc downstream-regulated gene 1 (NDRG1) has been proposed as a tumor suppressor gene in many different types of tumors, but its potential function and corresponding mechanism are not yet fully elucidated. This study aims to detect the possible function of NDRG1 in gastric cancer progression. In this study, 112 paired gastric cancer tissues and corresponding nonmalignant gastric tissues were utilized to identify the differential protein expression of NDRG1 by immunohistochemistry and its clinical significance was analyzed. Furthermore, 49 of 112 paired gastric specimens were used to detect the differential mRNA expression by real-time PCR. The over expression of NDRG1 in human gastric cancer cell line AGS by PcDNA3.1-NDRG1 transfection was utilized to detect the role of NDRG1 in regulating the biological behavior of gastric cancer. NDRG1 expression was significantly decreased in primary gastric cancer tissues, compared with its corresponding nonmalignant gastric tissues (p < 0.05), and its decreased expression was significantly associated with lymph node metastasis (p < 0.01), invasion depth (p < 0.01) and differentiation (p < 0.05). Additionally, the overall survival rate of gastric cancer patients with high expression of NDRG1 was higher than those with low expression during the follow-up period. NDRG1 overexpression suppressed cells proliferation, invasion and induced a G1 cell cycle arrest in gastric cancer. Furthermore, the down-regulation of NDRG1 in gastric cancer metastatic progression was correlated to E-cadherin and MMP-9. Our results verify that NDRG1 acts as a tumor suppressor gene and may play an important role in the metastasis progression and prognosis of gastric cancer. Title: Territrem and Butyrolactone Derivatives from a Marine-Derived Fungus Aspergillus Terreus Nong X, Wang Y, Zhang X, Zhou M, Xu X, Qi S Ref: Mar Drugs, 12:6113, 2014 : PubMed ESTHER: Nong_2014_Mar.Drugs_12_6113 PubMedSearch: Nong 2014 Mar.Drugs 12 6113 PubMedID: 25522319 Abstract Seventeen lactones including eight territrem derivatives (1-8) and nine butyrolactone derivatives (9-17) were isolated from a marine-derived fungus Aspergillus terreus SCSGAF0162 under solid-state fermentation of rice. Compounds 1-3 and 9-10 were new, and their structures were elucidated by spectroscopic analysis. The acetylcholinesterase inhibitory activity and antiviral activity of compounds 1-17 were evaluated. Among them, compounds 1 and 2 showed strong inhibitory activity against acetylcholinesterase with IC50 values of 4.2 +/- 0.6, 4.5 +/- 0.6 nM, respectively. This is the first time it has been reported that 3, 6, 10, 12 had evident antiviral activity towards HSV-1 with IC50 values of 16.4 +/- 0.6, 6.34 +/- 0.4, 21.8 +/- 0.8 and 28.9 +/- 0.8 mug.mL-1, respectively. Antifouling bioassay tests showed that compounds 1, 11, 12, 15 had potent antifouling activity with EC50 values of 12.9 +/- 0.5, 22.1 +/- 0.8, 7.4 +/- 0.6, 16.1 +/- 0.6 mug.mL-1 toward barnacle Balanus amphitrite larvae, respectively. Title: Identification of a novel salt tolerance gene in wild soybean by whole-genome sequencing Qi X, Li MW, Xie M, Liu X, Ni M, Shao G, Song C, Kay-Yuen Yim A, Tao Y and Lam HM <19 more author(s)> Qi X, Li MW, Xie M, Liu X, Ni M, Shao G, Song C, Kay-Yuen Yim A, Tao Y, Wong FL, Isobe S, Wong CF, Wong KS, Xu C, Li C, Wang Y, Guan R, Sun F, Fan G, Xiao Z, Zhou F, Phang TH, Tong SW, Chan TF, Yiu SM, Tabata S, Wang J, Xu X, Lam HM (- 19) Ref: Nat Commun, 5:4340, 2014 : PubMed ESTHER: Qi_2014_Nat.Commun_5_4340 PubMedSearch: Qi 2014 Nat.Commun 5 4340 PubMedID: 25004933 Gene_locus related to this paper: soybn-i1k636, soybn-i1j4c6, glyso-a0a0b2sjw6, soybn-a0a0r0i9y7, soybn-a0a0r0j241, soybn-i1kfz9, glyso-a0a0b2rre9, soybn-i1jx17 Abstract Using a whole-genome-sequencing approach to explore germplasm resources can serve as an important strategy for crop improvement, especially in investigating wild accessions that may contain useful genetic resources that have been lost during the domestication process. Here we sequence and assemble a draft genome of wild soybean and construct a recombinant inbred population for genotyping-by-sequencing and phenotypic analyses to identify multiple QTLs relevant to traits of interest in agriculture. We use a combination of de novo sequencing data from this work and our previous germplasm re-sequencing data to identify a novel ion transporter gene, GmCHX1, and relate its sequence alterations to salt tolerance. Rapid gain-of-function tests show the protective effects of GmCHX1 towards salt stress. This combination of whole-genome de novo sequencing, high-density-marker QTL mapping by re-sequencing and functional analyses can serve as an effective strategy to unveil novel genomic information in wild soybean to facilitate crop improvement. Title: Health hazard assessment of occupationally di-(2-ethylhexyl)-phthalate-exposed workers in China Wang W, Xu X, Fan CQ Ref: Chemosphere, 120C:37, 2014 : PubMed ESTHER: Wang_2014_Chemosphere_120C_37 PubMedSearch: Wang 2014 Chemosphere 120C 37 PubMedID: 24974312 Abstract Di-(2-ethylhexyl)-phthalate (DEHP) is a potential hazard to human health. The effects of occupational high level DEHP exposure on human health were evaluated by measuring the plasma cholinesterase, residues, renal and hepatic biochemical markers. The study was conducted in three representative polyvinyl chloride manufacturing facilities from large size (S1), medium side (S2) to small size (S3). Total 456 adult males including 352 exposed workers (occupational) and 104 control workers (background) were selected. The average DEHP concentrations in respirable particulate matter were 233, 291, and 707mugm-3 for S1-S3, respectively, compared with 0.26mugm-3 in the background atmosphere (labeled by S4). The results showed significant decreases in post exposure plasma cholinesterase (PChE) levels (<30%) from the exposed workers as compared to baseline. These exposed workers had been evaluated for plasma DEHP residues. Regression analyses explored that PChE decreased significantly with increasing plasma DEHP residues. Serum aspartate aminotransferase, alanine aminotransferase, creatinine, urea, gamma glutamyltransferase, malondialdehyde, total antioxidant and C-reactive protein were significantly raised as compared to the controls. Of the 352 exposed workers, 116 (33.0%) had a daily DEHP intake 22.7mugkgbw-1d-1 , which is more than 20mugkgbw-1d-1 specified by the US Environmental Protection Agency. The study demonstrated that occupational phthalate exposure produces health hazards. Title: Genome sequencing of the high oil crop sesame provides insight into oil biosynthesis Wang L, Yu S, Tong C, Zhao Y, Liu Y, Song C, Zhang Y, Zhang X, Wang Y and Varshney RK <12 more author(s)> Wang L, Yu S, Tong C, Zhao Y, Liu Y, Song C, Zhang Y, Zhang X, Wang Y, Hua W, Li D, Li F, Yu J, Xu C, Han X, Huang S, Tai S, Wang J, Xu X, Li Y, Liu S, Varshney RK (- 12) Ref: Genome Biol, 15:R39, 2014 : PubMed ESTHER: Wang_2014_Genome.Biol_15_R39 PubMedSearch: Wang 2014 Genome.Biol 15 R39 PubMedID: 24576357 Gene_locus related to this paper: sesin-a0a6i9snr9 Abstract BACKGROUND: Sesame, Sesamum indicum L., is considered the queen of oilseeds for its high oil content and quality, and is grown widely in tropical and subtropical areas as an important source of oil and protein. However, the molecular biology of sesame is largely unexplored. RESULTS: Here, we report a high-quality genome sequence of sesame assembled de novo with a contig N50 of 52.2 kb and a scaffold N50 of 2.1 Mb, containing an estimated 27,148 genes. The results reveal novel, independent whole genome duplication and the absence of the Toll/interleukin-1 receptor domain in resistance genes. Candidate genes and oil biosynthetic pathways contributing to high oil content were discovered by comparative genomic and transcriptomic analyses. These revealed the expansion of type 1 lipid transfer genes by tandem duplication, the contraction of lipid degradation genes, and the differential expression of essential genes in the triacylglycerol biosynthesis pathway, particularly in the early stage of seed development. Resequencing data in 29 sesame accessions from 12 countries suggested that the high genetic diversity of lipid-related genes might be associated with the wide variation in oil content. Additionally, the results shed light on the pivotal stage of seed development, oil accumulation and potential key genes for sesamin production, an important pharmacological constituent of sesame. CONCLUSIONS: As an important species from the order Lamiales and a high oil crop, the sesame genome will facilitate future research on the evolution of eudicots, as well as the study of lipid biosynthesis and potential genetic improvement of sesame. Title: Variations analysis of NLGN3 and NLGN4X gene in Chinese autism patients Xu X, Xiong Z, Zhang L, Liu Y, Lu L, Peng Y, Guo H, Zhao J, Xia K, Hu Z Ref: Mol Biol Rep, 41:4133, 2014 : PubMed ESTHER: Xu_2014_Mol.Biol.Rep_41_4133 PubMedSearch: Xu 2014 Mol.Biol.Rep 41 4133 PubMedID: 24570023 Abstract Autism is a neurodevelopmental disorder clinically characterized by impairment of social interaction, deficits in verbal communication, as well as stereotypic and repetitive behaviors. Several studies have implicated that abnormal synaptogenesis was involved in the incidence of autism. Neuroligins are postsynaptic cell adhesion molecules and interacted with neurexins to regulate the fine balance between excitation and inhibition of synapses. Recently, mutation analysis, cellular and mice models hinted neuroligin mutations probably affected synapse maturation and function. In this study, four missense variations [p.G426S (NLGN3), p.G84R (NLGN4X), p.Q162 K (NLGN4X) and p.A283T (NLGN4X)] in four different unrelated patients have been identified by PCR and direct sequencing. These four missense variations were absent in the 453 controls and have not been reported in 1000 Genomes Project. Bioinformatic analysis of the four missense variations revealed that p.G84R and p.A283T were "Probably Damaging". The variations may cause abnormal synaptic homeostasis and therefore trigger the patients more predisposed to autism. By case-control analysis, we identified the common SNPs (rs3747333 and rs3747334) in the NLGN4X gene significantly associated with risk for autism [p = 5.09E-005; OR 4.685 (95% CI 2.073-10.592)]. Our data provided a further evidence for the involvement of NLGN3 and NLGN4X gene in the pathogenesis of autism in Chinese population. Title: Mudskipper genomes provide insights into the terrestrial adaptation of amphibious fishes You X, Bian C, Zan Q, Xu X, Liu X, Chen J, Wang J, Qiu Y, Li W and Shi Q <31 more author(s)> You X, Bian C, Zan Q, Xu X, Liu X, Chen J, Wang J, Qiu Y, Li W, Zhang X, Sun Y, Chen S, Hong W, Li Y, Cheng S, Fan G, Shi C, Liang J, Tom Tang Y, Yang C, Ruan Z, Bai J, Peng C, Mu Q, Lu J, Fan M, Yang S, Huang Z, Jiang X, Fang X, Zhang G, Zhang Y, Polgar G, Yu H, Li J, Liu Z, Ravi V, Coon SL, Yang H, Venkatesh B, Shi Q (- 31) Ref: Nat Commun, 5:5594, 2014 : PubMed ESTHER: You_2014_Nat.Commun_5_5594 PubMedSearch: You 2014 Nat.Commun 5 5594 PubMedID: 25463417 Gene_locus related to this paper: 9gobi-a0a3b4bh68, 9gobi-a0a3b4bmj6, 9gobi-a0a3b4alj9, 9gobi-a0a3b4biy6, 9gobi-a0a3b4ah01, 9gobi-a0a3b3z8m7, 9gobi-a0a3b4aaj5, 9gobi-a0a3b4b6y7 Abstract Mudskippers are amphibious fishes that have developed morphological and physiological adaptations to match their unique lifestyles. Here we perform whole-genome sequencing of four representative mudskippers to elucidate the molecular mechanisms underlying these adaptations. We discover an expansion of innate immune system genes in the mudskippers that may provide defence against terrestrial pathogens. Several genes of the ammonia excretion pathway in the gills have experienced positive selection, suggesting their important roles in mudskippers' tolerance to environmental ammonia. Some vision-related genes are differentially lost or mutated, illustrating genomic changes associated with aerial vision. Transcriptomic analyses of mudskippers exposed to air highlight regulatory pathways that are up- or down-regulated in response to hypoxia. The present study provides a valuable resource for understanding the molecular mechanisms underlying water-to-land transition of vertebrates. Title: Complete Genome Sequence of Staphylococcus aureus XN108, an ST239-MRSA-SCCmec III Strain with Intermediate Vancomycin Resistance Isolated in Mainland China Zhang X, Xu X, Yuan W, Hu Q, Shang W, Hu X, Tong Y, Rao X Ref: Genome Announc, 2:, 2014 : PubMed ESTHER: Zhang_2014_Genome.Announc_2_e00449 PubMedSearch: Zhang 2014 Genome.Announc 2 e00449 PubMedID: 25059856 Abstract ST239-MRSA-SCCmec III (ST239, sequence type 239; MRSA, methicillin-resistant Staphylococcus aureus; SCCmec III, staphylococcal cassette chromosome mec type III) is the most predominant clone of hospital-acquired methicillin-resistant S. aureus in mainland China. We report here the complete genome sequence of XN108, the first vancomycin-intermediate S. aureus strain isolated from a steam-burned patient with a wound infection. Title: Single residues dictate the co-evolution of dual esterases: MCP hydrolases from the alpha/beta hydrolase family Alcaide M, Tornes J, Stogios PJ, Xu X, Gertler C, Di Leo R, Bargiela R, Lafraya A, Guazzaroni ME and Ferrer M <9 more author(s)> Alcaide M, Tornes J, Stogios PJ, Xu X, Gertler C, Di Leo R, Bargiela R, Lafraya A, Guazzaroni ME, Lopez-Cortes N, Chernikova TN, Golyshina OV, Nechitaylo TY, Plumeier I, Pieper DH, Yakimov MM, Savchenko A, Golyshin PN, Ferrer M (- 9) Ref: Biochemical Journal, 454:157, 2013 : PubMed ESTHER: Alcaide_2013_Biochem.J_454_157 PubMedSearch: Alcaide 2013 Biochem.J 454 157 PubMedID: 23750508 Gene_locus related to this paper: 9bact-r9qzf7, 9gamm-k0c6t6 Abstract Several members of the C-C MCP (meta-cleavage product) hydrolase family demonstrate an unusual ability to hydrolyse esters as well as the MCPs (including those from mono- and bi-cyclic aromatics). Although the molecular mechanisms responsible for such substrate promiscuity are starting to emerge, the full understanding of these complex enzymes is far from complete. In the present paper, we describe six distinct alpha/beta hydrolases identified through genomic approaches, four of which demonstrate the unprecedented characteristic of activity towards a broad spectrum of substrates, including p-nitrophenyl, halogenated, fatty acyl, aryl, glycerol, cinnamoyl and carbohydrate esters, lactones, 2-hydroxy-6-oxo-6-phenylhexa-2,4-dienoate and 2-hydroxy-6-oxohepta-2,4-dienoate. Using structural analysis and site-directed mutagenesis we have identified the three residues (Ser32, Val130 and Trp144) that determine the unusual substrate specificity of one of these proteins, CCSP0084. The results may open up new research avenues into comparative catalytic models, structural and mechanistic studies, and biotechnological applications of MCP hydrolases. Title: Genome Sequence of Mycoplasma columbinum Strain SF7 Guo Z, Xu X, Zheng Q, Li T, Kuang S, Zhang Z, Chen Y, Lu X, Zhou R and Jin H <1 more author(s)> Guo Z, Xu X, Zheng Q, Li T, Kuang S, Zhang Z, Chen Y, Lu X, Zhou R, Bi D, Jin H (- 1) Ref: Genome Announc, 1:e0015713, 2013 : PubMed ESTHER: Guo_2013_Genome.Announc_1_e0015713 PubMedSearch: Guo 2013 Genome.Announc 1 e0015713 PubMedID: 23599295 Abstract Mycoplasma columbinum is a member of nonglycolytic Mycoplasma species which can hydrolyze arginine. Increasingly research has revealed that M. columbinum is associated with respiratory disease of pigeons and that the respiratory disease symptoms could be eliminated via the use of mycoplasma treatment medicine. Here we report the genome sequence of M. columbinum strain SF7, which is the first genome report for M. columbinum. Title: Triptolide inhibits amyloid-beta production and protects neural cells by inhibiting CXCR2 activity Wang J, Shi ZQ, Xu X, Xin GZ, Chen J, Qi LW, Li P Ref: J Alzheimers Dis, 33:217, 2013 : PubMed ESTHER: Wang_2013_J.Alzheimers.Dis_33_217 PubMedSearch: Wang 2013 J.Alzheimers.Dis 33 217 PubMedID: 22986777 Abstract Triptolide, a biologically active natural product from Tripterygium wilfordii, protects neurons from inflammation-mediated damage. Our results showed for the first time that triptolide inhibited the expression of CXCR2 and presenilin in a neuroblastoma cell line SHSY5Ysw. Moreover, triptolide potently inhibited amyloid-beta1-42 production with IC50 value of 30 pM in HEK293sw cells or 2 nM in SHSY5Ysw cells, respectively. We also demonstrated that triptolide prevented primary cortical neurons from chemokine CXCL1-induced cytotoxicity. Therefore, our study indicates that the neural protective effect of triptolide is largely mediated by inhibiting CXCR2 activity. Title: Draft Genome Sequences of Three Salmonella enterica Serotype Agona Strains from China Zhang J, Cao G, Xu X, Jin H, Yang X, Allard M, Brown E, Meng J Ref: Genome Announc, 1:, 2013 : PubMed ESTHER: Zhang_2013_Genome.Announc_1_E00203 PubMedSearch: Zhang 2013 Genome.Announc 1 E00203 PubMedID: 23469342 Gene_locus related to this paper: salty-STY1441 Abstract Salmonellosis has been one of the major contributors to the global public health burden. Salmonella enterica serotype Agona has ranked among the top 10 and top 20 most frequent Salmonella serotypes isolated from human sources in China and the United States, respectively. We report draft genomes of three S. Agona strains from China. Title: Whole-Genome Sequences of Four Salmonella enterica Serotype Newport Strains from Humans Zhang J, Cao G, Xu X, Jin H, Zhang Q, Chen J, Yang X, Pan H, Zhang X and Meng J <2 more author(s)> Zhang J, Cao G, Xu X, Jin H, Zhang Q, Chen J, Yang X, Pan H, Zhang X, Allard M, Brown E, Meng J (- 2) Ref: Genome Announc, 1:E00213, 2013 : PubMed ESTHER: Zhang_2013_Genome.Announc_1_E00213 PubMedSearch: Zhang 2013 Genome.Announc 1 E00213 PubMedID: 23661485 Gene_locus related to this paper: salty-STY1441 Abstract Salmonellosis contributes significantly to the public health burden globally. Salmonella enterica serotype Newport is among Salmonella serotypes most associated with food-borne illness in the United States and China. It was thought to be polyphyletic and to contain different lineages. We report draft genomes of four S. Newport strains isolated from humans in China. Title: Lipases as biocatalysts for the synthesis of structured lipids Jala RC, Hu P, Yang T, Jiang Y, Zheng Y, Xu X Ref: Methods Mol Biol, 861:403, 2012 : PubMed ESTHER: Jala_2012_Methods.Mol.Biol_861_403 PubMedSearch: Jala 2012 Methods.Mol.Biol 861 403 PubMedID: 22426731 Abstract Structured lipids (SL) are broadly referred to as modified or synthetic oils and fats or lipids with functional or pharmaceutical applications. Some structured lipids, such as triglycerides that contain both long-chain (mainly essential) fatty acids and medium- or short-chain fatty acids and also artificial products that mimic the structure of natural materials, namely human milk fat substitutes and cocoa butter equivalents, have been discussed. Further, other modified or synthetic lipids, such as structured phospholipids and synthetic phenolic lipids are also included in this chapter. For all the products described in this chapter, enzymatic production in industry has been already conducted in one way or another. Cocoa butter equivalents, healthy oil containing medium-chain fatty acids, phosphatidyl serine, and phenol lipids from enzyme technology have been reported for commercial operation. As the demand for better quality functional lipids is increasing, the production of structured lipids becomes an interesting area. Thus, in this chapter we have discussed latest developments as well as present industrial situation of all commercially important structured lipids. Title: Identification and characterization of novel esterases from a deep-sea sediment metagenome Jiang X, Xu X, Huo Y, Wu Y, Zhu X, Zhang X, Wu M Ref: Arch Microbiol, 194:207, 2012 : PubMed ESTHER: Jiang_2012_Arch.Microbiol_194_207 PubMedSearch: Jiang 2012 Arch.Microbiol 194 207 PubMedID: 21861153 Gene_locus related to this paper: 9bact-H6BDX1, 9bact-h6bdx2 Abstract A deep-sea sediment metagenomic library was constructed and screened for lipolytic enzymes by activity-based approach. Nine novel lipolytic enzymes were identified, and the amino acid sequences shared 56% to 84% identity to other lipolytic enzymes in the database. Phylogenetic analysis showed that these enzymes belonged to family IV lipolytic enzymes. One of the lipolytic enzymes, Est6, was successfully cloned and expressed in Escherichia coli Rosetta in a soluble form. The recombinant protein was purified by Ni-nitrilotriacetic affinity chromatography column and characterized using p-nitrophenyl esters with various chain lengths. The est6 gene consisted of 909 bp that encoded 302 amino acid residues. Est6 was most similar to a lipolytic enzyme from uncultured bacterium (ACL67845, 61% identity) isolated from the South China Sea marine sediment metagenome. The characterization of Est6 revealed that it was a cold-active esterase and exhibited the highest activity toward p-nitrophenyl butyrate (C4) at 20 degrees C and pH 7.5. Title: Enhanced catalytic activity of lipase encapsulated in PCL nanofibers Song J, Kahveci D, Chen M, Guo Z, Xie E, Xu X, Besenbacher F, Dong M Ref: Langmuir, 28:6157, 2012 : PubMed ESTHER: Song_2012_Langmuir_28_6157 PubMedSearch: Song 2012 Langmuir 28 6157 PubMedID: 22397625 Abstract Use of biocatalysis for industrial synthetic chemistry is on the verge of significant growth. Enzyme immobilization as an effective strategy for improving the enzyme activity has emerged from developments especially in nanoscience and nanotechnology. Here, lipase from Burkholderia cepacia (LBC), as an example of the luxuriant enzymes, was successfully encapsulated in polycaprolactone (PCL) nanofibers, proven by X-ray photoelectron spectroscopy (XPS) and atomic force microscopy (AFM). Evaluated in both organic and aqueous medium, the activation factor of the encapsulated enzymes in the hydrolysis reaction was generally higher than that in the transesterification reaction. Enhanced catalytic activities were found when 5-20 w/w % of LBC was loaded. The effect of different solvents pretreatment on the activity of immobilized LBC was also investigated. The highest activation factor was found up to 14 for the sample containing acetone-treated LBC/PCL (10 w/w %). The encapsulated lipase reserved 50% of its original activity after the 10th run in the transesterification reaction in hexane medium. The mechanism of activation of lipase catalytic ability based on active PCL nanofiberous matrix is proposed. Title: Comparative analysis of the genomes of two field isolates of the rice blast fungus Magnaporthe oryzae Xue M, Yang J, Li Z, Hu S, Yao N, Dean RA, Zhao W, Shen M, Zhang H and Peng YL <8 more author(s)> Xue M, Yang J, Li Z, Hu S, Yao N, Dean RA, Zhao W, Shen M, Zhang H, Li C, Liu L, Cao L, Xu X, Xing Y, Hsiang T, Zhang Z, Xu JR, Peng YL (- 8) Ref: PLoS Genet, 8:e1002869, 2012 : PubMed ESTHER: Xue_2012_PLoS.Genet_8_E1002869 PubMedSearch: Xue 2012 PLoS.Genet 8 E1002869 PubMedID: 22876203 Gene_locus related to this paper: maggr-q0pnd2, mago7-g4mk92, mago7-g4mkc6, mago7-g4mkk9, mago7-g4mns9, mago7-g4ms19, mago7-g4mvm8, mago7-g4mvw5, mago7-g4mvw6, mago7-g4n6j4, mago7-g4nal1, mago7-g4nba0, mago7-g4nbs0, mago7-g4nc41, mago7-g4ncz9, mago7-g4nhn9, mago7-g4nil3, mago7-g4nky6, mago7-g5ehg6, mago7-g5ehv6, mago7-g4msm5, magoy-l7il05, magoy-l7i6m7, magoy-l7ic25 Abstract Rice blast caused by Magnaporthe oryzae is one of the most destructive diseases of rice worldwide. The fungal pathogen is notorious for its ability to overcome host resistance. To better understand its genetic variation in nature, we sequenced the genomes of two field isolates, Y34 and P131. In comparison with the previously sequenced laboratory strain 70-15, both field isolates had a similar genome size but slightly more genes. Sequences from the field isolates were used to improve genome assembly and gene prediction of 70-15. Although the overall genome structure is similar, a number of gene families that are likely involved in plant-fungal interactions are expanded in the field isolates. Genome-wide analysis on asynonymous to synonymous nucleotide substitution rates revealed that many infection-related genes underwent diversifying selection. The field isolates also have hundreds of isolate-specific genes and a number of isolate-specific gene duplication events. Functional characterization of randomly selected isolate-specific genes revealed that they play diverse roles, some of which affect virulence. Furthermore, each genome contains thousands of loci of transposon-like elements, but less than 30% of them are conserved among different isolates, suggesting active transposition events in M. oryzae. A total of approximately 200 genes were disrupted in these three strains by transposable elements. Interestingly, transposon-like elements tend to be associated with isolate-specific or duplicated sequences. Overall, our results indicate that gain or loss of unique genes, DNA duplication, gene family expansion, and frequent translocation of transposon-like elements are important factors in genome variation of the rice blast fungus. Title: Whole-genome sequence of Schistosoma haematobium Young ND, Jex AR, Li B, Liu S, Yang L, Xiong Z, Li Y, Cantacessi C, Hall RS and Gasser RB <17 more 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 (- 17) Ref: Nat Genet, 44:221, 2012 : PubMed 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 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. Title: Enhancement of activity and selectivity of Candida rugosa lipase and Candida antarctica lipase A by bioimprinting and/or immobilization for application in the selective ethanolysis of fish oil Kahveci D, Xu X Ref: Biotechnol Lett, 33:2065, 2011 : PubMed ESTHER: Kahveci_2011_Biotechnol.Lett_33_2065 PubMedSearch: Kahveci 2011 Biotechnol.Lett 33 2065 PubMedID: 21695486 Abstract Candida rugosa lipase (CRL) and Candida antarctica lipase A (CALA) with improved activity and selectivity were prepared for use in organic solvent media. CRL bioimprinted with fatty acids exhibited eightfold enhanced transesterification activity in hexane. Combination of bioimprinting and coating with lecithin or with immobilization did not improve the activity further. CALA was immobilized with and without bioimprinting, none of which improved the activity. All modified lipases were tested for selective ethanolysis of fish oil to concentrate omega-3 polyunsaturated fatty acids (PUFA). None of the preparations, except the immobilized ones catalysed ethanolysis. Immobilized CRL-catalyzed ethanolysis giving 27% (v/v) ethyl esters (EE) in 48 h, of which 43 mol% was oleic acid but no PUFA was detected in the EE fraction. Fatty acid selectivity of CALA was significantly improved by immobilization combined with bioimprinting, resulting in 5.5-fold lower omega-3 PUFA in EE. Title: An inserted alpha/beta subdomain shapes the catalytic pocket of Lactobacillus johnsonii cinnamoyl esterase Lai KK, Stogios PJ, Vu C, Xu X, Cui H, Molloy S, Savchenko A, Yakunin A, Gonzalez CF Ref: PLoS ONE, 6:e23269, 2011 : PubMed ESTHER: Lai_2011_PLoS.One_6_e23269 PubMedSearch: Lai 2011 PLoS.One 6 e23269 PubMedID: 21876742 Gene_locus related to this paper: lacjo-q74hk5 Inhibitor(s) related to this paper: Caffeic-acid Abstract BACKGROUND: Microbial enzymes produced in the gastrointestinal tract are primarily responsible for the release and biochemical transformation of absorbable bioactive monophenols. In the present work we described the crystal structure of LJ0536, a serine cinnamoyl esterase produced by the probiotic bacterium Lactobacillus johnsonii N6.2. METHODOLOGY/PRINCIPAL FINDINGS: We crystallized LJ0536 in the apo form and in three substrate-bound complexes. The structure showed a canonical alpha/beta fold characteristic of esterases, and the enzyme is dimeric. Two classical serine esterase motifs (GlyXSerXGly) can be recognized from the amino acid sequence, and the structure revealed that the catalytic triad of the enzyme is formed by Ser(106), His(225), and Asp(197), while the other motif is non-functional. In all substrate-bound complexes, the aromatic acyl group of the ester compound was bound in the deepest part of the catalytic pocket. The binding pocket also contained an unoccupied area that could accommodate larger ligands. The structure revealed a prominent inserted alpha/beta subdomain of 54 amino acids, from which multiple contacts to the aromatic acyl groups of the substrates are made. Inserts of this size are seen in other esterases, but the secondary structure topology of this subdomain of LJ0536 is unique to this enzyme and its closest homolog (Est1E) in the Protein Databank. CONCLUSIONS: The binding mechanism characterized (involving the inserted alpha/beta subdomain) clearly differentiates LJ0536 from enzymes with similar activity of a fungal origin. The structural features herein described together with the activity profile of LJ0536 suggest that this enzyme should be clustered in a new group of bacterial cinnamoyl esterases. Title: Acute DPP-4 inhibition modulates vascular tone through GLP-1 independent pathways Shah Z, Pineda C, Kampfrath T, Maiseyeu A, Ying Z, Racoma I, DeIuliis J, Xu X, Sun Q and Rajagopalan S <2 more author(s)> Shah Z, Pineda C, Kampfrath T, Maiseyeu A, Ying Z, Racoma I, DeIuliis J, Xu X, Sun Q, Moffatt-Bruce S, Villamena F, Rajagopalan S (- 2) Ref: Vascul Pharmacol, 55:2, 2011 : PubMed ESTHER: Shah_2011_Vascul.Pharmacol_55_2 PubMedSearch: Shah 2011 Vascul.Pharmacol 55 2 PubMedID: 21397040 Abstract Evidence from both clinical and experimental studies indicates that Di-peptidyl peptidase-IV (DPP-4) inhibition may mediate favorable effects on the cardiovascular system. The objective of this study was to examine the acute effects of DPP-4 inhibition on vascular responses and to study the underlying mechanisms of alteration in tone. Aortic segments from C57BL/6 mice were treated with vasoconstrictors and exposed to various doses of alogliptin, a selective DPP-4 inhibitor. Vasodilator responses were evaluated using pathway specific antagonists to elucidate mechanisms of response. In parallel experiments, cultured human umbilical vein endothelial cells (HUVEC) were exposed to varying concentrations of alogliptin to evaluate the effects on candidate vasodilator pathways. Alogliptin relaxed phenylephrine and U46619 pre-constricted aortic segments in a dose dependent manner. Relaxation responses were not affected by the glucagon-like peptide-1 (GLP-1) receptor antagonist, exendin fragment 9-39 (88 +/- 6 vs. 91 +/- 2, p < 0.001). Vascular relaxation to alogliptin was significantly decreased by endothelial denudation, L-N(G)-monomethyl-arginine citrate (L-NMMA) and by the soluble guanylate cyclase inhibitor ODQ. DPP-4 inhibition induced relaxation was completely abolished by a combination of L-NMMA, charybdotoxin and apamin. Incubation of HUVECs with alogliptin resulted in eNOS and Akt phosphorylation (Ser(1177) and Ser(473) respectively) paralleled by a rapid increase in nitric oxide. Inhibition of Src kinase decreased eNOS and Akt phosphorylation, in contrast to a lack of any effect on insulin mediated activation of the eNOS-Akt, suggesting that alogliptin mediates vasodilation through Src kinase mediated effects on eNOS-Akt. DPP-4 inhibition by alogliptin mediates rapid vascular relaxation via GLP-1 independent, Src-Akt-eNOS mediated NO release and the activation of vascular potassium channels. Title: Draft genome sequence of pigeonpea (Cajanus cajan), an orphan legume crop of resource-poor farmers Varshney RK, Chen W, Li Y, Bharti AK, Saxena RK, Schlueter JA, Donoghue MT, Azam S, Fan G and Jackson SA <21 more author(s)> Varshney RK, Chen W, Li Y, Bharti AK, Saxena RK, Schlueter JA, Donoghue MT, Azam S, Fan G, Whaley AM, Farmer AD, Sheridan J, Iwata A, Tuteja R, Penmetsa RV, Wu W, Upadhyaya HD, Yang SP, Shah T, Saxena KB, Michael T, McCombie WR, Yang B, Zhang G, Yang H, Wang J, Spillane C, Cook DR, May GD, Xu X, Jackson SA (- 21) Ref: Nat Biotechnol, 30:83, 2011 : PubMed ESTHER: Varshney_2011_Nat.Biotechnol_30_83 PubMedSearch: Varshney 2011 Nat.Biotechnol 30 83 PubMedID: 22057054 Gene_locus related to this paper: cajca-a0a151r9d2, cajca-a0a151u2m0, cajca-a0a151tes0, cajca-a0a151u784, cajca-a0a151sf79, cajca-a0a151qu18, cajca-a0a151sz37, cajca-a0a151ss18, cajca-a0a151rb44, cajca-a0a151ryr0, cajca-a0a151qzm6, cajca-a0a151rsm6, cajca-a0a151rsn1, cajca-a0a151tig2, cajca-a0a151rwt3, cajca-a0a151rx08, cajca-a0a151rws4, cajca-a0a151r0b7 Abstract Pigeonpea is an important legume food crop grown primarily by smallholder farmers in many semi-arid tropical regions of the world. We used the Illumina next-generation sequencing platform to generate 237.2 Gb of sequence, which along with Sanger-based bacterial artificial chromosome end sequences and a genetic map, we assembled into scaffolds representing 72.7% (605.78 Mb) of the 833.07 Mb pigeonpea genome. Genome analysis predicted 48,680 genes for pigeonpea and also showed the potential role that certain gene families, for example, drought tolerance-related genes, have played throughout the domestication of pigeonpea and the evolution of its ancestors. Although we found a few segmental duplication events, we did not observe the recent genome-wide duplication events observed in soybean. This reference genome sequence will facilitate the identification of the genetic basis of agronomically important traits, and accelerate the development of improved pigeonpea varieties that could improve food security in many developing countries. Title: The genome of the mesopolyploid crop species Brassica rapa Wang X, Wang H, Wang J, Sun R, Wu J, Liu S, Bai Y, Mun JH, Bancroft I and Zhang Z <88 more 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 (- 88) Ref: Nat Genet, 43:1035, 2011 : PubMed 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 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. Title: The genomic sequence of the Chinese hamster ovary (CHO)-K1 cell line Xu X, Nagarajan H, Lewis NE, Pan S, Cai Z, Liu X, Chen W, Xie M, Wang W and Palsson BO <12 more author(s)> Xu X, Nagarajan H, Lewis NE, Pan S, Cai Z, Liu X, Chen W, Xie M, Wang W, Hammond S, Andersen MR, Neff N, Passarelli B, Koh W, Fan HC, Wang J, Gui Y, Lee KH, Betenbaugh MJ, Quake SR, Famili I, Palsson BO (- 12) Ref: Nat Biotechnol, 29:735, 2011 : PubMed ESTHER: Xu_2011_Nat.Biotechnol_29_735 PubMedSearch: Xu 2011 Nat.Biotechnol 29 735 PubMedID: 21804562 Gene_locus related to this paper: crigr-g3hfm0, crigr-g3h894, crigr-a0a061hy43, crigr-g3h3f6, crigr-g3i9k7, crigr-g3i9k8, crigr-g3grm1, crigr-g3in33, crigr-g3i1j5, crigr-a0a061ika1, crigr-g3hqj0, crigr-g3hh02, crigr-g3h083, crigr-a0a3l7ib08, crigr-a0a061ihy9, crigr-g3ifk5, crigr-g3ily8, crigr-g3hvc7, crigr-g3gtp1, crigr-g3h7k6, crigr-g3hkm8 Abstract Chinese hamster ovary (CHO)-derived cell lines are the preferred host cells for the production of therapeutic proteins. Here we present a draft genomic sequence of the CHO-K1 ancestral cell line. The assembly comprises 2.45 Gb of genomic sequence, with 24,383 predicted genes. We associate most of the assembled scaffolds with 21 chromosomes isolated by microfluidics to identify chromosomal locations of genes. Furthermore, we investigate genes involved in glycosylation, which affect therapeutic protein quality, and viral susceptibility genes, which are relevant to cell engineering and regulatory concerns. Homologs of most human glycosylation-associated genes are present in the CHO-K1 genome, although 141 of these homologs are not expressed under exponential growth conditions. Many important viral entry genes are also present in the genome but not expressed, which may explain the unusual viral resistance property of CHO cell lines. We discuss how the availability of this genome sequence may facilitate genome-scale science for the optimization of biopharmaceutical protein production. Title: Genome sequence and analysis of the tuber crop potato Xu X, Pan S, Cheng S, Zhang B, Mu D, Ni P, Zhang G, Yang S, Li R and Visser RG <87 more author(s)> Xu X, Pan S, Cheng S, Zhang B, Mu D, Ni P, Zhang G, Yang S, Li R, Wang J, Orjeda G, Guzman F, Torres M, Lozano R, Ponce O, Martinez D, De la Cruz G, Chakrabarti SK, Patil VU, Skryabin KG, Kuznetsov BB, Ravin NV, Kolganova TV, Beletsky AV, Mardanov AV, Di Genova A, Bolser DM, Martin DM, Li G, Yang Y, Kuang H, Hu Q, Xiong X, Bishop GJ, Sagredo B, Mejia N, Zagorski W, Gromadka R, Gawor J, Szczesny P, Huang S, Zhang Z, Liang C, He J, Li Y, He Y, Xu J, Zhang Y, Xie B, Du Y, Qu D, Bonierbale M, Ghislain M, Herrera Mdel R, Giuliano G, Pietrella M, Perrotta G, Facella P, O'Brien K, Feingold SE, Barreiro LE, Massa GA, Diambra L, Whitty BR, Vaillancourt B, Lin H, Massa AN, Geoffroy M, Lundback S, DellaPenna D, Buell CR, Sharma SK, Marshall DF, Waugh R, Bryan GJ, Destefanis M, Nagy I, Milbourne D, Thomson SJ, Fiers M, Jacobs JM, Nielsen KL, Sonderkaer M, Iovene M, Torres GA, Jiang J, Veilleux RE, Bachem CW, De Boer J, Borm T, Kloosterman B, van Eck H, Datema E, Hekkert B, Goverse A, van Ham RC, Visser RG (- 87) Ref: Nature, 475:189, 2011 : PubMed ESTHER: Xu_2011_Nature_475_189 PubMedSearch: Xu 2011 Nature 475 189 PubMedID: 21743474 Gene_locus related to this paper: soltu-q2tqv0, soltu-q4h433, soltu-m0zl00, soltu-m1aw23, soltu-m0zxh5, soltu-m1d3q4, soltu-m1bz14, soltu-m1d3q6, sollc-k4b1g3, soltu-m0zzn8, soltu-m1ba60, sollc-k4bf33, soltu-m1c8d8, soltu-m1ced9, soltu-m1a385, soltu-m1bz15, soltu-m1a7s9, soltu-m1bc84, soltu-m1bpd1, sollc-k4bm34, soltu-m1a487, soltu-m1a5u0, soltu-m1cjx7, soltu-m1bvq8, soltu-m1baq1, soltu-m1cfh4, soltu-m1azl4, soltu-m0ztj0, soltu-m1d6d0 Abstract Potato (Solanum tuberosum L.) is the world's most important non-grain food crop and is central to global food security. It is clonally propagated, highly heterozygous, autotetraploid, and suffers acute inbreeding depression. Here we use a homozygous doubled-monoploid potato clone to sequence and assemble 86% of the 844-megabase genome. We predict 39,031 protein-coding genes and present evidence for at least two genome duplication events indicative of a palaeopolyploid origin. As the first genome sequence of an asterid, the potato genome reveals 2,642 genes specific to this large angiosperm clade. We also sequenced a heterozygous diploid clone and show that gene presence/absence variants and other potentially deleterious mutations occur frequently and are a likely cause of inbreeding depression. Gene family expansion, tissue-specific expression and recruitment of genes to new pathways contributed to the evolution of tuber development. The potato genome sequence provides a platform for genetic improvement of this vital crop. Title: Phenotypic analysis of images of zebrafish treated with Alzheimer's gamma-secretase inhibitors Arslanova D, Yang T, Xu X, Wong ST, Augelli-Szafran CE, Xia W Ref: BMC Biotechnol, 10:24, 2010 : PubMed ESTHER: Arslanova_2010_BMC.Biotechnol_10_24 PubMedSearch: Arslanova 2010 BMC.Biotechnol 10 24 PubMedID: 20307292 Abstract BACKGROUND: Several gamma-secretase inhibitors (GSI) are in clinical trials for the treatment of Alzheimer's disease (AD). This enzyme mediates the proteolytic cleavage of amyloid precursor protein (APP) to generate amyloid beta protein, Abeta, the pathogenic protein in AD. The gamma-secretase also cleaves Notch to generate Notch Intracellular domain (NICD), the signaling molecule that is implicated in tumorigenesis. Title: Complete genome sequence of the extremophilic Bacillus cereus strain Q1 with industrial applications Xiong Z, Jiang Y, Qi D, Lu H, Yang F, Yang J, Chen L, Sun L, Xu X and Jin Q <2 more author(s)> Xiong Z, Jiang Y, Qi D, Lu H, Yang F, Yang J, Chen L, Sun L, Xu X, Xue Y, Zhu Y, Jin Q (- 2) Ref: Journal of Bacteriology, 191:1120, 2009 : PubMed ESTHER: Xiong_2009_J.Bacteriol_191_1120 PubMedSearch: Xiong 2009 J.Bacteriol 191 1120 PubMedID: 19060151 Gene_locus related to this paper: bacah-a0rer5, bacan-BA0954, bacan-BA3703, bacan-BA4338, bacan-BA5009, bacan-DHBF, bacc1-q73br9, bacce-BC0192, bacce-BC0968, bacce-BC1788, bacce-BC2141, bacce-BC2171, bacce-BC4102, bacce-BC4854, bacce-BC4862, bacce-BC5130, bacce-c2mr40, bacce-PHAC, bacce-q72yu1, bacce-q736x9, baccq-b9j170, baccr-pepx, baccz-q636u4, bacti-q3elq7 Abstract Bacillus cereus strain Q1 was isolated from a deep-subsurface oil reservoir in the Daqing oil field in northeastern China. This strain is able to produce biosurfactants and to survive in extreme environments. Here we report the finished and annotated genome sequence of this organism. Title: Analyses of associations between three positionally cloned asthma candidate genes and asthma or asthma-related phenotypes in a Chinese population Zhou H, Hong X, Jiang S, Dong H, Xu X Ref: BMC Med Genet, 10:123, 2009 : PubMed ESTHER: Zhou_2009_BMC.Med.Genet_10_123 PubMedSearch: Zhou 2009 BMC.Med.Genet 10 123 PubMedID: 19951440 Gene_locus related to this paper: human-DPP10 Abstract BACKGROUND: Six asthma candidate genes, ADAM33, NPSR1, PHF11, DPP10, HLA-G, and CYFIP2, located at different chromosome regions have been positionally cloned following the reported linkage studies. For ADAM33, NPSR1, and CYFIP2, the associations with asthma or asthma-related phenotypes have been studied in East Asian populations such as Chinese and Japanese. However, for PHF11, DPP10, and HLA-G, none of the association studies have been conducted in Asian populations. Therefore, the aim of the present study is to test the associations between these three positionally cloned genes and asthma or asthma-related phenotypes in a Chinese population. Title: The structure of a putative S-formylglutathione hydrolase from Agrobacterium tumefaciens van Straaten KE, Gonzalez CF, Valladares RB, Xu X, Savchenko AV, Sanders DA Ref: Protein Science, 18:2196, 2009 : PubMed ESTHER: van Straaten_2009_Protein.Sci_18_2196 PubMedSearch: van Straaten 2009 Protein.Sci 18 2196 PubMedID: 19653299 Gene_locus related to this paper: agrt5-a9cj11 Abstract The structure of the Atu1476 protein from Agrobacterium tumefaciens was determined at 2 A resolution. The crystal structure and biochemical characterization of this enzyme support the conclusion that this protein is an S-formylglutathione hydrolase (AtuSFGH). The three-dimensional structure of AtuSFGH contains the alpha/beta hydrolase fold topology and exists as a homo-dimer. Contacts between the two monomers in the dimer are formed both by hydrogen bonds and salt bridges. Biochemical characterization reveals that AtuSFGH hydrolyzes C--O bonds with high affinity toward short to medium chain esters, unlike the other known SFGHs which have greater affinity toward shorter chained esters. A potential role for Cys54 in regulation of enzyme activity through S-glutathionylation is also proposed. Title: Complete genome of Phenylobacterium zucineum--a novel facultative intracellular bacterium isolated from human erythroleukemia cell line K562 Luo Y, Xu X, Ding Z, Liu Z, Zhang B, Yan Z, Sun J, Hu S, Hu X Ref: BMC Genomics, 9:386, 2008 : PubMed ESTHER: Luo_2008_BMC.Genomics_9_386 PubMedSearch: Luo 2008 BMC.Genomics 9 386 PubMedID: 18700039 Gene_locus related to this paper: phezh-b4r8z3, phezh-b4r801, phezh-b4r876, phezh-b4ras1, phezh-b4ras4, phezh-b4ray3, phezh-b4rb44, phezh-b4rd51, phezh-b4re02, phezh-b4rfb7, phezh-b4rfk3, phezh-b4rfq9, phezh-b4rfw5, phezh-b4rgf2, phezh-b4rh78, phezh-b4rh88, phezh-b4rhb1, phezh-b4rhb2, phezh-dhma, phezh-b4r875, phezh-b4rfb8, phezh-b4rbt7 Abstract BACKGROUND: Phenylobacterium zucineum is a recently identified facultative intracellular species isolated from the human leukemia cell line K562. Unlike the known intracellular pathogens, P. zucineum maintains a stable association with its host cell without affecting the growth and morphology of the latter. RESULTS: Here, we report the whole genome sequence of the type strain HLK1T. The genome consists of a circular chromosome (3,996,255 bp) and a circular plasmid (382,976 bp). It encodes 3,861 putative proteins, 42 tRNAs, and a 16S-23S-5S rRNA operon. Comparative genomic analysis revealed that it is phylogenetically closest to Caulobacter crescentus, a model species for cell cycle research. Notably, P. zucineum has a gene that is strikingly similar, both structurally and functionally, to the cell cycle master regulator CtrA of C. crescentus, and most of the genes directly regulated by CtrA in the latter have orthologs in the former. CONCLUSION: This work presents the first complete bacterial genome in the genus Phenylobacterium. Comparative genomic analysis indicated that the CtrA regulon is well conserved between C. crescentus and P. zucineum. Title: Characterization of ST-4821 complex, a unique Neisseria meningitidis clone Peng J, Yang L, Yang F, Yang J, Yan Y, Nie H, Zhang X, Xiong Z, Jiang Y and Jin Q <9 more author(s)> Peng J, Yang L, Yang F, Yang J, Yan Y, Nie H, Zhang X, Xiong Z, Jiang Y, Cheng F, Xu X, Chen S, Sun L, Li W, Shen Y, Shao Z, Liang X, Xu J, Jin Q (- 9) Ref: Genomics, 91:78, 2008 : PubMed ESTHER: Peng_2008_Genomics_91_78 PubMedSearch: Peng 2008 Genomics 91 78 PubMedID: 18031983 Gene_locus related to this paper: neigo-pip, neima-metx, neimb-q9k0t9, neime-ESD, neime-NMA2216, neime-NMB0276, neime-NMB1877 Abstract Ten outbreaks of a new serogroup C meningococcal disease emerged during 2003-2005 in China. The multilocus sequence typing results indicated that unique sequence type 4821 clone meningococci were responsible for these outbreaks. Herein, we determined the entire genomic DNA sequence of serogroup C isolate 053442, which belongs to ST-4821. Comparison of 053442 gene contents with other meningococcal genomes shows that they have similar characteristics, including thousands of repetitive elements and simple sequence repeats, numerous phase-variable genes, and similar virulence-related factors. However, many strain-specific regions were found in each genome. We also present the results of a genomic comparison of 28 ST-4821 complex isolates that were isolated from different serogroups using comparative genomic hybridization analysis. Genome comparison between the newly emerged hyperinvasive isolates belonging to different serogroups will further our understanding of their respective pathogenetic mechanisms. Title: A phospholipase A1 platelet activator from the wasp venom of Vespa magnifica (Smith) Yang H, Xu X, Ma D, Zhang K, Lai R Ref: Toxicon, 51:289, 2008 : PubMed ESTHER: Yang_2008_Toxicon_51_289 PubMedSearch: Yang 2008 Toxicon 51 289 PubMedID: 18023835 Gene_locus related to this paper: vesmg-pa1 Abstract Wasp is an important venomous animal that can induce human fatalities. Aortic thrombosis and cerebral infarction are major clinical symptoms after massive wasp stings but the reason leading to the envenomation manifestation is still not known. In this paper, a toxin protein is purified and characterized by Sephadex G-75 gel filtration, CM-Sephadex C-25 cationic exchange and fast protein liquid chromatography (FPLC) from the venom of the wasp, Vespa magnifica (Smith). This protein, named magnifin, contains phospholipase-like activity and induces platelet aggregation. The cDNA encoding magnifin is cloned from the venom sac cDNA library of the wasp. The predicted protein was deduced from the cDNA with a sequence composed of 337 amino acid residues. Magnifin is very similar to other phospholipase A(1) (PLA(1)), especially to other wasp allergen PLA(1). Magnifin can activate platelet aggregation and induce thrombosis in vivo. The current results proved that PLA(1) in wasp venom could be contributable to aortic thrombosis after massive wasp stings. Title: Complete genome sequence of Shigella flexneri 5b and comparison with Shigella flexneri 2a Nie H, Yang F, Zhang X, Yang J, Chen L, Wang J, Xiong Z, Peng J, Sun L and Jin Q <6 more author(s)> Nie H, Yang F, Zhang X, Yang J, Chen L, Wang J, Xiong Z, Peng J, Sun L, Dong J, Xue Y, Xu X, Chen S, Yao Z, Shen Y, Jin Q (- 6) Ref: BMC Genomics, 7:173, 2006 : PubMed ESTHER: Nie_2006_BMC.Genomics_7_173 PubMedSearch: Nie 2006 BMC.Genomics 7 173 PubMedID: 16822325 Gene_locus related to this paper: shifl-AES, shifl-BIOH, shifl-entf, shifl-FES, shifl-PTRB, shifl-S2753, shifl-SF1808, shifl-SF3046, shifl-yafa, shifl-YBFF, shifl-YCDJ, shifl-ycfp, shifl-YCJY, shifl-YFBB, shifl-YHET, shifl-YIEL, shifl-YJFP, shifl-YPFH, shiss-yeiG, shiss-yqia Abstract BACKGROUND: Shigella bacteria cause dysentery, which remains a significant threat to public health. Shigella flexneri is the most common species in both developing and developed countries. Five Shigella genomes have been sequenced, revealing dynamic and diverse features. To investigate the intra-species diversity of S. flexneri genomes further, we have sequenced the complete genome of S. flexneri 5b strain 8401 (abbreviated Sf8401) and compared it with S. flexneri 2a (Sf301). Title: Monitoring lipase-catalyzed butterfat interesterification with rapeseed oil by Fourier transform near-infrared spectroscopy Zhang H, Mu H, Xu X Ref: Anal Bioanal Chem, 386:1889, 2006 : PubMed ESTHER: Zhang_2006_Anal.Bioanal.Chem_386_1889 PubMedSearch: Zhang 2006 Anal.Bioanal.Chem 386 1889 PubMedID: 16964473 Abstract This work demonstrates the application of FT-NIR spectroscopy in order to monitor the enzymatic interesterification process for butterfat modification. The reactions were catalyzed by Lipozyme TL IM at 70 degrees C for the blend of butterfat/rapeseed oil (70/30, w/w) in a packed-bed reactor. The blend and interesterified fat samples were measured in liquid form at 70 degrees C by transmission mode-based FT-NIR over the spectral region 12000-4000 cm-1. The calibration of FT-NIR for conversion degree (evaluated by the triglyceride profile, which was represented by the triglyceride peak ratio) and solid fat content (SFC) of the interesterified products was carried out using partial least squares (PLS) regression. Good correlations were observed between the NIR spectra and ln (peak ratio), and between the NIR spectra and the SFC at 5 degrees C over the spectral range 5269-4513 cm-1. Overall, transmission-mode FT-NIR spectroscopy performed at 70 degrees C yielded conditions close to those used during the interesterification process, implying that this method could be used to control the enzymatic interesterification process online. Title: Monitoring lipase-catalyzed interesterification for bulky fat modification with FT-IR/NIR spectroscopy Chang T, Lai X, Zhang H, Sondergaard I, Xu X Ref: Journal of Agricultural and Food Chemistry, 53:9841, 2005 : PubMed ESTHER: Chang_2005_J.Agric.Food.Chem_53_9841 PubMedSearch: Chang 2005 J.Agric.Food.Chem 53 9841 PubMedID: 16366664 Abstract This work demonstrates the application of FT-IR and FT-NIR spectroscopy to monitor the enzymatic interesterification process for bulky fat modification. The reaction was conducted between palm stearin and coconut oil (70:30, w/w) with the catalysis of Lipozyme TL IM at 70 degrees C in a batch reactor. The blends and interesterified fat samples in liquid form were measured by attenuated total reflectance based FT-IR (spectra region, 1516-781 cm(-1)) and transmission mode based FT-NIR (spectra region, 5369-4752 cm(-1)) with the temperature of both controlled at 70 degrees C. The samples in solid form were also measured by reflectance-based FT-NIR (spectra regions, 7037-6039 and 5995-5612 cm(-1)) at room temperature. Calibrations of FT-IR and FT-NIR for conversion degrees (evaluated by triglyceride profile), solid fat contents (SFC), and dropping points of interesterified products were carried out by using partial least-squares regression. High correlations (r > 0.96) were obtained from cross validations of the data estimated by FT-IR, FT-NIR, and the above-mentioned conventional analytical methods, except for correlations (r = 0.90-0.95) between FT-IR and SFC profiles. Overall, FT-NIR spectroscopy coupled with transmission mode measured at 70 degrees C had the highest correlations, which also had the closest conditions to the sampled products in the process, indicating a great potential for implementation as an on-line control for monitoring the enzymatic interesterification process. Title: Differences in the intramolecular structure of structured oils do not affect pancreatic lipase activity in vitro or the absorption by rats of (n-3) fatty acids Porsgaard T, Xu X, Gottsche J, Mu H Ref: J Nutr, 135:1705, 2005 : PubMed ESTHER: Porsgaard_2005_J.Nutr_135_1705 PubMedSearch: Porsgaard 2005 J.Nutr 135 1705 PubMedID: 15987853 Abstract The fatty acid composition and intramolecular structure of dietary triacylglycerols (TAGs) influence their absorption. We compared the in vitro pancreatic lipase activity and the lymphatic transport in rats of fish oil and 2 enzymatically interesterified oils containing 10:0 and (n-3) PUFAs of marine origin to investigate whether the positional distribution of fatty acids influenced the overall bioavailability of (n-3) PUFAs in the body. The structured oils had the (n-3) PUFA either mainly at the sn-1,3 position (LML, M = medium-chain fatty acid, L = long-chain fatty acid) or mainly at the sn-2 position (MLM). Oils were administered to lymph-cannulated rats and lymph was collected for 24 h. The fatty acid composition as well as the lipid class distribution of lymph samples was determined. In vitro pancreatic lipase activity was greater when fish oil was the substrate than when the structured oils were the substrates (P < 0.001 at 40 min). This was consistent with a greater 8-h recovery of total fatty acids from fish oil compared with the 2 structured oils (P < 0.05). The absorption profiles of MLM and LML in rats and their in vitro rates of lipase activity did not differ. This indicates that the absorption rate is highly influenced by the lipase activity, which in turn is affected by the fatty acid composition and intramolecular structure. The lipid class distribution in lymph collected from the 3 groups of rats did not differ. In conclusion, the intramolecular structure did not affect the overall absorption of (n-3) PUFAs. Title: Enzymatic interesterification of butterfat with rapeseed oil in a continuous packed bed reactor Ronne TH, Yang T, Mu H, Jacobsen C, Xu X Ref: Journal of Agricultural and Food Chemistry, 53:5617, 2005 : PubMed ESTHER: Ronne_2005_J.Agric.Food.Chem_53_5617 PubMedSearch: Ronne 2005 J.Agric.Food.Chem 53 5617 PubMedID: 15998124 Abstract Lipase-catalyzed interesterification of butterfat blended with rapeseed oil (70/30, w/w) was investigated both in batch and in continuous reactions. Six commercially available immobilized lipases were screened in batch experiments, and the lipases, Lipozyme TL IM and Lipozyme RM IM, were chosen for further studies in a continuous packed bed reactor. TL IM gave a fast reaction and had almost reached equilibrium with a residence time of 30 min, whereas RM IM required 60 min. The effect of reaction temperature was more pronounced for RM IM. TL IM showed little effect on the interesterification degree when the temperature was raised from 60 degrees C to 90 degrees C, whereas RM IM had a positive effect when the temperature was increased from 40 degrees C to 80 degrees C. Even though TL IM is an sn-1,3 specific lipase, small changes in the sn-2 position of the triacylglycerol could be seen. The tendency was toward a reduction of the saturated fatty acid C14:0 and C16:0 and an increase of the long-chain saturated and unsaturated fatty acids (C18:0 and C18:1), especially at longer residence times (90 min). In prolonged continuous operation the activity of TL IM was high for the first 5 days, whereafter it dramatically decreased over the next 10 days to an activity level of 40%. In general, the study shows no significant difference for butterfat interesterification in terms of enzyme behavior from normal vegetable oils and fats even though it contains short-chain fatty acids and cholesterol. However, the release of short-chain fatty acids from enzymatic reactions makes the sensory quality unacceptable for direct edible applications. Title: Lipase-catalyzed acyl exchange of soybean phosphatidylcholine in n-Hexane: a critical evaluation of both acyl incorporation and product recovery Vikbjerg AF, Mu H, Xu X Ref: Biotechnol Prog, 21:397, 2005 : PubMed ESTHER: Vikbjerg_2005_Biotechnol.Prog_21_397 PubMedSearch: Vikbjerg 2005 Biotechnol.Prog 21 397 PubMedID: 15801777 Abstract Lipase-catalyzed acidolysis was examined for the production of structured phospholipids in a hexane system. In a practical operation of the reaction system, the formation of lyso-phospholipids from hydrolysis is often a serious problem, as demonstrated from previous studies. A clear elucidation of the issue and optimization of the system are essential for the practical applications in reality. The effects of enzyme dosage, reaction temperature, solvent amount, reaction time, and substrate ratio were optimized in terms of the acyl incorporation, which led to the products, and lyso-phospholipids formed by hydrolysis, which led to the low yields. The biocatalyst used was the commercial immobilized lipase Lipozyme TL IM and substrates used were phosphatidylcholine (PC) from soybean and caprylic acid. A response surface design was used to evaluate the influence of selected parameters and their relationships on the incorporation of caprylic acid and the corresponding recovery of PC. Incorporation of fatty acids increased with increasing enzyme dosage, reaction temperature, solvent amount, reaction time, and substrate ratio. Enzyme dosage had the most significant effect on the incorporation, followed by reaction time, reaction temperature, solvent amount, and substrate ratio. However the parameters had also a negative influence on the PC recovery. Solvent amount had the most negative effect on recovery, followed by enzyme dosage, temperature, and reaction time. Individually substrate ratio had no significant effect on the PC recovery. Interactions were observed between different parameters. On the basis of the models, the reaction was optimized for the maximum incorporation and maximum PC recovery. With all of the considerations, the optimal conditions are recommended as enzyme dosage 29%, reaction time 50 h, temperature 54 degrees C, substrate ratio 15 mol/mol caprylic acid/PC, and 5 mL of hexane per 3 g substrate. No additional water is necessary. Under these conditions, an incorporation of caprylic acid up to 46% and recovery of PC up to 60% can be obtained from the prediction. The prediction was confirmed from the verification experiments. Title: Genome dynamics and diversity of Shigella species, the etiologic agents of bacillary dysentery Yang F, Yang J, Zhang X, Chen L, Jiang Y, Yan Y, Tang X, Wang J, Xiong Z and Jin Q <17 more author(s)> Yang F, Yang J, Zhang X, Chen L, Jiang Y, Yan Y, Tang X, Wang J, Xiong Z, Dong J, Xue Y, Zhu Y, Xu X, Sun L, Chen S, Nie H, Peng J, Xu J, Wang Y, Yuan Z, Wen Y, Yao Z, Shen Y, Qiang B, Hou Y, Yu J, Jin Q (- 17) Ref: Nucleic Acids Research, 33:6445, 2005 : PubMed ESTHER: Yang_2005_Nucleic.Acids.Res_33_6445 PubMedSearch: Yang 2005 Nucleic.Acids.Res 33 6445 PubMedID: 16275786 Gene_locus related to this paper: ecoli-yeiG, shidy-IROD, shidy-q67dv1, shifl-AES, shifl-BIOH, shifl-entf, shifl-FES, shifl-PLDB, shifl-PTRB, shifl-S2753, shifl-SF1334, shifl-SF1808, shifl-SF3046, shifl-SF3908, shifl-yafa, shifl-YBFF, shifl-YCDJ, shifl-ycfp, shifl-YCJY, shifl-YFBB, shifl-YHET, shifl-YJFP, shifl-YPFH, shiss-yaim, shiss-yeiG, shiss-yqia Abstract The Shigella bacteria cause bacillary dysentery, which remains a significant threat to public health. The genus status and species classification appear no longer valid, as compelling evidence indicates that Shigella, as well as enteroinvasive Escherichia coli, are derived from multiple origins of E.coli and form a single pathovar. Nevertheless, Shigella dysenteriae serotype 1 causes deadly epidemics but Shigella boydii is restricted to the Indian subcontinent, while Shigella flexneri and Shigella sonnei are prevalent in developing and developed countries respectively. To begin to explain these distinctive epidemiological and pathological features at the genome level, we have carried out comparative genomics on four representative strains. Each of the Shigella genomes includes a virulence plasmid that encodes conserved primary virulence determinants. The Shigella chromosomes share most of their genes with that of E.coli K12 strain MG1655, but each has over 200 pseudogenes, 300 approximately 700 copies of insertion sequence (IS) elements, and numerous deletions, insertions, translocations and inversions. There is extensive diversity of putative virulence genes, mostly acquired via bacteriophage-mediated lateral gene transfer. Hence, via convergent evolution involving gain and loss of functions, through bacteriophage-mediated gene acquisition, IS-mediated DNA rearrangements and formation of pseudogenes, the Shigella spp. became highly specific human pathogens with variable epidemiological and pathological features. Title: A common haplotype of the nicotine acetylcholine receptor alpha 4 subunit gene is associated with vulnerability to nicotine addiction in men Feng Y, Niu T, Xing H, Xu X, Chen C, Peng S, Wang L, Laird N Ref: American Journal of Human Genetics, 75:112, 2004 : PubMed ESTHER: Feng_2004_Am.J.Hum.Genet_75_112 PubMedSearch: Feng 2004 Am.J.Hum.Genet 75 112 PubMedID: 15154117 Abstract Nicotine is the major addictive substance in cigarettes, and genes involved in sensing nicotine are logical candidates for vulnerability to nicotine addiction. We studied six single-nucleotide polymorphisms (SNPs) in the CHRNA4 gene and four SNPs in the CHRNB2 gene with respect to nicotine dependence in a collection of 901 subjects (815 siblings and 86 parents) from 222 nuclear families with multiple nicotine-addicted siblings. The subjects were assessed for addiction by both the Fagerstrom Test for Nicotine Dependence (FTND) and the Revised Tolerance Questionnaire (RTQ). Because only 5.8% of female offspring were smokers, only male subjects were included in the final analyses (621 men from 206 families). Univariate (single-marker) family-based association tests (FBATs) demonstrated that variant alleles at two SNPs, rs1044396 and rs1044397, in exon 5 of the CHRNA4 gene were significantly associated with a protective effect against nicotine addiction as either a dichotomized trait or a quantitative phenotype (i.e., age-adjusted FTND and RTQ scores), which was consistent with the results of the global haplotype FBAT. Furthermore, the haplotype-specific FBAT showed a common (22.5%) CHRNA4 haplotype, GCTATA, which was significantly associated with both a protective effect against nicotine addiction as a dichotomized trait (Z=-3.04, P<.005) and significant decreases of age-adjusted FTND (Z=-3.31, P<.005) or RTQ scores (Z=-2.73, P=.006). Our findings provide strong evidence suggesting a common CHRNA4 haplotype might be protective against vulnerability to nicotine addiction in men. Title: A sensitive method for the determination of the novel cholinesterase inhibitor ZT-1 and its active metabolite huperzine A in rat blood using liquid chromatography/tandem mass spectrometry Li C, Du F, Yu C, Xu X, Zheng J, Xu F, Zhu D Ref: Rapid Commun Mass Spectrom, 18:651, 2004 : PubMed ESTHER: Li_2004_Rapid.Commun.Mass.Spectrom_18_651 PubMedSearch: Li 2004 Rapid.Commun.Mass.Spectrom 18 651 PubMedID: 15052575 Inhibitor(s) related to this paper: ZT-1 Abstract ZT-1 has been developed as a novel acetylcholinesterase inhibitor, but is rapidly degraded to huperzine A (Hup A) in water or aqueous organic solvents. A sensitive method has been developed for simultaneous determination of ZT-1 and its active metabolite Hup A in blood, and was applied to the investigation of the pharmacokinetics of ZT-1 in rats. The method involves immediate hydrogenation of ZT-1 with sodium borohydride to the stable form rZT-1 following blood sampling. The NaBH4-treated blood sample is then submitted to liquid-liquid extraction, and the resultant extract is analyzed by liquid chromatography with electrospray ionization and tandem mass spectrometry. Huperzine B is used as internal standard for the quantification. ZT-1 was found to be rapidly absorbed in the intestinal tract, with a time to reach the peak blood concentration (Tpeak) of 5 min after an intragastric dose of ZT-1 embedded in povidone to rats at 0.5 mg ZT-1/kg. The mean maximum blood concentration (Cmax) and area under the blood level-time curve (AUC(0 --> 8)) of ZT-1 were 1.57 ng/mL and 0.48 ng. h/mL, respectively. The Tpeak, Cmax, and AUC values of the metabolite Hup A were 0.22 h, 109.9 ng/mL, and 96.3 ng. h/mL, respectively. Following an intravenous dose of 0.1 mg ZT-1/kg rat body weight, the blood concentration of ZT-1 was higher than that of Hup A, and the AUC(0 --> 8) values were 26.2 ng. h/mL for ZT-1 and 6.0 ng. h/mL for Hup A. The elimination half-lives (T1/2) of ZT-1 and Hup A were 0.68 and 1.47 h, respectively. The oral bioavailability (F) of intact ZT-1 in rats treated with ZT-1 embedded in povidone was very low, 0.37%. Title: Synthesis of structured triacylglycerols containing caproic acid by lipase-catalyzed acidolysis: optimization by response surface methodology Zhou D, Xu X, Mu H, Hoy CE, Adler-Nissen J Ref: Journal of Agricultural and Food Chemistry, 49:5771, 2001 : PubMed ESTHER: Zhou_2001_J.Agric.Food.Chem_49_5771 PubMedSearch: Zhou 2001 J.Agric.Food.Chem 49 5771 PubMedID: 11743762 Abstract Production in a batch reactor with a solvent-free system of structured triacylglycerols containing short-chain fatty acids by Lipozyme RM IM-catalyzed acidolysis between rapeseed oil and caproic acid was optimized using response surface methodology (RSM). Reaction time (t(r)), substrate ratio (S(r)), enzyme load (E(l), based on substrate), water content (W(c), based on enzyme), and reaction temperature (T(e)), the five most important parameters for the reaction, were chosen for the optimization. The range of each parameter was selected as follows: t(r) = 5-17 h; E(l) = 6-14 wt %; T(e) = 45-65 degrees C; S(r) = 2-6 mol/mol; and W(c) = 2-12 wt %. The biocatalyst was Lipozyme RM IM, in which Rhizomucor miehei lipase is immobilized on a resin. The incorporation of caproic acid into rapeseed oil was the main monitoring response. In addition, the contents of mono-incorporated structured triacylglycerols and di-incorporated structured triacylglycerols were also evaluated. The optimal reaction conditions for the incorporation of caproic acid and the content of di-incorporated structured triacylglycerols were as follows: t(r) = 17 h; S(r) = 5; E(l) = 14 wt %; W(c) = 10 wt %; T(e) = 65 degrees C. At these conditions, products with 55 mol % incorporation of caproic acid and 55 mol % di-incorporated structured triacylglycerols were obtained. Title: Paraoxonase polymorphism and its effect on male reproductive outcomes among Chinese pesticide factory workers Padungtod C, Niu T, Wang Z, Savitz DA, Christiani DC, Ryan LM, Xu X Ref: American Journal of Industrial Medicine, 36:379, 1999 : PubMed ESTHER: Padungtod_1999_Am.J.Ind.Med_36_379 PubMedSearch: Padungtod 1999 Am.J.Ind.Med 36 379 PubMedID: 10470002 Abstract BACKGROUND Serum paraoxonase has been associated with the metabolism of organophosphate pesticides in humans. Molecular analysis of the human paraoxonase gene (PON1) has revealed that Arg192 homozygotes have a greater detoxifying capability than Gln192 homozygotes. We examined the effects of PON1 genotypes on male reproductive outcomes and its interaction with exposure to organophosphate pesticides. METHODS: We studied 60 Chinese pesticide-factory workers and 89 textile-factory workers who were unexposed to pesticides. The respective allele frequencies of Arg192 and Gln192 were 0.62 and 0.38. Pesticide exposure among 36 exposed subjects and 12 unexposed subjects, regardless of gender, was assessed by personal measurement of pesticide residues over an entire 8-hr shift and measurement of urinary p-nitrophenol level over a 24-hr period. We analyzed semen and hormone data collected from male subjects. RESULTS: When the three PON1 genotypes were analyzed separately, a gene dose effect was not detected. We used the unexposed Arg192 homo/heterozygotes as the reference group, and re-analyzed the data. Exposed Arg192 homo/heterozygotes had significantly lower sperm count (chi 2 = 9.01, P < 0.01) and lower percentage of sperm with normal morphology (chi 2 = 4.18, P < 0.05) than the reference group. Both unexposed Gln192 homozygotes (chi 2 = 4.90, P < 0.05) and exposed Arg192 homo/heterozygotes (chi 2 = 10.00, P < 0.01) showed significantly lower sperm concentrations than the reference group. In addition, exposed Arg192 homo/heterozygotes had significantly higher serum LH levels (chi 2 = 7.94, P < 0.01) than the reference group. CONCLUSIONS: Because of a small sample size, our findings are highly preliminary. Nevertheless, it calls for further investigation of the interaction between the PON1 genotype and organophosphate pesticide exposure on male reproductive outcomes. Title: Reproductive hormone profile among pesticide factory workers Padungtod C, Lasley BL, Christiani DC, Ryan LM, Xu X Ref: J Occup Environ Med, 40:1038, 1998 : PubMed ESTHER: Padungtod_1998_J.Occup.Environ.Med_40_1038 PubMedSearch: Padungtod 1998 J.Occup.Environ.Med 40 1038 PubMedID: 9871879 Abstract Serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone levels, as well as urinary levels of FSH, LH, and E1C, a metabolite of testosterone, were measured to investigate the adverse reproductive effects of organophosphate pesticides among Chinese factory workers who were occupationally exposed to ethylparathion and methamidophos. Thirty-four exposed workers were randomly chosen and recruited from a large pesticide factory, and 44 unexposed workers were selected from a nearby textile factory. A quantitative pesticide exposure assessment was performed among a subset of the exposed and unexposed workers. Information on potential confounders was collected in an interview. A single blood sample was collected at the end of a work shift, when each subject also donated a semen sample. Three first-voided urine samples were collected from each worker on 3 consecutive days. Urinary p-nitrophenol level at 1 hour after the work shift correlated with serum (r = 0.71, P < 0.01) and urinary (r = 0.51, P = 0.04) FSH levels. Stratifying by the subjects' exposure status, we found a significant negative correlation among the exposed group between urinary FSH level and sperm count (r = -0.61, P < 0.01) and between urinary FSH level and sperm concentration (r = -0.53, P = 0.03). Pesticide exposure alone was significantly associated with serum LH level (beta [coefficient of exposure effect] = 0.79; 95% confidence interval [CI] = 0.42, 1.16) but not with serum FSH or testosterone or with any urinary hormone levels. With adjustment for age, rotating shift work, current cigarette smoking, and current alcohol consumption, exposure significantly increased the serum LH level by 1.1 mIU/mL (95% CI = 0.34, 1.82). Meanwhile, the serum FSH level was slightly elevated (beta [coefficient of exposure effect] = 1.38; 95% CI = -0.09, 2.85) and the serum testosterone level was decreased (beta = -55.13; 95% CI = -147.24, 37) with increased pesticide exposure. Age and rotating shift work appeared to act as confounders. We conclude that organophosphate pesticides have a small effect on male reproductive hormones, suggestive of a secondary hormonal disturbance after testicular damage. Title: The N-terminal domain of RGS4 confers receptor-selective inhibition of G protein signaling Zeng W, Xu X, Popov S, Mukhopadhyay S, Chidiac P, Swistok J, Danho W, Yagaloff KA, Fisher SL and Wilkie TM <2 more author(s)> Zeng W, Xu X, Popov S, Mukhopadhyay S, Chidiac P, Swistok J, Danho W, Yagaloff KA, Fisher SL, Ross EM, Muallem S, Wilkie TM (- 2) Ref: Journal of Biological Chemistry, 273:34687, 1998 : PubMed ESTHER: Zeng_1998_J.Biol.Chem_273_34687 PubMedSearch: Zeng 1998 J.Biol.Chem 273 34687 PubMedID: 9856989 Abstract Regulators of heterotrimeric G protein signaling (RGS) proteins are GTPase-activating proteins (GAPs) that accelerate GTP hydrolysis by Gq and Gi alpha subunits, thus attenuating signaling. Mechanisms that provide more precise regulatory specificity have been elusive. We report here that an N-terminal domain of RGS4 discriminated among receptor signaling complexes coupled via Gq. Accordingly, deletion of the N-terminal domain of RGS4 eliminated receptor selectivity and reduced potency by 10(4)-fold. Receptor selectivity and potency of inhibition were partially restored when the RGS4 box was added together with an N-terminal peptide. In vitro reconstitution experiments also indicated that sequences flanking the RGS4 box were essential for high potency GAP activity. Thus, RGS4 regulates Gq class signaling by the combined action of two domains: 1) the RGS box accelerates GTP hydrolysis by Galphaq and 2) the N terminus conveys high affinity and receptor-selective inhibition. These activities are each required for receptor selectivity and high potency inhibition of receptor-coupled Gq signaling. | |||||||
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