Author Report for: Zhao QNo contact information in database for Zhao Q
Sun H, Guo X, Zhu X, Gu P, Zhang W, Tao W, Wang D, Wu Y, Zhao Q and Zhang Y <2 more author(s)> Sun H, Guo X, Zhu X, Gu P, Zhang W, Tao W, Wang D, Wu Y, Zhao Q, Xu G, Fu X, Zhang Y (- 2) Ref: Mol Plant, :, 2023 : PubMed ESTHER: Sun_2023_Mol.Plant__ PubMedSearch: Sun 2023 Mol.Plant PubMedID: 36683328 Abstract Modern semi-dwarf rice varieties of the 'Green Revolution' require a high nitrogen (N) fertilizer supply to obtain a high yield. A better understanding of the interplay between N metabolic and developmental processes is required for improved N use efficiency (NUE) and agricultural sustainability. Here, we show that strigolactones (SLs) modulate root metabolic and developmental adaptations to low N availability, which ensure efficient uptake and translocation of available N. The key repressor DWARF 53 (D53) of the SL signalling interacts with the transcription factor GROWTH-REGULATING FACTOR 4 (GRF4) and prevents GRF4 from binding to its target gene promoters. N limitation induces the accumulation of SLs, which in turn promotes SL-mediated degradation of D53, leading to the release of GRF4 and thus promoting the genes expression associated with N metabolism. N limitation also induces degradation of the rice DELLA protein SLENDER RICE 1 (SLR1) in the D14- and D53-dependent manners, and that is effective for the release of GRF4 from the competitive inhibition caused by SLR1. Our findings reveal a previously unknown mechanism underlying SL and gibberellin crosstalk in response to N availability, which advances our understanding of plant growth-metabolic coordination that can be useful to improve NUE in high-yield crops. Title: CRISPR-Cas12a based fluorescence assay for organophosphorus pesticides in agricultural products Fu R, Wang Y, Liu Y, Liu H, Zhao Q, Zhang Y, Wang C, Li Z, Jiao B, He Y Ref: Food Chem, 387:132919, 2022 : PubMed ESTHER: Fu_2022_Food.Chem_387_132919 PubMedSearch: Fu 2022 Food.Chem 387 132919 PubMedID: 35421656 Abstract Herein, we propose a sensitive fluorescent assay for organophosphorus pesticides (OPs) detection based on a novel strategy of activating the CRISPR-Cas12a system. Specifically, acetylcholinesterase (AChE) hydrolyzes acetylthiocholine into thiocholine (TCh). Subsequently, TCh induces the degradation of MnO(2) nanosheets and generates sufficient Mn(2+) ions to activate the Mn(2+)-dependent DNAzyme. Then, as the catalytic product of activated DNAzyme, the short DNA strand activates the CRISPR-Cas12a system to cleave the fluorophore-quencher-labeled DNA reporter (FQ) probe effectively; thus, increasing the fluorescence intensity (FI) in the solution. However, in the presence of OPs, the activity of AChE is suppressed, resulting in a decrease in FI. Under optimized conditions, the limits of detection for paraoxon, dichlorvos, and demeton were 270, 406, and 218 pg/mL, respectively. Benefiting from the outstanding MnO(2) nanosheets properties and three rounds of enzymatic signal amplification, the proposed fluorescence assay holds great potential for the detection of OPs in agricultural products. Title: Evodiamine-A Privileged Structure with Broad-Ranging Biological Activities Li D, Li Y, Jiang X, Liu W, Zhao Q Ref: Mini Rev Med Chem, :, 2022 : PubMed ESTHER: Li_2022_Mini.Rev.Med.Chem__ PubMedSearch: Li 2022 Mini.Rev.Med.Chem PubMedID: 35379148 Abstract Evodiamine (EVO) is a natural quinolone alkaloid firstly isolated from the fruit of Evodia rutaecarpa, which is one of the most frequently used traditional Chinese herb for treating a variety of ailments including headaches, abdominal pain, vomiting, diarrhea, amenorrhea difficult menstruation, postpartum hemorrhage, and other diseases. Latest pharmacological studies showed that EVO possesses a broad spectrum of pharmacological activities through different mechanisms. However, its moderate activities and poor physicochemical properties hampered its clinical application. In this regard, the modification of EVO aiming at seeking derivatives with more potency and better physicochemical properties has been extensively emerging. These derivatives exhibit diverse biological activities including antitumor, anti-Alzheimer's disease, anti-pulmonary hypertension, anti-fungi, and thermogenic activities via a variety of mechanisms. Moreover, they were described to act as single, dual, or multiple inhibitors or agonists of many proteins such as topoisomerase I, topoisomerase II, tubulin, histone deacetylase, sirtuins, butyrylcholinesterase, phosphodiesterase 5, and transient receptor potential vanilloid 1. However, hitherto, there is no comprehensive review to systematically summarize the derivatives of EVO. In this perspective, this paper aims to provide a comprehensive description of them focused on their diverse biological activities. For each biological activity, the mechanisms and the main structure-activity relationships (SARs) will be presented in cases where adequate information is available. Finally, future directions of this class of compounds will be discussed. This review will be helpful in understanding and encouraging further exploration of EVO. Title: Toxic effects of waterborne benzylparaben on the growth, antioxidant capacity and lipid metabolism of Nile tilapia (Oreochromis niloticus) Lin H, Jia Y, Han F, Xia C, Zhao Q, Zhang J, Li E Ref: Aquat Toxicol, 248:106197, 2022 : PubMed ESTHER: Lin_2022_Aquat.Toxicol_248_106197 PubMedSearch: Lin 2022 Aquat.Toxicol 248 106197 PubMedID: 35623196 Abstract Benzylparaben (BzP) is a potential endocrine disruptor; however, its antioxidant defense, lipotoxicity and underlying mechanism of BzP in aquatic organisms are unknown. This study investigated the impacts of waterborne low-, environmental-related and high-level benzylparaben on the growth, antioxidant capacity, lipid metabolism and lipidomic response of Nile tilapia (Oreochromis niloticus). Juvenile tilapia (0.60 +/- 0.11 g) were exposed to 0, 5, 50, 500 and 5000 ng/L benzylparaben for 8 weeks in quadruplicate for each group. Benzylparaben increased the body crude fat content but decreased brain acetylcholinesterase activity in O. niloticus. Benzylparaben caused oxidative stress, leading to hepatic morphology damage and lipid metabolism disorders in fish. Lipidomic analysis identified 13 lipid classes in fish liver. Benzylparaben exposure induced metabolic disorders of glycerol phospholipids, glycerolipids and sphingomyelins in fish liver. These findings indicate that environmentally related benzylparaben levels (5 to 50 ng/L) could induce an antioxidant response, result in triglyceride accumulation, and increase adipocyte formation and fatty acid intake in tilapia. However, high benzylparaben concentrations inhibit lipid deposition, presumably due to the effects of the antioxidant system, and induce tissue inflammation. Therefore, this study provides new insights into the toxic effects and potential mechanism of benzylparaben in fish, especially from the aspect of lipid metabolism. Title: Discovery of novel tacrine derivatives as potent antiproliferative agents with CDKs inhibitory property Liu W, Wu L, Li D, Huang Y, Liu M, Tian C, Liu X, Jiang X, Hu X and Zhao Q <3 more author(s)> Liu W, Wu L, Li D, Huang Y, Liu M, Tian C, Liu X, Jiang X, Hu X, Gao X, Xu Z, Lu H, Zhao Q (- 3) Ref: Bioorg Chem, 126:105875, 2022 : PubMed ESTHER: Liu_2022_Bioorg.Chem_126_105875 PubMedSearch: Liu 2022 Bioorg.Chem 126 105875 PubMedID: 35623141 Abstract Tacrine was the first approved drug by the FDA for the treatment of Alzheimer's disease (AD) but was withdrawn from the market due to its dose-dependent hepatotoxicity. Herein, we describe our efforts toward the discovery of a novel series of tacrine derivatives for cancer therapeutics. Intensive structural modifications of tacrine led to the identification of N-(4-{9-[(3S)-3-aminopyrrolidin-1-yl]-5,6,7,8-tetrahydroacridin-2-yl}pyridin-2-yl)cyclopropanecarboxamide hydrochloride ((S)-45, ZLWT-37) as a potent antiproliferative agent (GI(50) = 0.029 microM for HCT116). In addition, ZLWT-37 exhibited lower inhibitory activity against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) compared to tacrine. The in vitro studies demonstrated that ZLWT-37 could significantly induce apoptosis and arrest the cell cycle in the G2/M phase in HCT116 cells. The in vivo studies revealed that compound ZLWT-37 showed excellent antitumor efficacy in HCT116 xenograft tumor model and favorable pharmacokinetics profiles (F% = 28.70%) as well as low toxicity in the acute toxicity test with a median lethal dose (LD(50)) of 380.3 mg/kg. Encouragingly, ZLWT-37 had no obvious hepatotoxicity, nephrotoxicity, and hematologic toxicity. Kinase assay suggested that ZLWT-37 possessed potent cyclin-dependent kinase 9 (CDK9) inhibitory activity (IC(50) = 0.002 microM) and good selectivity over CDK2 (IC(50) = 0.054 microM). Collectively, these findings indicate that compound ZLWT-37 is a promising anti-cancer agent that deserves further preclinical evaluation. Title: Design, synthesis and biological evaluation of novel coumarin derivatives as multifunctional ligands for the treatment of Alzheimer's disease Liu W, Wu L, Tian L, Chen H, Wu Z, Wang N, Liu X, Qiu J, Feng X and Zhao Q <2 more author(s)> Liu W, Wu L, Tian L, Chen H, Wu Z, Wang N, Liu X, Qiu J, Feng X, Xu Z, Jiang X, Zhao Q (- 2) Ref: Eur Journal of Medicinal Chemistry, 242:114689, 2022 : PubMed ESTHER: Liu_2022_Eur.J.Med.Chem_242_114689 PubMedSearch: Liu 2022 Eur.J.Med.Chem 242 114689 PubMedID: 36007469 Abstract Multi-targeted directed ligands (MTDLs) are emerging as promising Alzheimer's disease (AD) therapeutic possibilities. Coumarin is a multifunctional backbone with extensive bioactivity that has been utilized to develop innovative anti-neurodegenerative properties and is a desirable starting point for the construction of MTDLs. Herein, we explored and synthesized a series of novel coumarin derivatives and assessed their inhibitory effects on cholinesterase (AChE, BuChE), GSK-3beta, and BACE1. Among these compounds, compound 30 displayed the multifunctional profile of targeting the AChE (IC(50) = 1.313 +/- 0.099 microM) with a good selectivity over BuChE (SI = 24.623), GSK-3beta (19.30% inhibition at 20 microM), BACE1 (IC(50) = 1.227 +/- 0.112 microM), along with moderate HepG2 cytotoxicity, SH-SY5Y cytotoxicity, low HL-7702 cytotoxicity, as well as good blood-brain barrier (BBB) permeability. Kinetic and docking studies indicated that compound 30 was a competitive AChE inhibitor. Furthermore, acute toxicity experiments revealed that it was non-toxic at a dosage of 1000 mg/kg. The ADME prediction results indicate that 30 has acceptable physicochemical properties. Collectively, these findings demonstrated that compound 30 would be a potential multifunctional candidate for AD therapy. Title: Discovery of novel beta-carboline-1,2,3-triazole hybrids as AChE/GSK-3beta dual inhibitors for Alzheimer's disease treatment Liu W, Tian L, Wu L, Chen H, Wang N, Liu X, Zhao C, Wu Z, Jiang X and Zhao Q <2 more author(s)> Liu W, Tian L, Wu L, Chen H, Wang N, Liu X, Zhao C, Wu Z, Jiang X, Wu Q, Xu Z, Zhao Q (- 2) Ref: Bioorg Chem, 129:106168, 2022 : PubMed ESTHER: Liu_2022_Bioorg.Chem_129_106168 PubMedSearch: Liu 2022 Bioorg.Chem 129 106168 PubMedID: 36191431 Inhibitor(s) related to this paper: ZTL-11 Abstract Alzheimer's disease (AD) is characterized by progressive cognitive impairment and mental behavior. The combination inhibition of two essential AD targets, acetylcholinesterase (AChE) and glycogen synthase kinase-3beta (GSK-3beta), might be a breakthrough in the discovery of therapeutic success. Herein, 17 beta-carboline-1,2,3-triazole hybrids were designed, synthesized, and evaluated for their AChE and GSK-3beta inhibitory potential. The results indicated that compound 21 has the most potent inhibition against eeAChE (IC(50) = 0.20 +/- 0.02 microM), hAChE (IC(50) = 0.34 +/- 0.01 microM) and GSK-3beta (IC(50) = 1.14 +/- 0.05 microM) among these compounds. In addition, it inhibited hAChE in a mixed type manner and could occupy the binding pocket forming diverse interactions with the target of AChE and GSK-3beta. Moreover, compound 21 showed low cytotoxicity against SH-SY5Y and HepG2 cell lines and good BBB permeability. Compound 21 also attenuated the tau hyperphosphorylation in the Tau (P301L) 293T cell model. The ADME projection exhibited that compound 21 has acceptable physicochemical characteristics. This study provides new leads for the assessment of AChE and GSK-3beta dual inhibition as a promising strategy for AD treatment. Title: Natural Antioxidants, Tyrosinase and Acetylcholinesterase Inhibitors from Cercis glabra Leaves Lou Y, Xu T, Cao H, Zhao Q, Zhang P, Shu P Ref: Molecules, 27:, 2022 : PubMed ESTHER: Lou_2022_Molecules_27_ PubMedSearch: Lou 2022 Molecules 27 PubMedID: 36557801 Abstract Cercis glabra is a plant belonging to the legume family, whose flowers and barks are commonly used as food and traditional Chinese medicines. However, its leaves are usually disposed of as wastes. This research comprehensively investigated the bioactive constituents of C. glabra leaves, and two new phenolic, ceroffesters A-B (1-2) and thirteen known compounds (3-15) were isolated. Their structures were elucidated by spectroscopic methods such as nuclear magnetic resonance (1D NMR and 2D NMR), high-resolution electrospray ionization mass spectra (HR-ESI-MS), optical rotatory dispersion (ORD) and electronic circular dichroism (ECD). All of them were assessed for their antioxidant activities through ABTS, DPPH and PTIO methodologies, and evaluated for inhibitory activities against two enzymes (mushroom tyrosinase and acetylcholinesterase). As a result, compounds 3-6, 10 and 13 exhibited evident antioxidant activities. Meanwhile, compounds 5, 10 and 13 showed the most potent tyrosinase inhibitory activities, with IC(50) of 0.64, 0.65 and 0.59 mM, and compared with the positive control of 0.63 mM (kojic acid). In the initial concentration of 1 mg/mL, compounds 3, 5 and 6 demonstrated moderate inhibitory activities against acetylcholinesterase with 85.27 +/- 0.06%, 83.65 +/- 0.48% and 82.21 +/- 0.09%, respectively, compared with the positive control of 91.17 +/- 0.23% (donepezil). These bioactive components could be promising antioxidants, tyrosinase and acetylcholinesterase inhibitors. Title: Colorimetric Assay for Acetylcholinesterase Activity and Inhibitor Screening Based on Metal-Organic Framework Nanosheets Wang Y, Xue Y, Zhao Q, Wang S, Sun J, Yang X Ref: Analytical Chemistry, 94:16345, 2022 : PubMed ESTHER: Wang_2022_Anal.Chem_94_16345 PubMedSearch: Wang 2022 Anal.Chem 94 16345 PubMedID: 36444539 Abstract Alzheimer's disease (AD) is a common chronic neurodegenerative disease that manifests as cognitive impairment and behavioral deficits and severely threatens the health of the elderly. Acetylcholinesterase (AChE) plays a vital role in biological signaling and is an essential target for the early diagnosis and treatment of AD. Herein, 2D Zn-TCPP(Fe) nanosheets (NSs) employing Zn(2+) and Fe-bound tetrakis(4-carboxyphenyl)porphyrin ligands were prepared through a surfactant-assisted synthetic method. The ultrathin two-dimensional (2D) metal-organic framework structures exhibited high peroxidase-like activity, which allowed the catalysis of the H(2)O(2)-initiated oxidation of colorless 3,3',5,5'-tetramethylbenzidine (TMB) to blue oxidized TMB (ox-TMB). Such catalytic performance inspired us to develop a convenient, rapid, and sensitive acetylcholinesterase activity assay, during which AChE can catalyze the substrate acetylthiocholine (ATCh) to produce thiocholine (TCh), and TCh could especially enable the degradation of 2D Zn-TCPP(Fe) NSs accompanied by the reduction of ox-TMB production. Our proposed sensing system exhibited favorable selectivity and sensitivity (LOD of 0.029 mU/mL) and has excellent potential to evaluate AChE activity in human serum samples and to screen AChE inhibitors. This colorimetric assay could provide an alternative pathway for early diagnosis and drug screening of AD, facilitating the development of AD therapy. 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: Chain-locked precursor ion scanning based HPLC-MS/MS for in-depth molecular analysis of lipase-catalyzed transesterification of structured phospholipids containing -3 fatty acyl chains Zhang M, Wang P, Jin D, Jian S, Wu J, Huang M, Xie H, Zhao Q, Yang H and Shen Q <3 more author(s)> Zhang M, Wang P, Jin D, Jian S, Wu J, Huang M, Xie H, Zhao Q, Yang H, Luo P, Yuan H, Xue J, Shen Q (- 3) Ref: Food Chem, 399:133982, 2022 : PubMed ESTHER: Zhang_2022_Food.Chem_399_133982 PubMedSearch: Zhang 2022 Food.Chem 399 133982 PubMedID: 36027811 Abstract Lipase-catalyzed transesterification of structured phospholipids (sPLs) is a hot topic, but the structural variation of the fatty acyl chains in intact phospholipids at the molecular level remains unclear to date. The present study explored the detailed characteristics of synthesized phospholipids through high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) in precursor ion scan mode. The optimal conditions were in-depth inspected and determined for the reaction system, including phospholipase A1 as catalyst, 15% lipase loading, and 1% water content. The sPLs enriched with EPA/DHA were structurally and quantitatively characterized by focusing on the fragments of m/z 301.6 (eicosapentaenoic acid, EPA) and m/z 327.6 (docosahexaenoic acid, DHA), and the results were statistically analyzed using partial least squares discriminant analysis and clustered heatmap hierarchical clustering analysis. PC 38:6 (18:1/20:5), PC 38:7 (18:2/20:5), PC o-40:6 (o-18:0/22:6), and PE 40:8 (18:2/22:6) etc. were revealed as the main variables that were active in the reaction. Title: Oxidase-like Nanozyme-Mediated Altering of the Aspect Ratio of Gold Nanorods for Breaking through H(2)O(2)-Supported Multicolor Colorimetric Assay: Application in the Detection of Acetylcholinesterase Activity and Its Inhibitors Fu R, Zhou J, Wang Y, Liu Y, Liu H, Yang Q, Zhao Q, Jiao B, He Y Ref: ACS Appl Bio Mater, 4:3539, 2021 : PubMed ESTHER: Fu_2021_ACS.Appl.Bio.Mater_4_3539 PubMedSearch: Fu 2021 ACS.Appl.Bio.Mater 4 3539 PubMedID: 35014439 Abstract A convenient, fast, and colorful colorimetric platform with high resolution for acetylcholinesterase (AChE) activity and its inhibitors detection based on the regulation of oxidase-like nanozyme-mediated etching of gold nanorods (AuNRs) has been proposed in this work. MnO(2) nanosheets are selected as the nanozyme. Their excellent oxidase-like activity enables the etching process to proceed smoothly without the usage of unstable H(2)O(2). When AChE is present, it catalytically hydrolyzes acetylthiocholine (ATCh) to thiocholine (TCh). With high reducing ability, TCh induces the decomposition of MnO(2) nanosheets, causing them to lose their oxidase-like activity. Thus, the etching of AuNRs is hampered. Consequently, with the increasing concentration of AChE, an apparent change in the AuNRs solution color is observed. The proposed platform achieves high-sensitivity detection of AChE (limit of detection = 0.18 mU/mL). Furthermore, the proposed platform also has been demonstrated its applicability for its inhibitors detection. Benefiting from the advantages of convenient and high resolution of visual readout, the proposed platform holds great potential for the detection of AChE and its inhibitors in clinical diagnosis. Title: Identification of Conserved and Divergent Strigolactone Receptors in Sugarcane Reveals a Key Residue Crucial for Plant Branching Control Hu A, Zhao Q, Chen L, Zhao J, Wang Y, Feng K, Wu L, Xie M, Zhou X and Yao R <3 more author(s)> Hu A, Zhao Q, Chen L, Zhao J, Wang Y, Feng K, Wu L, Xie M, Zhou X, Xiao L, Ming Z, Zhang M, Yao R (- 3) Ref: Front Plant Sci, 12:747160, 2021 : PubMed ESTHER: Hu_2021_Front.Plant.Sci_12_747160 PubMedSearch: Hu 2021 Front.Plant.Sci 12 747160 PubMedID: 34858455 Gene_locus related to this paper: 9poal-a0a0d5nt23 Abstract Strigolactones (SLs) are a class of important plant hormones mainly regulating plant architecture such as branching, which is crucial for crop yield. It is valuable to study SL signaling pathway and its physiological function in sugarcane, the most important sugar crop, for further molecular breeding. Here, two putative SL receptors SsD14a/b and the interacting F-box protein SsMAX2 were identified in Saccharum spontaneum. SL induced both SsD14a and SsD14b to interact with SsMAX2 in yeast. SsD14a, but not SsD14b, could bind with AtMAX2 and AtSMXL7/SsSMXL7. Overexpression of SsD14a or SsMAX2 rescued the increased branching phenotypes of Arabidopsis thaliana d14-1 or max2-3 mutants, respectively. Moreover, the crystal structure of N-terminal truncated SsD14a was solved, with an overall structure identical to AtD14 and OsD14 in the open state, consistent with its conserved branching suppression capacity in Arabidopsis. In line with the biochemical observations, SsD14b could not completely complement in d14-1 although these two SsD14 proteins have almost identical primary sequences except for very few residues. Complement with the combination of SsD14b and SsMAX2 still failed to rescue the d14-1 max2-3 double mutant multi-branching phenotype, indicating SsD14b-AtSMXL7 complex formation is required for regulating branching. Mutagenesis analyses revealed that residue R310 at alpha10 helix of SsD14a was crucial for the binding with SsSMXL7/AtSMXL7 but not SsMAX2. The site-equivalent single-residue P304R substitution enabled SsD14b to bind with AtMAX2 and AtSMXL7/SsSMXL7 and to rescue the phenotype of d14-1 max2-3 together with SsMAX2. Moreover, this conserved Arg residue across species including rice and Arabidopsis determined the activity of SL receptors through maintaining their interaction with SMXL repressors. Taken together, our work identified conserved and divergent strigolactone receptors in sugarcane core SL signaling pathway and revealed a key residue crucial for plant branching control. Title: Discovery of novel beta-carboline derivatives as selective AChE inhibitors with GSK-3beta inhibitory property for the treatment of Alzheimer's disease Liu W, Liu X, Gao Y, Wu L, Huang Y, Chen H, Li D, Zhou L, Wang N and Zhao Q <2 more author(s)> Liu W, Liu X, Gao Y, Wu L, Huang Y, Chen H, Li D, Zhou L, Wang N, Xu Z, Jiang X, Zhao Q (- 2) Ref: Eur Journal of Medicinal Chemistry, 229:114095, 2021 : PubMed ESTHER: Liu_2021_Eur.J.Med.Chem_229_114095 PubMedSearch: Liu 2021 Eur.J.Med.Chem 229 114095 PubMedID: 34995924 Inhibitor(s) related to this paper: ZLWH-23 Abstract The natural product harmine, a representative beta-carboline alkaloid from the seeds of Peganum harmala L. (Zygophyllaceae), possesses a broad spectrum of biological activities. In this study, a novel series of harmine derivatives containing N-benzylpiperidine moiety were identified for the treatment of Alzheimer's disease (AD). The results showed that all the derivatives possessed significant anti-acetylcholinesterase (AChE) activity and good selectivity over butyrylcholinesterase (BChE). In particular, compound ZLWH-23 exhibited potent anti-AChE activity (IC(50) = 0.27 microM) and selective BChE inhibition (IC(50) = 20.82 microM), as well as acceptable glycogen synthase kinase-3 (GSK-3beta) inhibition (IC(50) = 6.78 microM). Molecular docking studies and molecular dynamics simulations indicated that ZLWH-23 could form stable interaction with AChE and GSK-3beta. Gratifyingly, ZLWH-23 exhibited good selectivity for GSK-3beta over multi-kinases and very low cytotoxicity towards SH-SY5Y, HEK-293T, HL-7702, and HepG2 cell lines. Importantly, ZLWH-23 displayed efficient reduction against tau hyperphosphorylation on Ser-396 site in Tau (P301L) 293T cell model. Collectively, harmine-based derivatives could be considered as possible drug leads for the development of AD therapies. Title: The cholinergic system, intelligence, and dental fluorosis in school-aged children with low-to-moderate fluoride exposure Wang S, Zhao Q, Li G, Wang M, Liu H, Yu X, Chen J, Li P, Dong L and Wang A <3 more author(s)> Wang S, Zhao Q, Li G, Wang M, Liu H, Yu X, Chen J, Li P, Dong L, Zhou G, Cui Y, Liu L, Wang A (- 3) Ref: Ecotoxicology & Environmental Safety, 228:112959, 2021 : PubMed ESTHER: Wang_2021_Ecotoxicol.Environ.Saf_228_112959 PubMedSearch: Wang 2021 Ecotoxicol.Environ.Saf 228 112959 PubMedID: 34808511 Abstract Disruption of cholinergic neurotransmission can affect cognition, but little is known about whether low-to-moderate fluoride exposure affects cholinergic system and its effect on the prevalence of dental fluorosis (DF) and intelligence quotient (IQ). A cross-sectional study was conducted to explore the associations of moderate fluoride exposure and cholinergic system in relation to children's DF and IQ. We recruited 709 resident children in Tianjin, China. Ion selective electrode method was used to detect fluoride concentrations in water and urine. Cholinergic system was assessed by the detection of choline acetyltransferase (ChAT), acetylcholinesterase (AChE) and acetylcholine (ACh) levels in serum. Compared with children in the first quartile, those in fourth quartile the risk of either developing DF or IQ < 120 increased by 19% and 20% for water and urinary fluoride. The risk of having both increased by 58% and 62% in third and fourth quartile for water fluoride, 52% and 65% for urinary fluoride. Water fluoride concentrations were positively associated with AChE and negatively associated with ChAT and ACh, trends were same for urinary fluoride except for ACh. The risk of either developing DF or having non-high intelligence rose by 22% (95%CI: 1.07%, 1.38%) for the fourth quartile than those in the first quartile of AChE, for having the both, the risk was 1.27 (95%CI: 1.07, 1.50), 1.37 (95%CI: 1.17, 1.62) and 1.44 (95%CI: 1.23, 1.68) in second, third and fourth quartiles. The mediation proportion by AChE between water fluoride and either developing DF or IQ < 120 was 15.7%. For both to exist, the proportion was 6.7% and 7.2% for water and urinary fluoride. Our findings suggest low-to-moderate fluoride exposure was associated with dysfunction of cholinergic system for children. AChE may partly mediate the prevalence of DF and lower probability of having superior and above intelligence. Title: Structure-guided engineering of a Thermobifida fusca cutinase for enhanced hydrolysis on natural polyester substrate Dong Q, Yuan S, Wu L, Su L, Zhao Q, Wu J, Huang W, Zhou J Ref: Bioresour. Bioprocess, 7:37, 2020 : PubMed ESTHER: Dong_2020_Bioresour.Bioprocess_7_37 PubMedSearch: Dong 2020 Bioresour.Bioprocess 7 37 Gene_locus related to this paper: thefu-q6a0i4 Abstract Cutinases could degrade insoluble polyester, including natural cutin and synthetic plastic. However, their turnover efficiency for polyester remains too low for industrial application. Herein, we report the 1.54-A resolution X-ray crystal structure of a cutinase from Thermobifida fusca and modeling structure in complex with a cutin mimic oligo-polyester C24H42O8. These efforts subsequently guided our design of cutinase variants with less bulky residues in the vicinity of the substrate binding site. The L90A and I213A variants exhibit increased hydrolysis activity (5- and 2.4-fold, respectively) toward cutin and also showed enhanced cotton scouring efficiency compared with the wild-type enzyme. Title: Improved production of recombinant Rhizomucor miehei lipase by coexpressing protein folding chaperones in Pichia pastoris, which triggered ER stress Huang J, Zhao Q, Chen L, Zhang C, Bu W, Zhang X, Zhang K, Yang Z Ref: Bioengineered, 11:375, 2020 : PubMed ESTHER: Huang_2020_Bioengineered_11_375 PubMedSearch: Huang 2020 Bioengineered 11 375 PubMedID: 32175802 Gene_locus related to this paper: rhimi-lipas Abstract Rhizomucor miehei lipase (RML) is a biocatalyst that widely used in laboratory and industrial. Previously, RML with a 70-amino acid propeptide (pRML) was cloned and expressed in P. pastoris. Recombinant strains with (strain containing 4-copy prml) and without ER stress (strain containing 2-copy prml) were obtained. However, the effective expression of pRML in P. pastoris by coexpressing ER-related elements in pRML-produced strain with or without ER stress has not been reported to date. In this study, an efficient way to produce functional pRML was explored in P. pastoris. The coexpression of protein folding chaperones, including PDI and ERO1, in different strains with or without ER stress, was investigated. PDI overexpression only increased pRML production in 4-copy strain from 705 U/mL to 1430 U/mL because it alleviated the protein folded stress, increased the protein concentration from 0.56 mg/mL to 0.65 mg/mL, and improved enzyme-specific activity from 1238 U/mg to 2186 U/mg. However, PDI coexpression could not improve pRML production in the 2-copy strain because it increased protein folded stress, while ERO1 coexpression in the two strains all had a negative effect on pRML expression. We also investigated the effect of the propeptide on the substrate specificity and the condition for pRML enzyme powder preparation. Results showed that the relative activity exceeded 80% when the substrates C8-C10 were detected at 35 degrees C and pH 6, and C8-C12 at 45 degrees C and pH 8. The optimal enzyme powder preparation pH was 7, and the maximum recovery rate for pRML was 73.19%. Title: Serum Cholinesterases, a Novel Marker of Clinical Activity in Inflammatory Bowel Disease: A Retrospective Case-Control Study Shao X, Yang L, Hu K, Shen R, Ye Q, Yuan X, Zhao Q, Shen J Ref: Mediators Inflamm, 2020:4694090, 2020 : PubMed ESTHER: Shao_2020_Mediators.Inflamm_2020_4694090 PubMedSearch: Shao 2020 Mediators.Inflamm 2020 4694090 PubMedID: 32733165 Abstract BACKGROUND: The aim of our study was to investigate whether serum cholinesterase (ChE) levels were associated with inflammatory bowel disease (IBD). MATERIALS AND METHODS: We conducted a retrospective case-control study to clarify the relationship between serum ChE levels and IBD that included 142 patients with ulcerative colitis (UC), 60 patients with Crohn's disease (CD), and 264 healthy controls (HCs). We used ROC curves to evaluate the diagnostic value of serum ChE levels for IBD. RESULTS: Substantially lower serum ChE levels were detected in patients with UC than in HCs (6376 U/L versus 8418 U/L, P < 0.001) and in patients with CD than in HCs (5181 U/L versus 8418 U/L, P < 0.001). Additionally, patients with CD displayed significantly lower serum ChE levels than patients with UC (5181 U/L versus 6376 U/L, P < 0.01). We also found that there was a negative association between serum ChE levels and the Crohn's Disease Activity Index (CDAI) score of patients with CD (P = 0.011) and the Simple Clinical Colitis Activity Index (SCCAI) score of patients with UC (P = 0.018). The area under the curve (AUC) for serum ChE for the diagnosis of IBD was 0.826, and the AUCs of serum ChE for the diagnosis of CD and UC were 0.890 and 0.800, respectively. CONCLUSIONS: Serum ChE levels have important clinical significance in the diagnosis and assessment of clinical activity in patients with IBD, and the cholinergic anti-inflammatory pathway may provide new ideas for targeted treatment of IBD. Title: Optimization of chemoenzymatic Baeyer-Villiger oxidation of cyclohexanone to sigma-caprolactone using response surface methodology Zhang Y, Jiang W, Lv K, Sun Y, Gao X, Zhao Q, Ren W, Wang F, Liu J Ref: Biotechnol Prog, 36:e2901, 2020 : PubMed ESTHER: Zhang_2020_Biotechnol.Prog_36_e2901 PubMedSearch: Zhang 2020 Biotechnol.Prog 36 e2901 PubMedID: 31465150 Abstract sigma-Caprolactone (sigma-CL) has attracted a great deal of attention and a high product concentration is of great significance for reducing production cost. The optimization of sigma-CL synthesis through chemoenzymatic Baeyer-Villiger oxidation mediated by immobilized Trichosporon laibacchii lipase was studied using response surface methodology (RSM). The yield of sigma-CL was 98.06% with about 1.2 M sigma-CL concentration that has a substantial increase mainly due to both better stability of the cross-linked immobilized lipase used and the optimum reaction conditions in which the concentration of cyclohexanone was 1.22 M, the molar ratio of cyclohexanone:urea hydrogen peroxide (UHP) was 1:1.3, and the reaction temperature was 56.5 degreesC. Based on our experimental results, it can be safely concluded that there are three reactions in this reaction system, not just two reactions, in which the third reaction is that the acetic acid formed reacts with UHP to form peracetic acid in situ catalyzed by the immobilized lipase. A quadratic polynomial model based on RSM experimental results was developed and the R(2) value of the equation is 0.9988, indicating that model can predict the experimental results with high precision. The experimental results also show that the molar ratio of cyclohexanone to UHP has very significant impact on the yield of sigma-CL (p < .0006). Title: Voacafrines A-N, aspidosperma-type monoterpenoid indole alkaloids from Voacanga africana with AChE inhibitory activity Zhao Q, Zhu WT, Ding X, Huo ZQ, Donkor PO, Adelakun TA, Hao XJ, Zhang Y Ref: Phytochemistry, 181:112566, 2020 : PubMed ESTHER: Zhao_2020_Phytochemistry_181_112566 PubMedSearch: Zhao 2020 Phytochemistry 181 112566 PubMedID: 33197743 Abstract Fourteen undescribed monoterpenoid indole alkaloids, voacafrines A-N, along with 7 known monoterpenoid indole alkaloids were isolated from the seeds of Voacanga africana Stapf. Among them, voacafrines A-G were aspidosperma-aspidosperma type bisindole alkaloids, while voacafrines H-N were aspidosperma-type monomers. Their structures and absolute configurations were elucidated by a combination of NMR, MS, and ECD analyses. Voacafrines A-C were characterized by an acetonyl moiety at C-5', while voacafrine H possessed a methoxymethyl moiety at C-14 within aspidosperma-type alkaloids. The acetylcholinesterase (AChE) inhibitory activity and cytotoxicity of voacafrines A-N were evaluated. Voacafrines A-C and E-G were bisindole alkaloids that exhibited AChE inhibitory activity with IC(50) values of 4.97-33.28 M, while voacafrines I and J were monomers that showed cytotoxicity against several human cancer cell lines with IC(50) values of 4.45-7.49 M. Title: Genomic Analysis of Microbulbifer sp. Strain A4B-17 and the Characterization of Its Metabolic Pathways for 4-Hydroxybenzoic Acid Synthesis Tian J, Zhu L, Wang W, Zhang L, Li Z, Zhao Q, Xing K, Feng Z, Peng X Ref: Front Microbiol, 9:3115, 2018 : PubMed ESTHER: Tian_2018_Front.Microbiol_9_3115 PubMedSearch: Tian 2018 Front.Microbiol 9 3115 PubMedID: 30619190 Abstract The marine bacterium Microbulbifer sp. A4B-17 produces secondary metabolites such as 4-hydroxybenzoic acid (4HBA) and esters of 4HBA (parabens). 4HBA is a useful material in the synthesis of the liquid crystal. Parabens are man-made compounds that have been extensively used since the 1920s in the cosmetic, pharmaceutical, and food industries for their effective antimicrobial activity. In this study, we completed the sequencing and annotation of the A4B-17 strain genome and found all genes for glucose utilization and 4HBA biosynthesis. Strain A4B-17 uses the Embden-Meyerhof-Parnas (EMP), hexose monophosphate (HMP), and Entner-Doudoroff (ED) pathways to utilize glucose. Other sugars such as fructose, sucrose, xylose, arabinose, galactose, mannitol, and glycerol supported cell growth and 4HBA synthesis. Reverse transcriptional analysis confirmed that the key genes involved in the glucose metabolism were functional. Paraben concentrations were proportionally increased by adding alcohols to the culture medium, indicating that strain A4B-17 synthesizes the 4HBA and the alcohols separately and an esterification reaction between them is responsible for the paraben synthesis. A gene that codes for a carboxylesterase was proposed to catalyze this reaction. The temperature and NaCl concentration for optimal growth were determined to be 35 degrees C and 22.8 g/L. Title: Expression of soluble epoxide hydrolase in renal tubular epithelial cells regulates macrophage infiltration and polarization in IgA nephropathy Wang Q, Liang Y, Qiao Y, Zhao X, Yang Y, Yang S, Li B, Zhao Q, Dong L and Liu Z <2 more author(s)> Wang Q, Liang Y, Qiao Y, Zhao X, Yang Y, Yang S, Li B, Zhao Q, Dong L, Quan S, Tian R, Liu Z (- 2) Ref: American Journal of Physiology Renal Physiol, 315:F915, 2018 : PubMed ESTHER: Wang_2018_Am.J.Physiol.Renal.Physiol_315_F915 PubMedSearch: Wang 2018 Am.J.Physiol.Renal.Physiol 315 F915 PubMedID: 29717935 Abstract Tubulointerstitial inflammatory cell infiltration and activation contribute to kidney inflammation and fibrosis. Epoxyeicosatrienoic acids (EETs), which are rapidly metabolized to dihydroxyeicosatrienoic acids by the soluble epoxide hydrolase (sEH), have multiple biological functions, including vasodilation, anti-inflammatory action, and others. Inhibition of sEH has been demonstrated to attenuate inflammation in many renal disease models. However, the relationship between sEH expression and macrophage polarization in the kidney remains unknown. In this study, we investigated the relationships between the level of sEH and clinical and pathological parameters in IgA nephropathy. The level of sEH expression positively correlated with proteinuria and infiltration of macrophages. sEH-positive tubules were found to be surrounded by macrophages. Furthermore, we found that incubation of immortalized human proximal tubular HK-2 cells with total urinary protein and overexpression of sEH promoted inflammatory factor production, which was associated with M1 polarization. We also exposed RAW264.7 mouse leukemic monocytes/macrophages to different HK-2 cell culture media conditioned by incubation with various substances affecting sEH amount or activity. We found that the upregulation of sEH promoted M1 polarization. However, pharmacological inhibition of sEH and supplementation with EETs reversed the conditioning effects of urinary proteins by inhibiting M1 polarization through the NF-kappaB pathway and stimulating M2 polarization through the phosphatidylinositol 3-kinase pathway. These data suggest that inhibition of sEH could be a new strategy to prevent the progression of inflammation and to attenuate renal tubulointerstitial fibrosis. Title: The metastatic suppressor NDRG1 inhibits EMT, migration and invasion through interaction and promotion of caveolin-1 ubiquitylation in human colorectal cancer cells Mi L, Zhu F, Yang X, Lu J, Zheng Y, Zhao Q, Wen X, Lu A, Wang M and Sun J <2 more author(s)> Mi L, Zhu F, Yang X, Lu J, Zheng Y, Zhao Q, Wen X, Lu A, Wang M, Zheng M, Ji J, Sun J (- 2) Ref: Oncogene, 36:4323, 2017 : PubMed ESTHER: Mi_2017_Oncogene_36_4323 PubMedSearch: Mi 2017 Oncogene 36 4323 PubMedID: 28346422 Gene_locus related to this paper: human-NDRG1 Abstract N-myc downstream-regulated gene 1 (NDRG1) has been reported to act as a key regulatory molecule in tumor progression-related signaling pathways, especially in tumor metastasis. However, the related mechanism has not been fully discovered yet. Herein we demonstrated that the novel molecule of cell migration and invasion, caveolin-1, has direct interaction with NDRG1 in human colorectal cancer (CRC) cells. Moreover, we discovered that NDRG1 reduces caveolin-1 protein expression through promoting its ubiquitylation and subsequent degradation via the proteasome in CRC cells. In addition, caveolin-1 mediates the suppressive function of NDRG1 in epithelial-mesenchymal transition, migration and invasion in vitro and metastasis in vivo. These results help to fulfill the potential mechanisms of NDRG1 in anti-metastatic treatment for human colorectal cancer. Title: Suppressive subtractive hybridization reveals different gene expression between high and low virulence strains of Cladosporium cladosporioides Gu Y, Liu Y, Cao S, Huang X, Zuo Z, Yu S, Deng J, Ding C, Yuan M and Ma X <8 more author(s)> Gu Y, Liu Y, Cao S, Huang X, Zuo Z, Yu S, Deng J, Ding C, Yuan M, Shen L, Wu R, Wen Y, Ren Z, Zhao Q, Peng G, Zhong Z, Wang C, Ma X (- 8) Ref: Microb Pathog, 100:276, 2016 : PubMed ESTHER: Gu_2016_Microb.Pathog_100_276 PubMedSearch: Gu 2016 Microb.Pathog 100 276 PubMedID: 27744104 Abstract Cladosporium cladosporioides is a ubiquitous fungus, causing infections in plants, humans, and animals. Suppression subtractive hybridization (SSH) and quantitative real-time PCR (qRT-PCR) were used in this study to identify differences in gene expression between two C. cladosporioides strains, the highly virulent Z20 strain and the lowly virulent Zt strain. A total of 61 unigenes from the forward library and 42 from the reverse library were identified. Gene ontology (GO) analysis showed that these genes were involved in various biological processes, cellular components and molecular functions. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that the unigenes in the forward library corresponded to 5 different pathways and the reverse library unigenes were involved in 3 different pathways. The qRT-PCR results indicated that expressions of APL1, GUD1, CSE1, SPBC3E7.04c and MFS were significantly different between Z20 and Zt strains, while genes encoding the senescence-associated proteins, pse1, nup107, mip1, pex2, icl1 and alpha/beta hydrolase exhibited no significant differences between the two strains. In addition, we found that 5 unigenes encoding mip1, chk1, icl1, alpha/beta hydrolase and beta-glucosidase may be associated with pathogenicity. One unigene (MFS) may be related to the resistance to 14 alpha-demethylase inhibitor fungicides, and 5 unigenes (PEX2, NUP107, PSE1, APL1, and SPBC3E7.04c) may be related to either low spore yield or earlier aging of the Zt strain. Our study may help better understand the molecular mechanism of C. cladosporioides infection, and therefore improve the treatment and prevention of C. cladosporioides induced diseases. Title: Bacterial cellulose synthesis mechanism of facultative anaerobe Enterobacter sp. FY-07 Ji K, Wang W, Zeng B, Chen S, Zhao Q, Chen Y, Li G, Ma T Ref: Sci Rep, 6:21863, 2016 : PubMed ESTHER: Ji_2016_Sci.Rep_6_21863 PubMedSearch: Ji 2016 Sci.Rep 6 21863 PubMedID: 26911736 Gene_locus related to this paper: 9entr-a0a127l3e1 Abstract Enterobacter sp. FY-07 can produce bacterial cellulose (BC) under aerobic and anaerobic conditions. Three potential BC synthesis gene clusters (bcsI, bcsII and bcsIII) of Enterobacter sp. FY-07 have been predicted using genome sequencing and comparative genome analysis, in which bcsIII was confirmed as the main contributor to BC synthesis by gene knockout and functional reconstitution methods. Protein homology, gene arrangement and gene constitution analysis indicated that bcsIII had high identity to the bcsI operon of Enterobacter sp. 638; however, its arrangement and composition were same as those of BC synthesizing operon of G. xylinum ATCC53582 except for the flanking sequences. According to the BC biosynthesizing process, oxygen is not directly involved in the reactions of BC synthesis, however, energy is required to activate intermediate metabolites and synthesize the activator, c-di-GMP. Comparative transcriptome and metabolite quantitative analysis demonstrated that under anaerobic conditions genes involved in the TCA cycle were downregulated, however, genes in the nitrate reduction and gluconeogenesis pathways were upregulated, especially, genes in three pyruvate metabolism pathways. These results suggested that Enterobacter sp. FY-07 could produce energy efficiently under anaerobic conditions to meet the requirement of BC biosynthesis. Title: Complete Genome Sequence of Bacillus pumilus Strain WP8, an Efficient Plant Growth-Promoting Rhizobacterium Kang Y, Shen M, Wang H, Zhao Q Ref: Genome Announc, 3:, 2015 : PubMed ESTHER: Kang_2015_Genome.Announc_3_0 PubMedSearch: Kang 2015 Genome.Announc 3 0 PubMedID: 25614565 Gene_locus related to this paper: 9baci-a0a0d7fsc6, 9baci-a0a0b4sbz3 Abstract Bacillus pumilus strain WP8 is an efficient plant growth-promoting rhizobacterium. Here, we present the complete genome of WP8 and its genes involved in plant growth promotion and biocontrol. Title: Efficient immobilization of acetylcholinesterase onto amino functionalized carbon nanotubes for the fabrication of high sensitive organophosphorus pesticides biosensors Yu G, Wu W, Zhao Q, Wei X, Lu Q Ref: Biosensors & Bioelectronics, 68C:288, 2015 : PubMed ESTHER: Yu_2015_Biosens.Bioelectron_68C_288 PubMedSearch: Yu 2015 Biosens.Bioelectron 68C 288 PubMedID: 25594160 Abstract This work introduced an efficient immobilization of acetylcholinesterase (AChE) onto amino functionalized carbon nanotubes (CNT-NH2), in order to fabricate high sensitive and practical organophosphorus pesticide (OPs) biosensors. Compared with the pristine, -COOH and -OH decorated CNTs, there were larger amount of enzymes adsorbed on the surface of CNT-NH2 with a favorable orientation and the best amperometric response was obtained on the AChE/CNT-NH2/GC electrode. Furthermore, the biosensor modified with CNT-NH2 showed a high affinity to acetylthiocholine chloride (ATCh) and could catalyze the hydrolysis of ATCh with an apparent Michaelis-Menten constant (Km) value of 67.4microM. Using paraoxon as a model compound, wide linear ranges from 0.2nM to 1nM and 1nM to 30nM, and a low detection limit of 0.08nM were obtained with satisfactory reproducibility and stability. Moreover, the biosensor had also been successfully employed for the determination of low concentrations of pesticides in real vegetable samples. This method could be extended to other functionalized nano-materials for their application in constructing biosensors. Title: Characteristics and Feasibility of Trans-Free Plastic Fats through Lipozyme TL IM-Catalyzed Interesterification of Palm Stearin and Akebia trifoliata Variety Australis Seed Oil Zhao SQ, Hu JN, Zhu XM, Bai CQ, Peng HL, Xiong H, Hu JW, Zhao Q Ref: Journal of Agricultural and Food Chemistry, 62:3293, 2014 : PubMed ESTHER: Zhao_2014_J.Agric.Food.Chem_62_3293 PubMedSearch: Zhao 2014 J.Agric.Food.Chem 62 3293 PubMedID: 24655125 Abstract Akebia trifoliata var. australis seed oil (ASO) was used as an edible oil in China. However, in-depth research studies on ASO have yet to be conducted for production of plastic fats in food industry. In this work, an immobilized lipase from Thermomyces lanuginosus (TL IM) was employed to catalyze palm stearin (PS) with different ratios of ASO in a laboratory-scale operation at 60 degreeC. The physical properties [e.g., fatty acid profile, slip melting point (SMP), solid fat content (SFC), polymorphic form, and microstructure] of physical blends (PBs) were analyzed and compared with those of the interesterified products (IPs). Results showed that SMPs of IPs (33.20-37.60 degreeC) decreased compared with those of PBs (48.03-49.30 degreeC). Meanwhile, IPs showed a good SFC range from 16.11% to 28.29% at 25 degreeC with mostly beta' polymorphic forms determined by X-ray diffraction analysis. It should be mentioned that no trans fatty acids (TFAs) were detected in any products, suggesting much more health-benefits of IPs. Texture tests showed that PBs (3318.19 +/- 86.67 g) were markedly harder than IPs (557.02 +/- 12.75 g). Conclusively, our study demonstrated that ASO can be utilized to produce trans-free plastic fats with good qualities through lipase-catalyzed interesterification. Title: Targeting the Metastasis Suppressor, NDRG1, Using Novel Iron Chelators: Regulation of Stress Fiber-Mediated Tumor Cell Migration via Modulation of the ROCK1/pMLC2 Signaling Pathway Sun J, Zhang D, Zheng Y, Zhao Q, Zheng M, Kovacevic Z, Richardson DR Ref: Molecular Pharmacology, 83:454, 2013 : PubMed ESTHER: Sun_2013_Mol.Pharmacol_83_454 PubMedSearch: Sun 2013 Mol.Pharmacol 83 454 PubMedID: 23188716 Abstract The iron-regulated metastasis suppressor, N-myc downstream-regulated gene 1 (NDRG1), is up-regulated by cellular iron depletion mediated by iron chelators and can inhibit cancer cell migration. However, the mechanism of how NDRG1 achieves this effect remains unclear. In this study, we implemented established and newly constructed NDRG1 overexpression and knockdown models using the DU145, HT29, and HCT116 cancer cell lines to investigate the molecular basis by which NDRG1 exerts its inhibitory effect on cell migration. Using these models, we demonstrated that NDRG1 overexpression inhibits cell migration by preventing actin-filament polymerization, stress fiber assembly and formation. In contrast, NDRG1 knockdown had the opposite effect. Moreover, we identified that NDRG1 inhibited an important regulatory pathway mediated by the Rho-associated, coiled-coil containing protein kinase 1 (ROCK1)/phosphorylated myosin light chain 2 (pMLC2) pathway that modulates stress fiber assembly. The phosphorylation of MLC2 is a key process in inducing stress fiber contraction, and this was shown to be markedly decreased or increased by NDRG1 overexpression or knockdown, respectively. The mechanism involved in the inhibition of MLC2 phosphorylation by NDRG1 was mediated by a significant (P < 0.001) decrease in ROCK1 expression that is a key kinase involved in MLC2 phosphorylation. Considering that NDRG1 is up-regulated after cellular iron depletion, novel thiosemicarbazone iron chelators (e.g., di-2-pyridylketone 4,4-dimethyl-3-thiosemicarbazone) were demonstrated to inhibit ROCK1/pMLC2-modulated actin-filament polymerization, stress fiber assembly, and formation via a mechanism involving NDRG1. These results highlight the role of the ROCK1/pMLC2 pathway in the NDRG1-mediated antimetastatic signaling network and the therapeutic potential of iron chelators at inhibiting metastasis. Title: Design, synthesis and biological evaluation of organophosphorous-homodimers as dual binding site acetylcholinesterase inhibitors Xie R, Zhao Q, Zhang T, Fang J, Mei X, Ning J, Tang Y Ref: Bioorganic & Medicinal Chemistry, 21:278, 2013 : PubMed ESTHER: Xie_2013_Bioorg.Med.Chem_21_278 PubMedSearch: Xie 2013 Bioorg.Med.Chem 21 278 PubMedID: 23200223 Abstract The cluster effect is an effective strategy to explore new lead compounds, and has been successfully applied in rational drug design and screening. A series of novel organophosphorous-homodimers were designed and synthesized based on the dual-site structure characteristics of acetylcholinesterase (AChE). The compounds were evaluated in vitro for their inhibitory activity to AChE extracted from Drosophila melanogaster and Musca domestic. Compound 4H showed an excellent inhibitor activity to both Drosophila melanogaster and Musca domestic with the corresponding IC(50) values of 23 and 168nM, respectively. Meanwhile, its activities against Drosophila melanogaster and Musca domestic AChE were more than 10,00,000 and 100,000-fold higher compared with the parent compound (MH), and was up to 245 and 107-fold higher than those of the positive control omethoate. The molecular docking study revealed that 4H possessed an optimal spacer length and can perfectly fit into the central pocket, active gorge, and peripheral site of DmAChE, and consequently exhibited highly improved inhibitor potency to DmAChE. The bioassay tests showed that 4 series compounds showed prominent insecticidal activities against both Lipaphser erysimi and Tetranychus cinnbarinus at a concentration of 200mg/L. The insecticide activity of compound 4H was particularly significant that can cause 96% mortality to Tetranychus cinnbarinus after 24h of treatment. Title: The MDGA1 gene confers risk to schizophrenia and bipolar disorder Li J, Liu J, Feng G, Li T, Zhao Q, Li Y, Hu Z, Zheng L, Zeng Z and Shi Y <2 more author(s)> Li J, Liu J, Feng G, Li T, Zhao Q, Li Y, Hu Z, Zheng L, Zeng Z, He L, Wang T, Shi Y (- 2) Ref: Schizophr Res, 125:194, 2011 : PubMed ESTHER: Li_2011_Schizophr.Res_125_194 PubMedSearch: Li 2011 Schizophr.Res 125 194 PubMedID: 21146959 Abstract OBJECTIVE: The structural, cytoarchitectural and functional brain abnormalities reported in patients with mental disorders may be due to aberrant neuronal migration influenced by cell adhesion molecules. MDGA1, like Ig-containing cell adhesion molecules, has several cell adhesion molecule-like domains. Moreover, Kahler et al. (2008) reported that the MDGA1 gene was a schizophrenia susceptibility gene in Scandinavian population. To further investigate whether the MDGA1 gene is a shared risk factor of schizophrenia, bipolar disorder and major depressive disorder in Chinese Han population, we conducted this study. Title: Ameliorative effects of yokukansan on learning and memory deficits in olfactory bulbectomized mice Yamada M, Hayashida M, Zhao Q, Shibahara N, Tanaka K, Miyata T, Matsumoto K Ref: J Ethnopharmacol, 135:737, 2011 : PubMed ESTHER: Yamada_2011_J.Ethnopharmacol_135_737 PubMedSearch: Yamada 2011 J.Ethnopharmacol 135 737 PubMedID: 21513784 Abstract AIM OF THE STUDY: Yokukansan (YKS) is a Japanese traditional herbal medicine and has been used for the treatment of the behavioral and psychological symptoms of dementia (BPSD). The present study aimed to clarify the effects of YKS on learning and memory impairments, and its mechanisms of action in olfactory bulbectomized (OBX) mice, one of the animal models of Alzheimer's disease (AD). MATERIALS AND METHODS: OBX or sham-operated ddY mice were treated with YKS or donepezil (DPZ), a reference drug, and their cognitive performances were tested by the modified Y-maze test, novel object recognition test, and fear conditioning test to elucidate the spatial working memory, non-spatial short-term memory, and long-term memory, respectively. After completing the behavioral experiments, the expression level of cholinergic marker proteins and the activity of acetylcholinesterase (AChE) in the brain were analyzed by western blotting and Ellman's method, respectively. RESULTS: OBX caused spatial working memory and non-spatial working memory impairments that were reversed by YKS and also by DPZ; however, YKS failed to affect the long-term memory deficits. Amelioration of the spatial working memory by YKS was reversible by scopolamine, a muscarinic receptor antagonist. YKS treatment reversed OBX-induced down-regulation of choline acetyltransferase and muscarinic muscarinic M(1) receptor expression without affecting muscarinic M(3) receptor expression or AChE activity. CONCLUSION: These results demonstrate that YKS improves short-term memory deficit caused by OBX and that the effect is at least partly mediated by muscarinic receptor stimulation and the normalization of central cholinergic systems. The present findings also suggest that YKS has a therapeutic effect not only on BPSD, but also on memory impairment of AD. Title: Homo- and hetero-dimers of inactive organophosphorous group binding at dual sites of AChE Zhao Q, Xie R, Zhang T, Fang J, Mei X, Ning J, Tang Y Ref: Bioorganic & Medicinal Chemistry Lett, 21:6404, 2011 : PubMed ESTHER: Zhao_2011_Bioorg.Med.Chem.Lett_21_6404 PubMedSearch: Zhao 2011 Bioorg.Med.Chem.Lett 21 6404 PubMedID: 21940169 Abstract Homo- and hetero-dimers of inactive organophosphorous group(s) dramatically enhanced the acetylcholinesterase (AChE; EC 3.1.1.7) inhibiting potency, with the highest potency observed at a tether length of 6 methylene groups (6d) for the homodimers, and 7 methylene groups (8e) for the heterodimers. The docking model of Drosophila melanogaster AChE suggested that 6d and 8e bound at the catalytic and peripheral sites of AChE, in which two organophosphorous groups of 6d individually oriented towards TRP83 of catalytic sites and TRP321 of peripheral sites, and phthalicimide group of 8e was appropriately arranged for a pi-pi interaction with the phenyl ring of TYR330, furthermore, the organophosphorous group introduced hydrophobic interaction with TRP83. The compounds prepared in this work demonstrated high insecticidal activity to Lipaphis erysimi and Tetranychus cinnbarinus at the concentration 300mg/L. Title: Draft genome sequence of the oilseed species Ricinus communis Chan AP, Crabtree J, Zhao Q, Lorenzi H, Orvis J, Puiu D, Melake-Berhan A, Jones KM, Redman J and Rabinowicz PD <8 more author(s)> Chan AP, Crabtree J, Zhao Q, Lorenzi H, Orvis J, Puiu D, Melake-Berhan A, Jones KM, Redman J, Chen G, Cahoon EB, Gedil M, Stanke M, Haas BJ, Wortman JR, Fraser-Liggett CM, Ravel J, Rabinowicz PD (- 8) Ref: Nat Biotechnol, 28:951, 2010 : PubMed ESTHER: Chan_2010_Nat.Biotechnol_28_951 PubMedSearch: Chan 2010 Nat.Biotechnol 28 951 PubMedID: 20729833 Gene_locus related to this paper: ricco-b9r7h7, ricco-b9re31, ricco-b9rgi7, ricco-b9riy7, ricco-b9rlg6, ricco-b9rm64, ricco-b9rsg5, ricco-b9rtk6, ricco-b9rtt3, ricco-b9ry83, ricco-b9s8p2, ricco-b9s817, ricco-b9sby7, ricco-b9scn1, ricco-b9scn2, ricco-b9scn3, ricco-b9scn5, ricco-b9ssj7, ricco-b9ssj8, ricco-b9sx01, ricco-b9szu0, ricco-b9t4l4, ricco-b9t5x2, ricco-b9tb84, ricco-b9rkb0, ricco-b9rru1, ricco-b9rdy5, ricco-b9tey4, ricco-b9sfw5, ricco-b9sjw6, ricco-b9shs6, ricco-b9rsl2, ricco-b9r7f8, ricco-b9rne4, ricco-b9r8z8 Abstract Castor bean (Ricinus communis) is an oilseed crop that belongs to the spurge (Euphorbiaceae) family, which comprises approximately 6,300 species that include cassava (Manihot esculenta), rubber tree (Hevea brasiliensis) and physic nut (Jatropha curcas). It is primarily of economic interest as a source of castor oil, used for the production of high-quality lubricants because of its high proportion of the unusual fatty acid ricinoleic acid. However, castor bean genomics is also relevant to biosecurity as the seeds contain high levels of ricin, a highly toxic, ribosome-inactivating protein. Here we report the draft genome sequence of castor bean (4.6-fold coverage), the first for a member of the Euphorbiaceae. Whereas most of the key genes involved in oil synthesis and turnover are single copy, the number of members of the ricin gene family is larger than previously thought. Comparative genomics analysis suggests the presence of an ancient hexaploidization event that is conserved across the dicotyledonous lineage. Title: Isolation and characterization of low-sulphur-tolerant mutants of Arabidopsis Wu Y, Zhao Q, Gao L, Yu XM, Fang P, Oliver DJ, Xiang CB Ref: J Exp Bot, 61:3407, 2010 : PubMed ESTHER: Wu_2010_J.Exp.Bot_61_3407 PubMedSearch: Wu 2010 J.Exp.Bot 61 3407 PubMedID: 20547563 Abstract Sulphur is an essential element for plant growth and development as well as for defence against biotic and abiotic stresses. Increasing sulphate utilization efficiency (SUE) is an important issue for crop improvement. Little is known about the genetic determinants of sulphate utilization efficiency. No gain-of-function mutants with improved SUE have been reported to date. Here the isolation and characterization of two low-sulphur-tolerant mutants, sue3 and sue4 are reported using a high-throughput genetic screen where a 'sulphur-free' solid medium was devised to give the selection pressure necessary to suppress the growth of the wild-type seedlings. Both mutants showed improved tolerance to low sulphur conditions and well-developed root systems. The mutant phenotype of both sue3 and sue4 was specific to sulphate deficiency and the mutants displayed enhanced tolerance to heavy metal and oxidative stress. Genetic analysis revealed that sue3 was caused by a single recessive nuclear mutation while sue4 was caused by a single dominant nuclear mutation. The recessive locus in sue3 is the previously identified VirE2-interacting Protein 1. The dominant locus in sue4 is a function-unknown locus activated by the four enhancers on the T-DNA. The function of SUE3 and SUE4 in low sulphur tolerance was confirmed either by multiple mutant alleles or by recapitulation analysis. Taken together, our results demonstrate that this genetic screen is a reasonable approach to isolate Arabidopsis mutants with improved low sulphur tolerance and potentially with enhanced sulphate utilization efficiency. The two loci identified in sue3 and sue4 should assist in understanding the molecular mechanisms of low sulphur tolerance. Title: Novel acetylcholinesterase inhibitors: Synthesis and structure-activity relationships of phthalimide alkyloxyphenyl N,N-dimethylcarbamate derivatives Zhao Q, Yang G, Mei X, Yuan H, Ning J Ref: Pesticide Biochemistry and Physiology, 95:131, 2009 : PubMed ESTHER: Zhao_2009_Pestic.Biochem.Physiol_95_131 PubMedSearch: Zhao 2009 Pestic.Biochem.Physiol 95 131 Abstract Based on the multiple binding sites of acetylcholinesterase (AChE), a series of AChE inhibitors: phthalimide alkyloxyphenyl N,N-dimethylcarbamate were designed and synthesized. AChE inhibitory activity and structure-activity relationship of the compounds were researched also. The influence of structural variations on the inhibitory potency was carefully investigated by modifying different alkyloxy chain length and position between phthalimide and phenyl N,N-dimethylcarbamate (PDM). The biological properties of the series were investigated by considering the activity on isolated enzyme. Some of the newly synthesized derivatives, when tested on isolated AChE from head of housefly (Musca domestica), were more active than PDM. The compounds J1, J2 and K1-K8 demonstrated higher inhibitory activity (5- to 404-fold) for AChE than that of PDM. In particular, compound K1 displayed the best AChE inhibition (404-fold higher than PDM), which suggested that phthalimide group of K1 strongly bound at the residues lining the gorge while phenyl N,N-dimethylcarbamate bound at the catalytic site. Title: A cocaine hydrolase engineered from human butyrylcholinesterase selectively blocks cocaine toxicity and reinstatement of drug seeking in rats Brimijoin S, Gao Y, Anker JJ, Gliddon LA, Lafleur D, Shah R, Zhao Q, Singh M, Carroll ME Ref: Neuropsychopharmacology, 33:2715, 2008 : PubMed ESTHER: Brimijoin_2008_Neuropsychopharmacology_33_2715 PubMedSearch: Brimijoin 2008 Neuropsychopharmacology 33 2715 PubMedID: 18199998 Abstract Successive rational mutations of human butyrylcholinesterase (BChE) followed by fusion to human serum albumin have yielded an efficient hydrolase that offers realistic options for therapy of cocaine overdose and abuse. This albumin-BChE prevented seizures in rats given a normally lethal cocaine injection (100 mg/kg, i.p.), lowered brain cocaine levels even when administered after the drug, and provided rescue after convulsions commenced. Moreover, it selectively blocked cocaine-induced reinstatement of drug seeking in rats that had previously self-administered cocaine. The enzyme treatment was well tolerated and may be worth exploring for clinical application in humans. Title: An albumin-butyrylcholinesterase for cocaine toxicity and addiction: catalytic and pharmacokinetic properties Gao Y, Lafleur D, Shah R, Zhao Q, Singh M, Brimijoin S Ref: Chemico-Biological Interactions, 175:83, 2008 : PubMed ESTHER: Gao_2008_Chem.Biol.Interact_175_83 PubMedSearch: Gao 2008 Chem.Biol.Interact 175 83 PubMedID: 18514640 Abstract Butyrylcholinesterase (BChE, EC 3.1.1.8) is important in human cocaine metabolism despite its limited ability to hydrolyze this drug. Efforts to improve the catalytic efficiency of this enzyme have led to a quadruple mutant cocaine hydrolase, "CocH", that in animal models of addiction appears promising for treatment of overdose and relapse. We incorporated the CocH mutations into a BChE-albumin fusion protein, "Albu-CocH", and evaluated the pharmacokinetics of the enzyme after i.v. injection in rats. As assessed from the time course of cocaine hydrolyzing activity in plasma, Albu-CocH redistributed into extracellular fluid (16% of estimated total body water) with a t(1/2) of 0.66h and it underwent elimination with a t(1/2) of 8h. These results indicate that the enzyme has ample stability for short-term applications and may be suitable for longer-term treatment as well. Present data also confirm the markedly enhanced power of Albu-CocH for cocaine hydrolysis and they support the view that Albu-CocH might prove valuable in treating phenomena associated with cocaine abuse. Title: The Rice Annotation Project Database (RAP-DB): 2008 update Tanaka T, Antonio BA, Kikuchi S, Matsumoto T, Nagamura Y, Numa H, Sakai H, Wu J, Itoh T and Echeverria M <80 more author(s)> Tanaka T, Antonio BA, Kikuchi S, Matsumoto T, Nagamura Y, Numa H, Sakai H, Wu J, Itoh T, Sasaki T, Aono R, Fujii Y, Habara T, Harada E, Kanno M, Kawahara Y, Kawashima H, Kubooka H, Matsuya A, Nakaoka H, Saichi N, Sanbonmatsu R, Sato Y, Shinso Y, Suzuki M, Takeda J, Tanino M, Todokoro F, Yamaguchi K, Yamamoto N, Yamasaki C, Imanishi T, Okido T, Tada M, Ikeo K, Tateno Y, Gojobori T, Lin YC, Wei FJ, Hsing YI, Zhao Q, Han B, Kramer MR, McCombie RW, Lonsdale D, O'Donovan CC, Whitfield EJ, Apweiler R, Koyanagi KO, Khurana JP, Raghuvanshi S, Singh NK, Tyagi AK, Haberer G, Fujisawa M, Hosokawa S, Ito Y, Ikawa H, Shibata M, Yamamoto M, Bruskiewich RM, Hoen DR, Bureau TE, Namiki N, Ohyanagi H, Sakai Y, Nobushima S, Sakata K, Barrero RA, Souvorov A, Smith-White B, Tatusova T, An S, An G, S OO, Fuks G, Messing J, Christie KR, Lieberherr D, Kim H, Zuccolo A, Wing RA, Nobuta K, Green PJ, Lu C, Meyers BC, Chaparro C, Piegu B, Panaud O, Echeverria M (- 80) Ref: Nucleic Acids Research, 36:D1028, 2008 : PubMed ESTHER: Tanaka_2008_Nucleic.Acids.Res_36_D1028 PubMedSearch: Tanaka 2008 Nucleic.Acids.Res 36 D1028 PubMedID: 18089549 Gene_locus related to this paper: orysa-Q9FW17, orysa-Q0JK71, orysa-B9EWJ8, orysa-Q5N7L1, orysa-pir7a, orysa-q2qyj1, orysj-q6yse8, orysa-q6yzk1, orysa-Q8S0U8, orysa-q33aq0, orysa-Q0J0A4, orysi-a2z179, orysi-a2zef2, orysi-b8a7e6, orysi-b8a7e7, orysi-b8bfe5, orysi-b8bhp9, orysj-b9fi05, orysj-b9fkb0, orysj-cgep, orysj-q0djj0, orysj-q0dud7, orysj-q0jaf0, orysj-q0jga1, orysj-q5jl22, orysj-q5jlw7, orysj-q6h7q9, orysj-q6yvk6, orysj-q7f8x1, orysj-q7xcx3, orysj-q9fwm6, orysj-q10j20, orysj-q10ss2, orysj-q69uw6, orysj-q94d71, orysj-q0iq98, orysj-b9gbs4, orysj-b9gbs1, orysj-pla4, orysj-pla1 Abstract The Rice Annotation Project Database (RAP-DB) was created to provide the genome sequence assembly of the International Rice Genome Sequencing Project (IRGSP), manually curated annotation of the sequence, and other genomics information that could be useful for comprehensive understanding of the rice biology. Since the last publication of the RAP-DB, the IRGSP genome has been revised and reassembled. In addition, a large number of rice-expressed sequence tags have been released, and functional genomics resources have been produced worldwide. Thus, we have thoroughly updated our genome annotation by manual curation of all the functional descriptions of rice genes. The latest version of the RAP-DB contains a variety of annotation data as follows: clone positions, structures and functions of 31 439 genes validated by cDNAs, RNA genes detected by massively parallel signature sequencing (MPSS) technology and sequence similarity, flanking sequences of mutant lines, transposable elements, etc. Other annotation data such as Gnomon can be displayed along with those of RAP for comparison. We have also developed a new keyword search system to allow the user to access useful information. The RAP-DB is available at: http://rapdb.dna.affrc.go.jp/ and http://rapdb.lab.nig.ac.jp/. Title: Dynamics of esterase alleles in Culex pipiens complex mosquitoes in Beijing Yan S, Wu Z, Cui F, Zhao Q, Qiao C Ref: J Econ Entomol, 101:1897, 2008 : PubMed ESTHER: Yan_2008_J.Econ.Entomol_101_1897 PubMedSearch: Yan 2008 J.Econ.Entomol 101 1897 PubMedID: 19133472 Inhibitor(s) related to this paper: Fenobucarb Abstract To investigate insecticide resistance levels and dynamic changes of carboxylesterase polymorphism with time in resistant populations of mosquitoes in the Culex pipiens complex, four field populations were collected in September 2006. The resistance levels of fourth-instar larvae to organophosphate (dichlorvos, parathion, and chlorpyrifos), carbamate (fenobucarb and propoxur), and pyrethroid (permethrin and tetramethrin) insecticides were determined by bioassay. Larvae had a low but significant resistance to organophosphate and carbamate insecticides but no significant resistance to pyrethroid insecticides. Starch gel electrophoresis revealed the presence of the overproduced esterases B1, A2-B2, A8-B8, A9-B9, and All-B11. The frequency of each overproduced esterases varied depending on its regional localities. Compared with previous surveys, the polymorphism of amplified esterase alleles in Beijing populations increased, although the resistance level to organophosphate insecticides declined. Title: Design of novel carbamate acetylcholinesterase inhibitors based on the multiple binding sites of acetylcholinesterase Zhao Q, Yang G, Mei X, Yuan H, Ning J Ref: Journal of Pesticide Science, 33:371, 2008 : PubMed ESTHER: Zhao_2008_J.Pestic.Sci_33_371 PubMedSearch: Zhao 2008 J.Pestic.Sci 33 371 Inhibitor(s) related to this paper: Metolcarb Abstract This work describes the design, synthesis, AChE inhibitory activity, and structure-activity relationship of compounds related to a recently discovered series of AChE inhibitors: phthalimide alkyloxyphenyl N-methylcarbamates. The influence of structural variations on inhibitory potency was carefully investigated by modifying different alkyloxy chain lengths and positions between phthalimide and phenyl N-methylcarbamate. The biological properties of the series were investigated in some detail by considering their activity on isolated enzymes. All of the newly synthesized derivatives, when tested on isolated AChE from the brain of the housefly (Musca domestica), were more active than phenyl N-methylcarbamate. In particular, compound I1 displayed the best AChE inhibition (352-fold higher than phenyl N-methylcarbamate, and 29-fold higher than metolcarb), which suggested that the phthalimide group of I1 bound strongly to the residues lining the gorge, and phenyl N-methylcarbamate bound at the catalytic sites. Title: Draft genome sequence of the sexually transmitted pathogen Trichomonas vaginalis Carlton JM, Hirt RP, Silva JC, Delcher AL, Schatz M, Zhao Q, Wortman JR, Bidwell SL, Alsmark UC and Johnson PJ <55 more author(s)> Carlton JM, Hirt RP, Silva JC, Delcher AL, Schatz M, Zhao Q, Wortman JR, Bidwell SL, Alsmark UC, Besteiro S, Sicheritz-Ponten T, Noel CJ, Dacks JB, Foster PG, Simillion C, Van de Peer Y, Miranda-Saavedra D, Barton GJ, Westrop GD, Muller S, Dessi D, Fiori PL, Ren Q, Paulsen I, Zhang H, Bastida-Corcuera FD, Simoes-Barbosa A, Brown MT, Hayes RD, Mukherjee M, Okumura CY, Schneider R, Smith AJ, Vanacova S, Villalvazo M, Haas BJ, Pertea M, Feldblyum TV, Utterback TR, Shu CL, Osoegawa K, de Jong PJ, Hrdy I, Horvathova L, Zubacova Z, Dolezal P, Malik SB, Logsdon JM, Jr., Henze K, Gupta A, Wang CC, Dunne RL, Upcroft JA, Upcroft P, White O, Salzberg SL, Tang P, Chiu CH, Lee YS, Embley TM, Coombs GH, Mottram JC, Tachezy J, Fraser-Liggett CM, Johnson PJ (- 55) Ref: Science, 315:207, 2007 : PubMed ESTHER: Carlton_2007_Science_315_207 PubMedSearch: Carlton 2007 Science 315 207 PubMedID: 17218520 Gene_locus related to this paper: triva-a2d7i4, triva-a2d9w5, triva-a2d766, triva-a2dah5, triva-a2dlx9, triva-a2dul1, triva-a2dy49, triva-a2e6h5, triva-a2e7p9, triva-a2e9l3, triva-a2e414, triva-a2e613, triva-a2e983, triva-a2eau8, triva-a2ekb9, triva-a2en58, triva-a2erp5, triva-a2et59, triva-a2f7u4, triva-a2f801, triva-a2fa76, triva-a2fbq3, triva-a2fe47, triva-a2fgl0, triva-a2fhp7, triva-a2fie6, triva-a2fk22, triva-a2fla2, triva-a2fqm0, triva-a2fqq2, triva-a2frq0, triva-a2frr3, triva-a2fsq9, triva-a2fsz5, triva-a2fux4, triva-a2fz57, triva-a2g2h0, triva-a2g9x0, triva-a2fqi4 Abstract We describe the genome sequence of the protist Trichomonas vaginalis, a sexually transmitted human pathogen. Repeats and transposable elements comprise about two-thirds of the approximately 160-megabase genome, reflecting a recent massive expansion of genetic material. This expansion, in conjunction with the shaping of metabolic pathways that likely transpired through lateral gene transfer from bacteria, and amplification of specific gene families implicated in pathogenesis and phagocytosis of host proteins may exemplify adaptations of the parasite during its transition to a urogenital environment. The genome sequence predicts previously unknown functions for the hydrogenosome, which support a common evolutionary origin of this unusual organelle with mitochondria. Title: Draft genome of the filarial nematode parasite Brugia malayi Ghedin E, Wang S, Spiro D, Caler E, Zhao Q, Crabtree J, Allen JE, Delcher AL, Guiliano DB and Scott AL <61 more author(s)> Ghedin E, Wang S, Spiro D, Caler E, Zhao Q, Crabtree J, Allen JE, Delcher AL, Guiliano DB, Miranda-Saavedra D, Angiuoli SV, Creasy T, Amedeo P, Haas B, El-Sayed NM, Wortman JR, Feldblyum T, Tallon L, Schatz M, Shumway M, Koo H, Salzberg SL, Schobel S, Pertea M, Pop M, White O, Barton GJ, Carlow CK, Crawford MJ, Daub J, Dimmic MW, Estes CF, Foster JM, Ganatra M, Gregory WF, Johnson NM, Jin J, Komuniecki R, Korf I, Kumar S, Laney S, Li BW, Li W, Lindblom TH, Lustigman S, Ma D, Maina CV, Martin DM, McCarter JP, McReynolds L, Mitreva M, Nutman TB, Parkinson J, Peregrin-Alvarez JM, Poole C, Ren Q, Saunders L, Sluder AE, Smith K, Stanke M, Unnasch TR, Ware J, Wei AD, Weil G, Williams DJ, Zhang Y, Williams SA, Fraser-Liggett C, Slatko B, Blaxter ML, Scott AL (- 61) Ref: Science, 317:1756, 2007 : PubMed ESTHER: Ghedin_2007_Science_317_1756 PubMedSearch: Ghedin 2007 Science 317 1756 PubMedID: 17885136 Gene_locus related to this paper: bruma-a8ndk6, bruma-a8njt8, bruma-a8nl88, bruma-a8npi4, bruma-a8npi6, bruma-a8p6g9, bruma-a8pah3, bruma-a8pc38, bruma-a8pek5, bruma-a8piq4, bruma-a8pnw8, bruma-a8psu4, bruma-a8pte1, bruma-a8q606, bruma-a8q632, bruma-a8q937, bruma-a8qav5, bruma-a8qbd9, bruma-a8qgj6, bruma-a8qh78, bruma-a8q143, bruma-a0a024mej5, bruma-a0a0k0jju9, bruma-a0a0i9n517 Abstract Parasitic nematodes that cause elephantiasis and river blindness threaten hundreds of millions of people in the developing world. We have sequenced the approximately 90 megabase (Mb) genome of the human filarial parasite Brugia malayi and predict approximately 11,500 protein coding genes in 71 Mb of robustly assembled sequence. Comparative analysis with the free-living, model nematode Caenorhabditis elegans revealed that, despite these genes having maintained little conservation of local synteny during approximately 350 million years of evolution, they largely remain in linkage on chromosomal units. More than 100 conserved operons were identified. Analysis of the predicted proteome provides evidence for adaptations of B. malayi to niches in its human and vector hosts and insights into the molecular basis of a mutualistic relationship with its Wolbachia endosymbiont. These findings offer a foundation for rational drug design. Title: Curated genome annotation of Oryza sativa ssp. japonica and comparative genome analysis with Arabidopsis thaliana Itoh T, Tanaka T, Barrero RA, Yamasaki C, Fujii Y, Hilton PB, Antonio BA, Aono H, Apweiler R and Sasaki T <85 more author(s)> Itoh T, Tanaka T, Barrero RA, Yamasaki C, Fujii Y, Hilton PB, Antonio BA, Aono H, Apweiler R, Bruskiewich R, Bureau T, Burr F, Costa de Oliveira A, Fuks G, Habara T, Haberer G, Han B, Harada E, Hiraki AT, Hirochika H, Hoen D, Hokari H, Hosokawa S, Hsing YI, Ikawa H, Ikeo K, Imanishi T, Ito Y, Jaiswal P, Kanno M, Kawahara Y, Kawamura T, Kawashima H, Khurana JP, Kikuchi S, Komatsu S, Koyanagi KO, Kubooka H, Lieberherr D, Lin YC, Lonsdale D, Matsumoto T, Matsuya A, McCombie WR, Messing J, Miyao A, Mulder N, Nagamura Y, Nam J, Namiki N, Numa H, Nurimoto S, O'Donovan C, Ohyanagi H, Okido T, Oota S, Osato N, Palmer LE, Quetier F, Raghuvanshi S, Saichi N, Sakai H, Sakai Y, Sakata K, Sakurai T, Sato F, Sato Y, Schoof H, Seki M, Shibata M, Shimizu Y, Shinozaki K, Shinso Y, Singh NK, Smith-White B, Takeda J, Tanino M, Tatusova T, Thongjuea S, Todokoro F, Tsugane M, Tyagi AK, Vanavichit A, Wang A, Wing RA, Yamaguchi K, Yamamoto M, Yamamoto N, Yu Y, Zhang H, Zhao Q, Higo K, Burr B, Gojobori T, Sasaki T (- 85) Ref: Genome Res, 17:175, 2007 : PubMed ESTHER: Itoh_2007_Genome.Res_17_175 PubMedSearch: Itoh 2007 Genome.Res 17 175 PubMedID: 17210932 Gene_locus related to this paper: orysa-Q7XTC5, orysa-Q852M6, orysa-Q8GSE8, orysa-Q9FYP7, orysa-Q5ZA26, orysa-Q5JLP6, orysa-Q8H5P5, orysa-Q7F1Y5, orysa-cbp3, orysa-cbpx, orysa-Q6YSZ8, orysa-Q9FW17, orysa-Q84QZ6, orysa-Q0JK71, orysa-B9EWJ8, orysa-Q6ZDG6, orysa-Q6ZDG5, orysa-Q658B2, orysa-Q5N7L1, orysa-Q8RYV9, orysa-Q8H3R3, orysa-Q5SNH3, orysa-pir7a, orysa-q2qnj4, orysa-q2qyj1, orysa-q2r077, orysa-Q4VWY7, orysa-q5smv5, orysa-q5z901, orysa-Q5ZBI5, orysa-q6atz0, orysa-q6i5q3, orysa-q6j657, orysa-q6k4q2, orysj-q6yse8, orysa-q6yy42, orysa-q6yzk1, orysa-q6z8b1, orysa-q6z995, orysa-q6zjq6, orysa-q7x7y5, orysa-Q7XC50, orysa-q7xr62, orysa-q7xr63, orysa-q7xsg1, orysa-q7xsq2, orysa-q7xts6, orysa-q7xv53, orysa-Q8LQS5, orysa-Q8RZ79, orysa-Q8S0U8, orysa-Q8W3C6, orysa-Q9LHX5, orysa-q53m20, orysa-q53nd8, orysa-q60e79, orysa-q67iz2, orysa-q67iz3, orysa-q67iz7, orysa-q67iz8, orysa-q67j02, orysa-q67j05, orysa-q67j09, orysa-q67j10, orysa-q67tr6, orysa-q67tv0, orysa-q69j38, orysa-q69y21, orysa-q75hy1, orysa-q75hy2, orysa-Q0J0A4, orysa-q651a8, orysa-q652g4, orysa-q688m8, orysa-Q6H8G1, orysi-a2z179, orysi-a2zef2, orysi-b8a7e6, orysi-b8a7e7, orysi-b8bfe5, orysi-b8bhp9, orysj-b9fi05, orysj-q0djj0, orysj-q0jaf0, orysj-q0jga1, orysj-q0jhi5, orysj-q5jl22, orysj-q5jlw7, orysj-q6h7q9, orysj-q6yvk6, orysj-q7f8x1, orysj-q7xcx3, orysj-q9fwm6, orysj-q10j20, orysj-q10ss2, orysj-q69uw6, orysj-q94d71, orysj-q0iq98, orysj-b9gbs4, orysj-b9gbs1 Abstract We present here the annotation of the complete genome of rice Oryza sativa L. ssp. japonica cultivar Nipponbare. All functional annotations for proteins and non-protein-coding RNA (npRNA) candidates were manually curated. Functions were identified or inferred in 19,969 (70%) of the proteins, and 131 possible npRNAs (including 58 antisense transcripts) were found. Almost 5000 annotated protein-coding genes were found to be disrupted in insertional mutant lines, which will accelerate future experimental validation of the annotations. The rice loci were determined by using cDNA sequences obtained from rice and other representative cereals. Our conservative estimate based on these loci and an extrapolation suggested that the gene number of rice is approximately 32,000, which is smaller than previous estimates. We conducted comparative analyses between rice and Arabidopsis thaliana and found that both genomes possessed several lineage-specific genes, which might account for the observed differences between these species, while they had similar sets of predicted functional domains among the protein sequences. A system to control translational efficiency seems to be conserved across large evolutionary distances. Moreover, the evolutionary process of protein-coding genes was examined. Our results suggest that natural selection may have played a role for duplicated genes in both species, so that duplication was suppressed or favored in a manner that depended on the function of a gene. Title: Genome sequence of Aedes aegypti, a major arbovirus vector Nene V, Wortman JR, Lawson D, Haas B, Kodira C, Tu ZJ, Loftus B, Xi Z, Megy K and Severson DW <85 more author(s)> Nene V, Wortman JR, Lawson D, Haas B, Kodira C, Tu ZJ, Loftus B, Xi Z, Megy K, Grabherr M, Ren Q, Zdobnov EM, Lobo NF, Campbell KS, Brown SE, Bonaldo MF, Zhu J, Sinkins SP, Hogenkamp DG, Amedeo P, Arensburger P, Atkinson PW, Bidwell S, Biedler J, Birney E, Bruggner RV, Costas J, Coy MR, Crabtree J, Crawford M, Debruyn B, Decaprio D, Eiglmeier K, Eisenstadt E, El-Dorry H, Gelbart WM, Gomes SL, Hammond M, Hannick LI, Hogan JR, Holmes MH, Jaffe D, Johnston JS, Kennedy RC, Koo H, Kravitz S, Kriventseva EV, Kulp D, LaButti K, Lee E, Li S, Lovin DD, Mao C, Mauceli E, Menck CF, Miller JR, Montgomery P, Mori A, Nascimento AL, Naveira HF, Nusbaum C, O'Leary S, Orvis J, Pertea M, Quesneville H, Reidenbach KR, Rogers YH, Roth CW, Schneider JR, Schatz M, Shumway M, Stanke M, Stinson EO, Tubio JM, Vanzee JP, Verjovski-Almeida S, Werner D, White O, Wyder S, Zeng Q, Zhao Q, Zhao Y, Hill CA, Raikhel AS, Soares MB, Knudson DL, Lee NH, Galagan J, Salzberg SL, Paulsen IT, Dimopoulos G, Collins FH, Birren B, Fraser-Liggett CM, Severson DW (- 85) Ref: Science, 316:1718, 2007 : PubMed ESTHER: Nene_2007_Science_316_1718 PubMedSearch: Nene 2007 Science 316 1718 PubMedID: 17510324 Gene_locus related to this paper: aedae-ACHE, aedae-ACHE1, aedae-glita, aedae-q0iea6, aedae-q0iev6, aedae-q0ifn6, aedae-q0ifn8, aedae-q0ifn9, aedae-q0ifp0, aedae-q0ig41, aedae-q1dgl0, aedae-q1dh03, aedae-q1dh19, aedae-q1hqe6, aedae-Q8ITU8, aedae-Q8MMJ6, aedae-Q8T9V6, aedae-q16e91, aedae-q16f04, aedae-q16f25, aedae-q16f26, aedae-q16f28, aedae-q16f29, aedae-q16f30, aedae-q16gq5, aedae-q16iq5, aedae-q16je0, aedae-q16je1, aedae-q16je2, aedae-q16ks8, aedae-q16lf2, aedae-q16lv6, aedae-q16m61, aedae-q16mc1, aedae-q16mc6, aedae-q16mc7, aedae-q16md1, aedae-q16ms7, aedae-q16nk5, aedae-q16rl5, aedae-q16rz9, aedae-q16si8, aedae-q16t49, aedae-q16wf1, aedae-q16x18, aedae-q16xp8, aedae-q16xu6, aedae-q16xw5, aedae-q16xw6, aedae-q16y04, aedae-q16y05, aedae-q16y06, aedae-q16y07, aedae-q16y39, aedae-q16y40, aedae-q16yg4, aedae-q16z03, aedae-q17aa7, aedae-q17av1, aedae-q17av2, aedae-q17av3, aedae-q17av4, aedae-q17b28, aedae-q17b29, aedae-q17b30, aedae-q17b31, aedae-q17b32, aedae-q17bm3, aedae-q17bm4, aedae-q17bv7, aedae-q17c44, aedae-q17cz1, aedae-q17d32, aedae-q17g39, aedae-q17g40, aedae-q17g41, aedae-q17g42, aedae-q17g43, aedae-q17g44, aedae-q17gb8, aedae-q17gr3, aedae-q17if7, aedae-q17if9, aedae-q17ig1, aedae-q17ig2, aedae-q17is4, aedae-q17l09, aedae-q17m26, aedae-q17mg9, aedae-q17mv4, aedae-q17mv5, aedae-q17mv6, aedae-q17mv7, aedae-q17mw8, aedae-q17mw9, aedae-q17nw5, aedae-q17nx5, aedae-q17pa4, aedae-q17q69, aedae-q170k7, aedae-q171y4, aedae-q172e0, aedae-q176i8, aedae-q176j0, aedae-q177k1, aedae-q177k2, aedae-q177l9, aedae-j9hic3, aedae-q179r9, aedae-u483, aedae-j9hj23, aedae-q17d68, aedae-q177c7, aedae-q0ifp1, aedae-a0a1s4fx83, aedae-a0a1s4g2m0, aedae-q1hr49 Abstract We present a draft sequence of the genome of Aedes aegypti, the primary vector for yellow fever and dengue fever, which at approximately 1376 million base pairs is about 5 times the size of the genome of the malaria vector Anopheles gambiae. Nearly 50% of the Ae. aegypti genome consists of transposable elements. These contribute to a factor of approximately 4 to 6 increase in average gene length and in sizes of intergenic regions relative to An. gambiae and Drosophila melanogaster. Nonetheless, chromosomal synteny is generally maintained among all three insects, although conservation of orthologous gene order is higher (by a factor of approximately 2) between the mosquito species than between either of them and the fruit fly. An increase in genes encoding odorant binding, cytochrome P450, and cuticle domains relative to An. gambiae suggests that members of these protein families underpin some of the biological differences between the two mosquito species. Title: Chotosan, a kampo formula, ameliorates chronic cerebral hypoperfusion-induced deficits in object recognition behaviors and central cholinergic systems in mice Zhao Q, Murakami Y, Tohda M, Obi R, Shimada Y, Matsumoto K Ref: J Pharmacol Sci, 103:360, 2007 : PubMed ESTHER: Zhao_2007_J.Pharmacol.Sci_103_360 PubMedSearch: Zhao 2007 J.Pharmacol.Sci 103 360 PubMedID: 17409635 Abstract We previously demonstrated that the Kampo formula chotosan (CTS) ameliorated spatial cognitive impairment via central cholinergic systems in a chronic cerebral hypoperfusion (P2VO) mouse model. In this study, the object discrimination tasks were used to determine if the ameliorative effects of CTS on P2VO-induced cognitive deficits are a characteristic pharmacological profile of this formula, with the aim of clarifying the mechanisms by which CTS enhances central cholinergic function in P2VO mice. The cholinesterase inhibitor tacrine (THA) and Kampo formula saikokeishito (SKT) were used as controls. P2VO impaired object discrimination performance in the object recognition, location, and context tests. Daily administration of CTS (750 mg/kg, p.o.) and THA (2.5 mg/kg, i.p.) improved the object discrimination deficits, whereas SKT (750 mg/kg, p.o.) did not. In ex vivo assays, tacrine but not CTS or SKT inhibited cortical cholinesterase activity. P2VO reduced the mRNA expression of m(3) and m(5) muscarinic receptors and choline acetyltransferase but not that of other muscarinic receptor subtypes in the cerebral cortex. Daily administration of CTS and THA but not SKT reversed these expression changes. These results suggest that CTS and THA improve P2VO-induced cognitive impairment by normalizing the deficit of central cholinergic systems and that the beneficial effect on P2VO-induced cognitive deficits is a distinctive pharmacological characteristic of CTS. Title: The protease complex consisting of dipeptidyl peptidase IV and seprase plays a role in the migration and invasion of human endothelial cells in collagenous matrices Ghersi G, Zhao Q, Salamone M, Yeh Y, Zucker S, Chen WT Ref: Cancer Research, 66:4652, 2006 : PubMed ESTHER: Ghersi_2006_Cancer.Res_66_4652 PubMedSearch: Ghersi 2006 Cancer.Res 66 4652 PubMedID: 16651416 Abstract Dipeptidyl peptidase IV (DPP4/CD26) and seprase/fibroblast activation protein alpha are homologous type II transmembrane, homodimeric glycoproteins that exhibit unique prolyl peptidase activities. Human DPP4 is ubiquitously expressed in epithelial and endothelial cells and serves multiple functions in cleaving the penultimate positioned prolyl bonds at the NH(2) terminus of a variety of physiologically important peptides in the circulation. Recent studies showed a linkage between DPP4 and down-regulation of certain chemokines and mitogenic growth factors, and degradation of denatured collagens (gelatin), suggesting a role of DPP4 in the cell invasive phenotype. Here, we found the existence of a novel protease complex consisting of DPP4 and seprase in human endothelial cells that were activated to migrate and invade in the extracellular matrix in vitro. DPP4 and seprase were coexpressed with the three major protease systems (matrix metalloproteinase, plasminogen activator, and type II transmembrane serine protease) at the cell surface and organize as a complex at invadopodia-like protrusions. Both proteases were colocalized at the endothelial cells of capillaries, but not large blood vessels, in invasive breast ductal carcinoma in vivo. Importantly, monoclonal antibodies against the gelatin-binding domain of DPP4 blocked the local gelatin degradation by endothelial cells in the presence of the major metallo- and serine protease systems that modified pericellular collagenous matrices and subsequent cell migration and invasion. Thus, we have identified a novel mechanism involving the DPP4 gelatin-binding domain of the DPP4-seprase complex that facilitates the local degradation of the extracellular matrix and the invasion of the endothelial cells into collagenous matrices. Title: Rationale for combination therapy with galantamine and memantine in Alzheimer's disease Grossberg GT, Edwards KR, Zhao Q Ref: Journal of Clinical Pharmacology, 46:17S, 2006 : PubMed ESTHER: Grossberg_2006_J.Clin.Pharmacol_46_17S PubMedSearch: Grossberg 2006 J.Clin.Pharmacol 46 17S PubMedID: 16809811 Abstract A combination of cholinergic and glutamatergic dysfunction appears to underlie the symptomatology of Alzheimer's disease. Therefore, one hypothesis is that treatment strategies should address impairments in both systems. Galantamine is an acetylcholinesterase inhibitor that, unlike other acetylcholinesterase inhibitors, has a postulated dual mode of action as a nicotinic receptor modulator. Galantamine has demonstrated long-term efficacy in improving or maintaining cognition, functionality, and behavior in patients with mild to moderate Alzheimer's disease. Memantine, a noncompetitive N-methyl-D-aspartate-receptor antagonist, reduces deterioration in cognition and function in patients with moderate to severe Alzheimer's disease. Pharmacokinetic and pharmacodynamic as well as ongoing observation studies support the concept of adjunctive therapy with memantine in patients with advanced moderate Alzheimer's disease currently treated with an established galantamine regimen. The potential to modulate both acetylcholine and glutamate pathways in Alzheimer's disease presents a novel treatment strategy for the management of mild to moderately severe Alzheimer's disease. Title: A review of the reference dose for chlorpyrifos Zhao Q, Dourson M, Gadagbui B Ref: Regul Toxicol Pharmacol, 44:111, 2006 : PubMed ESTHER: Zhao_2006_Regul.Toxicol.Pharmacol_44_111 PubMedSearch: Zhao 2006 Regul.Toxicol.Pharmacol 44 111 PubMedID: 16360256 Abstract Chlorpyrifos is an inhibitor of cholinesterase (ChE) and inhibition of ChE is believed to be the most sensitive effect in all animal species evaluated and in humans from previous evaluations. Recent literature, in particular epidemiology studies reporting associations between chlorpyrifos levels and fetal birth weight decreases, suggest the need to reevaluate the basis of the reference dose (RfD) for chlorpyrifos, however. In this paper, we evaluated newly available publications regarding chlorpyrifos toxicity and discuss the choice of critical effect--whether cholinesterase inhibition or developmental effect, the choice of appropriate species and study, the appropriate point of departure, and choice of uncertainty factors--including a discussion of the FQPA safety factor. We conclude that RBC cholinesterase inhibition is the critical effect, that human studies form the best choice of species--supported by a wealth of experimental animal data, that a NOAEL of 0.1 mg/kg/day is the most appropriate point of departure, and that a 10-fold factor for within human variability is sufficient to characterize the overall uncertainty in this rather large database. The resulting RfD is 0.01 mg/kg/day. Title: Lower birth weight as a critical effect of chlorpyrifos: a comparison of human and animal data Zhao Q, Gadagbui B, Dourson M Ref: Regul Toxicol Pharmacol, 42:55, 2005 : PubMed ESTHER: Zhao_2005_Regul.Toxicol.Pharmacol_42_55 PubMedSearch: Zhao 2005 Regul.Toxicol.Pharmacol 42 55 PubMedID: 15896443 Abstract Chlorpyrifos is an irreversible inhibitor of cholinesterase (ChE), and inhibition of ChE is believed to be the most sensitive effect in all animal species evaluated and in humans. Recent epidemiology studies reported associations between umbilical cord plasma chlorpyrifos levels and fetal birth weight decreases among minority women living in New York City during pregnancy. These associations raise questions whether impaired fetal development is the critical effect rather than the inhibition of ChE as is currently believed so. We analyze the available information from epidemiology studies and animal studies in order to identify the relative sensitivity of decreased birth weight and inhibition of ChE from exposure to chlorpyrifos. We find that the positive associations from some epidemiology studies are different from other epidemiology investigations. Moreover, a direct comparison of experimental animal neonatal information shows that cholinesterase inhibition is a more sensitive indicator of adverse effect than reduced body weight, and that neonates are equally, or perhaps less sensitive to cholinesterase inhibition than their maternal parent. Based on a review of human studies and comparison of human cord blood chlorpyrifos concentrations with blood chlorpyrifos concentrations that in animals caused effects with good dose-response, it appears unlikely that the exposure level encountered by the population reported in [Whyatt, R.M., Rauh, V., Barr, D.B., Camann, D.E., Andrews, H.F., Garfinkel, R., Hoepner, L.A., Diaz, D., Dietrich, J., Reyes, A., Tang, D., Kinney, P.L., Perera, F.P., 2004. Prenatal insecticide exposures and birth weight and length among an urban minority cohort. Environ. Health Perspect. 112, 1125-1132.] study would cause any fetal developmental effect. Moreover, the critical effect for chlorpyrifos still appears to be cholinesterase inhibition. Title: RGS17/RGSZ2, a novel regulator of Gi/o, Gz, and Gq signaling Mao H, Zhao Q, Daigle M, Ghahremani MH, Chidiac P, Albert PR Ref: Journal of Biological Chemistry, 279:26314, 2004 : PubMed ESTHER: Mao_2004_J.Biol.Chem_279_26314 PubMedSearch: Mao 2004 J.Biol.Chem 279 26314 PubMedID: 15096504 Abstract To identify novel regulators of Galpha(o), the most abundant G-protein in brain, we used yeast two-hybrid screening with constitutively active Galpha(o) as bait and identified a new regulator of G-protein signaling (RGS) protein, RGS17 (RGSZ2), as a novel human member of the RZ (or A) subfamily of RGS proteins. RGS17 contains an amino-terminal cysteine-rich motif and a carboxyl-terminal RGS domain with highest homology to hRGSZ1- and hRGS-Galpha-interacting protein. RGS17 RNA was strongly expressed as multiple species in cerebellum and other brain regions. The interactions between hRGS17 and active forms of Galpha(i1-3), Galpha(o), Galpha(z), or Galpha(q) but not Galpha(s) were detected by yeast two-hybrid assay, in vitro pull-down assay, and co-immunoprecipitation studies. Recombinant RGS17 acted as a GTPase-activating protein (GAP) on free Galpha(i2) and Galpha(o) under pre-steady-state conditions, and on M2-muscarinic receptor-activated Galpha(i1), Galpha(i2), Galpha(i3), Galpha(z), and Galpha(o) in steady-state GTPase assays in vitro. Unlike RGSZ1, which is highly selective for G(z), RGS17 exhibited limited selectivity for G(o) among G(i)/G(o) proteins. All RZ family members reduced dopamine-D2/Galpha(i)-mediated inhibition of cAMP formation and abolished thyrotropin-releasing hormone receptor/Galpha(q)-mediated calcium mobilization. RGS17 is a new RZ member that preferentially inhibits receptor signaling via G(i/o), G(z), and G(q) over G(s) to enhance cAMP-dependent signaling and inhibit calcium signaling. Differences observed between in vitro GAP assays and whole-cell signaling suggest additional determinants of the G-protein specificity of RGS GAP effects that could include receptors and effectors. Title: Sequence and analysis of rice chromosome 4 Feng Q, Zhang Y, Hao P, Wang S, Fu G, Huang Y, Li Y, Zhu J, Liu Y and Han B <61 more author(s)> Feng Q, Zhang Y, Hao P, Wang S, Fu G, Huang Y, Li Y, Zhu J, Liu Y, Hu X, Jia P, Zhao Q, Ying K, Yu S, Tang Y, Weng Q, Zhang L, Lu Y, Mu J, Zhang LS, Yu Z, Fan D, Liu X, Lu T, Li C, Wu Y, Sun T, Lei H, Li T, Hu H, Guan J, Wu M, Zhang R, Zhou B, Chen Z, Chen L, Jin Z, Wang R, Yin H, Cai Z, Ren S, Lv G, Gu W, Zhu G, Tu Y, Jia J, Chen J, Kang H, Chen X, Shao C, Sun Y, Hu Q, Zhang X, Zhang W, Wang L, Ding C, Sheng H, Gu J, Chen S, Ni L, Zhu F, Chen W, Lan L, Lai Y, Cheng Z, Gu M, Jiang J, Li J, Hong G, Xue Y, Han B (- 61) Ref: Nature, 420:316, 2002 : PubMed ESTHER: Feng_2002_Nature_420_316 PubMedSearch: Feng 2002 Nature 420 316 PubMedID: 12447439 Gene_locus related to this paper: orysa-Q7XTC5, orysa-Q7F959, orysa-q7f9i3, orysa-q7x7y5, orysa-q7xkj9, orysa-q7xr62, orysa-q7xr63, orysa-q7xr64, orysa-q7xsg1, orysa-q7xsq2, orysa-Q7XTM8, orysa-q7xts6, orysa-q7xue7, orysa-q7xv53, orysa-Q7XVB5, orysa-Q7XVG5, orysj-q0jaf0, orysj-q7f8x1 Abstract Rice is the principal food for over half of the population of the world. With its genome size of 430 megabase pairs (Mb), the cultivated rice species Oryza sativa is a model plant for genome research. Here we report the sequence analysis of chromosome 4 of O. sativa, one of the first two rice chromosomes to be sequenced completely. The finished sequence spans 34.6 Mb and represents 97.3% of the chromosome. In addition, we report the longest known sequence for a plant centromere, a completely sequenced contig of 1.16 Mb corresponding to the centromeric region of chromosome 4. We predict 4,658 protein coding genes and 70 transfer RNA genes. A total of 1,681 predicted genes match available unique rice expressed sequence tags. Transposable elements have a pronounced bias towards the euchromatic regions, indicating a close correlation of their distributions to genes along the chromosome. Comparative genome analysis between cultivated rice subspecies shows that there is an overall syntenic relationship between the chromosomes and divergence at the level of single-nucleotide polymorphisms and insertions and deletions. By contrast, there is little conservation in gene order between rice and Arabidopsis. Title: The genome sequence of the malaria mosquito Anopheles gambiae Holt RA, Subramanian GM, Halpern A, Sutton GG, Charlab R, Nusskern DR, Wincker P, Clark AG, Ribeiro JM and Hoffman SL <113 more author(s)> Holt RA, Subramanian GM, Halpern A, Sutton GG, Charlab R, Nusskern DR, Wincker P, Clark AG, Ribeiro JM, Wides R, Salzberg SL, Loftus B, Yandell M, Majoros WH, Rusch DB, Lai Z, Kraft CL, Abril JF, Anthouard V, Arensburger P, Atkinson PW, Baden H, de Berardinis V, Baldwin D, Benes V, Biedler J, Blass C, Bolanos R, Boscus D, Barnstead M, Cai S, Center A, Chaturverdi K, Christophides GK, Chrystal MA, Clamp M, Cravchik A, Curwen V, Dana A, Delcher A, Dew I, Evans CA, Flanigan M, Grundschober-Freimoser A, Friedli L, Gu Z, Guan P, Guigo R, Hillenmeyer ME, Hladun SL, Hogan JR, Hong YS, Hoover J, Jaillon O, Ke Z, Kodira C, Kokoza E, Koutsos A, Letunic I, Levitsky A, Liang Y, Lin JJ, Lobo NF, Lopez JR, Malek JA, McIntosh TC, Meister S, Miller J, Mobarry C, Mongin E, Murphy SD, O'Brochta DA, Pfannkoch C, Qi R, Regier MA, Remington K, Shao H, Sharakhova MV, Sitter CD, Shetty J, Smith TJ, Strong R, Sun J, Thomasova D, Ton LQ, Topalis P, Tu Z, Unger MF, Walenz B, Wang A, Wang J, Wang M, Wang X, Woodford KJ, Wortman JR, Wu M, Yao A, Zdobnov EM, Zhang H, Zhao Q, Zhao S, Zhu SC, Zhimulev I, Coluzzi M, della Torre A, Roth CW, Louis C, Kalush F, Mural RJ, Myers EW, Adams MD, Smith HO, Broder S, Gardner MJ, Fraser CM, Birney E, Bork P, Brey PT, Venter JC, Weissenbach J, Kafatos FC, Collins FH, Hoffman SL (- 113) Ref: Science, 298:129, 2002 : PubMed ESTHER: Holt_2002_Science_298_129 PubMedSearch: Holt 2002 Science 298 129 PubMedID: 12364791 Gene_locus related to this paper: anoga-a0nb77, anoga-a0nbp6, anoga-a0neb7, anoga-a0nei9, anoga-a0nej0, anoga-a0ngj1, anoga-a7ut12, anoga-a7uuz9, anoga-ACHE1, anoga-ACHE2, anoga-agCG44620, anoga-agCG44666, anoga-agCG45273, anoga-agCG45279, anoga-agCG45511, anoga-agCG46741, anoga-agCG47651, anoga-agCG47655, anoga-agCG47661, anoga-agCG47690, anoga-agCG48797, anoga-AGCG49362, anoga-agCG49462, anoga-agCG49870, anoga-agCG49872, anoga-agCG49876, anoga-agCG50851, anoga-agCG51879, anoga-agCG52383, anoga-agCG54954, anoga-AGCG55021, anoga-agCG55401, anoga-agCG55408, anoga-agCG56978, anoga-ebiG239, anoga-ebiG2660, anoga-ebiG5718, anoga-ebiG5974, anoga-ebiG8504, anoga-ebiG8742, anoga-glita, anoga-nrtac, anoga-q5tpv0, anoga-Q5TVS6, anoga-q7pm39, anoga-q7ppw9, anoga-q7pq17, anoga-Q7PQT0, anoga-q7q8m4, anoga-q7q626, anoga-q7qa14, anoga-q7qa52, anoga-q7qal7, anoga-q7qbj0, anoga-f5hl20, anoga-q7qkh2, anoga-a0a1s4h1y7, anoga-q7q887 Abstract Anopheles gambiae is the principal vector of malaria, a disease that afflicts more than 500 million people and causes more than 1 million deaths each year. Tenfold shotgun sequence coverage was obtained from the PEST strain of A. gambiae and assembled into scaffolds that span 278 million base pairs. A total of 91% of the genome was organized in 303 scaffolds; the largest scaffold was 23.1 million base pairs. There was substantial genetic variation within this strain, and the apparent existence of two haplotypes of approximately equal frequency ("dual haplotypes") in a substantial fraction of the genome likely reflects the outbred nature of the PEST strain. The sequence produced a conservative inference of more than 400,000 single-nucleotide polymorphisms that showed a markedly bimodal density distribution. Analysis of the genome sequence revealed strong evidence for about 14,000 protein-encoding transcripts. Prominent expansions in specific families of proteins likely involved in cell adhesion and immunity were noted. An expressed sequence tag analysis of genes regulated by blood feeding provided insights into the physiological adaptations of a hematophagous insect. Title: [Expression and characterization of carboxylesterase A2 in E. coli] Huang J, Qiao CL, Zhao Q, Wang P Ref: Shi Yan Sheng Wu Xue Bao, 35:77, 2002 : PubMed ESTHER: Huang_2002_Shi.Yan.Sheng.Wu.Xue.Bao_35_77 PubMedSearch: Huang 2002 Shi.Yan.Sheng.Wu.Xue.Bao 35 77 PubMedID: 15344323 Abstract The most commonly observed change that has been linked to resistance development is the increase in activity of carboxylesterases. The putative mechanism involves an overproduction of this enzyme for the sequestration and the hydroxylation of various organophosphate and carbamate insecticides. Carboxylesterases A2 cDNA was amplified from Culex quinquefasciatus by RT-PCR and sequenced consequently. Target gene was inserted into pET-28a to create prokaryotic expression plasmid pET-EstA2. When pET-EstA2 was transformed into E. coli BL21, the recombinant was induced by IPTG. A pure recombinant protein was obtained by affinity purification. Compared with carboxylesterase A2 purified from Culex quinquefasciatus, carboxylesterase A2, purified from the product of the transgenic of E. coli, has the same Km, but the Vm was higher than that of it, which shows that carboxylesterase A2, purified from the product of E. coli by affinity, is purer than that from Culex quinquefasciatus. The study on the expression and characterization of carboxylesterase A2 in E. coli is more useful for its future application. Title: A comparison of whole-genome shotgun-derived mouse chromosome 16 and the human genome Mural RJ, Adams MD, Myers EW, Smith HO, Miklos GL, Wides R, Halpern A, Li PW, Sutton GG and Stephenson LD <169 more author(s)> Mural RJ, Adams MD, Myers EW, Smith HO, Miklos GL, Wides R, Halpern A, Li PW, Sutton GG, Nadeau J, Salzberg SL, Holt RA, Kodira CD, Lu F, Chen L, Deng Z, Evangelista CC, Gan W, Heiman TJ, Li J, Li Z, Merkulov GV, Milshina NV, Naik AK, Qi R, Shue BC, Wang A, Wang J, Wang X, Yan X, Ye J, Yooseph S, Zhao Q, Zheng L, Zhu SC, Biddick K, Bolanos R, Delcher AL, Dew IM, Fasulo D, Flanigan MJ, Huson DH, Kravitz SA, Miller JR, Mobarry CM, Reinert K, Remington KA, Zhang Q, Zheng XH, Nusskern DR, Lai Z, Lei Y, Zhong W, Yao A, Guan P, Ji RR, Gu Z, Wang ZY, Zhong F, Xiao C, Chiang CC, Yandell M, Wortman JR, Amanatides PG, Hladun SL, Pratts EC, Johnson JE, Dodson KL, Woodford KJ, Evans CA, Gropman B, Rusch DB, Venter E, Wang M, Smith TJ, Houck JT, Tompkins DE, Haynes C, Jacob D, Chin SH, Allen DR, Dahlke CE, Sanders R, Li K, Liu X, Levitsky AA, Majoros WH, Chen Q, Xia AC, Lopez JR, Donnelly MT, Newman MH, Glodek A, Kraft CL, Nodell M, Ali F, An HJ, Baldwin-Pitts D, Beeson KY, Cai S, Carnes M, Carver A, Caulk PM, Center A, Chen YH, Cheng ML, Coyne MD, Crowder M, Danaher S, Davenport LB, Desilets R, Dietz SM, Doup L, Dullaghan P, Ferriera S, Fosler CR, Gire HC, Gluecksmann A, Gocayne JD, Gray J, Hart B, Haynes J, Hoover J, Howland T, Ibegwam C, Jalali M, Johns D, Kline L, Ma DS, MacCawley S, Magoon A, Mann F, May D, McIntosh TC, Mehta S, Moy L, Moy MC, Murphy BJ, Murphy SD, Nelson KA, Nuri Z, Parker KA, Prudhomme AC, Puri VN, Qureshi H, Raley JC, Reardon MS, Regier MA, Rogers YH, Romblad DL, Schutz J, Scott JL, Scott R, Sitter CD, Smallwood M, Sprague AC, Stewart E, Strong RV, Suh E, Sylvester K, Thomas R, Tint NN, Tsonis C, Wang G, Williams MS, Williams SM, Windsor SM, Wolfe K, Wu MM, Zaveri J, Chaturvedi K, Gabrielian AE, Ke Z, Sun J, Subramanian G, Venter JC, Pfannkoch CM, Barnstead M, Stephenson LD (- 169) Ref: Science, 296:1661, 2002 : PubMed ESTHER: Mural_2002_Science_296_1661 PubMedSearch: Mural 2002 Science 296 1661 PubMedID: 12040188 Gene_locus related to this paper: mouse-ABH15, mouse-Ces3b, mouse-Ces4a, mouse-dpp4, mouse-FAP, mouse-Lipg, mouse-Q8C1A9, mouse-rbbp9, mouse-SERHL, mouse-SPG21, mouse-w4vsp6 Abstract The high degree of similarity between the mouse and human genomes is demonstrated through analysis of the sequence of mouse chromosome 16 (Mmu 16), which was obtained as part of a whole-genome shotgun assembly of the mouse genome. The mouse genome is about 10% smaller than the human genome, owing to a lower repetitive DNA content. Comparison of the structure and protein-coding potential of Mmu 16 with that of the homologous segments of the human genome identifies regions of conserved synteny with human chromosomes (Hsa) 3, 8, 12, 16, 21, and 22. Gene content and order are highly conserved between Mmu 16 and the syntenic blocks of the human genome. Of the 731 predicted genes on Mmu 16, 509 align with orthologs on the corresponding portions of the human genome, 44 are likely paralogous to these genes, and 164 genes have homologs elsewhere in the human genome; there are 14 genes for which we could find no human counterpart. Title: Induction of acetylcholinesterase expression during apoptosis in various cell types Zhang XJ, Yang L, Zhao Q, Caen JP, He HY, Jin QH, Guo LH, Alemany M, Zhang LY, Shi YF Ref: Cell Death Differ, 9:790, 2002 : PubMed ESTHER: Zhang_2002_Cell.Death.Differ_9_790 PubMedSearch: Zhang 2002 Cell.Death.Differ 9 790 PubMedID: 12107822 Abstract Acetylcholinesterase (AChE) plays a key role in terminating neurotransmission at cholinergic synapses. AChE is also found in tissues devoid of cholinergic responses, indicating potential functions beyond neurotransmission. It has been suggested that AChE may participate in development, differentiation, and pathogenic processes such as Alzheimer's disease and tumorigenesis. We examined AChE expression in a number of cell lines upon induction of apoptosis by various stimuli. AChE is induced in all apoptotic cells examined as determined by cytochemical staining, immunological analysis, affinity chromatography purification, and molecular cloning. The AChE protein was found in the cytoplasm at the initiation of apoptosis and then in the nucleus or apoptotic bodies upon commitment to cell death. Sequence analysis revealed that AChE expressed in apoptotic cells is identical to the synapse type AChE. Pharmacological inhibitors of AChE prevented apoptosis. Furthermore, blocking the expression of AChE with antisense inhibited apoptosis. Therefore, our studies demonstrate that AChE is potentially a marker and a regulator of apoptosis. Title: Isolation of acetylcholinesterase G4 and G1 molecular isoforms from rat cortex Zhao Q, Tang XC Ref: Acta Pharmacol Sin, 23:173, 2002 : PubMed ESTHER: Zhao_2002_Acta.Pharmacol.Sin_23_173 PubMedSearch: Zhao 2002 Acta.Pharmacol.Sin 23 173 PubMedID: 11866880 Abstract AIM: To isolate the G4 and G1 molecular forms of acetylcholinesterase in rat cortex for interpreting the therapeutical effect of the AChE inhibitor drugs. METHODS: Size exclusion chromatography and ultracentrifugation were used to isolate and ascertain the G4 and G1 molecular forms of AChE. RESULTS: After size exclusion chromatography, two AChE active peaks were gotten. The putative molecular weights of the two highest AChE active fractions were around Mr 239 000 and Mr 68 000 respectively, which represented G4 and G1 AChE isoforms. The sedimentation coefficients of the Mr 239 000 and Mr 68 000 fractions were 10 S and 4 S, which also assigned to G4 and G1 AChE isoforms. CONCLUSION: The G4 and G1 isoforms of AChE could be gotten by size exclusion chromatography method. Title: Effects of huperzine A on acetylcholinesterase isoforms in vitro: comparison with tacrine, donepezil, rivastigmine and physostigmine Zhao Q, Tang XC Ref: European Journal of Pharmacology, 455:101, 2002 : PubMed ESTHER: Zhao_2002_Eur.J.Pharmacol_455_101 PubMedSearch: Zhao 2002 Eur.J.Pharmacol 455 101 PubMedID: 12445575 Abstract Five inhibitors of acetylcholinesterase, huperzine A, donepezil, tacrine, rivastigmine and physostigmine, were compared with regard to their effects on different molecular forms of acetylcholinesterase in cerebral cortex, hippocampus, and striatum from the rat brain. In general, huperzine A preferentially inhibited tetrameric acetylcholinesterase (G4 form), while tacrine and rivastigmine preferentially inhibited monomeric acetylcholinesterase (G1 form). Donepezil showed pronounced selectivity for G1 acetylcholinesterase in striatum and hippocampus, but not in cortex. Physostigmine showed no form-selectivity in any brain region. In cortex, the most potent inhibitors of G4 acetylcholinesterase were huperzine A (K(i) 7 x 10(-9) M) and donepezil (K(i) 4 x 10(-9) M). The potent inhibitors of cortical G1 acetylcholinesterase were donepezil (K(i) 3.5 x 10(-9) M) and tacrine (K(i) 2.3 x 10(-8) M). In hippocampus, huperzine A and physostigmine were the most potent inhibitors of G4 acetylcholinesterase, while donepezil and tacrine were most potent against G1 acetylcholinesterase. In striatum, huperzine A and donepezil were the most potent against G4 acetylcholinesterase, while again donepezil was the most potent against G1. Although the inhibition constants (K(i)) of these acetylcholinesterase inhibitors differed significantly from region to region, the nature of the inhibition did not vary. These results suggest that the use of acetylcholinesterase inhibitors in treatment of Alzheimer's disease must consider both form-specific and region-specific characteristics of acetylcholinesterase inhibition. Title: Association between low-density lipoprotein receptor-related protein gene, butyrylcholinesterase gene and Alzheimer' s disease in Chinese Bi S, Zhang Y, Wu J, Wang D, Zhao Q Ref: Chin Med Sci J, 16:71, 2001 : PubMed ESTHER: Bi_2001_Chin.Med.Sci.J_16_71 PubMedSearch: Bi 2001 Chin.Med.Sci.J 16 71 PubMedID: 12901493 Abstract OBJECTIVE: To research the relations between low-density lipoprotein receptor-related protein gene (LRP) polymorphism, butyrylcholinesterase gene (BchE) polymorphism and Alzheimer's disease (AD) in Chinese. Title: The sequence of the human genome Venter JC, Adams MD, Myers EW, Li PW, Mural RJ, Sutton GG, Smith HO, Yandell M, Evans CA and Zhu X <264 more author(s)> Venter JC, Adams MD, Myers EW, Li PW, Mural RJ, Sutton GG, Smith HO, Yandell M, Evans CA, Holt RA, Gocayne JD, Amanatides P, Ballew RM, Huson DH, Wortman JR, Zhang Q, Kodira CD, Zheng XH, Chen L, Skupski M, Subramanian G, Thomas PD, Zhang J, Gabor Miklos GL, Nelson C, Broder S, Clark AG, Nadeau J, McKusick VA, Zinder N, Levine AJ, Roberts RJ, Simon M, Slayman C, Hunkapiller M, Bolanos R, Delcher A, Dew I, Fasulo D, Flanigan M, Florea L, Halpern A, Hannenhalli S, Kravitz S, Levy S, Mobarry C, Reinert K, Remington K, Abu-Threideh J, Beasley E, Biddick K, Bonazzi V, Brandon R, Cargill M, Chandramouliswaran I, Charlab R, Chaturvedi K, Deng Z, Di Francesco V, Dunn P, Eilbeck K, Evangelista C, Gabrielian AE, Gan W, Ge W, Gong F, Gu Z, Guan P, Heiman TJ, Higgins ME, Ji RR, Ke Z, Ketchum KA, Lai Z, Lei Y, Li Z, Li J, Liang Y, Lin X, Lu F, Merkulov GV, Milshina N, Moore HM, Naik AK, Narayan VA, Neelam B, Nusskern D, Rusch DB, Salzberg S, Shao W, Shue B, Sun J, Wang Z, Wang A, Wang X, Wang J, Wei M, Wides R, Xiao C, Yan C, Yao A, Ye J, Zhan M, Zhang W, Zhang H, Zhao Q, Zheng L, Zhong F, Zhong W, Zhu S, Zhao S, Gilbert D, Baumhueter S, Spier G, Carter C, Cravchik A, Woodage T, Ali F, An H, Awe A, Baldwin D, Baden H, Barnstead M, Barrow I, Beeson K, Busam D, Carver A, Center A, Cheng ML, Curry L, Danaher S, Davenport L, Desilets R, Dietz S, Dodson K, Doup L, Ferriera S, Garg N, Gluecksmann A, Hart B, Haynes J, Haynes C, Heiner C, Hladun S, Hostin D, Houck J, Howland T, Ibegwam C, Johnson J, Kalush F, Kline L, Koduru S, Love A, Mann F, May D, McCawley S, McIntosh T, McMullen I, Moy M, Moy L, Murphy B, Nelson K, Pfannkoch C, Pratts E, Puri V, Qureshi H, Reardon M, Rodriguez R, Rogers YH, Romblad D, Ruhfel B, Scott R, Sitter C, Smallwood M, Stewart E, Strong R, Suh E, Thomas R, Tint NN, Tse S, Vech C, Wang G, Wetter J, Williams S, Williams M, Windsor S, Winn-Deen E, Wolfe K, Zaveri J, Zaveri K, Abril JF, Guigo R, Campbell MJ, Sjolander KV, Karlak B, Kejariwal A, Mi H, Lazareva B, Hatton T, Narechania A, Diemer K, Muruganujan A, Guo N, Sato S, Bafna V, Istrail S, Lippert R, Schwartz R, Walenz B, Yooseph S, Allen D, Basu A, Baxendale J, Blick L, Caminha M, Carnes-Stine J, Caulk P, Chiang YH, Coyne M, Dahlke C, Mays A, Dombroski M, Donnelly M, Ely D, Esparham S, Fosler C, Gire H, Glanowski S, Glasser K, Glodek A, Gorokhov M, Graham K, Gropman B, Harris M, Heil J, Henderson S, Hoover J, Jennings D, Jordan C, Jordan J, Kasha J, Kagan L, Kraft C, Levitsky A, Lewis M, Liu X, Lopez J, Ma D, Majoros W, McDaniel J, Murphy S, Newman M, Nguyen T, Nguyen N, Nodell M, Pan S, Peck J, Peterson M, Rowe W, Sanders R, Scott J, Simpson M, Smith T, Sprague A, Stockwell T, Turner R, Venter E, Wang M, Wen M, Wu D, Wu M, Xia A, Zandieh A, Zhu X (- 264) Ref: Science, 291:1304, 2001 : PubMed ESTHER: Venter_2001_Science_291_1304 PubMedSearch: Venter 2001 Science 291 1304 PubMedID: 11181995 Gene_locus related to this paper: human-AADAC, human-ABHD1, human-ABHD10, human-ABHD11, human-ACHE, human-BCHE, human-LDAH, human-ABHD18, human-CMBL, human-ABHD17A, human-KANSL3, human-LIPA, human-LYPLAL1, human-NDRG2, human-NLGN3, human-NLGN4X, human-NLGN4Y, human-PAFAH2, human-PREPL, human-RBBP9, human-SPG21 Abstract A 2.91-billion base pair (bp) consensus sequence of the euchromatic portion of the human genome was generated by the whole-genome shotgun sequencing method. The 14.8-billion bp DNA sequence was generated over 9 months from 27,271,853 high-quality sequence reads (5.11-fold coverage of the genome) from both ends of plasmid clones made from the DNA of five individuals. Two assembly strategies-a whole-genome assembly and a regional chromosome assembly-were used, each combining sequence data from Celera and the publicly funded genome effort. The public data were shredded into 550-bp segments to create a 2.9-fold coverage of those genome regions that had been sequenced, without including biases inherent in the cloning and assembly procedure used by the publicly funded group. This brought the effective coverage in the assemblies to eightfold, reducing the number and size of gaps in the final assembly over what would be obtained with 5.11-fold coverage. The two assembly strategies yielded very similar results that largely agree with independent mapping data. The assemblies effectively cover the euchromatic regions of the human chromosomes. More than 90% of the genome is in scaffold assemblies of 100,000 bp or more, and 25% of the genome is in scaffolds of 10 million bp or larger. Analysis of the genome sequence revealed 26,588 protein-encoding transcripts for which there was strong corroborating evidence and an additional approximately 12,000 computationally derived genes with mouse matches or other weak supporting evidence. Although gene-dense clusters are obvious, almost half the genes are dispersed in low G+C sequence separated by large tracts of apparently noncoding sequence. Only 1.1% of the genome is spanned by exons, whereas 24% is in introns, with 75% of the genome being intergenic DNA. Duplications of segmental blocks, ranging in size up to chromosomal lengths, are abundant throughout the genome and reveal a complex evolutionary history. Comparative genomic analysis indicates vertebrate expansions of genes associated with neuronal function, with tissue-specific developmental regulation, and with the hemostasis and immune systems. DNA sequence comparisons between the consensus sequence and publicly funded genome data provided locations of 2.1 million single-nucleotide polymorphisms (SNPs). A random pair of human haploid genomes differed at a rate of 1 bp per 1250 on average, but there was marked heterogeneity in the level of polymorphism across the genome. Less than 1% of all SNPs resulted in variation in proteins, but the task of determining which SNPs have functional consequences remains an open challenge. Title: The genome sequence of Drosophila melanogaster Adams MD, Celniker SE, Holt RA, Evans CA, Gocayne JD, Amanatides PG, Scherer SE, Li PW, Hoskins RA and Venter JC <185 more author(s)> Adams MD, Celniker SE, Holt RA, Evans CA, Gocayne JD, Amanatides PG, Scherer SE, Li PW, Hoskins RA, Galle RF, George RA, Lewis SE, Richards S, Ashburner M, Henderson SN, Sutton GG, Wortman JR, Yandell MD, Zhang Q, Chen LX, Brandon RC, Rogers YH, Blazej RG, Champe M, Pfeiffer BD, Wan KH, Doyle C, Baxter EG, Helt G, Nelson CR, Gabor GL, Abril JF, Agbayani A, An HJ, Andrews-Pfannkoch C, Baldwin D, Ballew RM, Basu A, Baxendale J, Bayraktaroglu L, Beasley EM, Beeson KY, Benos PV, Berman BP, Bhandari D, Bolshakov S, Borkova D, Botchan MR, Bouck J, Brokstein P, Brottier P, Burtis KC, Busam DA, Butler H, Cadieu E, Center A, Chandra I, Cherry JM, Cawley S, Dahlke C, Davenport LB, Davies P, de Pablos B, Delcher A, Deng Z, Mays AD, Dew I, Dietz SM, Dodson K, Doup LE, Downes M, Dugan-Rocha S, Dunkov BC, Dunn P, Durbin KJ, Evangelista CC, Ferraz C, Ferriera S, Fleischmann W, Fosler C, Gabrielian AE, Garg NS, Gelbart WM, Glasser K, Glodek A, Gong F, Gorrell JH, Gu Z, Guan P, Harris M, Harris NL, Harvey D, Heiman TJ, Hernandez JR, Houck J, Hostin D, Houston KA, Howland TJ, Wei MH, Ibegwam C, Jalali M, Kalush F, Karpen GH, Ke Z, Kennison JA, Ketchum KA, Kimmel BE, Kodira CD, Kraft C, Kravitz S, Kulp D, Lai Z, Lasko P, Lei Y, Levitsky AA, Li J, Li Z, Liang Y, Lin X, Liu X, Mattei B, McIntosh TC, McLeod MP, McPherson D, Merkulov G, Milshina NV, Mobarry C, Morris J, Moshrefi A, Mount SM, Moy M, Murphy B, Murphy L, Muzny DM, Nelson DL, Nelson DR, Nelson KA, Nixon K, Nusskern DR, Pacleb JM, Palazzolo M, Pittman GS, Pan S, Pollard J, Puri V, Reese MG, Reinert K, Remington K, Saunders RD, Scheeler F, Shen H, Shue BC, Siden-Kiamos I, Simpson M, Skupski MP, Smith T, Spier E, Spradling AC, Stapleton M, Strong R, Sun E, Svirskas R, Tector C, Turner R, Venter E, Wang AH, Wang X, Wang ZY, Wassarman DA, Weinstock GM, Weissenbach J, Williams SM, WoodageT, Worley KC, Wu D, Yang S, Yao QA, Ye J, Yeh RF, Zaveri JS, Zhan M, Zhang G, Zhao Q, Zheng L, Zheng XH, Zhong FN, Zhong W, Zhou X, Zhu S, Zhu X, Smith HO, Gibbs RA, Myers EW, Rubin GM, Venter JC (- 185) Ref: Science, 287:2185, 2000 : PubMed ESTHER: Adams_2000_Science_287_2185 PubMedSearch: Adams 2000 Science 287 2185 PubMedID: 10731132 Gene_locus related to this paper: drome-1vite, drome-2vite, drome-3vite, drome-a1z6g9, drome-abhd2, drome-ACHE, drome-b6idz4, drome-BEM46, drome-CG5707, drome-CG5704, drome-CG1309, drome-CG1882, drome-CG1986, drome-CG2059, drome-CG2493, drome-CG2528, drome-CG2772, drome-CG3160, drome-CG3344, drome-CG3523, drome-CG3524, drome-CG3734, drome-CG3739, drome-CG3744, drome-CG3841, drome-CG4267, drome-CG4382, drome-CG4390, drome-CG4572, drome-CG4582, drome-CG4851, drome-CG4979, drome-CG5068, drome-CG5162, drome-CG5355, drome-CG5377, drome-CG5397, drome-CG5412, drome-CG5665, drome-CG5932, drome-CG5966, drome-CG6018, drome-CG6113, drome-CG6271, drome-CG6283, drome-CG6295, drome-CG6296, drome-CG6414, drome-CG6431, drome-CG6472, drome-CG6567, drome-CG6675, drome-CG6753, drome-CG6847, drome-CG7329, drome-CG7367, drome-CG7529, drome-CG7632, drome-CG8058, drome-CG8093, drome-CG8233, drome-CG8424, drome-CG8425, drome-CG9059, drome-CG9186, drome-CG9287, drome-CG9289, drome-CG9542, drome-CG9858, drome-CG9953, drome-CG9966, drome-CG10116, drome-CG10163, drome-CG10175, drome-CG10339, drome-CG10357, drome-CG10982, drome-CG11034, drome-CG11055, drome-CG11309, drome-CG11319, drome-CG11406, drome-CG11598, drome-CG11600, drome-CG11608, drome-CG11626, drome-CG11935, drome-CG12108, drome-CG12869, drome-CG13282, drome-CG13562, drome-CG13772, drome-CG14034, drome-nlg3, drome-CG14717, drome-CG15101, drome-CG15102, drome-CG15106, drome-CG15111, drome-CG15820, drome-CG15821, drome-CG15879, drome-CG17097, drome-CG17099, drome-CG17101, drome-CG17191, drome-CG17192, drome-CG17292, drome-CG18258, drome-CG18284, drome-CG18301, drome-CG18302, drome-CG18493, drome-CG18530, drome-CG18641, drome-CG18815, drome-CG31089, drome-CG31091, drome-CG32333, drome-CG32483, drome-CG33174, drome-dnlg1, drome-este4, drome-este6, drome-GH02384, drome-GH02439, drome-glita, drome-KRAKEN, drome-lip1, drome-LIP2, drome-lip3, drome-MESK2, drome-nrtac, drome-OME, drome-q7k274, drome-Q9VJN0, drome-Q8IP31, drome-q9vux3 Abstract The fly Drosophila melanogaster is one of the most intensively studied organisms in biology and serves as a model system for the investigation of many developmental and cellular processes common to higher eukaryotes, including humans. We have determined the nucleotide sequence of nearly all of the approximately 120-megabase euchromatic portion of the Drosophila genome using a whole-genome shotgun sequencing strategy supported by extensive clone-based sequence and a high-quality bacterial artificial chromosome physical map. Efforts are under way to close the remaining gaps; however, the sequence is of sufficient accuracy and contiguity to be declared substantially complete and to support an initial analysis of genome structure and preliminary gene annotation and interpretation. The genome encodes approximately 13,600 genes, somewhat fewer than the smaller Caenorhabditis elegans genome, but with comparable functional diversity. Title: Genome sequence of an obligate intracellular pathogen of humans: Chlamydia trachomatis Stephens RS, Kalman S, Lammel C, Fan J, Marathe R, Aravind L, Mitchell W, Olinger L, Tatusov RL and Davis RW <2 more author(s)> Stephens RS, Kalman S, Lammel C, Fan J, Marathe R, Aravind L, Mitchell W, Olinger L, Tatusov RL, Zhao Q, Koonin EV, Davis RW (- 2) Ref: Science, 282:754, 1998 : PubMed ESTHER: Stephens_1998_Science_282_754 PubMedSearch: Stephens 1998 Science 282 754 PubMedID: 9784136 Gene_locus related to this paper: chltr-CT073, chltr-CT136, chltr-CT149, chltr-CT206 Abstract Analysis of the 1,042,519-base pair Chlamydia trachomatis genome revealed unexpected features related to the complex biology of chlamydiae. Although chlamydiae lack many biosynthetic capabilities, they retain functions for performing key steps and interconversions of metabolites obtained from their mammalian host cells. Numerous potential virulence-associated proteins also were characterized. Several eukaryotic chromatin-associated domain proteins were identified, suggesting a eukaryotic-like mechanism for chlamydial nucleoid condensation and decondensation. The phylogenetic mosaic of chlamydial genes, including a large number of genes with phylogenetic origins from eukaryotes, implies a complex evolution for adaptation to obligate intracellular parasitism. | |||||||
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