Author Report for: Wu ZNo contact information in database for Wu Z
Luo A, Wu Z, Li S, McReynolds CB, Wang D, Liu H, Huang C, He T, Zhang X and Yang C <4 more author(s)> Luo A, Wu Z, Li S, McReynolds CB, Wang D, Liu H, Huang C, He T, Zhang X, Wang Y, Liu C, Hammock BD, Hashimoto K, Yang C (- 4) Ref: J Transl Med, 21:71, 2023 : PubMed ESTHER: Luo_2023_J.Transl.Med_21_71 PubMedSearch: Luo 2023 J.Transl.Med 21 71 PubMedID: 36732752 Inhibitor(s) related to this paper: TPPU Abstract BACKGROUND: Patients suffering from chronic pain often also exhibit depression symptoms. Soluble epoxide hydrolase (sEH) inhibitors can decrease blood levels of inflammatory cytokines. However, whether inhibiting sEH signaling is beneficial for the comorbidity of pain and depression is unknown. METHODS: According to a sucrose preference test (SPT), spared nerve injury (SNI) mice were classified into pain with or without an anhedonia phenotype. Then, sEH protein expression and inflammatory cytokines were assessed in selected tissues. Furthermore, we used sEH inhibitor TPPU to determine the role of sEH in chronic pain and depression. Importantly, agonists and antagonists of aryl hydrocarbon receptor (AHR) and translocator protein (TSPO) were used to explore the pathogenesis of sEH signaling. RESULTS: In anhedonia-susceptible mice, the tissue levels of sEH were significantly increased in the medial prefrontal cortex (mPFC), hippocampus, spinal cord, liver, kidney, and gut. Importantly, serum CYP1A1 and inflammatory cytokines, such as interleukin 1beta (IL-1beta) and the tumor necrosis factor alpha (TNF-alpha), were increased simultaneously. TPPU improved the scores of mechanical withdrawal threshold (MWT) and SPT, and decreased the levels of serum CYP1A1 and inflammatory cytokines. AHR antagonist relieved the anhedonia behaviors but not the algesia behaviors in anhedonia-susceptible mice, whereas an AHR agonist abolished the antidepressant-like effect of TPPU. In addition, a TSPO agonist exerted a similar therapeutic effect to that of TPPU, whereas pretreatment with a TSPO antagonist abolished the antidepressant-like and analgesic effects of TPPU. CONCLUSIONS: sEH underlies the mechanisms of the comorbidity of chronic pain and depression and that TPPU exerts a beneficial effect on anhedonia behaviors in a pain model via AHR and TSPO signaling. Title: Discovery of two ent-atisane diterpenoid lactones with AChE inhibitory activity from the roots of Euphorbia fischeriana Wei J, Li Z, Shan M, Wu F, Li L, Ma Y, Wu J, Li X, Liu Y and Wu Z <2 more author(s)> Wei J, Li Z, Shan M, Wu F, Li L, Ma Y, Wu J, Li X, Liu Y, Hu Z, Zhang Y, Wu Z (- 2) Ref: Org Biomol Chem, :, 2023 : PubMed ESTHER: Wei_2023_Org.Biomol.Chem__ PubMedSearch: Wei 2023 Org.Biomol.Chem PubMedID: 37581482 Abstract Euphorlactone A (1), a rare rearranged ent-atisane norditerpenoid with an undescribed 3-nor-2,4-olide-ent-atisane scaffold, and euphorlactone B (2), a new ent-atisane diterpenoid with an unprecedented seven-membered lactone ring C, were isolated from the roots of Euphorbia fischeriana. Their planar structures with absolute configurations were extensively elucidated by analysis of 1D and 2D NMR data, electronic circular dichroism (ECD) calculations, Rh(2)(OCOCF(3))(4)-induced ECD curves, and single-crystal X-ray diffraction. Euphorlactone A (ELA) showed a remarkable AChE (acetylcholinesterase) inhibitory activity (IC(50) = 2.13 +/- 0.06 microM and K(i) = 0.058 microM), which was five times stronger than that of the positive control (rivastigmine, IC(50) = 12.46 +/- 0.82 microM), and further in vitro enzyme inhibition kinetic analysis and molecular docking studies were performed to investigate the AChE inhibitory mechanism. Title: Near-infrared-excitable acetylcholinesterase-activated fluorescent probe for sensitive and anti-interference detection of pesticides in colored food Wu Z, Hao Z, Chai Y, Li A, Wang C, Zhang X, Chen H, Lu C Ref: Biosensors & Bioelectronics, 233:115341, 2023 : PubMed ESTHER: Wu_2023_Biosens.Bioelectron_233_115341 PubMedSearch: Wu 2023 Biosens.Bioelectron 233 115341 PubMedID: 37099980 Abstract The development of a common and anti-interference acetylcholinesterase (AChE) inhibition assay for plant-originated food samples has been of great challenge because of the prevalent and strong signal interferences from natural pigments. Plant pigments normally exhibit non-negligible absorbance in the UV-visible region. As a result, the signals of a typical near-infrared (NIR) fluorescent probe could be disturbed through primary inner filter effect if it is excited by UV-visible light during plant sample analysis. In this work, an NIR-excitable AChE-activated fluorescent probe was biomimetically designed and synthesized. And the NIR-excitation strategy was utilized for the anti-interference detection of organophosphate and carbamate pesticides in colored samples with this probe. Sensitive and rapid response to AChE and pesticides was achieved due to the high affinity of the biomimetic recognition unit in the probe. The limits of detection for four representative pesticides including dichlorvos, carbofuran, chlorpyrifos and methamidophos reached 0.0186 microg/L, 2.20 microg/L, 12.3 microg/L and 13.6 microg/L, respectively. Most importantly, fluorescent response to pesticide contents could be accurately measured in the coexistence of different plant pigments by this probe, and the measured results showed completely irrelevance to the plant pigments and their colors. Taking advantage of such probe, the new developed AChE inhibition assay showed good sensitivity and anti-interference ability in the detection of organophosphate and carbamate pesticides in real samples. Title: Efficient enzymatic synthesis of chiral 2,3-dihydro-1,4-benzodioxane motif using engineered Candida antarctica lipase B Wu Z, Shi W, Jin M, Zhou W Ref: RSC Adv, 13:18953, 2023 : PubMed ESTHER: Wu_2023_RSC.Adv_13_18953 PubMedSearch: Wu 2023 RSC.Adv 13 18953 PubMedID: 37350861 Abstract Chiral motifs of 2,3-dihydro-1,4 benzodioxane are extensively utilized in diverse medicinal substances and bioactive natural compounds, exhibiting significant biological activities. Notable examples of such therapeutic agents include prosympal, dibozane, piperoxan, and doxazosin. In this work, using 1,4-benzodioxane-2-carboxylic acid methyl ester as the substrate, after screening 38 CALB covariant residues, we found that mutants A225F and A225F/T103A can catalyze the kinetic resolution of the substrate. The effect of temperature, cosolvent, and cosolvent concentration on kinetic resolution was investigated, revealing that the best results were achieved at 30 degreesC with 20% n-butanol as a cosolvent, resulting in an optimal resolution (e.e.(s) 97%, E = 278) at 50 mM substrate concentration. Structure analysis showed that mutation sites 225 and 103 are not among the sites that interact directly with the substrate, which means that covariant amino acids that interact remotely with the substrate also regulate enzyme catalysis. This research may provide us with a new strategy for enzyme evolution. Title: Toxicity and Physiological Effects of Nine Lamiaceae Essential Oils and Their Major Compounds on Reticulitermes dabieshanensis Yang X, Jin C, Wu Z, Han H, Zhang Z, Xie Y, Zhang D Ref: Molecules, 28:, 2023 : PubMed ESTHER: Yang_2023_Molecules_28_ PubMedSearch: Yang 2023 Molecules 28 PubMedID: 36903258 Abstract The volatile metabolites of Salvia sclarea, Rosmarinus officinalis, Thymus serpyllum, Mentha spicata, Melissa officinalis, Origanum majorana, Mentha piperita, Ocimum basilicum and Lavandula angustifolia were determined by gas chromatography-mass spectrometry. The vapor insecticidal properties of the analyzed essential oils and their compounds were screened using Reticulitermes dabieshanensis workers. The most effective oils were S. sclarea (major constituent linalyl acetate, 65.93%), R. officinalis (1,8-cineole, 45.56%), T. serpyllum (thymol, 33.59%), M. spicata (carvone, 58.68%), M. officinalis (citronellal, 36.99%), O. majorana (1,8-cineole, 62.29%), M. piperita (menthol, 46.04%), O. basilicum (eugenol, 71.08%) and L. angustifolia (linalool, 39.58%), which exhibited LC(50) values ranging from 0.036 to 1.670 microL/L. The lowest LC(50) values were recorded for eugenol (0.060 microL/L), followed by thymol (0.062 microL/L), carvone (0.074 microL/L), menthol (0.242 microL/L), linalool (0.250 microL/L), citronellal (0.330 microL/L), linalyl acetate (0.712 microL/L) and 1,8-cineole (1.478 microL/L). The increased activity of esterases (ESTs) and glutathione S-transferase (GST) were observed but only alongside the decreased activity of acetylcholinesterase (AChE) in eight main components. Our results indicate that S. sclarea, R. officinalis, T. serpyllum, M. spicata, M. officinalis, O. marjorana, M. piperita, O. basilicum and L. angustifolia essential oils (EOs) and their compounds, linalyl acetate, 1,8-cineole, thymol, carvone, citronellal, menthol, eugenol and linalool could be developed as control agents against termites. Title: Nanoclusterzyme for Dual Colorimetric Sensings: A Case Study on [Au(14) (Dppp)(5) I(4) ](2) Zhao H, You Q, Zhu W, Li J, Deng H, Li MB, Zhao Y, Wu Z Ref: Small, :e2207936, 2023 : PubMed ESTHER: Zhao_2023_Small__e2207936 PubMedSearch: Zhao 2023 Small e2207936 PubMedID: 37060229 Abstract The enzymatic activity of atomically precise metal nanoclusters has recently been recognized; however, the number of nanoclusterzymes is very small. Besides, the applications of nanoclusterzyme wait to be explored. Herein, a novel nanoclusterzyme is synthesized and its structure is majorly resolved by single-crystal X-ray diffraction and mass spectrometry, which reveal that the nanocluster consists of an Au(13) icosahedron capped by an exterior shell including four I, three Dppp (1,3-bis(diphenylphosphino) propane) ligands, and a rarely reported Dppp-Au-Dppp handle staple, which contributes a lot to the enzyme activity of [Au(14) (Dppp)(5) I(4) ](2+) nanocluster. The as-obtained nanocluster can catalyze oxygen to O(2) (-) under visible light irradiation with a specific activity up to 0.182 U.mg(-1) and lead to the blue color of 3,3',5,5'-tetramethylbenzidine (TMB) in both solution and solid states. With the addition of acetylcholinesterase (AChE), the blue color of (Au(14) + TMB) solution system disappears due to the nanoclusterzyme activity inhibition, but the further addition of organophosphorus pesticides (OPs) into the above mixture can restore the nanoclusterzyme and recover the blue color. Based on the color turn-off and on, the various nanoclusterzyme-containing systems are used to colorimetrically sense AChE and OPs with the detection limits reaching 0.04 mU.mL(-1) and 0.02 ng.mL(-1) , respectively. Title: Structural and mechanistic insights into enantioselectivity toward near-symmetric esters of a novel carboxylesterase RoCE Dou Z, Jia P, Chen X, Wu Z, Xu G, Ni Y Ref: Catal Sci Technol, 12:7448, 2022 : PubMed ESTHER: Dou_2022_Catal.Sci.Technol_12_7448 PubMedSearch: Dou 2022 Catal.Sci.Technol 12 7448 Gene_locus related to this paper: rhoop-RoCE Abstract A novel carboxylesterase designated as RoCE was identified from Rhodococcus opacus with high activity and enantioselectivity toward asymmetric esters such as ethyl 2,2-dimethylcyclopropane-1-carboxylate (DMCPE). Moreover, RoCE could catalyze the enantioselective resolution of near-symmetric oxyheterocyclic esters such as ethyl tetrahydro-2H-pyran-2-carboxylate (THPCE), which are generally regarded as 'hard-to-be-discriminated' by chemical and biological catalysts. The crystal structure of RoCE was resolved at a resolution of 1.78 A. Theozyme calculation, MD simulations and pre-reaction state analysis were performed to clarify the molecular basis for the enantioselectivity toward oxyheterocyclic carboxylic acid esters with a nearly symmetric structure. F166 plays an important role in manipulating the enantioselective recognition of (S)- and (R)-DMCPE through steric effect. The intrinsic symmetric structure of (S)- and (R)-THPCE is mainly responsible for the relatively lower enantioselectivity than DMCPE. By introducing hydrogen bond interactions, a mutant M144T was successfully obtained with an E value of 2.44-fold that of WT. MD simulations further prove the increased enantioselectivity of M144T in terms of pre-reaction state and binding free energy. This study provides a novel carboxylesterase and important molecular insights into the enantioselectivity of carboxylesterase toward heterocyclic carboxylic acid esters with a nearly symmetric structure, which will facilitate further engineering of the enantioselectivity of carboxylesterase. Title: PRDX6 knockout restrains the malignant progression of intrahepatic cholangiocarcinoma Li H, Wu Z, Zhong R, Zhang Q, Chen Q, Shen Y Ref: Med Oncol, 39:250, 2022 : PubMed ESTHER: Li_2022_Med.Oncol_39_250 PubMedSearch: Li 2022 Med.Oncol 39 250 PubMedID: 36209344 Abstract Intrahepatic cholangiocarcinoma (ICC) has a poor prognosis. The bifunctional protein peroxiredoxin 6 (PRDX6), which has both calcium-independent phospholipase A2 (iPLA2) and glutathione peroxidase (GPx) activity, participates in the development of multiple tumors. However, the function and clinical significance of PRDX6 in ICC remain unclear. In this study, we characterized PRDX6 in both human ICC and thioacetamide (TAA)-induced rat ICC. We found PRDX6 was significantly increased in ICC tissues, compared with the peritumoral tissues, and PRDX6 expression level was positively correlated with the malignant phenotype in ICC patients. Furthermore, PRDX6 genetic knockout significantly inhibited the tumor progression in rats. By using RNA sequencing analysis, we found 127 upregulated genes and 321 downregulated genes after PRDX6 knockout. In addition, we noticed a significant repression in the Wnt7a/b cascade, which has been shown to play an important role in the occurrence of ICC. We confirmed that gene expressions in the Wnt7a/b cascade were inhibited in ICC tissues after PRDX6 knockout by using qRT-PCR and immunohistochemistry analysis. Collectively, our findings suggest that PRDX6 may promote ICC by regulating the Wnt7a/b pathway, which could be a novel therapeutic target for ICC. 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: Synthesis, insecticidal activity, and mode of action of novel imidazopyridine mesoionic derivatives containing an amido group Liu Z, Song R, Zhang D, Wu R, Liu T, Wu Z, Zhang J, Hu D Ref: Pest Manag Sci, :, 2022 : PubMed ESTHER: Liu_2022_Pest.Manag.Sci__ PubMedSearch: Liu 2022 Pest.Manag.Sci PubMedID: 36054072 Abstract BACKGROUND: In our previous work, we applied a new synthetic strategy to design and synthesize a series of imidazopyridine mesoionic derivatives with an ester group. The newly synthesized compounds had excellent insecticidal activity against aphids; however, insecticidal activity against planthoppers was less than satisfactory. In the present study, we designed and synthesized a series of novel imidazopyridine mesoionic compounds, containing an amido group, and these compounds were found to have improved insecticidal activity against planthoppers. RESULTS: The bioassay results demonstrated that most of the target compounds had moderate-to-good insecticidal activity against Sogatella furcifera, and some exhibited good-to-excellent insecticidal activity against Aphis craccivora. Among them, compound C6 had the highest insecticidal activity against S. furcifera and A. craccivora, with LC(50) values of 10.5 and 2.09 microg mL(-1) , respectively. Proteomic results suggested that the differentially expressed proteins mainly were enriched in the nervous system-related pathways after compound C6 treatment. Enzymatic assay results showed that compound C6 and triflumezopyrim had a certain inhibitory effect on acetylcholinesterase. Molecular docking and real-time quantitative PCR results indicated that compound C6 not only may act on the nicotinic acetylcholine receptor, but also may interact with the alpha4 and beta1 subunits of this receptor. CONCLUSION: The results reported here contribute to the development of new mesoionic insecticides and further our understanding of the mode-of-action of imidazopyridine mesoionic derivatives. 2022 Society of Chemical Industry. 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: Research progress on the role of fibroblast activation protein in diagnosis and treatment of cancer Wu Z, Hua Y, Shen Q, Yu C Ref: Nucl Med Commun, 43:746, 2022 : PubMed ESTHER: Wu_2022_Nucl.Med.Commun_43_746 PubMedSearch: Wu 2022 Nucl.Med.Commun 43 746 PubMedID: 35506275 Abstract Fibroblast activation protein (FAP) is a type II transmembrane protein, which is over-expressed in cancer-associated fibroblasts (CAFs). CAFs are tumor stromal cells that constitute a major component of cancer volume and are reportedly related to tumorigenesis, angiogenesis, metastasis, promotion of drug resistance and induction of tumor immunity. FAP is widely acknowledged as the signature protein of CAFs. At present, FAP inhibitors (FAPI) have achieved ideal results in tumor PET/computed tomography (CT) imaging. Theoretically, FAP-targeted drugs can inhibit tumor progression. Nonetheless, no satisfactory therapeutic effect has been observed so far, which has impeded their implementation in clinical practice. In this review, we describe the characteristics of FAP and its role in the occurrence and development of cancer. We also highlight the potential value of targeting FAP to improve current diagnostic and therapeutic approaches. Title: In Vitro Metabolism of Donepezil in Liver Microsomes Using Non-Targeted Metabolomics Kim SE, Seo HJ, Jeong Y, Lee GM, Ji SB, Park SY, Wu Z, Lee S, Kim S, Liu KH Ref: Pharmaceutics, 13:, 2021 : PubMed ESTHER: Kim_2021_Pharmaceutics_13_ PubMedSearch: Kim 2021 Pharmaceutics 13 PubMedID: 34201744 Abstract Donepezil is a reversible acetylcholinesterase inhibitor that is currently the most commonly prescribed drug for the treatment of Alzheimer's disease. In general, donepezil is known as a safe and well-tolerated drug, and it was not associated with liver abnormalities in several clinical trials. However, rare cases of drug-related liver toxicity have been reported since it has become commercially available. Few studies have investigated the metabolic profile of donepezil, and the mechanism of liver damage caused by donepezil has not been elucidated. In this study, the in vitro metabolism of donepezil was investigated using liquid chromatography-tandem mass spectrometry based on a non-targeted metabolomics approach. To identify metabolites, the data were subjected to multivariate data analysis and molecular networking. A total of 21 donepezil metabolites (17 in human liver microsomes, 21 in mice liver microsomes, and 17 in rat liver microsomes) were detected including 14 newly identified metabolites. One potential reactive metabolite was identified in rat liver microsomal incubation samples. Metabolites were formed through four major metabolic pathways: (1) O-demethylation, (2) hydroxylation, (3) N-oxidation, and (4) N-debenzylation. This study indicates that a non-targeted metabolomics approach combined with molecular networking is a reliable tool to identify and detect unknown drug metabolites. Title: Highly accurate protein structure prediction for the human proteome Tunyasuvunakool K, Adler J, Wu Z, Green T, Zielinski M, idek A, Bridgland A, Cowie A, Meyer C and Hassabis D <23 more author(s)> Tunyasuvunakool K, Adler J, Wu Z, Green T, Zielinski M, idek A, Bridgland A, Cowie A, Meyer C, Laydon A, Velankar S, Kleywegt GJ, Bateman A, Evans R, Pritzel A, Figurnov M, Ronneberger O, Bates R, Kohl SAA, Potapenko A, Ballard AJ, Romera-Paredes B, Nikolov S, Jain R, Clancy E, Reiman D, Petersen S, Senior AW, Kavukcuoglu K, Birney E, Kohli P, Jumper J, Hassabis D (- 23) Ref: Nature, 596:590, 2021 : PubMed ESTHER: Tunyasuvunakool_2021_Nature_596_590 PubMedSearch: Tunyasuvunakool 2021 Nature 596 590 PubMedID: 34293799 Abstract Protein structures can provide invaluable information, both for reasoning about biological processes and for enabling interventions such as structure-based drug development or targeted mutagenesis. After decades of effort, 17% of the total residues in human protein sequences are covered by an experimentally determined structure(1). Here we markedly expand the structural coverage of the proteome by applying the state-of-the-art machine learning method, AlphaFold(2), at a scale that covers almost the entire human proteome (98.5% of human proteins). The resulting dataset covers 58% of residues with a confident prediction, of which a subset (36% of all residues) have very high confidence. We introduce several metrics developed by building on the AlphaFold model and use them to interpret the dataset, identifying strong multi-domain predictions as well as regions that are likely to be disordered. Finally, we provide some case studies to illustrate how high-quality predictions could be used to generate biological hypotheses. We are making our predictions freely available to the community and anticipate that routine large-scale and high-accuracy structure prediction will become an important tool that will allow new questions to be addressed from a structural perspective. Title: TIR signal promotes interactions between lipase-like proteins and ADR1-L1 receptor and ADR1-L1 oligomerization Wu Z, Tian L, Liu X, Zhang Y, Li X Ref: Plant Physiol, 187:681, 2021 : PubMed ESTHER: Wu_2021_Plant.Physiol_187_681 PubMedSearch: Wu 2021 Plant.Physiol 187 681 PubMedID: 34608964 Abstract TIR signaling promotes the interactions between lipase-like proteins EDS1/PAD4 and ADR1-L1 immune receptor, and oligomerization of ADR1-L1. Title: Near-infrared emission tracks inter-individual variability of carboxylesterase-2 via a novel molecular substrate Liu X, Li X, Dong P, Wu Z, Gao J, Wang Q Ref: Mikrochim Acta, 187:313, 2020 : PubMed ESTHER: Liu_2020_Mikrochim.Acta_187_313 PubMedSearch: Liu 2020 Mikrochim.Acta 187 313 PubMedID: 32377952 Abstract A low-molecular-weight molecule (4-(2-(3-(dicyanomethyl)-5,5-dimethylcyclohex-1-en-1-yl)vinyl)phenyl-benzoate, DDPB) has been developed. The organic framework possesses very weak fluorescence . The feasibility of the signal transduction has been performed via fluorometric titrations in solution. DDPB gives rise to responses to carboxylesterase 2 (CES2) based on "off-on" responses. The red emission at 670 nm has been derived from the enzyme-induced hydrolysis of ester linkages, thus suppressing the intramolecular charge transfer (ICT) effect and thereby generating the fluorescent segment. The optical excitation window for this probe is extended to the visible light range (lambdaex = 516 nm), and it will induce less harmful influence on biological substances. The detection limit for the measurement of CES2 concentration is as low as 2.33 mU/mL. The conventional studies concerning the activation process are generally performed within only a single liveing cell system. In this study, it is the first time that expression of carboxylesterase 2 in five kinds of cell lines (HeLa > C1498 > active T cell > Jurkat > unactive T cell) has been clarified by flow cytometry, Western blotting, and confocal microscopy analysis. The elucidation of CES2 and its variability in a variety of cells will open new ways for drug metabolism and disease prevention. Graphical abstract We reported a new "substrate-mediated light-on" strategy based on an ester bond cleavage reaction. Most of prepared nanomaterials and organic fluorophores possessed short wavelength emissions in the blue or green region which will not be difficult for cellular imaging. In this study, a novel functional molecule (DDPB) was considered as the substrate for CES2 and the optical "off-on" response was realized. DDPB was cell permeable and possessed very low cytotoxicity. Moreover, the identification of CES2 and their subtle changes in five different cells afforded the sequence for carboxylesterase-2 as Hela > C1498 > Active T cell > Jurkat > Unactive T cell. Inhibition studies showed that the hydrolysis of DDPB was effectively suppressed by bis-p-nitrophenyl phosphate and the cellular tracking results firmly supported this point. To our knowledge, the inter-individual variability for the CES2 expressions in five different cell lines has never been reported via the substrate induced optical changes. Title: Ratiometric sensors with selective fluorescence enhancement effects based on photonic crystals for the determination of acetylcholinesterase and its inhibitor Liu R, Bao L, Zhang S, Wu Z, Zhou J, Liu C, Yu R Ref: J Mater Chem B, 8:11001, 2020 : PubMed ESTHER: Liu_2020_J.Mater.Chem.B_8_11001 PubMedSearch: Liu 2020 J.Mater.Chem.B 8 11001 PubMedID: 33225325 Abstract Ratiometric fluorescent sensors are powerful tools for quantitative analyses. However, gold nano-clusters (AuNCs) as typical fluorophores in ratiometric sensors have some disadvantages, such as low luminous efficiency. In this study, a highly sensitive ratiometric fluorescence sensor was fabricated by the combination of AuNCs and fluorescein (FL), and the photonic crystals (PhCs) were used to selectively enhance the fluorescence intensity of AuNCs. This fluorescence sensor was used for the sensitive detection of acetylcholinesterase (AChE) and its inhibitor paraoxon. AChE can catalyze the hydrolysis of acetylthiocholine (ATCh) to form thiocholine (TCh), which can induce the fluorescence quenching of AuNCs while having no obvious influence on the fluorescence intensity of FL. AChE can be determined in the range from 0.1 to 25 mU mL-1 with a limit of detection (LOD) of 0.027 mU mL-1, and paraoxon can be determined in the range of 0.06 to 60 ng mL-1 with a LOD 0.025 ng mL-1. This method, as a new way to selectively improve the fluorescence signal of one of the fluorophores in the ratiometric sensor, would be a promising strategy for the sensitive determination of AChE and its inhibitor. Title: Effects of nucleo(s)tide analogs therapy on chronic hepatitis B as evaluated by hepatosplenic radionuclide angiography Wang L, Wu Z, Wang A, Jin X, Qiu Y Ref: Nucl Med Commun, :, 2020 : PubMed ESTHER: Wang_2020_Nucl.Med.Commun__ PubMedSearch: Wang 2020 Nucl.Med.Commun PubMedID: 31939901 Abstract OBJECTIVES: Hepatosplenic radionuclide angiography is a relatively noninvasive method for evaluating hepatic portal perfusion. We used hepatosplenic radionuclide angiography to assess the effects of nucleo(s)tide analogs therapy on patients with chronic hepatitis B (CHB). PATIENTS AND METHODS: A retrospective analysis was performed on patients who underwent hepatosplenic radionuclide angiography from January 2012 to May 2017 at the First Affiliated Hospital, College of Medicine, Zhejiang University. The correlations between the results of routine laboratory tests and hepatic perfusion index (HPI) were evaluated. The Wilcoxon signed-rank test and one-way ANOVA of repeated measures were used to compare the HPIs of patients who received nucleo(s)tide analogs therapy. RESULTS: There is a positive correlation between HPI and cholinesterase and serum albumin (ALB) and a negative correlation between HPI and aspartate aminotransferase-to-platelet ratio index and bilirubin (TBiL). An improvement in HPI was observed in patients with an initial HPI <61% after nucleo(s)tide analogs therapy. CONCLUSIONS: Hepatosplenic radionuclide angiography can reflect the functional reserve of the liver and monitor liver fibrosis indirectly. It can also comprehensively assess the effects of antiviral therapy on patients with CHB, and antiviral therapy is critical for the treatment of hepatitis. Title: Algorithm-based coevolution network identification reveals key functional residues of the alpha/beta hydrolase subfamilies Wu Z, Liu H, Xu L, Chen HF, Feng Y Ref: FASEB Journal, 34:1983, 2020 : PubMed ESTHER: Wu_2020_FASEB.J_34_1983 PubMedSearch: Wu 2020 FASEB.J 34 1983 PubMedID: 31907985 Abstract Covariant residues identified by computational algorithms have provided new insights into enzyme evolutionary routes. However, the reliability and accuracy of routine statistical coupling analysis (SCA) are unable to satisfy the needs of protein engineering because SCA depends only on sequence information. Here, we set up a new SCA algorithm, SCA.SIM, by integrating structure information and MD simulation data. The more reliable covariant residues with high-quality scores are obtained from sequence alignment weighted by residual movement for eight related subfamilies, belonging to alpha/beta hydrolase family, with Candida antarctica lipase B (CALB). The 38 predicted covariant residues are tested for function by high-throughput quantitative evaluation in combination with activity and thermostability assays of a mutant library and deep sequencing. Based on the landscapes of both activity and thermostability, most mutants play key roles in catalysis, and some mutants gain 2.4- to 6-fold increase in half-life at 50 degrees C and 9- to 12-fold improvement in catalytic efficiency. The activity of double mutants for A225F/T103A is higher than those of A225F and T103A which means that SCA.SIM method might be useful for identifying the allosteric coupling. The SCA.SIM algorithm can be used for protein coevolution and enzyme engineering research. Title: Insecticidal activity of triterpenoids and volatile oil from the stems of Tetraena mongolica Wu Z, Wei W, Cheng K, Zheng L, Ma C, Wang Y Ref: Pestic Biochem Physiol, 166:104551, 2020 : PubMed ESTHER: Wu_2020_Pestic.Biochem.Physiol_166_104551 PubMedSearch: Wu 2020 Pestic.Biochem.Physiol 166 104551 PubMedID: 32448415 Abstract Tetraena mongolica Maxim is a species of Zygophyllaceae endemic to China. Because few insect pests affect its growth and flowering, we speculated that this plant produces defensive chemicals that are insect repellents or antifeedants. The effects of different fractions from crude stem and leaf extracts on Pieris rapae were examined. The results confirmed that the ethyl acetate (EtOAc) fraction from the stems had insecticidal potential. Five compounds were isolated from the EtOAc fraction: a volatile oil [bis(2-ethylhexyl) benzene-1,2-dicarboxylate (1)], three triterpenoids 2E-3beta-(3,4-dihydroxycinnamoyl)-erythrodiol (2), 2Z-3beta-(3,4-dihydroxycinnamoyl)-erythrodiol (3), and 2E-3beta-(3,4-dihydroxyphenyl)-2-propenoate (4)], and one steroid [beta-sitosterol (5)]. Compounds 1-5 exhibited different degrees of insecticidal activity, including antifeedant and growth-inhibition effects. Compounds 1-5 inhibited the activity of carboxylesterase (CarE) and acetylcholinesterase (AChE) to different degrees. Compound 1 had the strongest antifeedant and growth-inhibition effects, and significantly inhibited the activity of CarE and AChE. Our results indicate that compounds 1-4 are the major bioactive insecticidal constituents of Tetraena mongolica. This work should facilitate the development and application of plant-derived botanical pesticides. Title: Transcriptome analysis of putative detoxification genes in the Asian citrus psyllid, Diaphorina citri Wu Z, Pu X, Shu B, Bin S, Lin J Ref: Pest Manag Sci, :, 2020 : PubMed ESTHER: Wu_2020_Pest.Manag.Sci__ PubMedSearch: Wu 2020 Pest.Manag.Sci PubMedID: 32483911 Abstract BACKGROUND: The Asian citrus psyllid, Diaphorina citri Kuwayama (Hemiptera: Psyllidae), is a notorious pest that transmits the causal agent of huanglongbing (also called citrus greening disease). Resistance to insecticide in this destructive pest poses a serious threat to the citrus industry. To date, no systemic studies on genes coding for detoxification enzymes has been carried out on D. citri. RESULTS: Multiple transcriptomes were generated through deep sequencing of RNA libraries. Candidate genes potentially involved in detoxification including cytochrome P450 monooxygenases (CYPs), glutathione S-transferases (GSTs), and esterases (ESTs) were systematically identified by searching the transcriptomes and a draft genome assembly. A total of 49, 14 and 20 genes were found encoding CYPs, GSTs, and ESTs, respectively, in D. citri. The total numbers of candidate detoxification genes were much smaller than the counterparts reported in other insect species, which may reflect the strict oligophagy of this insect species. Developmental stage- and tissue-specific expression patterns of the identified genes as well as their responses to insecticide treatments identified a small set of genes that could participate in detoxifying plant secondary metabolites and insecticides. CONCLUSION: Our studies represent the most comprehensive investigation to date on identification, characterization and expression profiling of detoxification genes in D. citri. The information revealed in this study shall be useful in designing strategies to manage this important insect pest. This article is protected by copyright. All rights reserved. Title: DIP-2 suppresses ectopic neurite sprouting and axonal regeneration in mature neurons Noblett N, Wu Z, Ding ZH, Park S, Roenspies T, Flibotte S, Chisholm AD, Jin Y, Colavita A Ref: Journal of Cell Biology, 218:125, 2019 : PubMed ESTHER: Noblett_2019_J.Cell.Biol_218_125 PubMedSearch: Noblett 2019 J.Cell.Biol 218 125 PubMedID: 30396999 Abstract Neuronal morphology and circuitry established during early development must often be maintained over the entirety of animal lifespans. Compared with neuronal development, the mechanisms that maintain mature neuronal structures and architecture are little understood. The conserved disco-interacting protein 2 (DIP2) consists of a DMAP1-binding domain and two adenylate-forming domains (AFDs). We show that the Caenorhabditis elegans DIP-2 maintains morphology of mature neurons. dip-2 loss-of-function mutants display a progressive increase in ectopic neurite sprouting and branching during late larval and adult life. In adults, dip-2 also inhibits initial stages of axon regeneration cell autonomously and acts in parallel to DLK-1 MAP kinase and EFA-6 pathways. The function of DIP-2 in maintenance of neuron morphology and in axon regrowth requires its AFD domains and is independent of its DMAP1-binding domain. Our findings reveal a new conserved regulator of neuronal morphology maintenance and axon regrowth after injury. Title: Effects of BIS-MEP on Reversing Amyloid Plaque Deposition and Spatial Learning and Memory Impairments in a Mouse Model of beta-Amyloid Peptide- and Ibotenic Acid-Induced Alzheimer's Disease Wang Y, Xia J, Shen M, Zhou Y, Wu Z, Shi Y, Xu J, Hou L, Zhang R and Wang H <4 more author(s)> Wang Y, Xia J, Shen M, Zhou Y, Wu Z, Shi Y, Xu J, Hou L, Zhang R, Qiu Z, Xie Q, Chen H, Zhang Y, Wang H (- 4) Ref: Front Aging Neurosci, 11:3, 2019 : PubMed ESTHER: Wang_2019_Front.Aging.Neurosci_11_3 PubMedSearch: Wang 2019 Front.Aging.Neurosci 11 3 PubMedID: 30723404 Inhibitor(s) related to this paper: bis9-(-)-nor-meptazinol Abstract Alzheimer's disease (AD) is the main type of dementia and is characterized by progressive memory loss and a notable decrease in cholinergic neuron activity. As classic drugs currently used in the clinic, acetylcholinesterase inhibitors (AChEIs) restore acetylcholine levels and relieve the symptoms of AD, but are insufficient at delaying the onset of AD. Based on the multi-target-directed ligand (MTDL) strategy, bis-(-)-nor-meptazinol (BIS-MEP) was developed as a multi-target AChEI that mainly targets AChE catalysis and the beta-amyloid (Abeta) aggregation process. In this study, we bilaterally injected Abeta oligomers and ibotenic acid (IBO) into the hippocampus of ICR mice and then subcutaneously injected mice with BIS-MEP to investigate its therapeutic effects and underlying mechanisms. According to the results from the Morris water maze test, BIS-MEP significantly improved the spatial learning and memory impairments in AD model mice. Compared with the vehicle control, the BIS-MEP treatment obviously inhibited the AChE activity in the mouse brain, consistent with the findings from the behavioral tests. The BIS-MEP treatment also significantly reduced the Abeta plaque area in both the hippocampus and cortex, suggesting that BIS-MEP represents a direct intervention for AD pathology. Additionally, the immunohistochemistry and ELISA results revealed that microglia (ionized calcium-binding adapter molecule 1, IBA1) and astrocyte (Glial fibrillary acidic protein, GFAP) activation and the secretion of relevant inflammatory factors (TNFalpha and IL-6) induced by Abeta were decreased by the BIS-MEP treatment. Furthermore, BIS-MEP showed more advantages than donepezil (an approved AChEI) as an Abeta intervention. Based on our findings, BIS-MEP improved spatial learning and memory deficits in AD mice by regulating acetylcholinesterase activity, Abeta deposition and the inflammatory response in the brain. Title: Musa balbisiana genome reveals subgenome evolution and functional divergence Wang Z, Miao H, Liu J, Xu B, Yao X, Xu C, Zhao S, Fang X, Jia C and Jin Z <30 more author(s)> Wang Z, Miao H, Liu J, Xu B, Yao X, Xu C, Zhao S, Fang X, Jia C, Wang J, Zhang J, Li J, Xu Y, Ma W, Wu Z, Yu L, Yang Y, Liu C, Guo Y, Sun S, Baurens FC, Martin G, Salmon F, Garsmeur O, Yahiaoui N, Hervouet C, Rouard M, Laboureau N, Habas R, Ricci S, Peng M, Guo A, Xie J, Li Y, Ding Z, Yan Y, Tie W, D'Hont A, Hu W, Jin Z (- 30) Ref: Nat Plants, 5:810, 2019 : PubMed ESTHER: Wang_2019_Nat.Plants_5_810 PubMedSearch: Wang 2019 Nat.Plants 5 810 PubMedID: 31308504 Gene_locus related to this paper: musam-m0tuu7, musam-a0a804kav5 Abstract Banana cultivars (Musa ssp.) are diploid, triploid and tetraploid hybrids derived from Musa acuminata and Musa balbisiana. We presented a high-quality draft genome assembly of M. balbisiana with 430 Mb (87%) assembled into 11 chromosomes. We identified that the recent divergence of M. acuminata (A-genome) and M. balbisiana (B-genome) occurred after lineage-specific whole-genome duplication, and that the B-genome may be more sensitive to the fractionation process compared to the A-genome. Homoeologous exchanges occurred frequently between A- and B-subgenomes in allopolyploids. Genomic variation within progenitors resulted in functional divergence of subgenomes. Global homoeologue expression dominance occurred between subgenomes of the allotriploid. Gene families related to ethylene biosynthesis and starch metabolism exhibited significant expansion at the pathway level and wide homoeologue expression dominance in the B-subgenome of the allotriploid. The independent origin of 1-aminocyclopropane-1-carboxylic acid oxidase (ACO) homoeologue gene pairs and tandem duplication-driven expansion of ACO genes in the B-subgenome contributed to rapid and major ethylene production post-harvest in allotriploid banana fruits. The findings of this study provide greater context for understanding fruit biology, and aid the development of tools for breeding optimal banana cultivars. Title: Carbon dots co-doped with nitrogen and chlorine for off-on fluorometric determination of the activity of acetylcholinesterase and for quantification of organophosphate pesticides Yang M, Liu M, Wu Z, He Y, Ge Y, Song G, Zhou J Ref: Mikrochim Acta, 186:585, 2019 : PubMed ESTHER: Yang_2019_Mikrochim.Acta_186_585 PubMedSearch: Yang 2019 Mikrochim.Acta 186 585 PubMedID: 31363918 Abstract Nitrogen and chlorine dually-doped carbon dots (N,Cl-CDs) were hydrothermally prepared starting from 4-chloro-1,2-diaminobenzene and dopamine. The N,Cl-CDs exhibit strong orange fluorescence, with excitation/emission maxima at 420/570 nm and a relative high quantum yield (15%). The N,Cl-CDs were employed to detect acetylcholinesterase (AChE) activity and organophosphate pesticides (OPs) which are enzyme inhibitors. Acetylthiocholine is enzymatically split by AChE to produce thiocholine which triggers the decomposition of Ellmans's reagent to form a yellow colored product (2-nitro-5-thiobenzoate anion). The product causes an inner filter effect (IEF) on the fluorescence of the N,Cl-CDs. Fluorescence decreases linearly in the 0.017 to 5.0 Unit.L(-1) AChE activity range, and the detection limit is 2 mUnit.L(-1). If organophosphates are present, the activity of AChE becomes increasingly blocked, and this leads to a less expressed IFE and an increasing recovery of fluorescence. This was used for the quantification of OPs. Response is linear in the 0.3-1000 mug.L(-1) OP concentration range with a 30 ng.L(-1) detection limit. Graphical abstractSchematic representation of the synthesis of nitrogen and chlorine dually-doped carbon dots (N,Cl-CDs) and the recognition of organophosphate pesticides by N,Cl-CDs. Title: Soluble epoxide hydrolase inhibitor, TUPS, attenuates isoproterenol/angiotensin II-induced cardiac hypertrophy through mammalian target of rapamycin-mediated autophagy inhibition Zhang H, Zhang K, Liang J, Yan W, Wu F, Xu W, Wu Z, Chen Y, Pan R, Wu G Ref: J Pharm Pharmacol, 71:1291, 2019 : PubMed ESTHER: Zhang_2019_J.Pharm.Pharmacol_71_1291 PubMedSearch: Zhang 2019 J.Pharm.Pharmacol 71 1291 PubMedID: 31215026 Inhibitor(s) related to this paper: TUPS Abstract OBJECTIVES: To investigate the potential role and mechanism of TUPS, a soluble epoxide hydrolase inhibitor, in cardiac hypertrophy. METHODS: Rat and H9C2 cell models of cardiac hypertrophy were induced by isoproterenol and angiotensin II, respectively, followed by TUPS treatment. The expression of hypertrophic markers, ANP and BNP, was determined by quantitative real-time PCR. The abundance of Beclin-1, LC3, p-AMPK and phosphorylated-mammalian target of rapamycin (p-mTOR) proteins was analysed by Western blot and immunohistocytology. Cell morphology and viability were evaluated by F-actin staining and MTS. H9C2 cells were transfected with GFP-LC3 to evaluate autophagy flux. KEY FINDINGS: TUPS significantly inhibited rat heart size, heart weight-to-body weight ratio, heart wall thickness, hypertrophic H9C2 cell swelling and viability suppression as well as the expression of ANP and BNP genes in hypertrophic models. In addition, autophagic markers Beclin-1 and LC3 were elevated in both cellular and animal models, which were suppressed by TUPS, with corresponding changes of autophagy flux. The abundance of p-AMPK was increased, while p-mTOR was decreased in hypertrophic cells, which were abolished by TUPS. Rapamycin decreased p-mTOR level, increased Beclin-1 and LC3 expression and induced cell size enlargement and cell viability inhibition in hypertrophic H9C2 cells treated with TUPS. CONCLUSIONS: TUPS inhibits cardiac hypertrophy by regulating mTOR/autophagy axis. Title: Enhancement of brain-targeting delivery of danshensu in rat through conjugation with pyrazine moiety to form danshensu-pyrazine ester Hui A, Yin H, Zhang Z, Zhou A, Chen J, Yang L, Wu Z, Zhang W Ref: Drug Deliv Transl Res, 8:787, 2018 : PubMed ESTHER: Hui_2018_Drug.Deliv.Transl.Res_8_787 PubMedSearch: Hui 2018 Drug.Deliv.Transl.Res 8 787 PubMedID: 29524164 Abstract Tetramethylpyrazine was introduced to the structure of danshensu (DSS) as P-glycoprotein (P-gp)-inhibiting carrier, designing some novel brain-targeting DSS-pyrazine derivatives via prodrug delivery strategy. Following the virtual screening, three DSS-pyrazine esters (DT1, DT2, DT3) were selected because of their better prediction parameters related to brain-targeting. Among them, DT3 was thought to be a promising candidate due to its appropriate bioreversible property in vitro release assay. Further investigation with regard to DT3's brain-targeting effects in vivo was also reported in this study. High-performance liquid chromatography-diode array detection (HPLC-DAD) method was established for the quantitative determination of DT3 and DSS in rat plasma, brain homogenate after intravenous injection. In vivo metabolism of DT3 indicated that it was first converted into DT1, DT2, then the generation of DSS, which could be the result of carboxylesterase activity in rat blood and brain tissue. Moreover, the brain pharmacokinetics of DT3 was significantly altered with 2.16 times increase in half-life compared with that of DSS, and its drug targeting index (DTI) was up to 16.95. Above these data demonstrated that DT3 had better tendency of brain-targeting delivery, which would be positive for the treatment of brain-related disorders. Title: GABAergic deficits and schizophrenia-like behaviors in a mouse model carrying patient-derived neuroligin-2 R215H mutation Jiang DY, Wu Z, Forsyth CT, Hu Y, Yee SP, Chen G Ref: Mol Brain, 11:31, 2018 : PubMed ESTHER: Jiang_2018_Mol.Brain_11_31 PubMedSearch: Jiang 2018 Mol.Brain 11 31 PubMedID: 29859117 Gene_locus related to this paper: human-NLGN2 Abstract Schizophrenia (SCZ) is a severe mental disorder characterized by delusion, hallucination, and cognitive deficits. We have previously identified from schizophrenia patients a loss-of-function mutation Arg(215)-->His(215) (R215H) of neuroligin 2 (NLGN2) gene, which encodes a cell adhesion molecule critical for GABAergic synapse formation and function. Here, we generated a novel transgenic mouse line with neuroligin-2 (NL2) R215H mutation. The single point mutation caused a significant loss of NL2 protein in vivo, reduced GABAergic transmission, and impaired hippocampal activation. Importantly, R215H KI mice displayed anxiety-like behavior, impaired pre-pulse inhibition (PPI), cognition deficits and abnormal stress responses, recapitulating several key aspects of schizophrenia-like behaviors. Our results demonstrate a significant impact of a single point mutation NL2 R215H on brain functions, providing a novel animal model for the study of schizophrenia and neuropsychiatric disorders. Title: A Neuronal piRNA Pathway Inhibits Axon Regeneration in C. elegans Kim KW, Tang NH, Andrusiak MG, Wu Z, Chisholm AD, Jin Y Ref: Neuron, 97:511, 2018 : PubMed ESTHER: Kim_2018_Neuron_97_511 PubMedSearch: Kim 2018 Neuron 97 511 PubMedID: 29395906 Abstract The PIWI-interacting RNA (piRNA) pathway has long been thought to function solely in the germline, but evidence for its functions in somatic cells is emerging. Here we report an unexpected role for the piRNA pathway in Caenorhabditis elegans sensory axon regeneration after injury. Loss of function in a subset of components of the piRNA pathway results in enhanced axon regrowth. Two essential piRNA factors, PRDE-1 and PRG-1/PIWI, inhibit axon regeneration in a gonad-independent and cell-autonomous manner. By smFISH analysis we find that prde-1 transcripts are present in neurons, as well as germ cells. The piRNA pathway inhibits axon regrowth independent of nuclear transcriptional silencing but dependent on the slicer domain of PRG-1/PIWI, suggesting that post-transcriptional gene silencing is involved. Our results reveal the neuronal piRNA pathway as a novel intrinsic repressor of axon regeneration. Title: Expanded genetic screening in Caenorhabditis elegans identifies new regulators and an inhibitory role for NAD(+) in axon regeneration Kim KW, Tang NH, Piggott CA, Andrusiak MG, Park S, Zhu M, Kurup N, Cherra SJ, 3rd, Wu Z and Jin Y <1 more author(s)> Kim KW, Tang NH, Piggott CA, Andrusiak MG, Park S, Zhu M, Kurup N, Cherra SJ, 3rd, Wu Z, Chisholm AD, Jin Y (- 1) Ref: Elife, 7:, 2018 : PubMed ESTHER: Kim_2018_Elife_7_ PubMedSearch: Kim 2018 Elife 7 PubMedID: 30461420 Abstract The mechanisms underlying axon regeneration in mature neurons are relevant to the understanding of normal nervous system maintenance and for developing therapeutic strategies for injury. Here, we report novel pathways in axon regeneration, identified by extending our previous function-based screen using the C. elegans mechanosensory neuron axotomy model. We identify an unexpected role of the nicotinamide adenine dinucleotide (NAD(+)) synthesizing enzyme, NMAT-2/NMNAT, in axon regeneration. NMAT-2 inhibits axon regrowth via cell-autonomous and non-autonomous mechanisms. NMAT-2 enzymatic activity is required to repress regrowth. Further, we find differential requirements for proteins in membrane contact site, components and regulators of the extracellular matrix, membrane trafficking, microtubule and actin cytoskeleton, the conserved Kelch-domain protein IVNS-1, and the orphan transporter MFSD-6 in axon regrowth. Identification of these new pathways expands our understanding of the molecular basis of axonal injury response and regeneration. Title: Design, synthesis, biological evaluation, and docking study of 4-isochromanone hybrids bearing N-benzyl pyridinium moiety as dual binding site acetylcholinesterase inhibitors (part II) Wang J, Wang C, Wu Z, Li X, Xu S, Liu J, Lan Q, Zhu Z, Xu J Ref: Chemical Biology Drug Des, 91:756, 2018 : PubMed ESTHER: Wang_2018_Chem.Biol.Drug.Des_91_756 PubMedSearch: Wang 2018 Chem.Biol.Drug.Des 91 756 PubMedID: 29112799 Abstract A series of novel 4-isochromanone compounds bearing N-benzyl pyridinium moiety were designed and synthesized as acetylcholinesterase (AChE) inhibitors. The biological evaluation showed that most of the target compounds exhibited potent inhibitory activities against AChE. Among them, compound 1q possessed the strongest anti-AChE activity with an IC50 value of 0.15 nm and high AChE/BuChE selectivity (SI > 5,000). Moreover, compound 1q had low toxicity in normal nerve cells and was relatively stable in rat plasma. Together, the current finding may provide a new approach for the discovery of novel anti-Alzheimer's disease agents. Title: Molluscicidal activity and mechanism of toxicity of a novel salicylanilide ester derivative against Biomphalaria species He P, Wang W, Sanogo B, Zeng X, Sun X, Lv Z, Yuan D, Duan L, Wu Z Ref: Parasit Vectors, 10:383, 2017 : PubMed ESTHER: He_2017_Parasit.Vectors_10_383 PubMedSearch: He 2017 Parasit.Vectors 10 383 PubMedID: 28793917 Abstract BACKGROUND: Schistosomiasis mansoni is one of the most important, but often neglected, tropical diseases transmitted by snails of the genus Biomphalaria. Control of the intermediate host snail plays a crucial role in preventing the spread of schistosomiasis. However, there is only one molluscicide, niclosamide, recommended by the World Health Organization. Niclosamide has been used for several decades but is toxic to non-target organisms. Therefore, it is necessary to optimize the scaffold of niclosamide and develop novel molluscicides with enhanced potency and decreased toxicity to non-target organisms. Title: A Select Subset of Electron Transport Chain Genes Associated with Optic Atrophy Link Mitochondria to Axon Regeneration in Caenorhabditis elegans Knowlton WM, Hubert T, Wu Z, Chisholm AD, Jin Y Ref: Front Neurosci, 11:263, 2017 : PubMed ESTHER: Knowlton_2017_Front.Neurosci_11_263 PubMedSearch: Knowlton 2017 Front.Neurosci 11 263 PubMedID: 28539870 Abstract The role of mitochondria within injured neurons is an area of active interest since these organelles are vital for the production of cellular energy in the form of ATP. Using mechanosensory neurons of the nematode Caenorhabditis elegans to test regeneration after neuronal injury in vivo, we surveyed genes related to mitochondrial function for effects on axon regrowth after laser axotomy. Genes involved in mitochondrial transport, calcium uptake, mitophagy, or fission and fusion were largely dispensable for axon regrowth, with the exception of eat-3/Opa1. Surprisingly, many genes encoding components of the electron transport chain were dispensable for regrowth, except for the iron-sulfur proteins gas-1, nduf-2.2, nduf-7, and isp-1, and the putative oxidoreductase rad-8. In these mutants, axonal development was essentially normal and axons responded normally to injury by forming regenerative growth cones, but were impaired in subsequent axon extension. Overexpression of nduf-2.2 or isp-1 was sufficient to enhance regrowth, suggesting that mitochondrial function is rate-limiting in axon regeneration. Moreover, loss of function in isp-1 reduced the enhanced regeneration caused by either a gain-of-function mutation in the calcium channel EGL-19 or overexpression of the MAP kinase DLK-1. While the cellular function of RAD-8 remains unclear, our genetic analyses place rad-8 in the same pathway as other electron transport genes in axon regeneration. Unexpectedly, rad-8 regrowth defects were suppressed by altered function in the ubiquinone biosynthesis gene clk-1. Furthermore, we found that inhibition of the mitochondrial unfolded protein response via deletion of atfs-1 suppressed the defective regrowth in nduf-2.2 mutants. Together, our data indicate that while axon regeneration is not significantly affected by general dysfunction of cellular respiration, it is sensitive to the proper functioning of a select subset of electron transport chain genes, or to the cellular adaptations used by neurons under conditions of injury. Title: Distinct cis elements in the 3' UTR of the C. elegans cebp-1 mRNA mediate its regulation in neuronal development Sharifnia P, Kim KW, Wu Z, Jin Y Ref: Developmental Biology, 429:240, 2017 : PubMed ESTHER: Sharifnia_2017_Dev.Biol_429_240 PubMedSearch: Sharifnia 2017 Dev.Biol 429 240 PubMedID: 28673818 Abstract The 3' untranslated regions (3' UTRs) of mRNAs mediate post-transcriptional regulation of genes in many biological processes. Cis elements in 3' UTRs can interact with RNA-binding factors in sequence-specific or structure-dependent manners, enabling regulation of mRNA stability, translation, and localization. Caenorhabditis elegans CEBP-1 is a conserved transcription factor of the C/EBP family, and functions in diverse contexts, from neuronal development and axon regeneration to organismal growth. Previous studies revealed that the levels of cebp-1 mRNA in neurons depend on its 3' UTR and are also negatively regulated by the E3 ubiquitin ligase RPM-1. Here, by systematically dissecting cebp-1's 3' UTR, we test the roles of specific cis elements in cebp-1 expression and function in neurons. We present evidence for a putative stem-loop in the cebp-1 3' UTR that contributes to basal expression levels of mRNA and to negative regulation by rpm-1. Mutant animals lacking the endogenous cebp-1 3' UTR showed a noticeable increased expression of cebp-1 mRNA and enhanced the neuronal developmental phenotypes of rpm-1 mutants. Our data reveal multiple cis elements within cebp-1's 3' UTR that help to optimize CEBP-1 expression levels in neuronal development. Title: Concurrent administration of thyroxine and donepezil induces plastic changes in the prefrontal cortex of adult hypothyroid rats Wang F, Wu Z, Zha X, Cai Y, Wu B, Jia X, Zhu D Ref: Mol Med Rep, 16:3233, 2017 : PubMed ESTHER: Wang_2017_Mol.Med.Rep_16_3233 PubMedSearch: Wang 2017 Mol.Med.Rep 16 3233 PubMedID: 28713915 Abstract The aim of the present study was to observe the effects of the concurrent administration of thyroxine (T4) and an acetylcholinesterase (AChE) inhibitor, donepezil (DON), on the hypothyroidisminduced ultrastructural changes of the prefrontal cortex (PFC) in adult rats. The acetylcholine (ACh) content and AChE activity was assessed, as well as the expressions of synaptotagmin1 (syt1) and SNAP25 were analyzed in the rats. Adding 0.05% propylthiouracil to rats' drinking water induced a hypothyroid rat model. The animals were treated with T4 and DON administered separately or in combination from the fifth week. Transmission electron microscope analysis revealed that hypothyroidism induced marked ultrastructural changes, including the neurons, the synapses and the myelin sheath in the PFC. T4 or DON treatment improved the morphologic features of the PFC, and the performance of the T4 combined DON group was the closest to the control group. Moreover, hypothyroidism significantly decreased the content of ACh (29.8%) and activity of AChE (27.8%), which were restored to control values by T4 admi-nistration. In addition, DON treatment restored ACh content to normal. At the protein level, hypothyroidism increased the levels of syt1 and SNAP25 in the PFC, both of which were not restored to control values following T4 administration, while concurrent administration of T4 and DON was able to induce this effect. These results suggested that adultonset hypothyroidism induce morphological, biochemical and molecular alterations in the PFC, combined administration of T4 and DON induce plastic changes in the PFC, different from that of the standard T4 therapy, and that the DON treatment may facilitate the recovery of synaptic protein impairments induced by hypothyroidism. Title: Sensitive inkjet printing paper-based colormetric strips for acetylcholinesterase inhibitors with indoxyl acetate substrate Wu Y, Sun Y, Xiao F, Wu Z, Yu R Ref: Talanta, 162:174, 2017 : PubMed ESTHER: Wu_2017_Talanta_162_174 PubMedSearch: Wu 2017 Talanta 162 174 PubMedID: 27837814 Abstract A new paper-based biosensing approach has been developed for sensitive and rapid detection of acetylcholinesterase (AChE) inhibitors. The biosensing zone of the paper strip is constructed with an inkjet printing method, and the biomolecule AChE is immobilized into two layers of biocompatible sol-gel-derived silica ink with a "sandwich" form. Indoxyl acetate (IDA) is used as a chromogenic substrate, which is colorless and can be catalytically hydrolyzed into blue-colored indigo dipolymer. When the enzymatic activity of AChE is inhibited after incubation with organophosphate pesticides (OPs), there is a decreased hydrolysis of IDA accompanying with a drop in color intensity. Paraoxon and trichlorfon are used as the representative OPs in the assay. Due to the low solubility and high molar absorption coefficient of the IDA dipolymer product, the paper-based strip can form a neat blue sensing zone and shows obviously improved sensitivity with a limit of detection (LOD) of 0.01ngmL-1 paraoxon and 0.04ngmL-1 trichlorfon (S/N=3) and the LODs for visual detection are 0.03ngmL-1 for paraoxon and 0.1ngmL-1 for trichlorfon comparing with the previously reported colorimetric methods. The concentrations of paraoxon in apple juice samples are also detected, and the results are in accord well with these results from high-performance liquid chromatography, showing great potential for on-site detection of OPs in practical application. The developed assay can be used to qualitatively and semiquantitatively estimate with naked eyes and quantitatively assess OPs through image analysis. Title: Synthesis of derivatives of cleistopholine and their anti-acetylcholinesterase and anti-beta-amyloid aggregation activity Wu Z, Liao W, Chen K, Qin J, Tang H Ref: Bioorg Chem, 76:228, 2017 : PubMed ESTHER: Wu_2017_Bioorg.Chem_76_228 PubMedSearch: Wu 2017 Bioorg.Chem 76 228 PubMedID: 29195093 Abstract A series of 6- and 9-substituted cleistopholine derivatives has been designed, synthesized and investigated to inhibit the aggregation of acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and beta-myloid (A beta). Results showed that these synthetic compounds had excellent AChE inhibitory activity and a significant in vitro inhibitory potency toward the self-induced A beta aggregation. When SH-SY5Y cells were treated with these substituted cleistopholine derivatives during they overexpressed the Swedish mutant form of human beta -amyloid precursor protein (APPsw), A beta 42 secretion levels were significantly reduced. According to a parallel artificial membrane permeation assay for BBB, seven out of these sixteen synthetic compounds probably could cross the blood-brain barrier (BBB) to reach their targets in the central nervous system (CNS). Title: Evolution of the diacylglycerol lipases Yuan D, Wu Z, Wang Y Ref: Prog Lipid Res, 64:85, 2016 : PubMed ESTHER: Yuan_2016_Prog.Lipid.Res_64_85 PubMedSearch: Yuan 2016 Prog.Lipid.Res 64 85 PubMedID: 27568643 Abstract Diacylglycerol lipases (DGLs) mainly catalyze "on-demand" biosynthesis of bioactive monoacylglycerols (MAGs) with different long fatty acyl chains, including 2-arachidonoylglycerol (2-AG), 2-linoleoylglycerol (2-LG), 2-oleoylglycerol (2-OG) and 2-palmitoylglycerol (2-PG). Enzymatic characterization of DGLs, their expression and distribution, and functional features has been elucidated from microorganisms to mammals in some extent. In mammals, biosynthesis, degradation and metabolism of these bioactive lipids intertwine and form a complicated biochemical pathway to affect the mammal neuromodulation of central nervous system and also other physiological processes in most peripheral organs and non-nervous tissue cells, and yet we still do not know if the neuromodulatory role of mammal DGL and MAGs is similar to invertebrates. Tracing the evolutionary history of DGLs from microorganisms to vertebrates will be an essential method to infer DGL and MAG research in organisms. In this review, we give an exhaustive explanation of the ancestral origin, divergence and evolutionary pattern through systemic searching of DGL orthologs in different species. Finally, we also summarize our recent work on the structural and functional studies of DGL in order to explore usage of DGLs in industry and the development of inhibitors for clinical intervention. Title: Optimization of Fermentation Medium for Extracellular Lipase Production from Aspergillus niger Using Response Surface Methodology Jia J, Yang X, Wu Z, Zhang Q, Lin Z, Guo H, Lin CS, Wang J, Wang Y Ref: Biomed Res Int, 2015:497462, 2015 : PubMed ESTHER: Jia_2015_Biomed.Res.Int_2015_497462 PubMedSearch: Jia 2015 Biomed.Res.Int 2015 497462 PubMedID: 26366414 Abstract Lipase produced by Aspergillus niger is widely used in various industries. In this study, extracellular lipase production from an industrial producing strain of A. niger was improved by medium optimization. The secondary carbon source, nitrogen source, and lipid were found to be the three most influential factors for lipase production by single-factor experiments. According to the statistical approach, the optimum values of three most influential parameters were determined: 10.5 g/L corn starch, 35.4 g/L soybean meal, and 10.9 g/L soybean oil. Using this optimum medium, the best lipase activity was obtained at 2,171 U/mL, which was 16.4% higher than using the initial medium. All these results confirmed the validity of the model. Furthermore, results of the Box-Behnken Design and quadratic models analysis indicated that the carbon to nitrogen (C/N) ratio significantly influenced the enzyme production, which also suggested that more attention should be paid to the C/N ratio for the optimization of enzyme production. Title: Design, synthesis, biological evaluation and docking study of 4-isochromanone hybrids bearing N-benzyl pyridinium moiety as dual binding site acetylcholinesterase inhibitors Wang C, Wu Z, Cai H, Xu S, Liu J, Jiang J, Yao H, Wu X, Xu J Ref: Bioorganic & Medicinal Chemistry Lett, 25:5212, 2015 : PubMed ESTHER: Wang_2015_Bioorg.Med.Chem.Lett_25_5212 PubMedSearch: Wang 2015 Bioorg.Med.Chem.Lett 25 5212 PubMedID: 26454504 Abstract A series of novel 4-isochromanone hybrids bearing N-benzyl pyridinium moiety as dual binding site acetylcholinesterase inhibitors have been designed and synthesized. The screening results showed that most of the compounds exhibited potent anti-AChE activity in the range of nM concentrations. The 1-(4-fluorobenzyl) substituted derivative 9d exhibited the most potent anti-AChE activity with IC50 value of 8.9nM and high AChE/BuChE selectivity (SI>230). Kinetic and molecular modeling studies suggested that compound 9d was mixed-type inhibitor, binding simultaneously to CAS and PAS of AChE. Besides, the preliminary structure-activity relationships were discussed. Title: Destabilization of strigolactone receptor DWARF14 by binding of ligand and E3-ligase signaling effector DWARF3 Zhao LH, Zhou XE, Yi W, Wu Z, Liu Y, Kang Y, Hou L, de Waal PW, Li S and Xu HE <9 more author(s)> Zhao LH, Zhou XE, Yi W, Wu Z, Liu Y, Kang Y, Hou L, de Waal PW, Li S, Jiang Y, Scaffidi A, Flematti GR, Smith SM, Lam VQ, Griffin PR, Wang Y, Li J, Melcher K, Xu HE (- 9) Ref: Cell Res, 25:1219, 2015 : PubMed ESTHER: Zhao_2015_Cell.Res_25_1219 PubMedSearch: Zhao 2015 Cell.Res 25 1219 PubMedID: 26470846 Gene_locus related to this paper: orysj-Q10QA5 Inhibitor(s) related to this paper: GR24 Abstract Strigolactones (SLs) are endogenous hormones and exuded signaling molecules in plant responses to low levels of mineral nutrients. Key mediators of the SL signaling pathway in rice include the alpha/beta-fold hydrolase DWARF 14 (D14) and the F-box component DWARF 3 (D3) of the ubiquitin ligase SCF(D3) that mediate ligand-dependent degradation of downstream signaling repressors. One perplexing feature is that D14 not only functions as the SL receptor but is also an active enzyme that slowly hydrolyzes diverse natural and synthetic SLs including GR24, preventing the crystallization of a binary complex of D14 with an intact SL as well as the ternary D14/SL/D3 complex. Here we overcome these barriers to derive a structural model of D14 bound to intact GR24 and identify the interface that is required for GR24-mediated D14-D3 interaction. The mode of GR24-mediated signaling, including ligand recognition, hydrolysis by D14, and ligand-mediated D14-D3 interaction, is conserved in structurally diverse SLs. More importantly, D14 is destabilized upon the binding of ligands and D3, thus revealing an unusual mechanism of SL recognition and signaling, in which the hormone, the receptor, and the downstream effectors are systematically destabilized during the signal transduction process. Title: Combined 3D-QSAR, molecular docking, and molecular dynamics study of tacrine derivatives as potential acetylcholinesterase (AChE) inhibitors of Alzheimer's disease Zhou A, Hu J, Wang L, Zhong G, Pan J, Wu Z, Hui A Ref: J Mol Model, 21:277, 2015 : PubMed ESTHER: Zhou_2015_J.Mol.Model_21_277 PubMedSearch: Zhou 2015 J.Mol.Model 21 277 PubMedID: 26438408 Abstract Acetylcholinesterase (AChE) is one of the key targets of drugs for treating Alzheimer's disease (AD). Tacrine is an approved drug with AChE-inhibitory activity. In this paper, 3D-QSAR, molecular docking, and molecular dynamics were carried out in order to study 60 tacrine derivatives and their AChE-inhibitory activities. 3D-QSAR modeling resulted in an optimal CoMFA model with q (2) = 0.552 and r (2) = 0.983 and an optimal CoMSIA model with q (2) = 0.581 and r (2) = 0.989. These QSAR models also showed that the steric and H-bond fields of these compounds are important influences on their activities. The interactions between these inhibitors and AChE were further explored through molecular docking and molecular dynamics simulation. A few key residues (Tyr70, Trp84, Tyr121, Trp279, and Phe330) at the binding site of AChE were identified. The results of this study improve our understanding of the mechanisms of AChE inhibitors and afford valuable information that should aid the design of novel potential AChE inhibitors. Graphical Abstract Superposition of backbone atoms of the lowest-energy structure obtained from MD simulation (magenta) onto those of the structure of the initial molecular docking model (green). Title: Maternal supplementation of nucleotides improves the behavioral development of prenatal ethanol-exposed mice Dong W, Wu Z, Xu L, Fang Y, Xu Y Ref: Cogn Affect Behavioral Neuroscience, 14:879, 2014 : PubMed ESTHER: Dong_2014_Cogn.Affect.Behav.Neurosci_14_879 PubMedSearch: Dong 2014 Cogn.Affect.Behav.Neurosci 14 879 PubMedID: 24146316 Abstract Maternal ethanol consumption during pregnancy can induce learning deficits in the offspring. The objective of this study was to assess whether supplementation of exogenous nucleotides during pregnancy and lactation would ameliorate prenatal ethanol-induced learning and memory deficits in the offspring of mice, and to explore the possible mechanisms. In the present study, pregnant C57BL/6J mice were exposed to ethanol (5 g/kg body weight) intragastrically from gestational day (GD) 6 to GD15. The dams in exogenous nucleotide intervention groups were fed with feed containing 0.01 %, 0.04 %, or 0.16 % nucleotide powder, with control and ethanol groups receiving normal feed. The dams were allowed to deliver naturally and to breast feed their offspring. After weaning, behavioral tests were carried out in the offspring of each group. Serum oxidation indexes were analyzed, and the hippocampus of each offspring was collected and detected for acetyl cholinesterase (AChE) activity and the expression of p-CREB, CREB, and BDNF. The results showed that maternal supplementation with exogenous nucleotides during pregnancy could ameliorate prenatal ethanol-induced learning and memory deficits in the offspring of mice, through improving their antioxidant capacity, reversing hippocampus AChE levels, and allowing the expression of some proteins related to learning and memory. However, different sensitivities were found between the two sexes. Title: Whole-genome sequencing of cultivated and wild peppers provides insights into Capsicum domestication and specialization Qin C, Yu C, Shen Y, Fang X, Chen L, Min J, Cheng J, Zhao S, Xu M and Zhang Z <58 more author(s)> Qin C, Yu C, Shen Y, Fang X, Chen L, Min J, Cheng J, Zhao S, Xu M, Luo Y, Yang Y, Wu Z, Mao L, Wu H, Ling-Hu C, Zhou H, Lin H, Gonzalez-Morales S, Trejo-Saavedra DL, Tian H, Tang X, Zhao M, Huang Z, Zhou A, Yao X, Cui J, Li W, Chen Z, Feng Y, Niu Y, Bi S, Yang X, Cai H, Luo X, Montes-Hernandez S, Leyva-Gonzalez MA, Xiong Z, He X, Bai L, Tan S, Liu D, Liu J, Zhang S, Chen M, Zhang L, Zhang Y, Liao W, Wang M, Lv X, Wen B, Liu H, Luan H, Yang S, Wang X, Xu J, Li X, Li S, Wang J, Palloix A, Bosland PW, Li Y, Krogh A, Rivera-Bustamante RF, Herrera-Estrella L, Yin Y, Yu J, Hu K, Zhang Z (- 58) Ref: Proc Natl Acad Sci U S A, 111:5135, 2014 : PubMed ESTHER: Qin_2014_Proc.Natl.Acad.Sci.U.S.A_111_5135 PubMedSearch: Qin 2014 Proc.Natl.Acad.Sci.U.S.A 111 5135 PubMedID: 24591624 Gene_locus related to this paper: capch-q75qh4, capan-a0a1u8fuf5, capan-a0a1u8gmz3, capan-a0a1u8f879, capan-a0a1u8ftr2, capan-a0a1u8g8s6 Abstract As an economic crop, pepper satisfies people's spicy taste and has medicinal uses worldwide. To gain a better understanding of Capsicum evolution, domestication, and specialization, we present here the genome sequence of the cultivated pepper Zunla-1 (C. annuum L.) and its wild progenitor Chiltepin (C. annuum var. glabriusculum). We estimate that the pepper genome expanded approximately 0.3 Mya (with respect to the genome of other Solanaceae) by a rapid amplification of retrotransposons elements, resulting in a genome comprised of approximately 81% repetitive sequences. Approximately 79% of 3.48-Gb scaffolds containing 34,476 protein-coding genes were anchored to chromosomes by a high-density genetic map. Comparison of cultivated and wild pepper genomes with 20 resequencing accessions revealed molecular footprints of artificial selection, providing us with a list of candidate domestication genes. We also found that dosage compensation effect of tandem duplication genes probably contributed to the pungent diversification in pepper. The Capsicum reference genome provides crucial information for the study of not only the evolution of the pepper genome but also, the Solanaceae family, and it will facilitate the establishment of more effective pepper breeding programs. Title: Comparative genomic analysis shows that Streptococcus suis meningitis isolate SC070731 contains a unique 105K genomic island Wu Z, Wang W, Tang M, Shao J, Dai C, Zhang W, Fan H, Yao H, Zong J and Lu C <2 more author(s)> Wu Z, Wang W, Tang M, Shao J, Dai C, Zhang W, Fan H, Yao H, Zong J, Chen D, Wang J, Lu C (- 2) Ref: Gene, 535:156, 2014 : PubMed ESTHER: Wu_2014_Gene_535_156 PubMedSearch: Wu 2014 Gene 535 156 PubMedID: 24316490 Gene_locus related to this paper: strej-e8uk64 Abstract Streptococcus suis (SS) is an important swine pathogen worldwide that occasionally causes serious infections in humans. SS infection may result in meningitis in pigs and humans. The pathogenic mechanisms of SS are poorly understood. Here, we provide the complete genome sequence of S. suis serotype 2 (SS2) strain SC070731 isolated from a pig with meningitis. The chromosome is 2,138,568bp in length. There are 1933 predicted protein coding sequences and 96.7% (57/59) of the known virulence-associated genes are present in the genome. Strain SC070731 showed similar virulence with SS2 virulent strains HA9801 and ZY05719, but was more virulent than SS2 virulent strain P1/7 in the zebrafish infection model. Comparative genomic analysis revealed a unique 105K genomic island in strain SC070731 that is absent in seven other sequenced SS2 strains. Further analysis of the 105K genomic island indicated that it contained a complete nisin locus similar to the nisin U locus in S. uberis strain 42, a prophage similar to S. oralis phage PH10 and several antibiotic resistance genes. Several proteins in the 105K genomic island, including nisin and RelBE toxin-antitoxin system, contribute to the bacterial fitness and virulence in other pathogenic bacteria. Further investigation of newly identified gene products, including four putative new virulence-associated surface proteins, will improve our understanding of SS pathogenesis. Title: Point Mutations Associated with Organophosphate and Carbamate Resistance in Chinese Strains of Culex pipiens quinquefasciatus (Diptera: Culicidae) Zhao M, Dong Y, Ran X, Wu Z, Guo X, Zhang Y, Xing D, Yan T, Wang G and Zhao T <3 more author(s)> Zhao M, Dong Y, Ran X, Wu Z, Guo X, Zhang Y, Xing D, Yan T, Wang G, Zhu X, Zhang H, Li C, Zhao T (- 3) Ref: PLoS ONE, 9:e95260, 2014 : PubMed ESTHER: Zhao_2014_PLoS.One_9_e952607 PubMedSearch: Zhao 2014 PLoS.One 9 e952607 PubMedID: 24788312 Gene_locus related to this paper: culpi-ACHE1 Abstract Acetylcholinesterase resistance has been well documented in many insects, including several mosquito species. We tested the resistance of five wild, Chinese strains of the mosquito Culex pipiens quinquefasciatus to two kinds of pesticides, dichlorvos and propoxur. An acetylcholinesterase gene (ace1) was cloned and sequenced from a pooled sample of mosquitoes from these five strains and the amino acids of five positions were found to vary (V185M, G247S, A328S, A391T, and T682A). Analysis of the correlation between mutation frequencies and resistance levels (LC50) suggests that two point mutations, G247S (r2 = 0.732, P = 0.065) and A328S (r2 = 0.891, P = 0.016), are associated with resistance to propoxur but not to dichlorvos. Although the V185M mutation was not associated with either dichlorvos or propoxur resistance, its RS genotype frequency was correlated with propoxur resistance (r2 = 0.815, P = 0.036). And the HWE test showed the A328S mutation is linked with V185M, also with G247S mutation. This suggested that these three mutations may contribute synergistically to propoxur resistance. The T682A mutation was negatively correlated with propoxur (r2 = 0.788, P = 0.045) resistance. Knowledge of these mutations may help design strategies for managing pesticide resistance in wild mosquito populations. Title: Synthesis and evaluation of paeonol derivatives as potential multifunctional agents for the treatment of Alzheimer's disease Zhou A, Wu H, Pan J, Wang X, Li J, Wu Z, Hui A Ref: Molecules, 20:1304, 2014 : PubMed ESTHER: Zhou_2014_Molecules_20_1304 PubMedSearch: Zhou 2014 Molecules 20 1304 PubMedID: 25594344 Abstract Alzheimer's disease (AD) is a progressive neurodegenerative brain disorder characterized by memory loss, language impairment, personality changes and intellectual decline. Taking into account the key pathological features of AD, such as low levels of acetylcholine, beta-amyloid (Abeta) aggregation, oxidative stress and dyshomeostasis of biometals, a new series of paeonol derivatives 5a-5d merging three different functions, i.e., antioxidant, anti-acetylcholinesterase (AChE) activity, metal chelating agents for AD treatment have been synthesized and characterized. Biological assays revealed that compared with paeonol (309.7 muM), 5a-5d had a lower DPPH IC50 value (142.8-191.6 muM). 5a-5d could significantly inhibit hydrogen peroxide-induced neuronal PC12 cell death assessed by MTT assay in the concentration range of 5-40 muM. AChE activity was effectively inhibited by 5a-5d, with IC50 values in the range of 0.61-7.04 muM. 5a-5d also exhibited good metal-chelating ability. All the above results suggested that paeonol derivatives may be promising multifunctional agents for AD treatment. Title: SHANK3 overexpression causes manic-like behaviour with unique pharmacogenetic properties Han K, Holder JL, Jr., Schaaf CP, Lu H, Chen H, Kang H, Tang J, Wu Z, Hao S and Zoghbi HY <6 more author(s)> Han K, Holder JL, Jr., Schaaf CP, Lu H, Chen H, Kang H, Tang J, Wu Z, Hao S, Cheung SW, Yu P, Sun H, Breman AM, Patel A, Lu HC, Zoghbi HY (- 6) Ref: Nature, 503:72, 2013 : PubMed ESTHER: Han_2013_Nature_503_72 PubMedSearch: Han 2013 Nature 503 72 PubMedID: 24153177 Abstract Mutations in SHANK3 and large duplications of the region spanning SHANK3 both cause a spectrum of neuropsychiatric disorders, indicating that proper SHANK3 dosage is critical for normal brain function. However, SHANK3 overexpression per se has not been established as a cause of human disorders because 22q13 duplications involve several genes. Here we report that Shank3 transgenic mice modelling a human SHANK3 duplication exhibit manic-like behaviour and seizures consistent with synaptic excitatory/inhibitory imbalance. We also identified two patients with hyperkinetic disorders carrying the smallest SHANK3-spanning duplications reported so far. These findings indicate that SHANK3 overexpression causes a hyperkinetic neuropsychiatric disorder. To probe the mechanism underlying the phenotype, we generated a Shank3 in vivo interactome and found that Shank3 directly interacts with the Arp2/3 complex to increase F-actin levels in Shank3 transgenic mice. The mood-stabilizing drug valproate, but not lithium, rescues the manic-like behaviour of Shank3 transgenic mice raising the possibility that this hyperkinetic disorder has a unique pharmacogenetic profile. Title: Myeloperoxidase, paraoxonase-1, and HDL form a functional ternary complex Huang Y, Wu Z, Riwanto M, Gao S, Levison BS, Gu X, Fu X, Wagner MA, Besler C and Hazen SL <14 more author(s)> Huang Y, Wu Z, Riwanto M, Gao S, Levison BS, Gu X, Fu X, Wagner MA, Besler C, Gerstenecker G, Zhang R, Li XM, Didonato AJ, Gogonea V, Tang WH, Smith JD, Plow EF, Fox PL, Shih DM, Lusis AJ, Fisher EA, Didonato JA, Landmesser U, Hazen SL (- 14) Ref: J Clinical Investigation, 123:3815, 2013 : PubMed ESTHER: Huang_2013_J.Clin.Invest_123_3815 PubMedSearch: Huang 2013 J.Clin.Invest 123 3815 PubMedID: 23908111 Abstract Myeloperoxidase (MPO) and paraoxonase 1 (PON1) are high-density lipoprotein-associated (HDL-associated) proteins mechanistically linked to inflammation, oxidant stress, and atherosclerosis. MPO is a source of ROS during inflammation and can oxidize apolipoprotein A1 (APOA1) of HDL, impairing its atheroprotective functions. In contrast, PON1 fosters systemic antioxidant effects and promotes some of the atheroprotective properties attributed to HDL. Here, we demonstrate that MPO, PON1, and HDL bind to one another, forming a ternary complex, wherein PON1 partially inhibits MPO activity, while MPO inactivates PON1. MPO oxidizes PON1 on tyrosine 71 (Tyr71), a modified residue found in human atheroma that is critical for HDL binding and PON1 function. Acute inflammation model studies with transgenic and knockout mice for either PON1 or MPO confirmed that MPO and PON1 reciprocally modulate each other's function in vivo. Further structure and function studies identified critical contact sites between APOA1 within HDL, PON1, and MPO, and proteomics studies of HDL recovered from acute coronary syndrome (ACS) subjects revealed enhanced chlorotyrosine content, site-specific PON1 methionine oxidation, and reduced PON1 activity. HDL thus serves as a scaffold upon which MPO and PON1 interact during inflammation, whereupon PON1 binding partially inhibits MPO activity, and MPO promotes site-specific oxidative modification and impairment of PON1 and APOA1 function. Title: DWARF 53 acts as a repressor of strigolactone signalling in rice Jiang L, Liu X, Xiong G, Liu H, Chen F, Wang L, Meng X, Liu G, Yu H and Li J <10 more author(s)> Jiang L, Liu X, Xiong G, Liu H, Chen F, Wang L, Meng X, Liu G, Yu H, Yuan Y, Yi W, Zhao L, Ma H, He Y, Wu Z, Melcher K, Qian Q, Xu HE, Wang Y, Li J (- 10) Ref: Nature, 504:401, 2013 : PubMed ESTHER: Jiang_2013_Nature_504_401 PubMedSearch: Jiang 2013 Nature 504 401 PubMedID: 24336200 Abstract Strigolactones (SLs) are a group of newly identified plant hormones that control plant shoot branching. SL signalling requires the hormone-dependent interaction of DWARF 14 (D14), a probable candidate SL receptor, with DWARF 3 (D3), an F-box component of the Skp-Cullin-F-box (SCF) E3 ubiquitin ligase complex. Here we report the characterization of a dominant SL-insensitive rice (Oryza sativa) mutant dwarf 53 (d53) and the cloning of D53, which encodes a substrate of the SCF(D3) ubiquitination complex and functions as a repressor of SL signalling. Treatments with GR24, a synthetic SL analogue, cause D53 degradation via the proteasome in a manner that requires D14 and the SCF(D3) ubiquitin ligase, whereas the dominant form of D53 is resistant to SL-mediated degradation. Moreover, D53 can interact with transcriptional co-repressors known as TOPLESS-RELATED PROTEINS. Our results suggest a model of SL signalling that involves SL-dependent degradation of the D53 repressor mediated by the D14-D3 complex. Title: Modulated dye retention for the signal-on fluorometric determination of acetylcholinesterase inhibitor Liao S, Han W, Ding H, Xie D, Tan H, Yang S, Wu Z, Shen G, Yu R Ref: Analytical Chemistry, 85:4968, 2013 : PubMed ESTHER: Liao_2013_Anal.Chem_85_4968 PubMedSearch: Liao 2013 Anal.Chem 85 4968 PubMedID: 23597308 Abstract A novel fluorometric assay method based on target-induced signal on was developed for acetylcholinesterase (AChE) inhibitor with obviously improved detection sensitivity. In this method, the AChE molecules catalyzed the hydrolysis of acetylthiocholine (ATCl) to form thiocholine, which in turn can specifically react with fluorescent squaraine derivative, a specific chemodosimeter for thiol-containing compounds, resulting in fluorescence quenching and offering a low fluorometric background for the further detection of AChE inhibitor. In the presence of AChE inhibitor, the catalytic hydrolysis of ATCl is blocked, and then the squaraine derivative remains intact and shows signal-on fluorescence. The amount of the remaining fluorescent squaraine derivative is positively correlated with that of the AChE inhibitor in solution. This new designed sensing system shows an obviously improved sensitivity toward target with a detection limit of 5 pg mL(-1) (0.018 nM) for the AChE inhibitor, comparing favorably with previously reported fluorometric methods. To our best knowledge, this new method is the first example of fluorometric enzymatic assay for AChE inhibitors based on such a signal-on principle and using a specific reaction, which has potential to offer an effective strategy for the detection of AChE inhibitors. Title: Evolution of Burkholderia pseudomallei in recurrent melioidosis Hayden HS, Lim R, Brittnacher MJ, Sims EH, Ramage ER, Fong C, Wu Z, Crist E, Chang J and Jacobs MA <10 more author(s)> Hayden HS, Lim R, Brittnacher MJ, Sims EH, Ramage ER, Fong C, Wu Z, Crist E, Chang J, Zhou Y, Radey M, Rohmer L, Haugen E, Gillett W, Wuthiekanun V, Peacock SJ, Kaul R, Miller SI, Manoil C, Jacobs MA (- 10) Ref: PLoS ONE, 7:e36507, 2012 : PubMed ESTHER: Hayden_2012_PLoS.ONE_7_E36507 PubMedSearch: Hayden 2012 PLoS.ONE 7 E36507 PubMedID: 22615773 Gene_locus related to this paper: burma-a5tq93, burma-q62mq7 Abstract Burkholderia pseudomallei, the etiologic agent of human melioidosis, is capable of causing severe acute infection with overwhelming septicemia leading to death. A high rate of recurrent disease occurs in adult patients, most often due to recrudescence of the initial infecting strain. Pathogen persistence and evolution during such relapsing infections are not well understood. Bacterial cells present in the primary inoculum and in late infections may differ greatly, as has been observed in chronic disease, or they may be genetically similar. To test these alternative models, we conducted whole-genome comparisons of clonal primary and relapse B. pseudomallei isolates recovered six months to six years apart from four adult Thai patients. We found differences within each of the four pairs, and some, including a 330 Kb deletion, affected substantial portions of the genome. Many of the changes were associated with increased antibiotic resistance. We also found evidence of positive selection for deleterious mutations in a TetR family transcriptional regulator from a set of 107 additional B. pseudomallei strains. As part of the study, we sequenced to base-pair accuracy the genome of B. pseudomallei strain 1026b, the model used for genetic studies of B. pseudomallei pathogenesis and antibiotic resistance. Our findings provide new insights into pathogen evolution during long-term infections and have important implications for the development of intervention strategies to combat recurrent melioidosis. Title: Acetylcholinesterase liquid crystal biosensor based on modulated growth of gold nanoparticles for amplified detection of acetylcholine and inhibitor Liao S, Qiao Y, Han W, Xie Z, Wu Z, Shen G, Yu R Ref: Analytical Chemistry, 84:45, 2012 : PubMed ESTHER: Liao_2012_Anal.Chem_84_45 PubMedSearch: Liao 2012 Anal.Chem 84 45 PubMedID: 22148672 Abstract A novel acetylcholinesterase (AChE) liquid crystal (LC) biosensor based on enzymatic growth of gold nanoparticles (Au NPs) has been developed for amplified detection of acetylcholine (ACh) and AChE inhibitor. In this method, AChE mediates the hydrolysis of acetylthiocholine (ATCl) to form thiocholine, and the latter further reduces AuCl(4)(-) to Au NPs without Au nanoseeds. This process, termed biometallization, leads to a great enhancement in the optical signal of the LC biosensor due to the large size of Au NPs, which can greatly disrupt the orientational arrangement of LCs. On the other hand, the hydrolysis of ATCl is inhibited in the presence of ACh or organophosphate pesticides (OPs, a AChE inhibitor), which will decrease the catalytic growth of Au NPs and, as a result, reduce the orientational response of LCs. On the basis of such an inhibition mechanism, the AChE LC biosensor can be used as an effective way to realize the detection of ACh and AChE inhibitors. The results showed that the AChE LC biosensor was highly sensitive to ACh with a detection limit of 15 mumol/L and OPs with a detection limit of 0.3 nmol/L. This study provides a simple and sensitive AChE LC biosensing approach and offers effective signal enhanced strategies for the development of enzyme LC biosensors. Title: Genome sequence of Corynebacterium glutamicum ATCC 14067, which provides insight into amino acid biosynthesis in coryneform bacteria Lv Y, Liao J, Wu Z, Han S, Lin Y, Zheng S Ref: Journal of Bacteriology, 194:742, 2012 : PubMed ESTHER: Lv_2012_J.Bacteriol_194_742 PubMedSearch: Lv 2012 J.Bacteriol 194 742 PubMedID: 22247536 Gene_locus related to this paper: corgl-Cgl1133, corgl-Cgl2249, corgl-CGL2393, corgl-q8nlr5, corgl-q8nlz1, corgt-g6wsn6 Abstract We report the genome sequence of Corynebacterium glutamicum ATCC 14067 (once named Brevibacterium flavum), which is useful for taxonomy research and further molecular breeding in amino acid production. Preliminary comparison with those of the reported coryneform strains revealed some notable differences that might be related to the difficulties in molecular manipulation. Title: Insights into pyrroindomycin biosynthesis reveal a uniform paradigm for tetramate/tetronate formation Wu Q, Wu Z, Qu X, Liu W Ref: Journal of the American Chemical Society, 134:17342, 2012 : PubMed ESTHER: Wu_2012_J.Am.Chem.Soc_134_17342 PubMedSearch: Wu 2012 J.Am.Chem.Soc 134 17342 PubMedID: 23062149 Gene_locus related to this paper: strrg-k7qrj3 Abstract The natural products pyrroindomycins (PYRs), active against various drug-resistant pathogens, possess a characteristic, cyclohexene ring spiro-linked tetramate moiety. In this study, investigation into PYR biosynthesis revealed two new proteins, both of which, phylogenetically distinct from but functionally substitutable to each other in vivo, individually catalyze a Dieckmann cyclization in vitro for converting an N-acetoacetyl-l-alanyl thioester into a tetramate. Their counterparts are commonly present in the biosynthetic pathways of spiro and polyether tetronates, supporting a uniform paradigm for tetronate/tetramate formation, which features an enzymatic way to generate the C-X (X = O or N) bond first and the C-C bond next in building of the 5-membered heterocycle. Title: Complete genome sequence of Haloarcula hispanica, a Model Haloarchaeon for studying genetics, metabolism, and virus-host interaction Liu H, Wu Z, Li M, Zhang F, Zheng H, Han J, Liu J, Zhou J, Wang S, Xiang H Ref: Journal of Bacteriology, 193:6086, 2011 : PubMed ESTHER: Liu_2011_J.Bacteriol_193_6086 PubMedSearch: Liu 2011 J.Bacteriol 193 6086 PubMedID: 21994921 Gene_locus related to this paper: halma-q5uym0 Abstract Haloarcula hispanica is an extremely halophilic archaeon that has an unusually low restriction barrier and is therefore significant for studying archaeal genetics, metabolism, and virus-host interactions. Here we report the complete genome sequence (3,890,005 bp) of H. hispanica strain CGMCC 1.2049, consisting of two chromosomes and one megaplasmid. Title: Genome sequence of Corynebacterium glutamicum S9114, a strain for industrial production of glutamate Lv Y, Wu Z, Han S, Lin Y, Zheng S Ref: Journal of Bacteriology, 193:6096, 2011 : PubMed ESTHER: Lv_2011_J.Bacteriol_193_6096 PubMedSearch: Lv 2011 J.Bacteriol 193 6096 PubMedID: 21994927 Gene_locus related to this paper: corgl-Cgl1133, corgl-Cgl2249, corgl-CGL2393, corgl-q8nlr5, corgt-g6wsn6 Abstract Here we report the genome sequence of Corynebacterium glutamicum S9114, an industrial producer widely used in production of glutamate in China. Preliminary comparison with the sequences of the Corynebacterium glutamicum strains ATCC 13032 and R revealed some notable mutagenesis that might be related to the high yield of glutamate. Title: The sequence and de novo assembly of the giant panda genome Li R, Fan W, Tian G, Zhu H, He L, Cai J, Huang Q, Cai Q, Li B and Yang H <103 more author(s)> Li R, Fan W, Tian G, Zhu H, He L, Cai J, Huang Q, Cai Q, Li B, Bai Y, Zhang Z, Zhang Y, Wang W, Li J, Wei F, Li H, Jian M, Nielsen R, Li D, Gu W, Yang Z, Xuan Z, Ryder OA, Leung FC, Zhou Y, Cao J, Sun X, Fu Y, Fang X, Guo X, Wang B, Hou R, Shen F, Mu B, Ni P, Lin R, Qian W, Wang G, Yu C, Nie W, Wang J, Wu Z, Liang H, Min J, Wu Q, Cheng S, Ruan J, Wang M, Shi Z, Wen M, Liu B, Ren X, Zheng H, Dong D, Cook K, Shan G, Zhang H, Kosiol C, Xie X, Lu Z, Li Y, Steiner CC, Lam TT, Lin S, Zhang Q, Li G, Tian J, Gong T, Liu H, Zhang D, Fang L, Ye C, Zhang J, Hu W, Xu A, Ren Y, Zhang G, Bruford MW, Li Q, Ma L, Guo Y, An N, Hu Y, Zheng Y, Shi Y, Li Z, Liu Q, Chen Y, Zhao J, Qu N, Zhao S, Tian F, Wang X, Wang H, Xu L, Liu X, Vinar T, Wang Y, Lam TW, Yiu SM, Liu S, Huang Y, Yang G, Jiang Z, Qin N, Li L, Bolund L, Kristiansen K, Wong GK, Olson M, Zhang X, Li S, Yang H (- 103) Ref: Nature, 463:311, 2010 : PubMed ESTHER: Li_2010_Nature_463_311 PubMedSearch: Li 2010 Nature 463 311 PubMedID: 20010809 Gene_locus related to this paper: ailme-ABH15, ailme-ACHE, ailme-BCHE, ailme-d2gtv3, ailme-d2gty9, ailme-d2gu87, ailme-d2gu97, ailme-d2gve7, ailme-d2gwu1, ailme-d2gx08, ailme-d2gyt0, ailme-d2gz36, ailme-d2gz37, ailme-d2gz38, ailme-d2gz39, ailme-d2gz40, ailme-d2h5r9, ailme-d2h7b7, ailme-d2h9c9, ailme-d2h794, ailme-d2hau7, ailme-d2hau8, ailme-d2hcd9, ailme-d2hdi6, ailme-d2heu6, ailme-d2hga4, ailme-d2hqw5, ailme-d2hs98, ailme-d2hsx4, ailme-d2hti6, ailme-d2htv3, ailme-d2htz6, ailme-d2huc7, ailme-d2hwj8, ailme-d2hwy7, ailme-d2hxm1, ailme-d2hyc8, ailme-d2hyv2, ailme-d2hz11, ailme-d2hza3, ailme-d2hzr4, ailme-d2i1l4, ailme-d2i2g8, ailme-g1l7m3, ailme-g1lu36, ailme-g1m769, ailme-g1mc29, ailme-g1mdj8, ailme-g1mdr5, ailme-g1mfp4, ailme-g1mfx5, ailme-g1lj41, ailme-g1lm28, ailme-g1l3u1, ailme-g1l7l1, ailme-g1m5i3, ailme-g1l2f6, ailme-g1lji5, ailme-g1lqk3, ailme-g1l8s9, ailme-d2h717, ailme-d2h718, ailme-d2h719, ailme-d2h720, ailme-g1m5v0, ailme-g1m5y7, ailme-g1lkt7, ailme-g1l2a1, ailme-g1lsc8, ailme-g1lrp4, ailme-d2gv02, ailme-g1mik5, ailme-g1ljr1, ailme-g1lxw7, ailme-d2h8b5, ailme-d2h2r2, ailme-d2h9w7, ailme-g1meh3, ailme-g1m719 Abstract Using next-generation sequencing technology alone, we have successfully generated and assembled a draft sequence of the giant panda genome. The assembled contigs (2.25 gigabases (Gb)) cover approximately 94% of the whole genome, and the remaining gaps (0.05 Gb) seem to contain carnivore-specific repeats and tandem repeats. Comparisons with the dog and human showed that the panda genome has a lower divergence rate. The assessment of panda genes potentially underlying some of its unique traits indicated that its bamboo diet might be more dependent on its gut microbiome than its own genetic composition. We also identified more than 2.7 million heterozygous single nucleotide polymorphisms in the diploid genome. Our data and analyses provide a foundation for promoting mammalian genetic research, and demonstrate the feasibility for using next-generation sequencing technologies for accurate, cost-effective and rapid de novo assembly of large eukaryotic genomes. Title: The genome of the cucumber, Cucumis sativus L Huang S, Li R, Zhang Z, Li L, Gu X, Fan W, Lucas WJ, Wang X, Xie B and Du Y <77 more author(s)> Huang S, Li R, Zhang Z, Li L, Gu X, Fan W, Lucas WJ, Wang X, Xie B, Ni P, Ren Y, Zhu H, Li J, Lin K, Jin W, Fei Z, Li G, Staub J, Kilian A, van der Vossen EA, Wu Y, Guo J, He J, Jia Z, Tian G, Lu Y, Ruan J, Qian W, Wang M, Huang Q, Li B, Xuan Z, Cao J, Asan, Wu Z, Zhang J, Cai Q, Bai Y, Zhao B, Han Y, Li Y, Li X, Wang S, Shi Q, Liu S, Cho WK, Kim JY, Xu Y, Heller-Uszynska K, Miao H, Cheng Z, Zhang S, Wu J, Yang Y, Kang H, Li M, Liang H, Ren X, Shi Z, Wen M, Jian M, Yang H, Zhang G, Yang Z, Chen R, Ma L, Liu H, Zhou Y, Zhao J, Fang X, Fang L, Liu D, Zheng H, Zhang Y, Qin N, Li Z, Yang G, Yang S, Bolund L, Kristiansen K, Li S, Zhang X, Wang J, Sun R, Zhang B, Jiang S, Du Y (- 77) Ref: Nat Genet, 41:1275, 2009 : PubMed ESTHER: Huang_2009_Nat.Genet_41_1275 PubMedSearch: Huang 2009 Nat.Genet 41 1275 PubMedID: 19881527 Gene_locus related to this paper: cucsa-a0a0a0ktw5, cucsa-a0a0a0lnt6, cucsa-a0a0a0kpn7, cucsa-a0a0a0lvt9, cucsa-a0a0a0kdx8, cucsa-a0a0a0m228, cucsa-a0a0a0kz31, cucsa-a0a0a0k5t5, cucsa-a0a0a0kfs7, cucsa-a0a0a0kjj7, cucsa-a0a0a0kzs7, cucsa-a0a0a0l0a6, cucsa-a0a0a0l4w4, cucsa-a0a0a0lpz0, cucsa-a0a0a0ls66 Abstract Cucumber is an economically important crop as well as a model system for sex determination studies and plant vascular biology. Here we report the draft genome sequence of Cucumis sativus var. sativus L., assembled using a novel combination of traditional Sanger and next-generation Illumina GA sequencing technologies to obtain 72.2-fold genome coverage. The absence of recent whole-genome duplication, along with the presence of few tandem duplications, explains the small number of genes in the cucumber. Our study establishes that five of the cucumber's seven chromosomes arose from fusions of ten ancestral chromosomes after divergence from Cucumis melo. The sequenced cucumber genome affords insight into traits such as its sex expression, disease resistance, biosynthesis of cucurbitacin and 'fresh green' odor. We also identify 686 gene clusters related to phloem function. The cucumber genome provides a valuable resource for developing elite cultivars and for studying the evolution and function of the plant vascular system. Title: Analysis of the genome of the Escherichia coli O157:H7 2006 spinach-associated outbreak isolate indicates candidate genes that may enhance virulence Kulasekara BR, Jacobs M, Zhou Y, Wu Z, Sims E, Saenphimmachak C, Rohmer L, Ritchie JM, Radey M and Miller SI <13 more author(s)> Kulasekara BR, Jacobs M, Zhou Y, Wu Z, Sims E, Saenphimmachak C, Rohmer L, Ritchie JM, Radey M, McKevitt M, Freeman TL, Hayden H, Haugen E, Gillett W, Fong C, Chang J, Beskhlebnaya V, Waldor MK, Samadpour M, Whittam TS, Kaul R, Brittnacher M, Miller SI (- 13) Ref: Infect Immun, 77:3713, 2009 : PubMed ESTHER: Kulasekara_2009_Infect.Immun_77_3713 PubMedSearch: Kulasekara 2009 Infect.Immun 77 3713 PubMedID: 19564389 Gene_locus related to this paper: eco57-b3a913, ecoli-Aes, ecoli-rutD, ecoli-bioh, ecoli-C0410, ecoli-dlhh, ecoli-entf, ecoli-fes, ecoli-MCMK, ecoli-mhpc, ecoli-pldb, ecoli-ptrb, ecoli-yafa, ecoli-yaim, ecoli-ybff, ecoli-ycfp, ecoli-ycjy, ecoli-yeiG, ecoli-YFBB, ecoli-yghX, ecoli-yhet, ecoli-yjfp, ecoli-YNBC, ecoli-ypfh, ecoli-ypt1, ecoli-yqia, ecoli-Z0347, ecoli-Z1341, ecoli-Z1930, ecoli-YfhR Abstract In addition to causing diarrhea, Escherichia coli O157:H7 infection can lead to hemolytic-uremic syndrome (HUS), a severe disease characterized by hemolysis and renal failure. Differences in HUS frequency among E. coli O157:H7 outbreaks have been noted, but our understanding of bacterial factors that promote HUS is incomplete. In 2006, in an outbreak of E. coli O157:H7 caused by consumption of contaminated spinach, there was a notably high frequency of HUS. We sequenced the genome of the strain responsible (TW14359) with the goal of identifying candidate genetic factors that contribute to an enhanced ability to cause HUS. The TW14359 genome contains 70 kb of DNA segments not present in either of the two reference O157:H7 genomes. We identified seven putative virulence determinants, including two putative type III secretion system effector proteins, candidate genes that could result in increased pathogenicity or, alternatively, adaptation to plants, and an intact anaerobic nitric oxide reductase gene, norV. We surveyed 100 O157:H7 isolates for the presence of these putative virulence determinants. A norV deletion was found in over one-half of the strains surveyed and correlated strikingly with the absence of stx(1). The other putative virulence factors were found in 8 to 35% of the O157:H7 isolates surveyed, and their presence also correlated with the presence of norV and the absence of stx(1), indicating that the presence of norV may serve as a marker of a greater propensity for HUS, similar to the correlation between the absence of stx(1) and a propensity for HUS. Title: Methylobacterium genome sequences: a reference blueprint to investigate microbial metabolism of C1 compounds from natural and industrial sources Vuilleumier S, Chistoserdova L, Lee MC, Bringel F, Lajus A, Zhou Y, Gourion B, Barbe V, Chang J and Lidstrom ME <26 more author(s)> Vuilleumier S, Chistoserdova L, Lee MC, Bringel F, Lajus A, Zhou Y, Gourion B, Barbe V, Chang J, Cruveiller S, Dossat C, Gillett W, Gruffaz C, Haugen E, Hourcade E, Levy R, Mangenot S, Muller E, Nadalig T, Pagni M, Penny C, Peyraud R, Robinson DG, Roche D, Rouy Z, Saenampechek C, Salvignol G, Vallenet D, Wu Z, Marx CJ, Vorholt JA, Olson MV, Kaul R, Weissenbach J, Medigue C, Lidstrom ME (- 26) Ref: PLoS ONE, 4:e5584, 2009 : PubMed ESTHER: Vuilleumier_2009_PLoS.ONE_4_E5584 PubMedSearch: Vuilleumier 2009 PLoS.ONE 4 E5584 PubMedID: 19440302 Gene_locus related to this paper: metc4-b7krz1, metea-c5asz7, metea-c5au09, metea-c5axg7, metea-c5b1t3, metea-c5b215, metea-c5b387, meted-c7cbs2, meted-c7ce76, meted-c7cfe3, meted-c7cfx5, meted-c7cg08, meted-c7cgc9, meted-c7cge7, meted-c7chb8, meted-c7ci36, meted-c7cln3, meted-c7cnd9, metep-a9vxp1, metep-a9w2b1, metep-a9w028, metex-orf5, metex-Q8RPA1, metpb-b1zjw5, metea-c5as87, metea-c5awv9, meted-c7cb08, metea-rutd, meted-rutd Abstract BACKGROUND: Methylotrophy describes the ability of organisms to grow on reduced organic compounds without carbon-carbon bonds. The genomes of two pink-pigmented facultative methylotrophic bacteria of the Alpha-proteobacterial genus Methylobacterium, the reference species Methylobacterium extorquens strain AM1 and the dichloromethane-degrading strain DM4, were compared. METHODOLOGY/PRINCIPAL FINDINGS: The 6.88 Mb genome of strain AM1 comprises a 5.51 Mb chromosome, a 1.26 Mb megaplasmid and three plasmids, while the 6.12 Mb genome of strain DM4 features a 5.94 Mb chromosome and two plasmids. The chromosomes are highly syntenic and share a large majority of genes, while plasmids are mostly strain-specific, with the exception of a 130 kb region of the strain AM1 megaplasmid which is syntenic to a chromosomal region of strain DM4. Both genomes contain large sets of insertion elements, many of them strain-specific, suggesting an important potential for genomic plasticity. Most of the genomic determinants associated with methylotrophy are nearly identical, with two exceptions that illustrate the metabolic and genomic versatility of Methylobacterium. A 126 kb dichloromethane utilization (dcm) gene cluster is essential for the ability of strain DM4 to use DCM as the sole carbon and energy source for growth and is unique to strain DM4. The methylamine utilization (mau) gene cluster is only found in strain AM1, indicating that strain DM4 employs an alternative system for growth with methylamine. The dcm and mau clusters represent two of the chromosomal genomic islands (AM1: 28; DM4: 17) that were defined. The mau cluster is flanked by mobile elements, but the dcm cluster disrupts a gene annotated as chelatase and for which we propose the name "island integration determinant" (iid). CONCLUSION/SIGNIFICANCE: These two genome sequences provide a platform for intra- and interspecies genomic comparisons in the genus Methylobacterium, and for investigations of the adaptive mechanisms which allow bacterial lineages to acquire methylotrophic lifestyles. Title: Transcriptional regulation of the human soluble epoxide hydrolase gene EPHX2 Tanaka H, Kamita SG, Wolf NM, Harris TR, Wu Z, Morisseau C, Hammock BD Ref: Biochimica & Biophysica Acta, 1779:17, 2008 : PubMed ESTHER: Tanaka_2008_Biochim.Biophys.Acta_1779_17 PubMedSearch: Tanaka 2008 Biochim.Biophys.Acta 1779 17 PubMedID: 18078836 Abstract Soluble epoxide hydrolase (sEH) is a multifunctional protein encoded by the EPHX2 gene. The biological functions and enzyme kinetics of sEH have been extensively investigated, however, little is known about its transcriptional regulation and mechanisms of tissue specific expression. Here, a luciferase gene based reporter assay was used to identify the minimal promoter and cis regulatory elements of EPHX2. The minimal promoter was identified as a GC-rich region between nts -374 and +28 with respect to the putative transcriptional start site. A reporter plasmid carrying this minimal promoter showed higher or similar activities in comparison to a reporter plasmid carrying nts -5,974 to +28 of EPHX2 in 9 human cell lines that were tested. Sp1 binding sites that are involved in augmenting the minimal promoter activity of EPHX2 were identified by nested deletion analysis, site-specific mutation, electrophoretic mobility shift assay, and chromatin immunoprecipitation assay. Title: Carboxylesterase 2 is downregulated in colorectal cancer following progression of the disease Tang X, Wu H, Wu Z, Wang G, Wang Z, Zhu D Ref: Cancer Invest, 26:178, 2008 : PubMed ESTHER: Tang_2008_Cancer.Invest_26_178 PubMedSearch: Tang 2008 Cancer.Invest 26 178 PubMedID: 18259949 Abstract Expression of carboxylesterase 2 in colorectal tumor tissues and serum carboxylesterase 2 levels at different stages of the disease were investigated by Western blotting. Carboxylesterase 2 was decreasing in tumor tissues from TNM stages 0 through IV (n = 20); the expression of carboxylesterase 2 was similar between "normal" and tumor tissues (n = 20); serum carboxylesterase 2 levels were similar among patients at different stages of the disease. These results indicate that local expression of carboxylesterase 2 is downregulated following progression of the disease; carboxylesterase 2 expression is altered in histology "normal" tissues from stages I through IV before histopathological changes. Title: Genome sequence of the fish pathogen Renibacterium salmoninarum suggests reductive evolution away from an environmental Arthrobacter ancestor Wiens GD, Rockey DD, Wu Z, Chang J, Levy R, Crane S, Chen DS, Capri GR, Burnett JR and Strom MS <6 more author(s)> Wiens GD, Rockey DD, Wu Z, Chang J, Levy R, Crane S, Chen DS, Capri GR, Burnett JR, Sudheesh PS, Schipma MJ, Burd H, Bhattacharyya A, Rhodes LD, Kaul R, Strom MS (- 6) Ref: Journal of Bacteriology, 190:6970, 2008 : PubMed ESTHER: Wiens_2008_J.Bacteriol_190_6970 PubMedSearch: Wiens 2008 J.Bacteriol 190 6970 PubMedID: 18723615 Gene_locus related to this paper: rensm-a9wkt8, rensm-a9wlc2, rensm-a9wlt1, rensm-a9wml4, rensm-a9wml5, rensm-a9wne6, rensm-a9wnw6, rensm-a9wp39, rensm-a9wpl6, rensm-a9wr45, rensm-a9wrg0, rensm-a9ws98, rensm-a9wup0, rensm-a9wup5, rensm-a9wkp8, rensm-a9wkp3, rensm-a9wn22, rensm-a9wt82 Abstract Renibacterium salmoninarum is the causative agent of bacterial kidney disease and a significant threat to healthy and sustainable production of salmonid fish worldwide. This pathogen is difficult to culture in vitro, genetic manipulation is challenging, and current therapies and preventative strategies are only marginally effective in preventing disease. The complete genome of R. salmoninarum ATCC 33209 was sequenced and shown to be a 3,155,250-bp circular chromosome that is predicted to contain 3,507 open-reading frames (ORFs). A total of 80 copies of three different insertion sequence elements are interspersed throughout the genome. Approximately 21% of the predicted ORFs have been inactivated via frameshifts, point mutations, insertion sequences, and putative deletions. The R. salmoninarum genome has extended regions of synteny to the Arthrobacter sp. strain FB24 and Arthrobacter aurescens TC1 genomes, but it is approximately 1.9 Mb smaller than both Arthrobacter genomes and has a lower G+C content, suggesting that significant genome reduction has occurred since divergence from the last common ancestor. A limited set of putative virulence factors appear to have been acquired via horizontal transmission after divergence of the species; these factors include capsular polysaccharides, heme sequestration molecules, and the major secreted cell surface antigen p57 (also known as major soluble antigen). Examination of the genome revealed a number of ORFs homologous to antibiotic resistance genes, including genes encoding beta-lactamases, efflux proteins, macrolide glycosyltransferases, and rRNA methyltransferases. The genome sequence provides new insights into R. salmoninarum evolution and may facilitate identification of chemotherapeutic targets and vaccine candidates that can be used for prevention and treatment of infections in cultured salmonids. Title: The genome of a lepidopteran model insect, the silkworm Bombyx mori Xia Q, Wang J, Zhou Z, Li R, Fan W, Cheng D, Cheng T, Qin J, Duana J and Morishita S <88 more author(s)> Xia Q, Wang J, Zhou Z, Li R, Fan W, Cheng D, Cheng T, Qin J, Duana J, Xu H, Li Q, Li N, Wang M, Dai F, Liu C, Lin Y, Zhao P, Zhang H, Liu S, Zha X, Li C, Zhao A, Pan M, Pan G, Shen Y, Gao Z, Wang Z, Wang G, Wu Z, Hou Y, Chai C, Yu Q, He N, Zhang Z, Li S, Yang H, Lu C, Xiang Z, Mita K, Kasahara M, Nakatani Y, Yamamoto K, Abe H, Ahsan B, Daimoni T, Doi K, Fujii T, Fujiwara H, Fujiyama A, Futahashi R, Hashimotol S, Ishibashi J, Iwami M, Kadono-Okuda K, Kanamori H, Kataoka H, Katsuma S, Kawaoka S, Kawasaki H, Kohara Y, Kozaki T, Kuroshu RM, Kuwazaki S, Matsushima K, Minami H, Nagayasu Y, Nakagawa T, Narukawa J, Nohata J, Ohishi K, Ono Y, Osanai-Futahashi M, Ozaki K, Qu W, Roller L, Sasaki S, Sasaki T, Seino A, Shimomura M, Shin-I T, Shinoda T, Shiotsuki T, Suetsugu Y, Sugano S, Suwa M, Suzuki Y, Takiya S, Tamura T, Tanaka H, Tanaka Y, Touhara K, Yamada T, Yamakawa M, Yamanaka N, Yoshikawa H, Zhong YS, Shimada T, Morishita S (- 88) Ref: Insect Biochemistry & Molecular Biology, 38:1036, 2008 : PubMed ESTHER: Xia_2008_Insect.Biochem.Mol.Biol_38_1036 PubMedSearch: Xia 2008 Insect.Biochem.Mol.Biol 38 1036 PubMedID: 19121390 Gene_locus related to this paper: bommo-a0mnw6, bommo-a1yw85, bommo-a9ls22, bommo-ACHE1, bommo-ACHE2, bommo-b0fgv8, bommo-b1q137, bommo-b1q139, bommo-b1q140, bommo-b1q141, bommo-b2zdz0, bommo-b3gef6, bommo-b3gef7, bommo-b3gs55, bommo-b3gs56, bommo-d2ktu3, bommo-d2ktu5, bommo-d9ile0, bommo-e1cga5, bommo-e1cga6, bommo-g8fpz6, bommo-h9iu43, bommo-h9iu46, bommo-h9iu47.1, bommo-h9iu47.2, bommo-h9iue5, bommo-h9ivg2, bommo-h9iwj7, bommo-h9iwj8, bommo-h9ix58, bommo-h9ixi1.1, bommo-h9ixi1.2, bommo-h9iy47, bommo-h9izw1, bommo-h9j0s4, bommo-h9j1y0, bommo-h9j3r0, bommo-h9j3w6, bommo-h9j3w7, bommo-h9j5t0, bommo-h9j8g3, bommo-h9j9k9, bommo-h9j066, bommo-h9j067, bommo-h9j593, bommo-h9j594, bommo-h9j990, bommo-h9jde8, bommo-h9jde9, bommo-h9jdf0, bommo-h9jds4, bommo-h9jle7, bommo-h9jn83, bommo-h9jn85, bommo-h9jrg2, bommo-h9jyh9, bommo-JHE, bommo-m1rmh6, bommo-q1hq05, bommo-q4tte1, bommo-h9j592, bommo-h9j604, bommo-h9jpm8, bommo-h9iss4, bommo-h9j2c7 Abstract Bombyx mori, the domesticated silkworm, is a major insect model for research, and the first lepidopteran for which draft genome sequences became available in 2004. Two independent data sets from whole-genome shotgun sequencing were merged and assembled together with newly obtained fosmid- and BAC-end sequences. The remarkably improved new assembly is presented here. The 8.5-fold sequence coverage of an estimated 432 Mb genome was assembled into scaffolds with an N50 size of approximately 3.7 Mb; the largest scaffold was 14.5 million base pairs. With help of a high-density SNP linkage map, we anchored 87% of the scaffold sequences to all 28 chromosomes. A particular feature was the high repetitive sequence content estimated to be 43.6% and that consisted mainly of transposable elements. We predicted 14,623 gene models based on a GLEAN-based algorithm, a more accurate prediction than the previous gene models for this species. Over three thousand silkworm genes have no homologs in other insect or vertebrate genomes. Some insights into gene evolution and into characteristic biological processes are presented here and in other papers in this issue. The massive silk production correlates with the existence of specific tRNA clusters, and of several sericin genes assembled in a cluster. The silkworm's adaptation to feeding on mulberry leaves, which contain toxic alkaloids, is likely linked to the presence of new-type sucrase genes, apparently acquired from bacteria. The silkworm genome also revealed the cascade of genes involved in the juvenile hormone biosynthesis pathway, and a large number of cuticular protein genes. 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: The DNA sequence and biological annotation of human chromosome 1 Gregory SG, Barlow KF, McLay KE, Kaul R, Swarbreck D, Dunham A, Scott CE, Howe KL, Woodfine K and Prigmore E <169 more author(s)> Gregory SG, Barlow KF, McLay KE, Kaul R, Swarbreck D, Dunham A, Scott CE, Howe KL, Woodfine K, Spencer CC, Jones MC, Gillson C, Searle S, Zhou Y, Kokocinski F, McDonald L, Evans R, Phillips K, Atkinson A, Cooper R, Jones C, Hall RE, Andrews TD, Lloyd C, Ainscough R, Almeida JP, Ambrose KD, Anderson F, Andrew RW, Ashwell RI, Aubin K, Babbage AK, Bagguley CL, Bailey J, Beasley H, Bethel G, Bird CP, Bray-Allen S, Brown JY, Brown AJ, Buckley D, Burton J, Bye J, Carder C, Chapman JC, Clark SY, Clarke G, Clee C, Cobley V, Collier RE, Corby N, Coville GJ, Davies J, Deadman R, Dunn M, Earthrowl M, Ellington AG, Errington H, Frankish A, Frankland J, French L, Garner P, Garnett J, Gay L, Ghori MR, Gibson R, Gilby LM, Gillett W, Glithero RJ, Grafham DV, Griffiths C, Griffiths-Jones S, Grocock R, Hammond S, Harrison ES, Hart E, Haugen E, Heath PD, Holmes S, Holt K, Howden PJ, Hunt AR, Hunt SE, Hunter G, Isherwood J, James R, Johnson C, Johnson D, Joy A, Kay M, Kershaw JK, Kibukawa M, Kimberley AM, King A, Knights AJ, Lad H, Laird G, Lawlor S, Leongamornlert DA, Lloyd DM, Loveland J, Lovell J, Lush MJ, Lyne R, Martin S, Mashreghi-Mohammadi M, Matthews L, Matthews NS, Mclaren S, Milne S, Mistry S, Moore MJ, Nickerson T, O'Dell CN, Oliver K, Palmeiri A, Palmer SA, Parker A, Patel D, Pearce AV, Peck AI, Pelan S, Phelps K, Phillimore BJ, Plumb R, Rajan J, Raymond C, Rouse G, Saenphimmachak C, Sehra HK, Sheridan E, Shownkeen R, Sims S, Skuce CD, Smith M, Steward C, Subramanian S, Sycamore N, Tracey A, Tromans A, Van Helmond Z, Wall M, Wallis JM, White S, Whitehead SL, Wilkinson JE, Willey DL, Williams H, Wilming L, Wray PW, Wu Z, Coulson A, Vaudin M, Sulston JE, Durbin R, Hubbard T, Wooster R, Dunham I, Carter NP, McVean G, Ross MT, Harrow J, Olson MV, Beck S, Rogers J, Bentley DR, Banerjee R, Bryant SP, Burford DC, Burrill WD, Clegg SM, Dhami P, Dovey O, Faulkner LM, Gribble SM, Langford CF, Pandian RD, Porter KM, Prigmore E (- 169) Ref: Nature, 441:315, 2006 : PubMed ESTHER: Gregory_2006_Nature_441_315 PubMedSearch: Gregory 2006 Nature 441 315 PubMedID: 16710414 Gene_locus related to this paper: human-LYPLAL1, human-PPT1, human-TMCO4, human-TMEM53 Abstract The reference sequence for each human chromosome provides the framework for understanding genome function, variation and evolution. Here we report the finished sequence and biological annotation of human chromosome 1. Chromosome 1 is gene-dense, with 3,141 genes and 991 pseudogenes, and many coding sequences overlap. Rearrangements and mutations of chromosome 1 are prevalent in cancer and many other diseases. Patterns of sequence variation reveal signals of recent selection in specific genes that may contribute to human fitness, and also in regions where no function is evident. Fine-scale recombination occurs in hotspots of varying intensity along the sequence, and is enriched near genes. These and other studies of human biology and disease encoded within chromosome 1 are made possible with the highly accurate annotated sequence, as part of the completed set of chromosome sequences that comprise the reference human genome. Title: The involvement of calcineurin in acetylcholine receptor redistribution in muscle Madhavan R, Zhao XT, Chan F, Wu Z, Peng HB Ref: Molecular & Cellular Neurosciences, 23:587, 2003 : PubMed ESTHER: Madhavan_2003_Mol.Cell.Neurosci_23_587 PubMedSearch: Madhavan 2003 Mol.Cell.Neurosci 23 587 PubMedID: 12932439 Abstract In this study the intracellular signaling involved in acetylcholine receptor (AChR) redistribution in muscle was investigated. In cultured Xenopus embryonic muscle cells, both the dispersal of preexisting AChR clusters and the induction of new AChR clusters by growth factor-coated polystyrene beads were inhibited by two specific antagonists of the ser/thr phosphatase calcineurin (CaN), Cyclosporin A, (CsA) and FK-506, but not by KN-93 that blocks CaM kinases. Moreover, CaN inhibition decreased AChR clustering in Xenopus muscle cells by beads coated with antibodies that cross-link and activate the agrin receptor MuSK (muscle-specific kinase) and reduced the agrin-induced tyrosine phosphorylation of MuSK in cultured mouse (C2) myotubes. Last, the length and the number of AChR clusters generated by agrin in C2 myotubes were decreased by treatment with CsA, but not KN-93, and following the forced expression of a dominant negative CaN mutant in these cells, but not wild-type CaN or reporter green fluorescent protein. Collectively, our results support a role for CaN signaling in the redistribution of AChRs in muscle induced by synaptogenic signals. Title: The genome of the natural genetic engineer Agrobacterium tumefaciens C58 Wood DW, Setubal JC, Kaul R, Monks DE, Kitajima JP, Okura VK, Zhou Y, Chen L, Wood GE and Nester EW <41 more author(s)> Wood DW, Setubal JC, Kaul R, Monks DE, Kitajima JP, Okura VK, Zhou Y, Chen L, Wood GE, Almeida NF, Jr., Woo L, Chen Y, Paulsen IT, Eisen JA, Karp PD, Bovee D, Sr., Chapman P, Clendenning J, Deatherage G, Gillet W, Grant C, Kutyavin T, Levy R, Li MJ, McClelland E, Palmieri A, Raymond C, Rouse G, Saenphimmachak C, Wu Z, Romero P, Gordon D, Zhang S, Yoo H, Tao Y, Biddle P, Jung M, Krespan W, Perry M, Gordon-Kamm B, Liao L, Kim S, Hendrick C, Zhao ZY, Dolan M, Chumley F, Tingey SV, Tomb JF, Gordon MP, Olson MV, Nester EW (- 41) Ref: Science, 294:2317, 2001 : PubMed ESTHER: Wood_2001_Science_294_2317 PubMedSearch: Wood 2001 Science 294 2317 PubMedID: 11743193 Gene_locus related to this paper: agrt5-a9cf94, agrt5-a9cfa9, agrt5-a9cfs8, agrt5-a9cfu7, agrt5-a9cie7, agrt5-a9cj11, agrt5-a9cjp2, agrt5-a9cki2, agrt5-a9ckr2, agrt5-a9ckt2, agrt5-a9cle4, agrt5-a9clq8, agrt5-a9clq9, agrt5-q7cx24, agrt5-q7d1j0, agrt5-q7d1j3, agrt5-q7d3m5, agrt5-y5261, agrtu-ACVB, agrtu-ATTS, agrtu-ATU0253, agrtu-ATU0403, agrtu-ATU0841, agrtu-ATU1045, agrtu-ATU1102, agrtu-ATU1572, agrtu-ATU1617, agrtu-ATU1826, agrtu-ATU1842, agrtu-ATU2061, agrtu-ATU2126, agrtu-ATU2171, agrtu-ATU2409, agrtu-ATU2452, agrtu-ATU2481, agrtu-ATU2497, agrtu-ATU2576, agrtu-ATU3428, agrtu-ATU3651, agrtu-ATU3652, agrtu-ATU4238, agrtu-ATU5190, agrtu-ATU5193, agrtu-ATU5275, agrtu-ATU5296, agrtu-ATU5348, agrtu-ATU5389, agrtu-ATU5446, agrtu-ATU5495, agrtu-CPO, agrtu-DHAA, agrtu-DLHH, agrtu-EPHA, agrtu-GRST, agrtu-PCA, agrtu-PCAD, agrtu-PHBC, agrtu-PTRB, agrt5-a9cji8 Abstract The 5.67-megabase genome of the plant pathogen Agrobacterium tumefaciens C58 consists of a circular chromosome, a linear chromosome, and two plasmids. Extensive orthology and nucleotide colinearity between the genomes of A. tumefaciens and the plant symbiont Sinorhizobium meliloti suggest a recent evolutionary divergence. Their similarities include metabolic, transport, and regulatory systems that promote survival in the highly competitive rhizosphere; differences are apparent in their genome structure and virulence gene complement. Availability of the A. tumefaciens sequence will facilitate investigations into the molecular basis of pathogenesis and the evolutionary divergence of pathogenic and symbiotic lifestyles. Title: Complete genome sequence of Pseudomonas aeruginosa PAO1, an opportunistic pathogen Stover CK, Pham XQ, Erwin AL, Mizoguchi SD, Warrener P, Hickey MJ, Brinkman FS, Hufnagle WO, Kowalik DJ and Olson MV <21 more author(s)> Stover CK, Pham XQ, Erwin AL, Mizoguchi SD, Warrener P, Hickey MJ, Brinkman FS, Hufnagle WO, Kowalik DJ, Lagrou M, Garber RL, Goltry L, Tolentino E, Westbrock-Wadman S, Yuan Y, Brody LL, Coulter SN, Folger KR, Kas A, Larbig K, Lim R, Smith K, Spencer D, Wong GK, Wu Z, Paulsen IT, Reizer J, Saier MH, Hancock RE, Lory S, Olson MV (- 21) Ref: Nature, 406:959, 2000 : PubMed ESTHER: Stover_2000_Nature_406_959 PubMedSearch: Stover 2000 Nature 406 959 PubMedID: 10984043 Gene_locus related to this paper: pseae-clipa, pseae-CPO, pseae-metx, pseae-PA0201, pseae-PA0231, pseae-PA0308, pseae-PA0368, pseae-PA0480, pseae-PA0502, pseae-PA0543, pseae-PA0599, pseae-PA0829, pseae-PA1166, pseae-PA1211, pseae-PA1239, pseae-PA1291, pseae-PA1304, pseae-PA1510, pseae-PA1558, pseae-PA1597, pseae-PA1621, pseae-PA1622, pseae-PA1680, pseae-PA1771, pseae-PA1888, pseae-PA1907, pseae-PA1990, pseae-PA2086, pseae-PA2098, pseae-PA2168, pseae-PA2302, pseae-PA2411, pseae-PA2425, pseae-PA2451, pseae-PA2540, pseae-PA2682, pseae-PA2689, pseae-PA2745, pseae-PA2764, pseae-PA2927, pseae-PA2934, pseae-PA2949, pseae-PA3053, pseae-PA3132, pseae-PA3226, pseae-PA3301, pseae-PA3324, pseae-PA3327, pseae-PA3429, pseae-PA3509, pseae-PA3586, pseae-PA3628, pseae-PA3695, pseae-PA3734, pseae-PA3829, pseae-PA3859, pseae-PA3994, pseae-PA4008, pseae-PA4152, pseae-PA4440, pseae-PA4968, pseae-PA5080, pseae-PA5384, pseae-PA5513, pseae-PCHC, pseae-PCHF, pseae-PHAC1, pseae-PHAC2, pseae-phaD, pseae-phag, pseae-PVDD, pseae-q9i4b9, pseae-q9i538, pseae-rhla, pseae-Y2218, pseae-q9hyv3, pseae-q9i252, pseae-q9i6m9 Abstract Pseudomonas aeruginosa is a ubiquitous environmental bacterium that is one of the top three causes of opportunistic human infections. A major factor in its prominence as a pathogen is its intrinsic resistance to antibiotics and disinfectants. Here we report the complete sequence of P. aeruginosa strain PAO1. At 6.3 million base pairs, this is the largest bacterial genome sequenced, and the sequence provides insights into the basis of the versatility and intrinsic drug resistance of P. aeruginosa. Consistent with its larger genome size and environmental adaptability, P. aeruginosa contains the highest proportion of regulatory genes observed for a bacterial genome and a large number of genes involved in the catabolism, transport and efflux of organic compounds as well as four potential chemotaxis systems. We propose that the size and complexity of the P. aeruginosa genome reflect an evolutionary adaptation permitting it to thrive in diverse environments and resist the effects of a variety of antimicrobial substances. | |||||||
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