Author Report for: Sun HNo contact information in database for Sun H
Jiang N, Li X, Wang Q, Baihetiyaer B, Fan X, Li M, Sun H, Yin X, Wang J Ref: Chemosphere, :137846, 2023 : PubMed ESTHER: Jiang_2023_Chemosphere__137846 PubMedSearch: Jiang 2023 Chemosphere 137846 PubMedID: 36646180 Abstract Propofol is an intravenous anesthetic injection extensively used in clinic, which has been proved to be neurotoxic in humans. Improper use and disposal of propofol may lead to its release into the aquatic environment, but the potential ecological risk of propofol to aquatic organisms remains poorly understood. For this study, we comprehensively explored the ecotoxicological effects and potential mechanisms of propofol (0.04, 0.2 and 2 mg L(-1)) on 120 hpf zebrafish (Danio rerio) embryos from physiological, biochemical, and molecular perspectives. The results showed that propofol has moderate toxicity on zebrafish embryos (96 h LC(50) = 4.260 mg L(-1)), which could significantly reduce the hatchability and delay the development. Propofol can trigger reactive oxygen species (ROS) generation, lipid peroxidation (Malondialdehyde, MDA) and DNA damage (8-hydroxy-2-deoxyguanosine, 8-OHdG). The glutathione peroxidase (GPX) activity of zebrafish embryos in 0.04 and 0.2 mg L(-1) propofol treatment group was activated in response to oxidative damage, while activities of superoxide dismutase (SOD), catalase (CAT) and GPX in zebrafish treated with 2 mg L(-1) was significant inhibited compared with the control group (p0.05). Moreover, the expression of antioxidant genes and related pathways was inhibited. Apoptosis was investigated at genes level and histochemistry. Molecular docking confirmed that propofol could change in the secondary structure of acetylcholinesterase (AChE) and competitively inhibited acetylcholine (ACh) binding to AChE, which may disturb the nervous system. These results described toxic response and molecular mechanism in zebrafish embryos, providing multiple aspects about ecological risk assessment of propofol in water environment. Title: Strigolactone and gibberellin signalling coordinately regulates metabolic adaptations to changes in nitrogen availability in rice Sun H, Guo X, Zhu X, Gu P, Zhang W, Tao W, Wang D, Wu Y, Zhao Q and Zhang Y <2 more author(s)> Sun H, Guo X, Zhu X, Gu P, Zhang W, Tao W, Wang D, Wu Y, Zhao Q, Xu G, Fu X, Zhang Y (- 2) Ref: Mol Plant, :, 2023 : PubMed ESTHER: Sun_2023_Mol.Plant__ PubMedSearch: Sun 2023 Mol.Plant PubMedID: 36683328 Abstract Modern semi-dwarf rice varieties of the 'Green Revolution' require a high nitrogen (N) fertilizer supply to obtain a high yield. A better understanding of the interplay between N metabolic and developmental processes is required for improved N use efficiency (NUE) and agricultural sustainability. Here, we show that strigolactones (SLs) modulate root metabolic and developmental adaptations to low N availability, which ensure efficient uptake and translocation of available N. The key repressor DWARF 53 (D53) of the SL signalling interacts with the transcription factor GROWTH-REGULATING FACTOR 4 (GRF4) and prevents GRF4 from binding to its target gene promoters. N limitation induces the accumulation of SLs, which in turn promotes SL-mediated degradation of D53, leading to the release of GRF4 and thus promoting the genes expression associated with N metabolism. N limitation also induces degradation of the rice DELLA protein SLENDER RICE 1 (SLR1) in the D14- and D53-dependent manners, and that is effective for the release of GRF4 from the competitive inhibition caused by SLR1. Our findings reveal a previously unknown mechanism underlying SL and gibberellin crosstalk in response to N availability, which advances our understanding of plant growth-metabolic coordination that can be useful to improve NUE in high-yield crops. Title: N-Benzyl Benzamide Derivatives as Selective Sub-Nanomolar Butyrylcholinesterase Inhibitors for Possible Treatment in Advanced Alzheimer's Disease Du C, Wang L, Guan Q, Yang H, Chen T, Liu Y, Li Q, Lyu W, Lu X and Sun H <6 more author(s)> Du C, Wang L, Guan Q, Yang H, Chen T, Liu Y, Li Q, Lyu W, Lu X, Chen Y, Liu H, Feng F, Liu W, Liu Z, Li W, Sun H (- 6) Ref: Journal of Medicinal Chemistry, :, 2022 : PubMed ESTHER: Du_2022_J.Med.Chem__ PubMedSearch: Du 2022 J.Med.Chem PubMedID: 35969197 Inhibitor(s) related to this paper: S11-1014 Abstract Herein, we report a series of selective sub-nanomolar inhibitors against butyrylcholinesterase (BChE). These compounds, bearing a novel N-benzyl benzamide scaffold, inhibited BChE with IC(50) from picomolar to nanomolar. The inhibitory activity was confirmed by the surface plasmon resonance assay, showing a sub-nanomolar K(D) value, which revealed that the compounds exert the inhibitory effect through directly binding to BChE. Several compounds showed neuroprotective effects verified by the oxidative damage model. Furthermore, the safety of S11-1014 and S11-1033 was demonstrated by the in vivo acute toxicity test. In the behavior study, 0.5 mg/kg S11-1014 or S11-1033 exhibited a marked therapeutic effect, which was almost equal to the treatment with 1 mg/kg rivastigmine, against the cognitive impairment induced by Abeta(1-42). The pharmacokinetics studies characterized the metabolic stability of S11-1014. Thus, N-benzyl benzamide inhibitors are promising compounds with drug-like properties for improving cognitive dysfunction, providing a potential strategy for the treatment of Alzheimer's disease. Title: Identification and receptor mechanism of TIR-catalyzed small molecules in plant immunity Huang S, Jia A, Song W, Hessler G, Meng Y, Sun Y, Xu L, Laessle H, Jirschitzka J and Chai J <10 more author(s)> Huang S, Jia A, Song W, Hessler G, Meng Y, Sun Y, Xu L, Laessle H, Jirschitzka J, Ma S, Xiao Y, Yu D, Hou J, Liu R, Sun H, Liu X, Han Z, Chang J, Parker JE, Chai J (- 10) Ref: Science, :, 2022 : PubMed ESTHER: Huang_2022_Science__ PubMedSearch: Huang 2022 Science Gene_locus related to this paper: arath-eds1, arath-PAD4 Abstract Plant nucleotide-binding leucine-rich repeat-containing (NLR) receptors with an N-terminal Toll/interleukin-1 receptor (TIR) domain sense pathogen effectors to enable TIR-encoded NADase activity for immune signaling. TIR-NLR signaling requires helper NLRs N requirement gene 1 (NRG1) and Activated Disease Resistance 1 (ADR1), and Enhanced Disease Susceptibility 1 (EDS1) that forms a heterodimer with each of its paralogs Phytoalexin Deficient 4 (PAD4) and Senescence-Associated Gene101 (SAG101). Here, we show that TIR-containing proteins catalyze production of 2'-(5''-phosphoribosyl)-5'-adenosine mono-/di-phosphate (pRib-AMP/ADP) in vitro and in planta. Biochemical and structural data demonstrate that EDS1-PAD4 is a receptor complex for pRib-AMP/ADP, which allosterically promote EDS1-PAD4 interaction with ADR1-L1 but not NRG1A. Our study identifies TIR-catalyzed pRib-AMP/ADP as a missing link in TIR signaling via EDS1-PAD4 and as likely second messengers for plant immunity. Title: A highly effective and stable butyrylcholinesterase inhibitor with multi-faceted neuroprotection and cognition improvement Li Q, Xiong B, Wang Y, Lyu W, Xing S, Chen Y, Liao Q, He S, Feng F and Sun H <1 more author(s)> Li Q, Xiong B, Wang Y, Lyu W, Xing S, Chen Y, Liao Q, He S, Feng F, Liu W, Sun H (- 1) Ref: Eur Journal of Medicinal Chemistry, 239:114510, 2022 : PubMed ESTHER: Li_2022_Eur.J.Med.Chem_239_114510 PubMedSearch: Li 2022 Eur.J.Med.Chem 239 114510 PubMedID: 35728508 Inhibitor(s) related to this paper: Cpd20-Benzimidazol-Oxadiazol Abstract Butyrylcholinesterase (BChE) has been more and more attractive for treating neurodegenerative diseases, especially Alzheimer's disease (AD). In this study, we conducted activity and druggability optimization based on the structures that were previously reported. Most compounds exhibited pronounced BChE inhibitory capacity with nanomolar IC(50) values. Based on the results of inhibiting activity and cyto-safety evaluations, two compounds (7, eqBChE IC(50) = 2.94 nM, hBChE IC(50) = 34.6 nM, and 20, eqBChE IC(50) = 0.15 nM, hBChE IC(50) = 45.2 nM) have been selected as candidates. High stability of compound 20 contributed to significantly improved blood concentration and tissue exposure, resulting in a reduced administration and effective dose in pharmacodynamic experiments. Two candidates exhibited remarkable neuroprotective properties and cognition improving activity, by benefiting cholinergic system, reducing the total Abeta amount and increasing the ghrelin content. Simultaneous modulation in the center and periphery greatly improves the efficiency of BChE inhibitors. Considering the regulation on ghrelin level, BChE inhibition could improve not only symptoms but also nutritional status of AD patients. Title: Identification of Novel Organophosphate Esters in Hydroponic Lettuces (Lactuca sativa L.): Biotransformation and Acropetal Translocation Li X, Yao Y, Chen H, Zhang Q, Li C, Zhao L, Guo S, Cheng Z, Wang Y and Sun H <1 more author(s)> Li X, Yao Y, Chen H, Zhang Q, Li C, Zhao L, Guo S, Cheng Z, Wang Y, Wang L, Sun H (- 1) Ref: Environ Sci Technol, :, 2022 : PubMed ESTHER: Li_2022_Environ.Sci.Technol__ PubMedSearch: Li 2022 Environ.Sci.Technol PubMedID: 35849551 Abstract The absorption, translocation, and biotransformation behaviors of organophosphate esters (OPEs) and diesters (OPdEs) in a hydroponic system were investigated. The lateral root was found as the main accumulation and biotransformation place of OPEs and OPdEs in lettuce. The nontarget analysis using high-resolution mass spectrometry revealed five hydroxylated metabolites and five conjugating metabolites in the OPE exposure group, among which methylation, acetylation, and palmitoyl conjugating OPEs were reported as metabolites for the first time. Particularly, methylation on phosphate can be a significant process for plant metabolism, and methyl diphenyl phosphate (MDPP) accounted for the majority of metabolites. The translocation factor values of most identified OPE metabolites are negatively associated with their predicted logarithmic octanol-water partitioning coefficient (log K(ow)) values (0.75-2.45), indicating that hydrophilicity is a dominant factor in the translocation of OPE metabolites in lettuce. In contrast, palmitoyl conjugation may lead to an enhanced acropetal translocation and those with log K(ow) values < 0 may have limited translocation potential. Additionally, OPE diesters produced from the biotransformation of OPEs in lettuce showed a higher acropetal translocation potential than those exposed directly. These results further emphasize the necessity to consider biotransformation as an utmost important factor in the accumulation and acropetal translocation potential of OPEs in plants. Title: Design, synthesis, and biological evaluation of aromatic tertiary amine derivatives as selective butyrylcholinesterase inhibitors for the treatment of Alzheimer's disease Lu X, Qin N, Liu Y, Du C, Feng F, Liu W, Chen Y, Sun H Ref: Eur Journal of Medicinal Chemistry, 243:114729, 2022 : PubMed ESTHER: Lu_2022_Eur.J.Med.Chem_243_114729 PubMedSearch: Lu 2022 Eur.J.Med.Chem 243 114729 PubMedID: 36084535 Inhibitor(s) related to this paper: Aromatic-tertiary-amine-17c Abstract Butyrylcholinesterase (BChE) is recently regarded as a biomarker in progressed Alzheimer's disease (AD), the development of selective BChE inhibitors has attracted a great deal of interest and may be a viable therapeutic strategy for AD. Previously, an aromatic tertiary amine derivative (S17-1001) was screened and validated as a selective BChE inhibitor. Structured-based molecular modification guided the synthesis of 43 analogs. Biological test of cholinesterase inhibition, in vitro blood brain barrier permeation assay, neurotoxicity assay and neuroprotective effects assay indicated two optimal compounds 17c and 19c. Both compounds showed selective BChE inhibitory (hBChE < 20 nM, eeAChE > 10 microM), good BBB permeation and primary cell safety. Besides, 17c can dose-response protect cell from Abeta(1-42) induced damage. It also demonstrated that 17c and 19c were able to restore cognitive impairment in vivo test. These data suggest that 17c and 19c represent promising candidate for follow-up in the drug-discovery process against AD. Title: The Detoxification Enzymatic Responses of Plutella xylostella (Lepidoptera: Plutellidae) to Cantharidin Sun H, Wang P, Wei C, Li Y, Zhang Y Ref: J Econ Entomol, :, 2022 : PubMed ESTHER: Sun_2022_J.Econ.Entomol__ PubMedSearch: Sun 2022 J.Econ.Entomol PubMedID: 36073195 Abstract Plutella xylostella (L.) (Lepidoptera: Plutellidae) is one of the most destructive pests of Brassicaceae vegetables. Cantharidin is an insect-derived defensive toxin, which has been reported to have toxicity to a variety of pests and especially lepidopteran pests. Although the toxicity of cantharidin on P. xylostella has been demonstrated, there is little information available on the specific detoxification response of P. xylostella against cantharidin. This study investigates the enzymatic response (including serine/threonine phosphatases [PSPs], carboxylesterases [CarEs], glutathione-S-transferases [GSTs], and cytochrome P450 monooxygenases [P450]) in P. xylostella to the sublethal and low lethal concentrations of cantharidin (LC10 and LC25). Results showed that the inhibitory activity of PSPs was increased and then decreased in vivo, while PSPs activity could be almost completely inhibited in vitro. Interestingly, the activities of detoxification enzymes (GST, CarE, and P450) in P. xylostella displayed a trend of decreasing and then increasing after exposure to the two concentrations of cantharidin. Notably, the increase in P450 enzyme activity was the most significant. The increasing trend of detoxification enzyme activity was congruent with the recovery trend of PSPs activity. This study contributes to our understanding of the detoxification mechanism of cantharidin in P. xylostella and helps in the further development of biogenic agents. Title: Substrate-dependent inhibition of hypericin on human carboxylesterase 2: implications for herb-drug combination Wang D, Zhao T, Zhao S, Chen J, Dou T, Ge G, Wang C, Sun H, Liu K and Wu J <1 more author(s)> Wang D, Zhao T, Zhao S, Chen J, Dou T, Ge G, Wang C, Sun H, Liu K, Meng Q, Wu J (- 1) Ref: Curr Drug Metab, :, 2022 : PubMed ESTHER: Wang_2022_Curr.Drug.Metab__ PubMedSearch: Wang 2022 Curr.Drug.Metab PubMedID: 35114918 Abstract BACKGROUND: Hypericin is the main active ingredient of St. John's wort, a Chinese herb commonly used in treating depression. Previous studies have shown that hypericin can strongly inhibit human cytochrome P450 (CYP) enzyme activities; however, its potential interactions that inhibit human carboxylesterases 2 (hCE2) were unclear. PURPOSE: The study aimed to investigate the inhibition of hypericin on hCE2. METHODS: The inhibition of hypericin on hCE2 was studied by using N-(2-butyl-1,3-dioxo-2,3-dihydro-1H-phenalen-6-yl)-2-chloroacetamide (NCEN). The type of inhibition of hypericin on hCE2 and the corresponding inhibition constant (Ki) value were determined. The inhibition of hypericin on hCE2 in living cells was discussed. The herb-drug interactions (HDI) risk of hypericin and hCE2 in vivo was predicted by estimating the drug concentration-time curve (AUC) ratio of hypericin and hypericin free. To understand the inhibition mechanism of hypericin on the activity of hCE2 in-depth, molecular docking was performed. RESULTS: The half-maximal inhibitory concentration (IC50) values of hypericin against the hydrolysis of NCEN and irinotecan (CPT-11) were calculated to be 26.59 microM and 112.8 microM, respectively. Hypericin inhibited the hydrolysis of NCEN and CPT-11. Their Ki values were 10.53 microM and 81.77 microM, respectively. Moreover, hypericin distinctly suppressed hCE2 activity in living cells. In addition, the AUC of hCE2 metabolic drugs with metabolic sites similar to NCEN was estimated to increase by up to 5%, in the presence of hypericin. More importantly, the exposure of CPT-11 in the intestinal epithelium was predicted to increase by 2%-69% following the oral co-administration of hypericin. Further, molecular simulations indicated that hypericin could strongly interact with ASP98, PHE307, and ARG355 to form four hydrogen bonds within hCE2. CONCLUSION: These findings are of considerable clinical significance to the combination of hypericin-containing herbs and drugs metabolized by hCE2. Title: Design, synthesis and evaluation of fused hybrids with acetylcholinesterase inhibiting and Nrf2 activating functions for Alzheimer's disease Wang Y, Xiong B, Lin H, Li Q, Yang H, Qiao Y, Xu Z, Lyu W, Qu W and Sun H <3 more author(s)> Wang Y, Xiong B, Lin H, Li Q, Yang H, Qiao Y, Xu Z, Lyu W, Qu W, Liu W, Chen Y, Feng F, Sun H (- 3) Ref: Eur Journal of Medicinal Chemistry, 244:114806, 2022 : PubMed ESTHER: Wang_2022_Eur.J.Med.Chem_244_114806 PubMedSearch: Wang 2022 Eur.J.Med.Chem 244 114806 PubMedID: 36223681 Abstract Designing of multiple-target directed ligands (MTDLs) has emerged as an attractive strategy for Alzheimer's disease (AD). Fusing the benzylpiperidine motif from AChE inhibitor donepezil and the 1,2,4-oxadiazole core from the Nrf2 activator 25 that was previously reported, we designed and synthesized a series of multifunctional anti-AD hybrids. The optimal hybrid 15a exhibited excellent AChE inhibitory (eeAChE IC(50) = 0.07 +/- 0.01 microM; hAChE IC(50) = 0.38 +/- 0.04 microM) and significant Nrf2 inductivity. It upregulated the protein and transcription level of Nrf2 and its downstream proteins HO-1, NQO1, and GCLM and promoted Nrf2 translocation from cytoplasm into nuclei. Additionally, 15a exhibited important neuroprotective function in protecting the cells from being damaged by H(2)O(2) and Abeta(1-42) aggregation and exerted antioxidant stress and anti-inflammatory activities in reducing the production of ROS and pro-inflammatory cytokines. Moreover, 15a effectively shortened the latency time and escape distance to the target, increased the arrival times, and simplified the tracks in Morris water maze test induced by scopolamine and Abeta(1-42). At the same time, it significantly reduced the levels of proinflammatory factors in the mice model brains. These effects of 15a in improving cognition and alleviating inflammation were even better than the combination of AChE inhibitor and Nrf2 activator, suggesting a remarkable benefit for AD treatment. 15a could serve as a novel hit compound with Nrf2 inductive activity and AChE inhibitory activity for further research. Title: Design, synthesis, biological evaluation and molecular modeling of N-isobutyl-N-((2-(p-tolyloxymethyl)thiazol-4yl)methyl)benzo[d][1,3] dioxole-5-carboxamides as selective butyrylcholinesterase inhibitors Xi M, Feng C, Du K, Lv W, Du C, Shen R, Sun H Ref: Bioorganic & Medicinal Chemistry Lett, :128602, 2022 : PubMed ESTHER: Xi_2022_Bioorg.Med.Chem.Lett__128602 PubMedSearch: Xi 2022 Bioorg.Med.Chem.Lett 128602 PubMedID: 35124202 Abstract Butyrylcholinesterase (BuChE) is recently regarded as a biomarker in progressed Alzheimer's disease (AD). Development of selective BuChE inhibitors has attracted a great deal of interest and may be a viable therapeutic strategy for AD. Recently, we reported the N-isobutyl-N-((2-(p-tolyloxymethyl)thiazol-4-yl)methyl)benzo[d][1,3]dioxole-5-carboxamide (1) as a selective BuChE inhibitor. Subsequently, 33 analogs were synthesized and assessed by AChE/BuChE activities, indicating an optimal compound 23. Further kinetic tests suggested a competitive manner. Molecular docking and Molecular dynamics (MD) simulation showed that it interacted with several residues in active site gorge of BuChE, possibly contributing to its selectivity and competitive pattern. Moreover, it showed low cytotoxicity and high blood brain barrier (BBB) permeability. Taken together, 23 was a promising BuChE inhibitor for the treatment of AD. Title: SARM1 deletion in parvalbumin neurons is associated with autism-like behaviors in mice Xiang L, Wu Q, Sun H, Miao X, Lv Z, Liu H, Chen L, Gu Y, Chen J and Huang Z <13 more author(s)> Xiang L, Wu Q, Sun H, Miao X, Lv Z, Liu H, Chen L, Gu Y, Chen J, Zhou S, Jiang H, Du S, Zhou Y, Dong H, Fan Y, Miao S, Lu Q, Chang L, Wang H, Lu Y, Xu X, Wang W, Huang Z (- 13) Ref: Cell Death Dis, 13:638, 2022 : PubMed ESTHER: Xiang_2022_Cell.Death.Dis_13_638 PubMedSearch: Xiang 2022 Cell.Death.Dis 13 638 PubMedID: 35869039 Abstract Autism spectrum disorder (ASD), a group of neurodevelopmental disorder diseases, is characterized by social deficits, communication difficulties, and repetitive behaviors. Sterile alpha and TIR motif-containing 1 protein (SARM1) is known as an autism-associated protein and is enriched in brain tissue. Moreover, SARM1 knockdown mice exhibit autism-like behaviors. However, its specific mechanism in ASD pathogenesis remains unclear. Here we generated parvalbumin-positive interneurons (PVI)-specific conditional SARM1 knockout (SARM1(PV)-CKO) mice. SARM1(PV)-CKO male mice showed autism-like behaviors, such as mild social interaction deficits and repetitive behaviors. Moreover, we found that the expression level of parvalbumin was reduced in SARM1(PV)-CKO male mice, together with upregulated apoptosis-related proteins and more cleaved-caspase-3-positive PVIs, suggesting that knocking out SARM1 may cause a reduction in the number of PVIs due to apoptosis. Furthermore, the expression of c-fos was shown to increase in SARM1(PV)-CKO male mice, in combination with upregulation of excitatory postsynaptic proteins such as PSD-95 or neuroligin-1, indicating enhanced excitatory synaptic input in mutant mice. This notion was further supported by the partial rescue of autism-like behavior deficits by the administration of GABA receptor agonists in SARM1(PV)-CKO male mice. In conclusion, our findings suggest that SARM1 deficiency in PVIs may be involved in the pathogenesis of ASD. Title: Response of xenobiotic biodegradation and metabolic genes in Tribolium castaneum following eugenol exposure Zhang Y, Gao S, Zhang P, Sun H, Lu R, Yu R, Li Y, Zhang K, Li B Ref: Mol Genet Genomics, :, 2022 : PubMed ESTHER: Zhang_2022_Mol.Genet.Genomics__ PubMedSearch: Zhang 2022 Mol.Genet.Genomics PubMedID: 35419714 Abstract Eugenol, a plant-derived component possessing small side effects, has an insecticidal activity to Tribolium castaneum; however, the underlying molecular mechanisms of eugenol acting on T. castaneum are currently unclear. Here, a nerve conduction carboxylesterase and a detoxifying glutathione S-transferase were significantly inhibited after eugenol exposure, resulting in the paralysis or death of beetles. Then, RNA-sequencing of eugenol-exposed and control samples identified 362 differentially expressed genes (DEGs), containing 206 up-regulated and 156 down-regulated genes. RNA-seq data were validated further by qRT-PCR. GO analysis revealed that DEGs were associated with 1308 GO terms of which the most enriched GO terms were catalytic activity, and integral component of membrane; KEGG pathway analysis showed that these DEGs were distributed in 151 different pathways, of which some pathways associated with metabolism of xenobiotics or drug were significantly enriched, which indicated that eugenol most likely disturbed the processes of metabolism, and detoxication. Moreover, several DEGs including Hexokinase type 2, Isocitrate dehydrogenase, and Cytochrome b-related protein, might participate in the respiratory metabolism of eugenol-exposed beetles. Some DEGs encoding CYP, UGT, GST, OBP, CSP, and ABC transporter were involved in the xenobiotic or drug metabolism pathway, which suggested that these genes of T. castaneum participated in the response to eugenol exposure. Additionally, TcOBPC11/ TcGSTs7, detected by qRT-PCR and RNA-interference against these genes, significantly increased the mortality of eugenol-treated T. castaneum, providing further evidence for the involvement of OBP/GST in eugenol metabolic detoxification in T. castaneum. These results aid eugenol insecticidal mechanisms and provide the basis of insect control. Title: Insights into mechanisms involved in the uptake, translocation, and metabolism of phthalate esters in Chinese cabbage (Brassica rapa var. chinensis) Cheng Z, Wang Y, Qiao B, Zhang Q, Sun H Ref: Sci Total Environ, 768:144945, 2021 : PubMed ESTHER: Cheng_2021_Sci.Total.Environ_768_144945 PubMedSearch: Cheng 2021 Sci.Total.Environ 768 144945 PubMedID: 33736326 Abstract In the present study, the uptake and translocation mechanisms of phthalate esters (PAEs) and their primary mono esters metabolites (mPAEs), and the mechanisms of PAEs metabolism in plants were elucidated. The objectives of this study were to: (i) elucidate the fractionation of PAEs and mPAEs in Chinese cabbage (Brassica rapa var. chinensis) by hydroponic experiment, (ii) investigate the PAEs and mPAEs uptake mechanisms in root by inhibitor experiments, (iii) explain the molecular mechanisms of PAE interactions with the plant macromolecules by proteomics analysis and molecular docking, and (iv) reveal the involvement of carboxylesterase in the plant metabolism of PAEs. The results demonstrated that both the apoplastic and symplastic pathways contributed to the uptake of di-n-butyl phthalate (DnBP), di-(2-ethylhexyl) phthalate (DEHP), mono-n-butyl phthalate (MnBP), and mono-(2-ethylhexyl) phthalate (MEHP) by vacuum-infiltration-centrifugation method. The energy-dependent active process was involved for the uptake of DnBP, DEHP, MnBP, and MEHP. The passive uptake pathways of anion mPAEs and neutral PAEs differ. Aquaporins contributed to the uptake of anion MnBP and MEHP, and slow-type anion channel was also responsible for the uptake of anion MEHP. Molecular interactions of PAEs and macromolecules were further characterized by proteomic analysis and molecular docking. PAEs were transferred via non-specific lipid transfer protein by binding hydroponic amino acid residues. The carboxylesterase enzyme was attributed to the metabolism of PAEs to form mPAEs by using crude enzyme extract and commercial pure enzyme. This study provides both experimental and theoretical evidence for uptake, accumulation, and metabolism of PAEs in plants. Title: Discovery of 2-(cyclopropanecarboxamido)-N-(5-((1-(4-fluorobenzyl)piperidin-4-yl)methoxy)pyridin-3-yl)isonicotinamide as a potent dual AChE/GSK3beta inhibitor for the treatment of Alzheimer's disease: Significantly increasing the level of acetylcholine in the brain without affecting that in intestine Jiang X, Liu C, Zou M, Xie H, Lin T, Lyu W, Xu J, Li Y, Feng F and Liu W <1 more author(s)> Jiang X, Liu C, Zou M, Xie H, Lin T, Lyu W, Xu J, Li Y, Feng F, Sun H, Liu W (- 1) Ref: Eur Journal of Medicinal Chemistry, 223:113663, 2021 : PubMed ESTHER: Jiang_2021_Eur.J.Med.Chem_223_113663 PubMedSearch: Jiang 2021 Eur.J.Med.Chem 223 113663 PubMedID: 34198150 Abstract Acetylcholinesterase (AChE) inhibitors are currently the first-line drugs approved by the FDA for the treatment of Alzheimer's disease (AD). However, a short effective-window limits their therapeutic benefits. Clinical studies have confirmed that the combination of AChE inhibitors and neuroprotective agents exhibits better anti-AD effects. We have previously reported that the dual AChE/GSK3beta (Glycogen synthase kinase 3beta) modulators have both neuroprotective effects and cognitive impairment-improvement effects. In this study, we characterized a new backbone of the AChE/GSK3beta inhibitor 11c. It was identified as a highly potent AChE inhibitor and was found superior to donepezil, the first-line drug for the treatment of AD. In vivo studies confirmed that 11c significantly inhibited the activity of AChE in the brain but had little effect on the activity of AChE in the intestine. This advantage of 11c was expected to reduce the peripheral side effects caused by donepezil. Furthermore, biomarker studies have shown that 11c also improved the levels of acetylcholine and synaptophysin in the brain and exhibited neuroprotective effects. Preliminary in vivo and in vitro research results underline the exciting potential of compound 11c in the treatment of AD. Title: Biogenetic cantharidin is a promising leading compound to manage insecticide resistance of Mythimna separata (Lepidoptera: Noctuidae) Li Y, Sun H, Yasoob H, Tian Z, Li R, Zheng S, Liu J, Zhang Y Ref: Pestic Biochem Physiol, 172:104769, 2021 : PubMed ESTHER: Li_2021_Pestic.Biochem.Physiol_172_104769 PubMedSearch: Li 2021 Pestic.Biochem.Physiol 172 104769 PubMedID: 33518040 Abstract Cantharidin (CTD) is a natural toxin with effective toxicity to lepidopteran pests. Nevertheless, little information is available on whether pests develop resistance to CTD. After being exposed to CTD (50 mg/L to 90 mg/L) or 10 generations, the resistance ratio of laboratory selected cantharidin-resistant Mythimna separata (Cantharidin-SEL) strain was only elevated 1.95-fold. Meanwhile, the developmental time for M. separata was prolonged (delayed1.65 in males and 1.84 days in females). The reported CTD target, the serine/threonine phosphatases (PSPs), have not been shown significant activity variation during the whole process of CTD-treatment. The activity of detoxification enzymes (cytochrome monooxygenase P450, glutathione-S-transferase (GST) and carboxylesterase) were affected by CTD selection, but this change was not mathematically significant. More importantly, no obvious cross-resistance with other commonly used insecticides was observed in the M. separata population treated with CTD for 10 generations (resistance ratios were all lower 2.5). Overall, M. separata is unlikely to produce target-site insensitivity resistance, metabolic resistance to CTD. Meanwhile, cantharidin-SEL is not prone to develop cross-resistance with other insecticides. These results indicate that CTD is a promising biogenetic lead compound which can be applied in the resistance management on M. separata. Title: Characterization of a novel sn1,3 lipase from Ricinus communis L. suitable for production of oleic acid-palmitic acid-glycerol oleate Li Y, Li G, Sun H, Chen Y Ref: Sci Rep, 11:6913, 2021 : PubMed ESTHER: Li_2021_Sci.Rep_11_6913 PubMedSearch: Li 2021 Sci.Rep 11 6913 PubMedID: 33767251 Abstract The hydrolysis properties of lipase in castor was evaluated using two different substrate forms (tripalmitic glycerides and trioleic glycerides) to catalyze the reaction under different operational conditions. RcLipase was obtained from castor seeds and results show that RcLipase is a conservative serine lipase with a conserved catalytic center (SDH) and a conserved pentapeptide (GXSXG). This enzyme exhibited the greatest activity and tolerance to chloroform and toluene when it was expressed in Pichia pastoris GS115 at 40 degC and pH 8.0. Zn and Cu ions exerted obvious inhibitory effects on the enzyme, and displayed good hydrolytic activity for long-chain natural and synthetic lipids. HPLC analysis showed that this enzyme has 1,3 regioselectivity when glycerol tripalmitate and oleic acid are used as substrates. The fatty acid composition in the reaction product was 21.3% oleic acid and 79.1% sn-2 palmitic acid. Title: Highly Potent and Selective Butyrylcholinesterase Inhibitors for Cognitive Improvement and Neuroprotection Li Q, Chen Y, Xing S, Liao Q, Xiong B, Wang Y, Lu W, He S, Feng F and Sun H <1 more author(s)> Li Q, Chen Y, Xing S, Liao Q, Xiong B, Wang Y, Lu W, He S, Feng F, Liu W, Sun H (- 1) Ref: Journal of Medicinal Chemistry, :, 2021 : PubMed ESTHER: Li_2021_J.Med.Chem__ PubMedSearch: Li 2021 J.Med.Chem PubMedID: 33973470 Inhibitor(s) related to this paper: S06-1011 Abstract Butyrylcholinesterase (BChE) has been considered as a potential therapeutic target for Alzheimer's disease (AD) because of its compensation capacity to hydrolyze acetylcholine (ACh) and its close association with Abeta deposit. Here, we identified S06-1011 (hBChE IC(50) = 16 nM) and S06-1031 (hBChE IC(50) = 25 nM) as highly effective and selective BChE inhibitors, which were proved to be safe and long-acting. Candidate compounds exhibited neuroprotective effects and the ability to improve cognition in scopolamine- and Abeta(1-42) peptide-induced cognitive deficit models. The best candidate S06-1011 increased the level of ghrelin, a substrate of BChE, which can function as improving the mental mood appetite. The weight gain of the S06-1011-treated group remarkably increased. Hence, BChE inhibition not only plays a protective role against dementia but also exerts a great effect on treating and nursing care. Title: Synthesis and activity of miconazole derivatives as dual BChE/IDO1 inhibitors for the treatment of Alzheimer's disease Lu X, Liu Y, Qin N, Yang H, Qiao Y, Jiang X, Chen Y, Feng F, Liu W and Sun H <1 more author(s)> Lu X, Liu Y, Qin N, Yang H, Qiao Y, Jiang X, Chen Y, Feng F, Liu W, Zhou Y, Sun H (- 1) Ref: Future Med Chem, 13:1105, 2021 : PubMed ESTHER: Lu_2021_Future.Med.Chem_13_1105 PubMedSearch: Lu 2021 Future.Med.Chem 13 1105 PubMedID: 33960203 Abstract Background: Alzheimer's disease is a multifactorial neurological disorder seen in elderly people. Loss of cholinergic transmission and unbalanced tryptophan metabolism kynurenine pathway have been demonstrated in neuropsychiatric diseases. Methods & results: Among the two series of synthesized compounds, compounds 5c and 5h were identified as effective dual BChE/IDO1 inhibitors, with well-balanced micromolar activity. Compounds 5c and 5h exhibited promising ability to ameliorate behavioral impairment by Morris water maze. The safety of miconazole analogs was also validated by PC12 and SH-SY5Y cell lines. Conclusion: These results highlight the ability of 5c and 5h to treat Alzheimer's disease. Title: Synthesis and bio-evaluation of a novel selective butyrylcholinesterase inhibitor discovered through structure-based virtual screening Xing S, Chen Y, Xiong B, Lu W, Li Q, Wang Y, Jiao M, Feng F, Liu W, Sun H Ref: Int J Biol Macromol, 166:1352, 2021 : PubMed ESTHER: Xing_2021_Int.J.Biol.Macromol_166_1352 PubMedSearch: Xing 2021 Int.J.Biol.Macromol 166 1352 PubMedID: 33161083 Abstract In recent years, butyrylcholinesterase (BChE) has gradually gained worldwide interests as a novel target for treating Alzheimer's disease (AD). Here, two pharmacophore models were generated using Schrodinger suite and used to virtually screen ChemDiv database, from which three hits were obtained. Among them, 2513-4169 displayed the highest inhibitory activity and selectivity against BChE (eeAChE IC(50) > 10 microM, eqBChE IC(50) = 3.73 +/- 1.90 microM). Molecular dynamic (MD) simulation validated the binding pattern of 2513-4169 in BChE, and it could form a various of receptor-ligand interactions with adjacent residues. In vitro cytotoxicity assay proved the safety of 2513-4169 on diverse neural cell lines. Moreover, the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) assay performed on SH-SY5Y cells proved the neuroprotective effect of 2513-4169 against toxic Abeta(1)(-)(42). In vivo behavioral study further confirmed the great efficacy of 2513-4169 on reversing Abeta(1)(-)(42)-induced cognitive impairment of mice and clearing the toxic Abeta(1)(-)(42) in brains. Moreover, 2513-4169 was proved to be able to cross blood-brain barrier (BBB) through a parallel artificial membrane permeation assay of BBB (PAMPA-BBB). Taken together, 2513-4169 is a promising lead compound for future optimization to discover anti-AD treating agents. Title: Structure and therapeutic uses of butyrylcholinesterase: Application in detoxification, Alzheimer's disease, and fat metabolism Xing S, Li Q, Xiong B, Chen Y, Feng F, Liu W, Sun H Ref: Med Res Rev, 41:858, 2021 : PubMed ESTHER: Xing_2021_Med.Res.Rev_41_858 PubMedSearch: Xing 2021 Med.Res.Rev 41 858 PubMedID: 33103262 Abstract Structural information of butyrylcholinesterase (BChE) and its variants associated with several diseases are discussed here. Pure human BChE has been proved safe and effective in treating organophosphorus (OPs) poisoning and has completed Phase 1 and 2 pharmacokinetic (PK) and safety studies. The introduction of specific mutations into native BChE to endow it a self-reactivating property has gained much progress in producing effective OPs hydrolases. The hydrolysis ability of native BChE on cocaine has been confirmed but was blocked to clinical application due to poor PK properties. Several BChE mutants with elevated cocaine hydrolysis activity were published, some of which have shown safety and efficiency in treating cocaine addiction of human. The increased level of BChE in progressed Alzheimer's disease patients made it a promising target to elevate acetylcholine level and attenuate cognitive status. A variety of selective BChE inhibitors with high inhibitory activity published in recent years are reviewed here. BChE could influence the weight and insulin secretion and resistance of BChE knockout (KO) mice through hydrolyzing ghrelin. The BChE-ghrelin pathway could also regulate aggressive behaviors of BChE-KO mice. Title: Comparison of the Inhibitory Effects of Clotrimazoleand Ketoconazole against Human Carboxylesterase 2 Zhao T, Wang D, Shan Z, Chen J, Dou T, Ge G, Wang C, Meng Q, Sun H and Wu J <1 more author(s)> Zhao T, Wang D, Shan Z, Chen J, Dou T, Ge G, Wang C, Meng Q, Sun H, Liu K, Wu J (- 1) Ref: Curr Drug Metab, :, 2021 : PubMed ESTHER: Zhao_2021_Curr.Drug.Metab__ PubMedSearch: Zhao 2021 Curr.Drug.Metab PubMedID: 33568030 Abstract BACKGROUND: Both clotrimazole and ketoconazole have been verified that they have an inhibitory effect on CYP3A4. hCE2 is an enzyme closely related to the side effects of several anti-cancer drugs. However, the interactions between hCE2 and clotrimazole and ketoconazole remain unclear. OBJECTIVE: The objective of this study was to investigate and compare the inhibition behaviors of these two antifungal agents, ketoconazole and clotrimazole, on the human liver microsome hCE2 and to explore the underlying mechanism. METHODS: The inhibitory effects were investigated in human liver microsomes (HLMs) using fluorescein diacetate (FD), N-(2-butyl-1,3-dioxo-2,3-dihydro-1H-phenalen-6-yl)-2-chloroacetamide (NCEN) and irinotecan (CPT-11) as substrates of hCE2. RESULTS: Clotrimazole significantly inhibited the hCE2 activity, which was manifested by attenuated fluorescence when the substrates were FD and NCEN. The inhibitory effect of clotrimazole towards hCE2 was much stronger than that of ketoconazole, and the inhibitory behaviors displayed substrate-dependent inhibition. The IC50 value of clotrimazole with CPT-11 as the substate increased by 5 and 37 times than that with FD and NCEN respectively. Furthermore, the inhibitions of clotrimazole towards hCE2-mediated hydrolysis of FD, NCEN and CPT-11 were all in competitive mode with the Ki values of 0.483 microM, 8.63 microM and 29.0 microM, respectively. Molecular docking result of clotrimazole binding to hCE2 illustrated that clotrimazole could efficiently orient itself in the Z site cavity of hCE2. CONCLUSION: Clotrimazole displayed a strong inhibitory effect against hCE2, which might be used as a potential combined agent co-administrated with CPT-11 to alleviate the hCE2-mediated severe side effects. Title: Gamete binning: chromosome-level and haplotype-resolved genome assembly enabled by high-throughput single-cell sequencing of gamete genomes Campoy JA, Sun H, Goel M, Jiao WB, Folz-Donahue K, Wang N, Rubio M, Liu C, Kukat C and Schneeberger K <2 more author(s)> Campoy JA, Sun H, Goel M, Jiao WB, Folz-Donahue K, Wang N, Rubio M, Liu C, Kukat C, Ruiz D, Huettel B, Schneeberger K (- 2) Ref: Genome Biol, 21:306, 2020 : PubMed ESTHER: Campoy_2020_Genome.Biol_21_306 PubMedSearch: Campoy 2020 Genome.Biol 21 306 PubMedID: 33372615 Gene_locus related to this paper: pruar-a0a6j5xc26, pruar-a0a6j5xjr9 Abstract Generating chromosome-level, haplotype-resolved assemblies of heterozygous genomes remains challenging. To address this, we developed gamete binning, a method based on single-cell sequencing of haploid gametes enabling separation of the whole-genome sequencing reads into haplotype-specific reads sets. After assembling the reads of each haplotype, the contigs are scaffolded to chromosome level using a genetic map derived from the gametes. We assemble the two genomes of a diploid apricot tree based on whole-genome sequencing of 445 individual pollen grains. The two haplotype assemblies (N50: 25.5 and 25.8 Mb) feature a haplotyping precision of greater than 99% and are accurately scaffolded to chromosome-level. Title: FAM172A inhibits EMT in pancreatic cancer via ERK-MAPK signaling Chen Y, Liu P, Shen D, Liu H, Xu L, Wang J, Sun H, Wu H Ref: Biol Open, 9:, 2020 : PubMed ESTHER: Chen_2020_Biol.Open_9_bio048462 PubMedSearch: Chen 2020 Biol.Open 9 bio048462 PubMedID: 31988090 Gene_locus related to this paper: human-f172a Abstract FAM172A, as a newly discovered gene, is little known in cancer development, especially in pancreatic cancer (PC). We investigated the potential role and molecular mechanism of FAM172A in epithelial to mesenchymal transition (EMT) in both human clinical samples and PC cells. FAM172A was downregulated in human PC tissues compared with that in non-cancerous pancreas cells by immunohistochemistry and qRT-PCR. FAM172A expression was negatively associated with tumor size (P=0.015), T stage (P=0.006), lymph node metastasis (P=0.028) and the worst prognosis of PC patients (P=0.004). Meanwhile, a positive relationship between FAM172A and E-cadherin (E-cad) (r=0.381, P=0.002) was observed in clinical samples, which contributed to the better prognosis of PC patients (P=0.014). FAM172A silencing induced EMT in both AsPC-1 and BxPC-3 cells, including inducing the increase of Vimentin, MMP9 and pERK and the decrease of E-cad and beta-catenin expression, stimulating EMT-like cell morphology and enhancing cell invasion and migration in PC cells. However, MEK1 inhibitor PD98059 reversed FAM172A silencing-enhanced EMT in PC cells. We conclude that FAM172A inhibits EMT of PC cells via ERK-MAPK signaling. Title: Design, Synthesis, and Evaluation of Acetylcholinesterase and Butyrylcholinesterase Dual-Target Inhibitors against Alzheimer's Diseases Guo Y, Yang H, Huang Z, Tian S, Li Q, Du C, Chen T, Liu Y, Sun H, Liu Z Ref: Molecules, 25:, 2020 : PubMed ESTHER: Guo_2020_Molecules_25_ PubMedSearch: Guo 2020 Molecules 25 PubMedID: 31979317 Abstract A series of novel compounds 6a-h, 8i-1, 10s-v, and 16a-d were synthesized and evaluated, together with the known analogs 11a-f, for their inhibitory activities towards acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). The inhibitory activities of AChE and BChE were evaluated in vitro by Ellman method. The results show that some compounds have good inhibitory activity against AChE and BChE. Among them, compound 8i showed the strongest inhibitory effect on both AChE (eeAChE IC50 = 0.39 muM) and BChE (eqBChE IC50 = 0.28 muM). Enzyme inhibition kinetics and molecular modeling studies have shown that compound 8i bind simultaneously to the peripheral anionic site (PAS) and the catalytic sites (CAS) of AChE and BChE. In addition, the cytotoxicity of compound 8i is lower than that of Tacrine, indicating its potential safety as anti-Alzheimer's disease (anti-AD) agents. In summary, these data suggest that compound 8i is a promising multipotent agent for the treatment of AD. Title: Rational design and biological evaluation of a new class of thiazolopyridyl tetrahydroacridines as cholinesterase and GSK-3 dual inhibitors for Alzheimer's disease Jiang X, Zhou J, Wang Y, Chen L, Duan Y, Huang J, Liu C, Chen Y, Liu W and Qu W <2 more author(s)> Jiang X, Zhou J, Wang Y, Chen L, Duan Y, Huang J, Liu C, Chen Y, Liu W, Sun H, Feng F, Qu W (- 2) Ref: Eur Journal of Medicinal Chemistry, 207:112751, 2020 : PubMed ESTHER: Jiang_2020_Eur.J.Med.Chem_207_112751 PubMedSearch: Jiang 2020 Eur.J.Med.Chem 207 112751 PubMedID: 32950908 Abstract A key factor in the success of the MTDLs drug discovery approach is the selection of suitable target proteins. Based on the results of our previous research regarding dual-target inhibitors of AChE/GSK-3beta and analysis of target proteins, in the current study, 28 hybrids were designed and synthesized. Docking studies allowed us to rationalize the binding mode of the synthesized compounds in both targets. In vitro enzyme inhibition studies identified compound GT15 as a lead molecule with preferential AChE/GSK-3beta inhibition (hAChE IC(50) = 1.2 +/- 0.1 nM; hGSK-3beta IC(50) = 22.2 +/- 1.4 nM). In addition, GT15 showed high kinase selectivity for GSK-3, except for DYRK1, with inhibition rate of 83.69% and 67.94% against DYRK1alpha and DYRK1beta at a concentration of 20 muM. The compound also exhibited good permeability across the blood-brain-barrier and ability to inhibit the phosphorylation of tau protein. Upon oral administration, GT15 exhibited promising cognitive improvement in the scopolamine-induced cognitive deficit mice in the Morris water maze model. These results suggest that AChE and GSK-3 based multitargeted approach have therapeutic potential for Alzheimer's disease. Title: Discovery of potent glycogen synthase kinase 3/cholinesterase inhibitors with neuroprotection as potential therapeutic agent for Alzheimer's disease Jiang X, Wang Y, Liu C, Xing C, Lyu W, Wang S, Li Q, Chen T, Chen Y and Sun H <2 more author(s)> Jiang X, Wang Y, Liu C, Xing C, Lyu W, Wang S, Li Q, Chen T, Chen Y, Feng F, Liu W, Sun H (- 2) Ref: Bioorganic & Medicinal Chemistry, 30:115940, 2020 : PubMed ESTHER: Jiang_2020_Bioorg.Med.Chem_30_115940 PubMedSearch: Jiang 2020 Bioorg.Med.Chem 30 115940 PubMedID: 33340937 Abstract In the present work, a novel series of pyridinethiazole bearing benzylpiperidine hybrids were designed and synthesized as dual-target inhibitors of GSK-3beta/AChE. Among them, GD29 was the most promising candidate, with an IC(50) value of 0.3 M for hAChE and an IC(50) value of 0.003 M for hGSK-3beta, respectively. The compounds exhibited good drug-like properties with optimal inhibitory enzyme activities. Moreover, GD29 showed anti-inflammatory properties at micromolar concentrations and displayed interesting neuroprotective profiles in an in vitro model of oxidative stress-induced neuronal death. Notably, the compounds also exhibited good permeability across the blood-brain-barrier (BBB) both in vitro. Central cholinomimetic activity was confirmed using a scopolamine-induced cognition impairment model in Institute of Cancer Research (ICR) mice upon oral administration. The current work identified optimized compounds and explored the therapeutic potential of glycogen synthase kinase 3/cholinesterase inhibition for the treatment of AD. Title: Reasonably activating Nrf2: A long-term, effective and controllable strategy for neurodegenerative diseases Li Q, Xing S, Chen Y, Liao Q, Liu Y, He S, Feng F, Zhang J, Liu W and Sun H <2 more author(s)> Li Q, Xing S, Chen Y, Liao Q, Liu Y, He S, Feng F, Zhang J, Liu W, Guo Q, Sun Y, Sun H (- 2) Ref: Eur Journal of Medicinal Chemistry, 185:111862, 2020 : PubMed ESTHER: Li_2020_Eur.J.Med.Chem_185_111862 PubMedSearch: Li 2020 Eur.J.Med.Chem 185 111862 PubMedID: 31735576 Abstract Neurodegenerative diseases are a variety of debilitating and fatal disorder in central nervous system (CNS). Besides targeting neuronal activity by influencing neurotransmitters or their corresponding receptors, modulating the underlying processes that lead to cell death, such as oxidative stress and mitochondrial dysfunction, should also be emphasized as an assistant strategy for neurodegeneration therapy. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) has been closely verified to be related to anti-inflammation and oxidative stress, rationally regulating its belonging pathway and activating Nrf2 is emphasized to be a potential treatment approach. There have existed multiple Nrf2 activators with different mechanisms and diverse structures, but those applied for neuro-disorders are still limited. On the basis of research arrangement and compound summary, we put forward the limitations of existing Nrf2 activators for neurodegenerative diseases and their future developing directions in enhancing the blood-brain barrier permeability to make Nrf2 activators function in CNS and designing Nrf2-based multi-target-directed ligands to affect multiple nodes in pathology of neurodegenerative diseases. Title: Discovery and Biological Evaluation of a Novel Highly Potent Selective Butyrylcholinsterase Inhibitor Li Q, Xing S, Chen Y, Liao Q, Xiong B, He S, Lu W, Liu Y, Yang H and Sun H <2 more author(s)> Li Q, Xing S, Chen Y, Liao Q, Xiong B, He S, Lu W, Liu Y, Yang H, Feng F, Liu W, Sun H (- 2) Ref: Journal of Medicinal Chemistry, 63:10030, 2020 : PubMed ESTHER: Li_2020_J.Med.chem_63_10030 PubMedSearch: Li 2020 J.Med.chem 63 10030 PubMedID: 32787113 Inhibitor(s) related to this paper: 8012-9656 Abstract To discover novel BChE inhibitors, a hierarchical virtual screening protocol followed by biochemical evaluation was applied. The most potent compound 8012-9656 (eqBChE IC(50) = 0.18 +/- 0.03 M, hBChE IC(50) = 0.32 +/- 0.07 M) was purchased and synthesized. It inhibited BChE in a noncompetitive manner and could occupy the binding pocket forming diverse interactions with the target. 8012-9656 was proven to be safe in vivo and in vitro and showed comparable performance in ameliorating the scopolamine-induced cognition impairment to tacrine. Additionally, treatment with 8012-9656 could almost entirely recover the Abeta(1-42) (icv)-impaired cognitive function to the normal level and showed better behavioral performance than donepezil. The evaluation of the Abeta(1-42) total amount confirmed its anti-amyloidogenic profile. Moreover, 8012-9656 possessed blood-brain barrier (BBB) penetrating ability, a long T(1/2), and low intrinsic clearance. Hence, the novel potential BChE inhibitor 8012-9656 can be considered as a promising lead compound for further investigation of anti-AD agents. Title: Identification of key residues of carboxylesterase PxEst-6 involved in pyrethroid metabolism in Plutella xylostella (L.) Li Y, Sun H, Tian Z, Ye X, Li R, Li X, Zheng S, Liu J, Zhang Y Ref: J Hazard Mater, 407:124612, 2020 : PubMed ESTHER: Li_2020_J.Hazard.Mater_407_124612 PubMedSearch: Li 2020 J.Hazard.Mater 407 124612 PubMedID: 33338816 Gene_locus related to this paper: pluxy-f1c4b8 Abstract The long-term and excessive use of insecticides has led to severe environmental problems and the evolution of insecticide resistance in insects. Carboxylesterases (CarEs) are important detoxification enzymes conferring insecticide resistance on insects. Herein, the detoxification process of Plutella xylostella (L.) carboxylesterase 6 (PxEst-6), one representative P. xylostella carboxylesterase, is investigated with cypermethrin, bifenthrin, cyfluthrin and lambda-cyhalothrin. RT-qPCR shows that PxEst-6 is highly expressed in the midgut and cuticles of the third instar larvae. Exposure to pyrethroid insecticides resulted in PxEst-6 up-regulation in a short time. Metabolic assays indicate that PxEst-6 has the capacity to metabolize these pyrethroid insecticides. The combination of molecular docking, binding mode analyses and alanine mutations demonstrated that His451, Lys458 and Gln431 were key residues of PxEst-6 for metabolizing pyrethroids and the acetate groups derived from pyrethroids were key sites for being metabolized by PxEst-6. H451- and K458-derived hydrogen bond (H-bond) interactions with the pyrethroid acetate groups and the polar interactions with the pyrethroid acetate group provided by the Q431 sidechain were crucial to the pyrethroids' metabolism by PxEst-6. Our study contributes to revealing the reasons for pyrethroid resistance in P. xylostella, and provides a fundamental basis for the development of novel pyrethroid insecticides. Title: Design, synthesis and biological evaluation of novel carboline-cinnamic acid hybrids as multifunctional agents for treatment of Alzheimer's disease Liao Q, Li Q, Zhao Y, Jiang P, Yan Y, Sun H, Liu W, Feng F, Qu W Ref: Bioorg Chem, 99:103844, 2020 : PubMed ESTHER: Liao_2020_Bioorg.Chem_99_103844 PubMedSearch: Liao 2020 Bioorg.Chem 99 103844 PubMedID: 32325336 Abstract Alzheimer's disease (AD) is a complex neurodegenerative disease with multiple pathological features. Multifunctional compounds able to simultaneously interact with several pathological components have been considered as a solution to treat the complex pathologies of neurodegenerative diseases. beta-carboline and cinnamic acid have been extensively studied for their widespread biological effects in treatment of AD, further application is limited due to its poor solubility and high toxicity. Herein, a series of carboline-cinnamic acid hybrids was designed and synthesized to obtain new multifunctional molecules with low toxicity and good physicochemical properties. In particular, e3 and e12 exhibited significant inhibition of Abeta aggregation (inhibitory rate at 25 M: 65% and 72% respectively), moderate BuChE inhibition, excellent neuroprotective effects and low neurotoxicity. Furthermore, in the AD mice model, e3 and e12 could restore learning and memory function to a comparable level to that of the control and did not exhibit any acute toxicity in vivo at a relatively high dose of 600 mg/kg. Thus, these new compounds can be further studied as multifunctional molecules for AD. Title: Design, synthesis, in vitro and in vivo evaluation of benzylpiperidine-linked 1,3-dimethylbenzimidazolinones as cholinesterase inhibitors against Alzheimer's disease Mo J, Chen T, Yang H, Guo Y, Li Q, Qiao Y, Lin H, Feng F, Liu W and Sun H <2 more author(s)> Mo J, Chen T, Yang H, Guo Y, Li Q, Qiao Y, Lin H, Feng F, Liu W, Chen Y, Liu Z, Sun H (- 2) Ref: J Enzyme Inhib Med Chem, 35:330, 2020 : PubMed ESTHER: Mo_2020_J.Enzyme.Inhib.Med.Chem_35_330 PubMedSearch: Mo 2020 J.Enzyme.Inhib.Med.Chem 35 330 PubMedID: 31856607 Abstract Cholinesterase inhibitor plays an important role in the treatment of patients with Alzheimer's disease (AD). Herein, we report the medicinal chemistry efforts leading to a new series of 1,3-dimethylbenzimidazolinone derivatives. Among the synthesised compounds, 15b and 15j showed submicromolar IC50 values (15b, eeAChE IC50 = 0.39 +/- 0.11 microM; 15j, eqBChE IC50 = 0.16 +/- 0.04 microM) towards acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Kinetic and molecular modelling studies revealed that 15b and 15j act in a competitive manner. 15b and 15j showed neuroprotective effect against H2O2-induced oxidative damage on PC12 cells. This effect was further supported by their antioxidant activity determined in a DPPH assay in vitro. Morris water maze test confirmed the memory amelioration effect of the two compounds in a scopolamine-induced mouse model. Moreover, the hepatotoxicity of 15b and 15j was lower than tacrine. In summary, these data suggest 15b and 15j are promising multifunctional agents against AD. Title: Adipogenic activity of 2-ethylhexyl diphenyl phosphate via peroxisome proliferator-activated receptor gamma pathway Sun W, Duan X, Chen H, Zhang L, Sun H Ref: Sci Total Environ, 711:134810, 2020 : PubMed ESTHER: Sun_2020_Sci.Total.Environ_711_134810 PubMedSearch: Sun 2020 Sci.Total.Environ 711 134810 PubMedID: 31812418 Inhibitor(s) related to this paper: TPHP, Diphenyl-phosphate, EHDPP Abstract Recent studies have shown that exposure to some organophosphates, such as triphenyl phosphate (TPHP) and diphenyl phosphate (DPHP), can affect adipogenesis in preadipocytes. 2-Ethylhexyl diphenyl phosphate (EHDPP), an organophosphate, is frequently detected in various environmental media. However, there is less information about the toxicity effects and the mechanism by which EHDPP affects preadipocytes. In the present study, we investigated whether EHDPP could induce differentiation in 3T3-L1 preadipocytes through the peroxisome proliferator-activated receptor gamma (PPARgamma) signaling pathway. The fluorescence competitive binding assay and the dual-luciferase reporter gene assay were used to assess the binding affinity and activation of PPARgamma, and the results showed that EHDPP can bind to the ligand binding domain of PPARgamma (PPARgamma-LBD) and activate PPARgamma in vitro. Exposure to EHDPP for 10 days extensively induced adipogenesis in 3T3-L1 preadipocytes as assessed by lipid accumulation and gene expression of adipogenic markers of fatty acid binding protein 4 (FABP4), lipoprotein lipase (Lpl), adiponectin (Adip), and fatty acid synthase (Fasn). Furthermore, the preadipocytes differentiation was blocked by the PPARgamma-specific antagonist GW9662, indicating that the PPARgamma signaling pathway plays an important part in 3T3-L1 cell differentiation induced by EHDPP. Taken together, EHDPP can bind to PPARgamma-LBD, activate PPARgamma receptor, and induce cell differentiation via the PPARgamma signaling pathway in 3T3-L1 preadipocytes. Title: Discovery of a Selective 6-Hydroxy-1, 4-Diazepan-2-one Containing Butyrylcholinesterase Inhibitor by Virtual Screening and MM-GBSA Rescoring Zhou Y, Hu Y, Lu X, Yang H, Li Q, Du C, Chen Y, Hong KH, Sun H Ref: Dose Response, 18:1559325820938526, 2020 : PubMed ESTHER: Zhou_2020_Dose.Response_18_1559325820938526 PubMedSearch: Zhou 2020 Dose.Response 18 1559325820938526 PubMedID: 32636723 Abstract Alzheimer disease (AD) is the most common form of dementia characterized by the loss of cognitive abilities through the death of central neuronal cells. In this study, structure-based virtual screens of 2 central nervous system-targeted libraries followed by molecular mechanics/generalized born surface area rescoring were performed to discover novel, selective butyrylcholinesterase (BChE) inhibitors, which are one of the most effective therapeutic strategies for the treatments in late-stage AD. Satisfyingly, compound 5 was identified as a highly selective low micromolar inhibitor of BChE (BChE IC50 = 1.4 muM). The binding mode prediction and kinetic analysis were performed to obtain detailed information about compound 5. Besides, a preliminary structure-activity relationship investigation of compound 5 was carried out for further development of the series. The present results provided a valuable chemical template with a novel scaffold for the development of selective BChE inhibitors. Title: Novel BuChE-IDO1 inhibitors from sertaconazole: Virtual screening, chemical optimization and molecular modeling studies Zhou Y, Lu X, Du C, Liu Y, Wang Y, Ho Hong K, Chen Y, Sun H Ref: Bioorganic & Medicinal Chemistry Lett, :127756, 2020 : PubMed ESTHER: Zhou_2020_Bioorg.Med.Chem.Lett__127756 PubMedSearch: Zhou 2020 Bioorg.Med.Chem.Lett 127756 PubMedID: 33359445 Abstract In our effort towards the identification of novel BuChE-IDO1 dual-targeted inhibitor for the treatment of Alzheimer's disease (AD), sertaconazole was identified through a combination of structure-based virtual screening followed by MM-GBSA rescoring. Preliminary chemical optimization was performed to develop more potent and selective sertaconazole analogues. In consideration of the selectivity and the inhibitory activity against target proteins, compounds 5c and 5d were selected for the next study. Further modification of compound 5c led to the generation of compound 10g with notably improved selectivity towards BuChE versus AChE. The present study provided us with a good starting point to further design potent and selective BuChE-IDO1 inhibitors, which may benefit the treatment of late stage AD. Title: Complement Receptor C5aR1 Inhibition Reduces Pyroptosis in hDPP4-Transgenic Mice Infected with MERS-CoV Jiang Y, Li J, Teng Y, Sun H, Tian G, He L, Li P, Chen Y, Guo Y and Sun S <2 more author(s)> Jiang Y, Li J, Teng Y, Sun H, Tian G, He L, Li P, Chen Y, Guo Y, Zhao G, Zhou Y, Sun S (- 2) Ref: Viruses, 11:, 2019 : PubMed ESTHER: Jiang_2019_Viruses_11_ PubMedSearch: Jiang 2019 Viruses 11 PubMedID: 30634407 Abstract Middle East respiratory syndrome coronavirus (MERS-CoV) is a highly pathogenic virus with a crude mortality rate of ~35%. Previously, we established a human DPP4 transgenic (hDPP4-Tg) mouse model in which we studied complement overactivation-induced immunopathogenesis. Here, to better understand the pathogenesis of MERS-CoV, we studied the role of pyroptosis in THP-1 cells and hDPP4 Tg mice with MERS-CoV infection. We found that MERS-CoV infection induced pyroptosis and over-activation of complement in human macrophages. The hDPP4-Tg mice infected with MERS-CoV overexpressed caspase-1 in the spleen and showed high IL-1beta levels in serum, suggesting that pyroptosis occurred after infection. However, when the C5a-C5aR1 axis was blocked by an anti-C5aR1 antibody (Ab), expression of caspase-1 and IL-1beta fell. These data indicate that MERS-CoV infection induces overactivation of complement, which may contribute to pyroptosis and inflammation. Pyroptosis and inflammation were suppressed by inhibiting C5aR1. These results will further our understanding of the pathogenesis of MERS-CoV infection. Title: Expansion of the scaffold diversity for the development of highly selective butyrylcholinesterase (BChE) inhibitors: Discovery of new hits through the pharmacophore model generation, virtual screening and molecular dynamics simulation Lu X, Yang H, Li Q, Chen Y, Zhou Y, Feng F, Liu W, Guo Q, Sun H Ref: Bioorg Chem, 85:117, 2018 : PubMed ESTHER: Lu_2019_Bioorg.Chem_85_117 PubMedSearch: Lu 2019 Bioorg.Chem 85 117 PubMedID: 30605885 Inhibitor(s) related to this paper: S17-1001 Abstract Butyrylcholinesterase (BChE) is recently considered as a new target for the treatment of Alzheimer's disease (AD). There is an increasing interest in the development of BChE inhibitors. In the present study, a set of pharmacophore models for BChE was developed and validated. Based on the models, virtual screening was performed on five compound collections, from which seventeen potential hits were retained for biological investigation. In total, eight of these seventeen potential hits showed selective BChE inhibitory activity. Moreover, four compounds displayed IC50 values in sub-micromolar range on eqBChE and three displayed IC50 values <2muM on huBChE. The diverse scaffolds of the active compounds provided good starting point further development of selective BChE inhibitors. As far as we concerned, here we disclose the first selective pharmacophore model targeting BChE. The high rate of the model in the identification of active hits indicates it is a valuable tool for the development of selective BChE inhibitors, which may benefit the treatment of AD. Title: Design, synthesis, biological evaluation, and molecular modeling studies of quinoline-ferulic acid hybrids as cholinesterase inhibitors Mo J, Yang H, Chen T, Li Q, Lin H, Feng F, Liu W, Qu W, Guo Q and Sun H <2 more author(s)> Mo J, Yang H, Chen T, Li Q, Lin H, Feng F, Liu W, Qu W, Guo Q, Chi H, Chen Y, Sun H (- 2) Ref: Bioorg Chem, 93:103310, 2019 : PubMed ESTHER: Mo_2019_Bioorg.Chem_93_103310 PubMedSearch: Mo 2019 Bioorg.Chem 93 103310 PubMedID: 31586704 Abstract A series of quinoline-ferulic acid hybrids has been designed, synthesized, and evaluated as cholinesterase inhibitors. Most of the compounds showed good inhibitory activities toward both acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Among them, 10f was found to be the most potent inhibitor against AChE (IC50=0.62+/-0.17mum), and 14 was the most potent inhibitor against BChE (IC50=0.10+/-0.01mum). Representative compounds, such as 10f and 12g, act in a competitive manner when they inhibit AChE or BChE. Molecular docking and dynamic simulation revealed that the synthesized compounds bind to the target by simultaneously interacting with the catalytic active site (CAS) and the peripheral anionic site (PAS) of both AChE and BChE. The U-shaped confirmation was preferred when 12g bound to BChE, which was different from the linear conformation of 10f bound to AChE. Cell-based assays have confirmed the moderate neuroprotective effects of compounds 10f and 12g against H2O2-induced oxidative damage towards PC12 cells. Moreover, the hepatotoxicity of 12g was lower than that of tacrine, indicating its potential safety as an anti-Alzheimer's agent. In summary, we report a new chemotype of multifunctional hybrid, which may be further modified to develop new anti-Alzheimer's agents. Title: Analysis of the SNP rs3747333 and rs3747334 in NLGN4X gene in autism spectrum disorder: a meta-analysis Sun H, Yang Y, Zhang L, Wu H, Zhang H, Li H Ref: Ann Gen Psychiatry, 18:6, 2019 : PubMed ESTHER: Sun_2019_Ann.Gen.Psychiatry_18_6 PubMedSearch: Sun 2019 Ann.Gen.Psychiatry 18 6 PubMedID: 31139237 Gene_locus related to this paper: human-NLGN4X Abstract Background: The SNP rs3747333 and rs3747334 in Neuroligin 4X (NLGN4X) gene have been demonstrated to be associated with the susceptibility to Autism spectrum disorder (ASDs; MIM 209850), but the results are inconsistent. Therefore, a meta-analysis of eligible studies reporting the association between rs3747333 and rs3747334 and ASD was carried out to enhance the reliability of published results. Methods: A systematic literature search was performed using PubMed, Web of Science, Cochrane Library to search English articles concerning the relation between rs3747333, rs3747334 and ASD up to Sep. 21th, 2017. Summary odds ratios (OR) and 95% confidence interval (CI) were used to evaluate the risk of rs3747333, rs3747334 in the ASD. The heterogeneity and publication bias of the eligible studies were also evaluated. Results: Six eligible studies involving 1284 subjects (735 patients and 549 healthy controls) were included in this meta-analysis. Overall, the results indicated that there was no significant risk elevation between rs3747333, rs3747334 variants and ASD (OR = 0.39, 95% CI 0.10-1.60). Furthermore, sensitivity analysis and publication bias analysis confirmed this result. Conclusions: In conclusion, our meta-analysis suggests that the rs3747333, rs3747334 in NLGN4X gene are not frequent causes of ASD. Title: Infraspecific Variation of Huperzine A and B in Icelandic Huperzia selago Complex Xu M, Heidmarsson S, Thorsteinsdottir M, Wasowicz P, Sun H, Deng T, Omarsdottir S, Olafsdottir ES Ref: Planta Med, 85:160, 2019 : PubMed ESTHER: Xu_2019_Planta.Med_85_160 PubMedSearch: Xu 2019 Planta.Med 85 160 PubMedID: 30290396 Abstract The alkaloids huperzine A and huperzine B were originally isolated from the Chinese club moss Huperzia serrata. They are known inhibitors of acetylcholinesterase, and especially huperzine A shows pharmaceutical potential for the treatment of Alzheimer's disease. Its supply heavily relies on natural plant sources belonging to the genus Huperzia, which shows considerable interspecific huperzine A variations. Furthermore, taxonomic controversy remains in this genus, particularly in the Huperzia selago group. With focus on Icelandic H. selago taxa, we aimed to explore the relatedness of Huperzia species using multi-locus phylogenetic analysis, and to investigate correlations between huperzine A contents, morphotypes, and genotypes. Phylogenetic analysis was performed with five chloroplastic loci (the intergenic spacer between the photosystem II protein D1 gene and the tRNA-His gene, maturase K, ribulose-1,5-bisphosphate carboxylase/oxygenase large subunit, tRNA-Leu, and the intergenic spacer region between tRNA-Leu and tRNA-Phe). Huperzine A and huperzine B contents were determined using an HPLC-UV method. The phylogenetic analysis suggests that previously proposed Huperzia appressa and Huperzia arctica should not be considered species, but rather subspecies of H. selago. Three genotypes of Icelandic H. selago were identified and presented in a haplotype networking diagram. A significantly (p < 0.05) higher amount of huperzine A was found in H. selago genotype 3 (264 - 679 microg/g) than genotype 1 (20 - 180 microg/g), where the former shows a typical green and reflexed "selago" morphotype. The huperzine A content in genotype 3 is comparable to Chinese H. serrata and a good alternative huperzine A source. Genotype 2 contains multiple morphotypes with a broad huperzine A content (113 - 599 microg/g). The content of huperzine B in Icelandic taxa (6 - 13 microg/g) is much lower than that in Chinese H. serrata (79 - 207 microg/g). Title: Discovery, molecular dynamic simulation and biological evaluation of structurally diverse cholinesterase inhibitors with new scaffold through shape-based pharmacophore virtual screening Yang H, Du C, Li Q, Chen T, Lu X, Feng F, Chen Y, Liu W, Sun H Ref: Bioorg Chem, 92:103294, 2019 : PubMed ESTHER: Yang_2019_Bioorg.Chem_92_103294 PubMedSearch: Yang 2019 Bioorg.Chem 92 103294 PubMedID: 31557623 Abstract Designing small molecule inhibitors targeting cholinesterases (ChEs) is considered as an efficient strategy for the treatment of Alzheimer's disease (AD). In the present study, based on a shaped-based pharmacophore (SBP) model that we reported previously, virtual screening was performed on four commercial compound databases, from which eight small molecules containing new structurally scaffolds were retained and evaluated. In general, six of these potential hits were identified to be selective ChEs inhibitors. Three compounds exhibited IC50 values and Ki values in micromolar range on acetylcholinesterase (AChE), the most active compound 4 showed IC50 value of 6.31+/-2.68muM and Ki value of 4.76muM. Other three compounds displayed IC50 values and Ki values in micromolar range on butyrylcholinesterase (BChE) with high target selectivity, the most active compound 1 showed IC50 value of 3.87+/-2.48muM and Ki value of 1.52muM. Multiple biological evaluations were performed to determine their cytotoxicity, cyto-protective effects, antioxidant effect as well as druglike properties. These compounds provide new cores for the further design and optimization, with the aim to discover new ChEs inhibitors for the treatment of AD. Title: Synthesis and bioevaluation of new tacrine-cinnamic acid hybrids as cholinesterase inhibitors against Alzheimer's disease Chen Y, Zhu J, Mo J, Yang H, Jiang X, Lin H, Gu K, Pei Y, Wu L and Sun H <5 more author(s)> Chen Y, Zhu J, Mo J, Yang H, Jiang X, Lin H, Gu K, Pei Y, Wu L, Tan R, Hou J, Chen J, Lv Y, Bian Y, Sun H (- 5) Ref: J Enzyme Inhib Med Chem, 33:290, 2018 : PubMed ESTHER: Chen_2018_J.Enzyme.Inhib.Med.Chem_33_290 PubMedSearch: Chen 2018 J.Enzyme.Inhib.Med.Chem 33 290 PubMedID: 29278947 Abstract Small molecule cholinesterases inhibitor (ChEI) provides an effective therapeutic strategy to treat Alzheimer's disease (AD). Currently, the discovery of new ChEI with multi-target effect is still of great importance. Herein, we report the synthesis, structure-activity relationship study and biological evaluation of a series of tacrine-cinnamic acid hybrids as new ChEIs. All target compounds are evaluated for their in vitro cholinesterase inhibitory activities. The representatives which show potent activity on cholinesterase, are evaluated for the amyloid beta-protein self-aggregation inhibition and in vivo assays. The optimal compound 19, 27, and 30 (human AChE IC50 = 10.2 +/- 1.2, 16.5 +/- 1.7, and 15.3 +/- 1.8 nM, respectively) show good performance in ameliorating the scopolamine-induced cognition impairment and preliminary safety in hepatotoxicity evaluation. These compounds deserve further evaluation for the development of new therapeutic agents against AD. Title: Donepezil-based multi-functional cholinesterase inhibitors for treatment of Alzheimer's disease Li Q, He S, Chen Y, Feng F, Qu W, Sun H Ref: Eur Journal of Medicinal Chemistry, 158:463, 2018 : PubMed ESTHER: Li_2018_Eur.J.Med.Chem_158_463 PubMedSearch: Li 2018 Eur.J.Med.Chem 158 463 PubMedID: 30243151 Abstract Alzheimer's disease (AD) is one of the most common neurodegenerative disorders in elderly people. Considering the multifactorial nature of AD, the concept of multi-target-directed ligands (MTDLs) has recently emerged as a new strategy for designing therapeutic agents on AD. MTDLs are confirmed to simultaneously affect diverse targets which contribute to etiology of AD. As the most potent approved drug, donepezil affects various events of AD, like inhibiting cholinesterases activities, anti-Abeta aggregation, anti-oxidative stress et al. Modifications of donepezil or hybrids with pharmacophores of donepezil in recent five years are summarized in this article. On the basis of case studies, our concerns and opinions about development of donepezil derivatives, designing of MTDLs, and perspectives for AD treatments are discussed in final part. Title: Investigation of multi-target-directed ligands (MTDLs) with butyrylcholinesterase (BuChE) and indoleamine 2,3-dioxygenase 1 (IDO1) inhibition: The design, synthesis of miconazole analogues targeting Alzheimer's disease Lu X, He SY, Li Q, Yang H, Jiang X, Lin H, Chen Y, Qu W, Feng F and Sun H <2 more author(s)> Lu X, He SY, Li Q, Yang H, Jiang X, Lin H, Chen Y, Qu W, Feng F, Bian Y, Zhou Y, Sun H (- 2) Ref: Bioorganic & Medicinal Chemistry, 26:1665, 2018 : PubMed ESTHER: Lu_2018_Bioorg.Med.Chem_26_1665 PubMedSearch: Lu 2018 Bioorg.Med.Chem 26 1665 PubMedID: 29475581 Abstract In our endeavor towards the development of potent multi-target ligands for the treatment of Alzheimer's disease, miconazole was identified to show BuChE-IDO1 dual-target inhibitory effects. Morris water maze test indicated that miconazole obviously ameliorated the cognitive function impaired by scopolamine. Furthermore, it showed good safety in primary hepatotoxicity evaluation. Based on these results, we designed, synthesized, and evaluated a series of miconazole derivatives as BuChE-IDO1 dual-target inhibitors. Out of the 12 compounds, 5i and 5j exhibited the best potency in enzymatic evaluation, thus were selected for subsequent behavioral study, in which the two compounds exerted much improved effect than tacrine. Meanwhile, 5i and 5j displayed no apparent hepatotoxicity. The results suggest that miconazole analogue offers an attractive starting point for further development of new BuChE-IDO1 dual-target inhibitors against Alzheimer's disease. Title: Inhibition of Soluble Epoxide Hydrolase 2 Ameliorates Diabetic Keratopathy and Impaired Wound Healing in Mouse Corneas Sun H, Lee P, Yan C, Gao N, Wang J, Fan X, Yu FS Ref: Diabetes, 67:1162, 2018 : PubMed ESTHER: Sun_2018_Diabetes_67_1162 PubMedSearch: Sun 2018 Diabetes 67 1162 PubMedID: 29615440 Abstract EPHX2 (encoding soluble epoxide hydrolase [sEH]) converts biologically active epoxyeicosatrienoic acids (EETs), anti-inflammatory and profibrinolytic effectors, into the less biologically active metabolites, dihydroxyeicostrienoic acids. We sought to characterize the expression and the function of EPHX2 in diabetic corneas and during wound healing. The expression of EPHX2 at both mRNA and protein levels, as well as sEH enzymatic activity, was markedly upregulated in the tissues/cells, including corneal epithelial cells as well as the retina of human type 2 and mouse type 1 (streptozotocin [STZ] induced) and/or type 2 diabetes. Ephx2 depletion had no detectable effects on STZ-induced hyperglycemia but prevented the development of tear deficiency. Ephx2(-/-) mice showed an acceleration of hyperglycemia-delayed epithelium wound healing. Moreover, inhibition of sEH increased the rate of epithelium wound closure and restored hyperglycemia-suppressed STAT3 activation and heme oxygenase-1 (HO-1) expression in the diabetic corneas. Treatment of diabetic corneas with cobalt protoporphyrin, a well-known HO-1 inducer, restored wound-induced HO-1 upregulation and accelerated delayed wound healing. Finally, Ephx2 depletion enhanced sensory innervation and regeneration in diabetic corneas at 1 month after epithelial debridement. Our data suggest that increased sEH activity may be a contributing factor for diabetic corneal complications; targeting sEH pharmacologically or supplementing EETs may represent a new, adjunctive therapy for treating diabetic keratopathy. Title: Rapid Screening and Characterization of Acetylcholinesterase Inhibitors from Yinhuang Oral Liquid Using Ultrafiltration-liquid Chromatography-electrospray Ionization Tandem Mass Spectrometry Zhang H, Guo Y, Meng L, Sun H, Yang Y, Gao Y, Sun J Ref: Pharmacogn Mag, 14:248, 2018 : PubMed ESTHER: Zhang_2018_Pharmacogn.Mag_14_248 PubMedSearch: Zhang 2018 Pharmacogn.Mag 14 248 PubMedID: 29720840 Abstract Background: At present, approximately 17-25 million people in the world suffer from Alzheimer's disease (AD). The most efficacious and acceptable therapeutic drug clinically are the acetylcholinesterase inhibitors (AChEIs). Yinhuang oral liquid is a Chinese medicine preparation which contains AChEIs according to the literatures. However, no strategy has been presented for rapid screening and identification of AChEIs from Yinhuang oral liquid. Objective: To develop a method for rapid screening and identification of AChEIs from Yinhuang oral liquid using ultrafiltration-liquid chromatography-electrospray ionization tandem mass spectrometry (UF-LC-ESI-MS/MS). Materials and Methods: In this study, UF incubation conditions such as enzyme concentration, incubation time, and incubation temperature were optimized so as to get better screening results. The AChEIs from Yinhuang oral liquid were identified by high-performance liquid chromatography-ESI-MS and the improved Ellman method was used for the AChE inhibitory activity test in vitro. Results: The results showed that Yinhuang oral liquid can inhibit the activity of AChE. We screened and identified seven compounds with potential AChE inhibitory activity from Yinhuang oral liquid, which provided experimental basis for the treatment and prevention of AD. Conclusion: The current technique was used to directly screen the active ingredients with acetylcholinesterase inhibition from complex traditional Chinese medicine, which was simple, rapid, accurate, and suitable for high-throughput screening of AChEI from complex systems. SUMMARY: A UF-LC-ESI-MS/MS method for rapid screening and identification of AChEIs from Yinhuang oral liquid was developedSeven compounds were screened and identified with potential AChE inhibitory activity from Yinhuang oral liquidIt provided experimental basis of Yinhuang oral liquid for the treating and preventing AD. Abbreviations used: (AD): Alzheimer's disease; (UF-LC-ESI-MS/MS): ultrafiltration-liquid chromatography-electrospray ionization tandem mass spectrometry; (AChEIs): acetylcholinesterase inhibitors. Title: Synthesis, pharmacology and molecular docking on multifunctional tacrine-ferulic acid hybrids as cholinesterase inhibitors against Alzheimer's disease Zhu J, Yang H, Chen Y, Lin H, Li Q, Mo J, Bian Y, Pei Y, Sun H Ref: J Enzyme Inhib Med Chem, 33:496, 2018 : PubMed ESTHER: Zhu_2018_J.Enzyme.Inhib.Med.Chem_33_496 PubMedSearch: Zhu 2018 J.Enzyme.Inhib.Med.Chem 33 496 PubMedID: 29405075 Abstract The cholinergic hypothesis has long been a "polar star" in drug discovery for Alzheimer's disease (AD), resulting in many small molecules and biological drug candidates. Most of the drugs marketed for AD are cholinergic. Herein, we report our efforts in the discovery of cholinesterases inhibitors (ChEIs) as multi-target-directed ligands. A series of tacrine-ferulic acid hybrids have been designed and synthesised. All these compounds showed potent acetyl-(AChE) and butyryl cholinesterase(BuChE) inhibition. Among them, the optimal compound 10g, was the most potent inhibitor against AChE (electrophorus electricus (eeAChE) half maximal inhibitory concentration (IC50) = 37.02 nM), it was also a strong inhibitor against BuChE (equine serum (eqBuChE) IC50 = 101.40 nM). Besides, it inhibited amyloid beta-protein self-aggregation by 65.49% at 25 muM. In subsequent in vivo scopolamine-induced AD models, compound 10g obviously ameliorated the cognition impairment and showed preliminary safety in hepatotoxicity evaluation. These data suggest compound 10g as a promising multifunctional agent in the drug discovery process against AD. Title: Non-neuronal cholinergic activity is potentiated in myasthenia gravis Han B, Zhang C, Liu S, Xia Y, Sun H, Gong Z, Simard AR, Liu Q, Hao J Ref: BMC Neurol, 17:28, 2017 : PubMed ESTHER: Han_2017_BMC.Neurol_17_28 PubMedSearch: Han 2017 BMC.Neurol 17 28 PubMedID: 28178923 Abstract BACKGROUND: Non-neuronal acetylcholine (ACh) restricts autoimmune responses and attenuates inflammation by cholinergic anti-inflammation pathway. To date, the implication of ACh in myasthenia gravis (MG) remained unexplored. This study aimed to investigate the possible relationship between ACh levels, anti-muscle-specific tyrosine kinase (MuSK) antibody titers, main clinical features and outcomes of MG patients. METHODS: We successfully measured ACh levels in human peripheral blood mononuclear cells (PBMCs) from 125 MG patients and 50 matched healthy controls by using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). We assessed the quantitative MG (QMG) scores for each patient and titered anti-MuSK antibody. RESULTS: We found that PBMC-derived ACh level was significantly higher in MG patients, especially in patients of class III, IV-V, compared with that in controls (0.142 +/- 0.108 vs. 0.075 +/- 0.014 ng/million cells, p = 0.0003) according to the Myasthenia Gravis Foundation of America clinical classification. Importantly, we also found that ACh levels were positively correlated with QMG scores (r = 0.83, p < 0.0001) and anti-MuSK Ab levels (r = 0.85, p < 0.0001). CONCLUSIONS: Our demonstration of elevated ACh levels in PBMCs of MG patients foreshadows potential new avenues for MG research and treatment. Title: Recent progress in the identification of selective butyrylcholinesterase inhibitors for Alzheimer's disease Li Q, Yang H, Chen Y, Sun H Ref: Eur Journal of Medicinal Chemistry, 132:294, 2017 : PubMed ESTHER: Li_2017_Eur.J.Med.Chem_132_294 PubMedSearch: Li 2017 Eur.J.Med.Chem 132 294 PubMedID: 28371641 Inhibitor(s) related to this paper: CHEMBL4079247 Abstract Alzheimer's disease (AD) is one of the most prevalent neurodegenerative disorders with notable factor of dysfunction in cholinergic system. Low ACh level can be observed in the pathogenesis of AD. Several AChE inhibitors have already been used for clinical treatments. However, other than normal conditions, ACh is mostly hydrolyzed by BuChE in progressed AD. Account for an increased level of BuChE and decreased level of AChE in the late stage of AD, development of selective BuChE inhibitor is of vital importance. Up till now, compounds with various scaffolds have been discovered to selectively inhibit BuChE. Different effective anti-BuChE molecules are concluded in this review. Title: Therapeutic Agents in Alzheimer's Disease Through a Multi-targetdirected Ligands Strategy: Recent Progress Based on Tacrine Core Lin H, Li Q, Gu K, Zhu J, Jiang X, Chen Y, Sun H Ref: Curr Top Med Chem, 17:3000, 2017 : PubMed ESTHER: Lin_2017_Curr.Top.Med.Chem_17_3000 PubMedSearch: Lin 2017 Curr.Top.Med.Chem 17 3000 PubMedID: 28714419 Abstract Alzheimer's Disease (AD) is one of the most common forms of dementia in elderly people. To date, efficacious therapeutic agent for the treatment of AD is still very limited, so it has long been a challenging and attractive task to discover new anti-AD drugs. Considering the multifactorial nature of AD, recently, the concept of Multi-Target-Directed Ligands (MTDLs) has emerged as a new strategy for designing therapeutic agents on AD. MTDLs are believed to exert their effects through simultaneously affecting multiple targets which contribute to etiology of AD. Therefore, MTDLs are considered to be more efficacious than mono-target agents. Tacrine is the first drug approved by Food and Drug Administration (FDA). Although the clinical use of tacrine is restricted because of its hepatotoxicity, the high Ligand Efficiency (LE) of this compound makes it an ideal component for designing MTDLs. This article provides an update review of the advances on the development of MTDLs based on tacrine. Case studies are carefully selected to show the detailed strategy on medicinal modification of Tacrine-Based MTDLs. Finally, several concerns and opinions on designing new MTDLs are discussed as well. Title: Karyotype Stability and Unbiased Fractionation in the Paleo-Allotetraploid Cucurbita Genomes Sun H, Wu S, Zhang G, Jiao C, Guo S, Ren Y, Zhang J, Zhang H, Gong G and Xu Y <7 more author(s)> Sun H, Wu S, Zhang G, Jiao C, Guo S, Ren Y, Zhang J, Zhang H, Gong G, Jia Z, Zhang F, Tian J, Lucas WJ, Doyle JJ, Li H, Fei Z, Xu Y (- 7) Ref: Mol Plant, 10:1293, 2017 : PubMed ESTHER: Sun_2017_Mol.Plant_10_1293 PubMedSearch: Sun 2017 Mol.Plant 10 1293 PubMedID: 28917590 Gene_locus related to this paper: cucma-a0a6j1jlb1, cucma-a0a6j1i8e2 Abstract The Cucurbita genus contains several economically important species in the Cucurbitaceae family. Here, we report high-quality genome sequences of C. maxima and C. moschata and provide evidence supporting an allotetraploidization event in Cucurbita. We are able to partition the genome into two homoeologous subgenomes based on different genetic distances to melon, cucumber, and watermelon in the Benincaseae tribe. We estimate that the two diploid progenitors successively diverged from Benincaseae around 31 and 26 million years ago (Mya), respectively, and the allotetraploidization happened at some point between 26 Mya and 3 Mya, the estimated date when C. maxima and C. moschata diverged. The subgenomes have largely maintained the chromosome structures of their diploid progenitors. Such long-term karyotype stability after polyploidization has not been commonly observed in plant polyploids. The two subgenomes have retained similar numbers of genes, and neither subgenome is globally dominant in gene expression. Allele-specific expression analysis in the C. maxima x C. moschata interspecific F(1) hybrid and their two parents indicates the predominance of trans-regulatory effects underlying expression divergence of the parents, and detects transgressive gene expression changes in the hybrid correlated with heterosis in important agronomic traits. Our study provides insights into polyploid genome evolution and valuable resources for genetic improvement of cucurbit crops. Title: Comparative genomics reveals high biological diversity and specific adaptations in the industrially and medically important fungal genus Aspergillus de Vries RP, Riley R, Wiebenga A, Aguilar-Osorio G, Amillis S, Uchima CA, Anderluh G, Asadollahi M, Askin M and Grigoriev IV <107 more author(s)> de Vries RP, Riley R, Wiebenga A, Aguilar-Osorio G, Amillis S, Uchima CA, Anderluh G, Asadollahi M, Askin M, Barry K, Battaglia E, Bayram O, Benocci T, Braus-Stromeyer SA, Caldana C, Canovas D, Cerqueira GC, Chen F, Chen W, Choi C, Clum A, Dos Santos RA, Damasio AR, Diallinas G, Emri T, Fekete E, Flipphi M, Freyberg S, Gallo A, Gournas C, Habgood R, Hainaut M, Harispe ML, Henrissat B, Hilden KS, Hope R, Hossain A, Karabika E, Karaffa L, Karanyi Z, Krasevec N, Kuo A, Kusch H, LaButti K, Lagendijk EL, Lapidus A, Levasseur A, Lindquist E, Lipzen A, Logrieco AF, Maccabe A, Makela MR, Malavazi I, Melin P, Meyer V, Mielnichuk N, Miskei M, Molnar AP, Mule G, Ngan CY, Orejas M, Orosz E, Ouedraogo JP, Overkamp KM, Park HS, Perrone G, Piumi F, Punt PJ, Ram AF, Ramon A, Rauscher S, Record E, Riano-Pachon DM, Robert V, Rohrig J, Ruller R, Salamov A, Salih NS, Samson RA, Sandor E, Sanguinetti M, Schutze T, Sepcic K, Shelest E, Sherlock G, Sophianopoulou V, Squina FM, Sun H, Susca A, Todd RB, Tsang A, Unkles SE, van de Wiele N, van Rossen-Uffink D, Oliveira JV, Vesth TC, Visser J, Yu JH, Zhou M, Andersen MR, Archer DB, Baker SE, Benoit I, Brakhage AA, Braus GH, Fischer R, Frisvad JC, Goldman GH, Houbraken J, Oakley B, Pocsi I, Scazzocchio C, Seiboth B, vanKuyk PA, Wortman J, Dyer PS, Grigoriev IV (- 107) Ref: Genome Biol, 18:28, 2017 : PubMed ESTHER: de Vries_2017_Genome.Biol_18_28 PubMedSearch: de Vries 2017 Genome.Biol 18 28 PubMedID: 28196534 Gene_locus related to this paper: asptu-a0a1l9nhd0, aspve-a0a1l9pxx8, aspve-a0a1l9q4m3, aspwe-a0a1l9s133, 9euro-a0a1l9t3v9, aspwe-a0a1l9rcx6, aspna-g3y5a6, aspgl-a0a1l9v4d3, 9euro-a0a1l9sa36, aspsb-a0a319eji6, aspve-a0a1l9px96, 9euro-a0a1l9tay1, aspgl-a0a1l9vbc0, aspc5-a0a1r3rh65, 9euro-a0a2v5i956, aspwe-a0a1l9rpp6, aspna-g3xpw9, aspve-a0a1l9plv1, 9euro-a0a1l9tk47, aspve-a0a1l9pde9, aspve-a0a1l9pz72, aspwe-a0a1l9rde6, 9euro-a0a1l9tdb5, aspkw-g7xq95, aspbc-a0a1l9u6h4, aspbc-a0a1l9u2l4, asptc-a0a1l9mx83, aspgl-a0a1l9ve90, aspve-a0a1l9pvz9, 9euro-a0a1l9tdh3, aspc5-a0a1r3rmn9, aspwe-a0a1l9rlq2, asptc-a0a1l9nby7, aspng-a0a100i8t9, aspc5-a0a1r3rem6, aspbc-a0a1l9uy89, aspa1-anee, aspa1-aneh, aspa1-acrc, aspbc-alba, aspa1-acui Abstract BACKGROUND: The fungal genus Aspergillus is of critical importance to humankind. Species include those with industrial applications, important pathogens of humans, animals and crops, a source of potent carcinogenic contaminants of food, and an important genetic model. The genome sequences of eight aspergilli have already been explored to investigate aspects of fungal biology, raising questions about evolution and specialization within this genus. RESULTS: We have generated genome sequences for ten novel, highly diverse Aspergillus species and compared these in detail to sister and more distant genera. Comparative studies of key aspects of fungal biology, including primary and secondary metabolism, stress response, biomass degradation, and signal transduction, revealed both conservation and diversity among the species. Observed genomic differences were validated with experimental studies. This revealed several highlights, such as the potential for sex in asexual species, organic acid production genes being a key feature of black aspergilli, alternative approaches for degrading plant biomass, and indications for the genetic basis of stress response. A genome-wide phylogenetic analysis demonstrated in detail the relationship of the newly genome sequenced species with other aspergilli. CONCLUSIONS: Many aspects of biological differences between fungal species cannot be explained by current knowledge obtained from genome sequences. The comparative genomics and experimental study, presented here, allows for the first time a genus-wide view of the biological diversity of the aspergilli and in many, but not all, cases linked genome differences to phenotype. Insights gained could be exploited for biotechnological and medical applications of fungi. Title: Identification of 4-aminoquinoline core for the design of new cholinesterase inhibitors Chen Y, Bian Y, Sun Y, Kang C, Yu S, Fu T, Li W, Pei Y, Sun H Ref: PeerJ, 4:e2140, 2016 : PubMed ESTHER: Chen_2016_PeerJ_4_e2140 PubMedSearch: Chen 2016 PeerJ 4 e2140 PubMedID: 27441112 Abstract Inhibition of acetylcholinesterase (AChE) using small molecules is still one of the most successful therapeutic strategies in the treatment of Alzheimer's disease (AD). Previously we reported compound T5369186 with a core of quinolone as a new cholinesterase inhibitor. In the present study, in order to identify new cores for the designing of AChE inhibitors, we screened different derivatives of this core with the aim to identify the best core as the starting point for further optimization. Based on the results, we confirmed that only 4-aminoquinoline (compound 04 and 07) had cholinesterase inhibitory effects. Considering the simple structure and high inhibitory potency against AChE, 4-aminoquinoline provides a good starting core for further designing novel multifunctional AChEIs. Title: Comparative Genomics of Early-Diverging Mushroom-Forming Fungi Provides Insights into the Origins of Lignocellulose Decay Capabilities Nagy LG, Riley R, Tritt A, Adam C, Daum C, Floudas D, Sun H, Yadav JS, Pangilinan J and Hibbett DS <11 more author(s)> Nagy LG, Riley R, Tritt A, Adam C, Daum C, Floudas D, Sun H, Yadav JS, Pangilinan J, Larsson KH, Matsuura K, Barry K, LaButti K, Kuo R, Ohm RA, Bhattacharya SS, Shirouzu T, Yoshinaga Y, Martin FM, Grigoriev IV, Hibbett DS (- 11) Ref: Molecular Biology Evolution, 33:959, 2016 : PubMed ESTHER: Nagy_2016_Mol.Biol.Evol_33_959 PubMedSearch: Nagy 2016 Mol.Biol.Evol 33 959 PubMedID: 26659563 Gene_locus related to this paper: 9homo-a0a164swv2, 9homo-a0a164tl22, 9homo-a0a164vkv1, 9homo-a0a164y4j9, 9homo-a0a164y4l9, 9homo-a0a164ytj2, 9homo-a0a164zeu0, exigl-a0a165as65, exigl-a0a165ck85, 9basi-a0a165cm83, 9aphy-a0a165dbf1, 9aphy-a0a165dbf3, 9basi-a0a165dcb7, 9aphy-a0a165ddj9, exigl-a0a165dj22, exigl-a0a165dmd7, 9aphy-a0a165egr5, 9basi-a0a165ekd3, 9basi-a0a165enc9, 9basi-a0a165end6, 9basi-a0a165epz3, 9basi-a0a165eq46, 9basi-a0a165eq95, 9basi-a0a165eqk7, 9basi-a0a165eup2, 9aphy-a0a165fb02, 9aphy-a0a165fmr9, 9aphy-a0a165g3p1, 9basi-a0a165g673, 9basi-a0a165g6g2, 9aphy-a0a165gec2, 9basi-a0a165gfp7, 9aphy-a0a165h505, 9aphy-a0a165hd72, 9aphy-a0a165hrk1, exigl-a0a165hzc8, 9basi-a0a165i2y7, 9basi-a0a165iru3, 9basi-a0a165is19, 9basi-a0a165is40, exigl-a0a165j2r4, exigl-a0a165j754, 9basi-a0a165jg92, 9basi-a0a165jgb0, exigl-a0a165ke04, exigl-a0a165kpb0, exigl-a0a165l7g6, 9aphy-a0a165lux8, 9aphy-a0a165luy2.1, 9aphy-a0a165luy2.2, exigl-a0a165m310, 9aphy-a0a165mxa5, 9aphy-a0a165mxc8, 9aphy-a0a165mxe4, exigl-a0a165mz73, 9homo-a0a165nfz4, 9homo-a0a165ng04, 9aphy-a0a165nry3, 9homo-a0a165ntf3, 9homo-a0a165p2a0, 9aphy-a0a165ph74, 9homo-a0a165phz5, exigl-a0a165pm12, exigl-a0a165pu90, exigl-a0a165puh2, 9aphy-a0a165q9t4, 9homo-a0a165qeb7, 9homo-a0a165qeh8, 9aphy-a0a165qqm2, 9aphy-a0a165quj0, 9aphy-a0a165qul3, exigl-a0a165qxy0, 9aphy-a0a165r6t2, 9aphy-a0a165r8g4, 9aphy-a0a165tfc7, 9homo-a0a165tgm2, 9homo-a0a165tzv4, 9homo-a0a165tzw4, 9homo-a0a165uez3, 9homo-a0a165ugh4, 9homo-a0a165ugp4, 9homo-a0a165ugq6, 9homo-a0a165uh51, 9aphy-a0a165umj9, 9homo-a0a165us14, 9homo-a0a165xi11, 9homo-a0a165xmw5, 9homo-a0a165xmx9, 9homo-a0a165xsk7, 9homo-a0a165y3k8, 9homo-a0a165yhg3, 9homo-a0a165ymb3, 9homo-a0a165yt77, 9homo-a0a165ytu4, 9homo-a0a165zr30, 9homo-a0a166a1g9, 9homo-a0a166a1h1, exigl-a0a166abe4, 9homo-a0a166akq6, exigl-a0a166al33, 9homo-a0a166arm1, 9homo-a0a166as45, 9homo-a0a166as65, 9homo-a0a166as77, exigl-a0a166auh4, 9homo-a0a166azk8, exigl-a0a166azz6, 9homo-a0a166bss2, 9homo-a0a166bsu9, 9homo-a0a166bui6, 9homo-a0a166crl5, 9homo-a0a166d8q4, 9homo-a0a166dss7, 9homo-a0a166dtg8, 9homo-a0a166du49, 9homo-a0a166du64, 9homo-a0a166e1z2, 9homo-a0a166eec5, 9homo-a0a166eux5, 9homo-a0a166evw5, 9homo-a0a166ey75, 9homo-a0a166eyq0, 9homo-a0a166ez78, 9homo-a0a166eze7, 9homo-a0a166fh25, 9homo-a0a166g4k8, 9homo-a0a166gct1, 9homo-a0a166gf56, 9homo-a0a166gsr8, 9homo-a0a166j6i1, 9homo-a0a166jiu0, 9homo-a0a166jr36, 9homo-a0a166kia8, 9homo-a0a166ks21, 9homo-a0a166kvn8, 9homo-a0a166kxf0, 9homo-a0a166kxg2, 9homo-a0a166lcs7, 9homo-a0a166lw48, 9homo-a0a166lyz4, 9homo-a0a166puu7.1, 9homo-a0a166puu7.2, 9homo-a0a166puz0, 9homo-a0a166pv75, 9homo-a0a166pva0, 9homo-a0a166pvf7, 9homo-a0a166px11, 9homo-a0a166q635, 9basi-a0a167gl88, 9basi-a0a167gl97, 9basi-a0a167gla5, 9basi-a0a167hca0, 9basi-a0a167hrt3, 9basi-a0a167hru7, 9basi-a0a167k219, 9basi-a0a167k232, 9basi-a0a167k265, 9basi-a0a167l6m6, 9basi-a0a167lrl7, 9basi-a0a167lt70, 9basi-a0a167mtk7, 9basi-a0a167n1z0, 9basi-a0a167p9x5, 9basi-a0a167qks1, 9basi-a0a167qkt4, 9basi-a0a167qky5, 9basi-a0a167qln8, 9basi-a0a167rpp7, 9homo-a0a167u8e3, 9homo-a0a167v1m8, 9homo-a0a166hqx0, 9homo-a0a166l842, exigl-a0a165n4f2, exigl-a0a165q512, 9agam-a0a165nq75, 9agam-a0a166cv75, 9agam-a0a165mvt4, 9agam-a0a164t8q2, 9agam-a0a166flp0 Abstract Evolution of lignocellulose decomposition was one of the most ecologically important innovations in fungi. White-rot fungi in the Agaricomycetes (mushrooms and relatives) are the most effective microorganisms in degrading both cellulose and lignin components of woody plant cell walls (PCW). However, the precise evolutionary origins of lignocellulose decomposition are poorly understood, largely because certain early-diverging clades of Agaricomycetes and its sister group, the Dacrymycetes, have yet to be sampled, or have been undersampled, in comparative genomic studies. Here, we present new genome sequences of ten saprotrophic fungi, including members of the Dacrymycetes and early-diverging clades of Agaricomycetes (Cantharellales, Sebacinales, Auriculariales, and Trechisporales), which we use to refine the origins and evolutionary history of the enzymatic toolkit of lignocellulose decomposition. We reconstructed the origin of ligninolytic enzymes, focusing on class II peroxidases (AA2), as well as enzymes that attack crystalline cellulose. Despite previous reports of white rot appearing as early as the Dacrymycetes, our results suggest that white-rot fungi evolved later in the Agaricomycetes, with the first class II peroxidases reconstructed in the ancestor of the Auriculariales and residual Agaricomycetes. The exemplars of the most ancient clades of Agaricomycetes that we sampled all lack class II peroxidases, and are thus concluded to use a combination of plesiomorphic and derived PCW degrading enzymes that predate the evolution of white rot. Title: Comparative genomics of biotechnologically important yeasts Riley R, Haridas S, Wolfe KH, Lopes MR, Hittinger CT, Goker M, Salamov AA, Wisecaver JH, Long TM and Jeffries TW <29 more author(s)> Riley R, Haridas S, Wolfe KH, Lopes MR, Hittinger CT, Goker M, Salamov AA, Wisecaver JH, Long TM, Calvey CH, Aerts AL, Barry KW, Choi C, Clum A, Coughlan AY, Deshpande S, Douglass AP, Hanson SJ, Klenk HP, LaButti KM, Lapidus A, Lindquist EA, Lipzen AM, Meier-Kolthoff JP, Ohm RA, Otillar RP, Pangilinan JL, Peng Y, Rokas A, Rosa CA, Scheuner C, Sibirny AA, Slot JC, Stielow JB, Sun H, Kurtzman CP, Blackwell M, Grigoriev IV, Jeffries TW (- 29) Ref: Proc Natl Acad Sci U S A, 113:9882, 2016 : PubMed ESTHER: Riley_2016_Proc.Natl.Acad.Sci.U.S.A_113_9882 PubMedSearch: Riley 2016 Proc.Natl.Acad.Sci.U.S.A 113 9882 PubMedID: 27535936 Gene_locus related to this paper: wicaa-a0a1e3nx95, cybjn-a0a1e4s739, 9asco-a0a1q2yku6, ogapd-w1qjr8, 9asco-a0a1e3pdp5, lipst-a0a1e3qdq0, 9asco-a0a1e4tg55 Abstract Ascomycete yeasts are metabolically diverse, with great potential for biotechnology. Here, we report the comparative genome analysis of 29 taxonomically and biotechnologically important yeasts, including 16 newly sequenced. We identify a genetic code change, CUG-Ala, in Pachysolen tannophilus in the clade sister to the known CUG-Ser clade. Our well-resolved yeast phylogeny shows that some traits, such as methylotrophy, are restricted to single clades, whereas others, such as l-rhamnose utilization, have patchy phylogenetic distributions. Gene clusters, with variable organization and distribution, encode many pathways of interest. Genomics can predict some biochemical traits precisely, but the genomic basis of others, such as xylose utilization, remains unresolved. Our data also provide insight into early evolution of ascomycetes. We document the loss of H3K9me2/3 heterochromatin, the origin of ascomycete mating-type switching, and panascomycete synteny at the MAT locus. These data and analyses will facilitate the engineering of efficient biosynthetic and degradative pathways and gateways for genomic manipulation. Title: Strigolactones are required for nitric oxide to induce root elongation in response to nitrogen and phosphate deficiencies in rice Sun H, Bi Y, Tao J, Huang S, Hou M, Xue R, Liang Z, Gu P, Yoneyama K and Zhang Y <3 more author(s)> Sun H, Bi Y, Tao J, Huang S, Hou M, Xue R, Liang Z, Gu P, Yoneyama K, Xie X, Shen Q, Xu G, Zhang Y (- 3) Ref: Plant Cell Environ, 39:1473, 2016 : PubMed ESTHER: Sun_2016_Plant.Cell.Environ_39_1473 PubMedSearch: Sun 2016 Plant.Cell.Environ 39 1473 PubMedID: 27194103 Abstract The response of the root system architecture to nutrient deficiencies is critical for sustainable agriculture. Nitric oxide (NO) is considered a key regulator of root growth, although the mechanisms remain unknown. Phenotypic, cellular and genetic analyses were undertaken in rice to explore the role of NO in regulating root growth and strigolactone (SL) signalling under nitrogen-deficient and phosphate-deficient conditions (LN and LP). LN-induced and LP-induced seminal root elongation paralleled NO production in root tips. NO played an important role in a shared pathway of LN-induced and LP-induced root elongation via increased meristem activity. Interestingly, no responses of root elongation were observed in SL d mutants compared with wild-type plants, although similar NO accumulation was induced by sodium nitroprusside (SNP) application. Application of abamine (the SL inhibitor) reduced seminal root length and pCYCB1;1::GUS expression induced by SNP application in wild type; furthermore, comparison with wild type showed lower SL-signalling genes in nia2 mutants under control and LN treatments and similar under SNP application. Western blot analysis revealed that NO, similar to SL, triggered proteasome-mediated degradation of D53 protein levels. Therefore, we presented a novel signalling pathway in which NO-activated seminal root elongation under LN and LP conditions, with the involvement of SLs. Title: The Association Between Epoxide Hydrolase Genetic Variant and Effectiveness of Nicotine Replacement Therapy in a Han Chinese Population Wang F, Liu Y, Guo S, Chen D, Sun H Ref: Neurosci Bull, 32:545, 2016 : PubMed ESTHER: Wang_2016_Neurosci.Bull_32_545 PubMedSearch: Wang 2016 Neurosci.Bull 32 545 PubMedID: 27783326 Title: Evolution of novel wood decay mechanisms in Agaricales revealed by the genome sequences of Fistulina hepatica and Cylindrobasidium torrendii Floudas D, Held BW, Riley R, Nagy LG, Koehler G, Ransdell AS, Younus H, Chow J, Chiniquy J and Hibbett DS <10 more author(s)> Floudas D, Held BW, Riley R, Nagy LG, Koehler G, Ransdell AS, Younus H, Chow J, Chiniquy J, Lipzen A, Tritt A, Sun H, Haridas S, LaButti K, Ohm RA, Kues U, Blanchette RA, Grigoriev IV, Minto RE, Hibbett DS (- 10) Ref: Fungal Genet Biol, 76:78, 2015 : PubMed ESTHER: Floudas_2015_Fungal.Genet.Biol_76_78 PubMedSearch: Floudas 2015 Fungal.Genet.Biol 76 78 PubMedID: 25683379 Gene_locus related to this paper: 9agar-a0a0d6zyq5, 9agar-a0a0d7a2p9, 9agar-a0a0d7a2v2, 9agar-a0a0d7abt2, 9agar-a0a0d7acd3, 9agar-a0a0d7acx0, 9agar-a0a0d7acx9, 9agar-a0a0d7adg2, 9agar-a0a0d7a6d0, 9agar-a0a0d7aen7, 9agar-a0a0d7aez7, 9agar-a0a0d7ahq5, 9agar-a0a0d7akr6, 9agar-a0a0d7al29, 9agar-a0a0d7an16, 9agar-a0a0d7ann7, 9agar-a0a0d7anv1, 9homo-a0a0d7atv2, 9homo-a0a0d7ay28, 9homo-a0a0d7ayz7, 9homo-a0a0d7b1w8, 9homo-a0a0d7b2p0, 9homo-a0a0d7b4n4, 9homo-a0a0d7b624, 9homo-a0a0d7b7r3, 9homo-a0a0d7b7w3, 9homo-a0a0d7bac5, 9homo-a0a0d7bav7, 9homo-a0a0d7bbx7, 9homo-a0a0d7bdn7, 9homo-a0a0d7bgj9, 9homo-a0a0d7biw2, 9homo-a0a0d7bqi1, 9homo-a0a0d7bv80, 9agar-a0a0d7b6f6, 9agar-a0a0d7b976, 9agar-a0a0d7aeu9, 9agar-a0a0d7ag53, 9agar-a0a0d7b8a5 Abstract Wood decay mechanisms in Agaricomycotina have been traditionally separated in two categories termed white and brown rot. Recently the accuracy of such a dichotomy has been questioned. Here, we present the genome sequences of the white-rot fungus Cylindrobasidium torrendii and the brown-rot fungus Fistulina hepatica both members of Agaricales, combining comparative genomics and wood decay experiments. C. torrendii is closely related to the white-rot root pathogen Armillaria mellea, while F. hepatica is related to Schizophyllum commune, which has been reported to cause white rot. Our results suggest that C. torrendii and S. commune are intermediate between white-rot and brown-rot fungi, but at the same time they show characteristics of decay that resembles soft rot. Both species cause weak wood decay and degrade all wood components but leave the middle lamella intact. Their gene content related to lignin degradation is reduced, similar to brown-rot fungi, but both have maintained a rich array of genes related to carbohydrate degradation, similar to white-rot fungi. These characteristics appear to have evolved from white-rot ancestors with stronger ligninolytic ability. F. hepatica shows characteristics of brown rot both in terms of wood decay genes found in its genome and the decay that it causes. However, genes related to cellulose degradation are still present, which is a plesiomorphic characteristic shared with its white-rot ancestors. Four wood degradation-related genes, homologs of which are frequently lost in brown-rot fungi, show signs of pseudogenization in the genome of F. hepatica. These results suggest that transition toward a brown-rot lifestyle could be an ongoing process in F. hepatica. Our results reinforce the idea that wood decay mechanisms are more diverse than initially thought and that the dichotomous separation of wood decay mechanisms in Agaricomycotina into white rot and brown rot should be revisited. Title: Synthesis and potent inhibitory activities of carboxybenzyl-substituted 8-(3-(R)-aminopiperidin-1-yl)-7-(2-chloro/cyanobenzyl)-3-methyl-3,7-dihydro-purin e-2,6-diones as dipeptidyl peptidase IV (DPP-IV) inhibitors Mo DW, Dong S, Sun H, Chen JS, Pang JX, Xi BM, Chen WH Ref: Bioorganic & Medicinal Chemistry Lett, 25:1872, 2015 : PubMed ESTHER: Mo_2015_Bioorg.Med.Chem.Lett_25_1872 PubMedSearch: Mo 2015 Bioorg.Med.Chem.Lett 25 1872 PubMedID: 25838146 Abstract Fourteen 3-methyl-3,7-dihydro-purine-2,6-dione derivatives 1-14 bearing carboxybenzyl and 2-chloro/cyanobenzyl groups at the N-1 and N-7 positions, respectively, were synthesized as dipeptidyl peptidase IV (DPP-IV) inhibitors. These compounds were characterized on the basis of NMR ((1)H and (13)C) and ESI MS data. In vitro bioassay indicates that most of these compounds showed moderate to good inhibitory activities against DPP-IV. Among them, compound 13 (IC50=36nM) exhibited comparable activity with a positive control, Sitagliptin (IC50=16nM). In addition, the structure-activity relationship of these compounds is also briefly discussed. Title: Efficient kinetic resolution of phenyl glycidyl ether by a novel epoxide hydrolase from Tsukamurella paurometabola Wu K, Wang H, Sun H, Wei D Ref: Applied Microbiology & Biotechnology, 99:9511, 2015 : PubMed ESTHER: Wu_2015_Appl.Microbiol.Biotechnol_99_9511 PubMedSearch: Wu 2015 Appl.Microbiol.Biotechnol 99 9511 PubMedID: 26088175 Gene_locus related to this paper: tsupd-d5us69 Abstract Enantioselective hydrolysis of racemic epoxides mediated by epoxide hydrolases (EHs) is one of the most promising approaches to obtain enantiopure epoxides. In this study, we identified and characterized a novel EH (TpEH1) from Tsukamurella paurometabola by analyzing the conserved catalytic residues of EH. TpEH1 was overexpressed and purified, and its catalytic properties were studied using racemic phenyl glycidyl ether (PGE) and its derivatives as substrates. TpEH1 showed excellent enantioselectivity to the substrates PGE, 3-methylPGE, and 3-nitroPGE. The highest enantioselectivity (E > 100) was achieved when 3-nitroPGE was used as the substrate. The recombinant Escherichia coli TpEH1 demonstrated high substrate tolerance toward PGE and could hydrolyze PGE at concentrations of up to 400 mM (60 g/L) with high enantioselectivity (E = 65), giving (R)-PGE with enantiomeric excess of more than 99 % ee and 45 % yield within 1 h. This concentration of PGE is the highest reported concentration catalyzed by native EHs to date. Thus, the easily available and highly active E. coli TpEH1 showed great potential for the practical preparation of optically pure (R)-PGE. Title: Genome sequencing of four Aureobasidium pullulans varieties: biotechnological potential, stress tolerance, and description of new species Gostincar C, Ohm RA, Kogej T, Sonjak S, Turk M, Zajc J, Zalar P, Grube M, Sun H and Gunde-Cimerman N <7 more author(s)> Gostincar C, Ohm RA, Kogej T, Sonjak S, Turk M, Zajc J, Zalar P, Grube M, Sun H, Han J, Sharma A, Chiniquy J, Ngan CY, Lipzen A, Barry K, Grigoriev IV, Gunde-Cimerman N (- 7) Ref: BMC Genomics, 15:549, 2014 : PubMed ESTHER: Gostincar_2014_BMC.Genomics_15_549 PubMedSearch: Gostincar 2014 BMC.Genomics 15 549 PubMedID: 24984952 Gene_locus related to this paper: aurpu-a0a1a7mdx5, 9pezi-a0a074w0m0, 9pezi-a0a074wgq7, aurpu-a0a074xfg8, 9pezi-a0a074y586, 9pezi-a0a074yqf6, 9pezi-a0a074w5k8, aurpu-a0a074x6a3, 9pezi-a0a074z3s4, 9pezi-a0a074x4q0, 9pezi-a0a074w2e2, 9pezi-a0a074x294, aurpu-a0a074y1y2, aurpu-a0a074x9w9, 9pezi-a0a074ydw7, 9pezi-a0a074w1z9, 9pezi-a0a074wvx0, 9pezi-a0a074vkc4, 9pezi-a0a074y2z2, 9pezi-a0a074vlb9, aurpu-a0a074x490, 9pezi-a0a074ydn0, 9pezi-a0a074wng0, 9pezi-a0a074yhi1, 9pezi-a0a074yp94, 9pezi-a0a074wbe1, 9pezi-a0a074wm90, 9pezi-a0a074ww95, aurpu-a0a074xg41, aurpu-a0a074xtu4, 9pezi-a0a074y8g8, aurpu-a0a074ysb8, 9pezi-a0a074zem7, 9pezi-a0a074yvw8, 9pezi-a0a074w278, aurpu-a0a074xxz9, 9pezi-a0a074y9f0, aurpu-a0a074xzv0, 9pezi-a0a074wce5, 9pezi-a0a074wmz5, 9pezi-a0a074vr83, 9pezi-a0a074w4l5, 9pezi-a0a074wwv4, 9pezi-a0a074w5f4, aurpu-a0a074xir3, aurpu-a0a074xnm6, 9pezi-a0a074zhr2, 9pezi-a0a074vzq8, 9pezi-a0a074web5, aurpu-a0a074xz32, 9pezi-a0a074ybl0, aurpu-a0a074xl81, 9pezi-a0a074vaq7, 9pezi-a0a074wuj9, aurpu-a0a074xyu0, 9pezi-a0a074vfi8, 9pezi-a0a074wih8, aurpu-a0a074xj03, 9pezi-a0a074vze0, 9pezi-a0a074w5u8, 9pezi-a0a074wui5, 9pezi-a0a074xhu0, aurpu-a0a074xyg1, 9pezi-a0a074yct6, 9pezi-a0a074zd60, 9pezi-a0a074w686, aurpu-a0a074xr93, 9pezi-a0a074y1r2, 9pezi-a0a074z801, 9pezi-a0a074y6a8, 9pezi-a0a074vg30, aurpu-a0a074wzm8, 9pezi-a0a074y7g9, 9pezi-a0a074vwd1, 9pezi-a0a074whl7, aurpu-a0a074x6c3, 9pezi-a0a074yak1, aurpu-a0a074x5y4, 9pezi-a0a074yaq1, aurpu-a0a074xm87, 9pezi-a0a074wgg7, 9pezi-a0a074vky7, aurpu-a0a074xpr5, 9pezi-a0a074zrg4, 9pezi-a0a074w1f9, aurpu-a0a074xft8, 9pezi-a0a074y5i5, aurpu-a0a074xla0, 9pezi-a0a074w5n7, 9pezi-a0a074wey0, aurpu-a0a074y3b0, 9pezi-a0a074vrn9, 9pezi-a0a074zgu9, aurpu-a0a074xlv7, 9pezi-a0a074wgb6, 9pezi-a0a074wgj7, 9pezi-a0a074vrg4, 9pezi-a0a074ya42, 9pezi-a0a074xnr8, aurpu-a0a074x443, 9pezi-a0a074yex2, 9pezi-a0a074xu89, aurpu-a0a074xxq7, 9pezi-a0a074vih4, aurse-a0a074ydf4, aurse-a0a074yt75, aurpu-a0a074y000 Abstract BACKGROUND: Aureobasidium pullulans is a black-yeast-like fungus used for production of the polysaccharide pullulan and the antimycotic aureobasidin A, and as a biocontrol agent in agriculture. It can cause opportunistic human infections, and it inhabits various extreme environments. To promote the understanding of these traits, we performed de-novo genome sequencing of the four varieties of A. pullulans. Title: Analysis of the Phlebiopsis gigantea genome, transcriptome and secretome provides insight into its pioneer colonization strategies of wood Hori C, Ishida T, Igarashi K, Samejima M, Suzuki H, Master E, Ferreira P, Ruiz-Duenas FJ, Held B and Cullen D <31 more author(s)> Hori C, Ishida T, Igarashi K, Samejima M, Suzuki H, Master E, Ferreira P, Ruiz-Duenas FJ, Held B, Canessa P, Larrondo LF, Schmoll M, Druzhinina IS, Kubicek CP, Gaskell JA, Kersten P, St John F, Glasner J, Sabat G, Splinter BonDurant S, Syed K, Yadav J, Mgbeahuruike AC, Kovalchuk A, Asiegbu FO, Lackner G, Hoffmeister D, Rencoret J, Gutierrez A, Sun H, Lindquist E, Barry K, Riley R, Grigoriev IV, Henrissat B, Kues U, Berka RM, Martinez AT, Covert SF, Blanchette RA, Cullen D (- 31) Ref: PLoS Genet, 10:e1004759, 2014 : PubMed ESTHER: Hori_2014_PLoS.Genet_10_E1004759 PubMedSearch: Hori 2014 PLoS.Genet 10 E1004759 PubMedID: 25474575 Gene_locus related to this paper: phlgi-a0a0c3nds0, phlgi-a0a0c3niq6, phlgi-a0a0c3pc91, phlgi-a0a0c3pv58, phlgi-a0a0c3rra0, phlgi-a0a0c3rvc4, phlgi-a0a0c3rvu0, phlgi-a0a0c3s394, phlgi-a0a0c3s606, phlgi-a0a0c3s673, phlgi-a0a0c3s8d3, phlgi-a0a0c3sce4, phlgi-a0a0c3sdt8 Abstract Collectively classified as white-rot fungi, certain basidiomycetes efficiently degrade the major structural polymers of wood cell walls. A small subset of these Agaricomycetes, exemplified by Phlebiopsis gigantea, is capable of colonizing freshly exposed conifer sapwood despite its high content of extractives, which retards the establishment of other fungal species. The mechanism(s) by which P. gigantea tolerates and metabolizes resinous compounds have not been explored. Here, we report the annotated P. gigantea genome and compare profiles of its transcriptome and secretome when cultured on fresh-cut versus solvent-extracted loblolly pine wood. The P. gigantea genome contains a conventional repertoire of hydrolase genes involved in cellulose/hemicellulose degradation, whose patterns of expression were relatively unperturbed by the absence of extractives. The expression of genes typically ascribed to lignin degradation was also largely unaffected. In contrast, genes likely involved in the transformation and detoxification of wood extractives were highly induced in its presence. Their products included an ABC transporter, lipases, cytochrome P450s, glutathione S-transferase and aldehyde dehydrogenase. Other regulated genes of unknown function and several constitutively expressed genes are also likely involved in P. gigantea's extractives metabolism. These results contribute to our fundamental understanding of pioneer colonization of conifer wood and provide insight into the diverse chemistries employed by fungi in carbon cycling processes. Title: Genomic adaptations of the halophilic Dead Sea filamentous fungus Eurotium rubrum Kis-Papo T, Weig AR, Riley R, Persoh D, Salamov A, Sun H, Lipzen A, Wasser SP, Rambold G and Nevo E <1 more author(s)> Kis-Papo T, Weig AR, Riley R, Persoh D, Salamov A, Sun H, Lipzen A, Wasser SP, Rambold G, Grigoriev IV, Nevo E (- 1) Ref: Nat Commun, 5:3745, 2014 : PubMed ESTHER: Kis-Papo_2014_Nat.Commun_5_3745 PubMedSearch: Kis-Papo 2014 Nat.Commun 5 3745 PubMedID: 24811710 Gene_locus related to this paper: 9euro-a0a017sa42, 9euro-a0a017s0c9, 9euro-a0a017s186, 9euro-a0a017s8c9, 9euro-a0a017s6r6 Abstract The Dead Sea is one of the most hypersaline habitats on Earth. The fungus Eurotium rubrum (Eurotiomycetes) is among the few species able to survive there. Here we highlight its adaptive strategies, based on genome analysis and transcriptome profiling. The 26.2 Mb genome of E. rubrum shows, for example, gains in gene families related to stress response and losses with regard to transport processes. Transcriptome analyses under different salt growth conditions revealed, among other things differentially expressed genes encoding ion and metabolite transporters. Our findings suggest that long-term adaptation to salinity requires cellular and metabolic responses that differ from short-term osmotic stress signalling. The transcriptional response indicates that halophilic E. rubrum actively counteracts the salinity stress. Many of its genes encode for proteins with a significantly higher proportion of acidic amino acid residues. This trait is characteristic of the halophilic prokaryotes as well, supporting the theory of convergent evolution under extreme hypersaline stress. Title: Extensive sampling of basidiomycete genomes demonstrates inadequacy of the white-rot/brown-rot paradigm for wood decay fungi Riley R, Salamov AA, Brown DW, Nagy LG, Floudas D, Held BW, Levasseur A, Lombard V, Morin E and Grigoriev IV <15 more author(s)> Riley R, Salamov AA, Brown DW, Nagy LG, Floudas D, Held BW, Levasseur A, Lombard V, Morin E, Otillar R, Lindquist EA, Sun H, LaButti KM, Schmutz J, Jabbour D, Luo H, Baker SE, Pisabarro AG, Walton JD, Blanchette RA, Henrissat B, Martin F, Cullen D, Hibbett DS, Grigoriev IV (- 15) Ref: Proc Natl Acad Sci U S A, 111:9923, 2014 : PubMed ESTHER: Riley_2014_Proc.Natl.Acad.Sci.U.S.A_111_9923 PubMedSearch: Riley 2014 Proc.Natl.Acad.Sci.U.S.A 111 9923 PubMedID: 24958869 Gene_locus related to this paper: pleos-a0a067nlj6, 9agar-a0a067t0n0, 9agar-a0a067sha0, 9homo-a0a067pav0, pleos-a0a067n337, 9homo-a0a067pz82, 9homo-a0a067m7p7, pleos-a0a067p245, 9homo-a0a067lrz6, 9homo-a0a067m4r5, 9homo-a0a067mr63, 9homo-a0a067mrq8, 9agar-a0a067t4j6, 9homo-a0a067pdz2, 9homo-a0a067q2n9, 9agar-a0a067tsx5, 9homo-a0a067mfq5, 9homo-a0a067qc90, pleos-a0a067p113, 9homo-a0a067pwi6, 9agar-a0a067s6d7, 9agar-a0a067tie7, pleos-a0a067ngc3, 9agar-a0a067st69, 9agar-a0a067t6h9, 9agar-a0a067tj80, pleos-a0a067npl2, 9agar-a0a067sm07, 9agar-a0a067tar9, 9agar-a0a067tid6, 9agar-a0a067u335, pleos-a0a067ndv5, pleos-a0a067nqw6, 9homo-a0a067pkj2, 9agar-a0a067t683, 9homo-a0a067mgl1, 9agar-a0a067sg35, 9homo-a0a067q7g6, 9agar-a0a067tub0, 9agar-a0a067t8f5, 9agar-a0a067tj19, 9homo-a0a067pyu9, 9agar-a0a067tjp8, 9agar-a0a067sjg9, 9agar-a0a067u0h4, pleos-a0a067nxe9, 9agar-a0a067sqt2, 9agar-a0a067tgx3, 9homo-a0a067psv8, 9agar-a0a067sq58, 9homo-a0a067m4m0, 9agar-a0a067tqz5, pleos-a0a067new9, 9homo-a0a067m9v3, 9agar-a0a067tlx5, 9agar-a0a067tfq4, pleos-a0a067nln4, pleos-a0a067ndf5, pleos-a0a067nn26, pleos-a0a067nfv2, 9homo-a0a067pnd3, 9agar-a0a067sw48, pleos-a0a067neg3, pleos-a0a067nz51, pleos-a0a067naf9, pleos-a0a067nad7, 9agar-a0a067sxe2, 9agar-a0a067slu3, pleos-a0a067n7p8, pleos-a0a067nl60, pleos-a0a067ncd0, 9agar-a0a067th99, 9agar-a0a067sp22, pleos-a0a067pbw7, 9homo-a0a067q916, 9homo-a0a067pwe5, galm3-a0a067scb0, galm3-popa Abstract Basidiomycota (basidiomycetes) make up 32% of the described fungi and include most wood-decaying species, as well as pathogens and mutualistic symbionts. Wood-decaying basidiomycetes have typically been classified as either white rot or brown rot, based on the ability (in white rot only) to degrade lignin along with cellulose and hemicellulose. Prior genomic comparisons suggested that the two decay modes can be distinguished based on the presence or absence of ligninolytic class II peroxidases (PODs), as well as the abundance of enzymes acting directly on crystalline cellulose (reduced in brown rot). To assess the generality of the white-rot/brown-rot classification paradigm, we compared the genomes of 33 basidiomycetes, including four newly sequenced wood decayers, and performed phylogenetically informed principal-components analysis (PCA) of a broad range of gene families encoding plant biomass-degrading enzymes. The newly sequenced Botryobasidium botryosum and Jaapia argillacea genomes lack PODs but possess diverse enzymes acting on crystalline cellulose, and they group close to the model white-rot species Phanerochaete chrysosporium in the PCA. Furthermore, laboratory assays showed that both B. botryosum and J. argillacea can degrade all polymeric components of woody plant cell walls, a characteristic of white rot. We also found expansions in reducing polyketide synthase genes specific to the brown-rot fungi. Our results suggest a continuum rather than a dichotomy between the white-rot and brown-rot modes of wood decay. A more nuanced categorization of rot types is needed, based on an improved understanding of the genomics and biochemistry of wood decay. Title: Comparative genome structure, secondary metabolite, and effector coding capacity across Cochliobolus pathogens Condon BJ, Leng Y, Wu D, Bushley KE, Ohm RA, Otillar R, Martin J, Schackwitz W, Grimwood J and Turgeon BG <20 more author(s)> Condon BJ, Leng Y, Wu D, Bushley KE, Ohm RA, Otillar R, Martin J, Schackwitz W, Grimwood J, MohdZainudin N, Xue C, Wang R, Manning VA, Dhillon B, Tu ZJ, Steffenson BJ, Salamov A, Sun H, Lowry S, LaButti K, Han J, Copeland A, Lindquist E, Barry K, Schmutz J, Baker SE, Ciuffetti LM, Grigoriev IV, Zhong S, Turgeon BG (- 20) Ref: PLoS Genet, 9:e1003233, 2013 : PubMed ESTHER: Condon_2013_PLoS.Genet_9_E1003233 PubMedSearch: Condon 2013 PLoS.Genet 9 E1003233 PubMedID: 23357949 Gene_locus related to this paper: cocsn-m2rnc6, coch5-m2tnl8, coch4-n4xap8, sett2-r0j560, cocsn-m2thl9, coch5-m2v1s2, coch4-n4xzy1, cocsn-m2sqr3, cocsn-m2rnk8, coch4-n4xdv7, coch5-m2uds0, coch5-m2um94, sett2-r0i8c5, coch4-n4wlc8, coch4-n4x9p3, cocsn-m2rh47, cocsn-m2qz08, sett2-r0jqq6, sett2-r0imb6, coch4-n4x7u3, cocsn-m2rv02, cocsn-m2sy95, coch5-m2ubd5, cocsn-m2t3d2, sett2-r0kl84, sett2-r0jts7, coch4-n4x2h3, sett2-r0jxt9, coch4-n4x7r9, cocsn-m2sh75, cocsn-m2t5z2, coch5-m2ucf6, sett2-r0k664, cocsn-m2t3q1, sett2-r0k4b4, cocsn-m2t4i1, coch5-m2th93, cocsn-m2svm8, cocsn-m2s6q4, cocsn-m2s5h5, coch4-n4xf94, sett2-r0kdl8, cocsn-m2qvi9, sett2-r0kfg6, cocsn-m2szq4, sett2-r0j437, coch4-n4x7j4, coch5-m2twk3, coch5-m2usf2, sett2-r0kjt7, sett2-r0k7y2, cocsn-m2th03, sett2-r0iy92, sett2-r0kbr9, sett2-r0k997, coch5-m2sik6, sett2-r0jzj5, cocsn-m2r0j6, coch4-n4x6a4, cocsn-m2s7a5, cocsn-m2sv79, sett2-r0knx4, sett2-r0ksh8, sett2-r0ip86, cocmi-w6yyy3, cocsn-m2sqe4, coch4-n4xzc8, cocvi-w7eyp1, cocmi-w6zf65, cocvi-w7er28, cocca-w6yw25, cocvi-w7e2g6, cocmi-w6z7k5, cocca-w6ys73, cocca-w6ydq2, cocca-w6y7i5, cocmi-w6yyr0, cocca-w6yh47, cocmi-w6zju4, cocca-w6ynq5, cocmi-w6zm44, cocca-w6xx85, cocmi-w6z011, cocca-w6yre4, cocmi-w6z9l3, cocca-w6yfp7, cocmi-w6zlc2, cocca-w6yar2, cocmi-w6yjr7, cocca-w6yhs1, cocca-w6xux8, cocmi-w6z9s8, cocca-w6yq27, cocmi-w6zqk9, cocca-w6xq19, cocca-w6y1r6, cocca-w6ygj2, cocmi-w6zgn4, cocca-w6ybh2, cocmi-w6z710, cocca-w6yk86, cocmi-w6zjz2, cocmi-w6z7f2, cocca-w6xn57, cocca-w6ybq4, cocmi-w6yxn5, cocmi-w6zf08, cocsn-m2rtg8, cocmi-w6zuj7, cocca-w6xtb2, cocca-w6yk97, coch5-m2t2x3, cocmi-w6z646, cocsn-m2sze4, sett2-r0kjg6, cocmi-w6yrn5, sett2-r0k5q0, cocvi-w7ezb7, sett2-r0jtm1, cocmi-w6ywa1, cocsn-m2t3e8, coch5-m2ulw5, coch5-m2urw9, sett2-r0knn5, cocmi-w6ysb2, cocvi-w7eag7, cocca-w6y1v2, sett2-r0i9k2, coch5-m2uul8, cocsn-m2sl21 Abstract The genomes of five Cochliobolus heterostrophus strains, two Cochliobolus sativus strains, three additional Cochliobolus species (Cochliobolus victoriae, Cochliobolus carbonum, Cochliobolus miyabeanus), and closely related Setosphaeria turcica were sequenced at the Joint Genome Institute (JGI). The datasets were used to identify SNPs between strains and species, unique genomic regions, core secondary metabolism genes, and small secreted protein (SSP) candidate effector encoding genes with a view towards pinpointing structural elements and gene content associated with specificity of these closely related fungi to different cereal hosts. Whole-genome alignment shows that three to five percent of each genome differs between strains of the same species, while a quarter of each genome differs between species. On average, SNP counts among field isolates of the same C. heterostrophus species are more than 25x higher than those between inbred lines and 50x lower than SNPs between Cochliobolus species. The suites of nonribosomal peptide synthetase (NRPS), polyketide synthase (PKS), and SSP-encoding genes are astoundingly diverse among species but remarkably conserved among isolates of the same species, whether inbred or field strains, except for defining examples that map to unique genomic regions. Functional analysis of several strain-unique PKSs and NRPSs reveal a strong correlation with a role in virulence. 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: Dynamics of fecal microbial communities in children with diarrhea of unknown etiology and genomic analysis of associated Streptococcus lutetiensis Jin D, Chen C, Li L, Lu S, Li Z, Zhou Z, Jing H, Xu Y, Du P and Xu J <8 more author(s)> Jin D, Chen C, Li L, Lu S, Li Z, Zhou Z, Jing H, Xu Y, Du P, Wang H, Xiong Y, Zheng H, Bai X, Sun H, Wang L, Ye C, Gottschalk M, Xu J (- 8) Ref: BMC Microbiol, 13:141, 2013 : PubMed ESTHER: Jin_2013_BMC.Microbiol_13_141 PubMedSearch: Jin 2013 BMC.Microbiol 13 141 PubMedID: 23782707 Abstract BACKGROUND: The sequences of the 16S rRNA genes extracted from fecal samples provide insights into the dynamics of fecal microflora. This potentially gives valuable etiological information for patients whose conditions have been ascribed to unknown pathogens, which cannot be accomplished using routine culture methods. We studied 33 children with diarrhea who were admitted to the Children's Hospital in Shanxi Province during 2006. Title: Draft genome of the wheat A-genome progenitor Triticum urartu Ling HQ, Zhao S, Liu D, Wang J, Sun H, Zhang C, Fan H, Li D, Dong L and Zhang A <39 more author(s)> Ling HQ, Zhao S, Liu D, Wang J, Sun H, Zhang C, Fan H, Li D, Dong L, Tao Y, Gao C, Wu H, Li Y, Cui Y, Guo X, Zheng S, Wang B, Yu K, Liang Q, Yang W, Lou X, Chen J, Feng M, Jian J, Zhang X, Luo G, Jiang Y, Liu J, Wang Z, Sha Y, Zhang B, Tang D, Shen Q, Xue P, Zou S, Wang X, Liu X, Wang F, Yang Y, An X, Dong Z, Zhang K, Luo MC, Dvorak J, Tong Y, Yang H, Li Z, Wang D, Zhang A (- 39) Ref: Nature, 496:87, 2013 : PubMed ESTHER: Ling_2013_Nature_496_87 PubMedSearch: Ling 2013 Nature 496 87 PubMedID: 23535596 Gene_locus related to this paper: triua-m8a764, triua-m8ag96, triua-m7zp69, wheat-w5d1z6, wheat-w5d232, wheat-w5bnf5, triua-t1nm05, wheat-w5cae4, triua-m7ytf7, wheat-w5f1j8, triua-m8ad49, wheat-a0a077s1q2, wheat-a0a3b6c2m6, triua-m7zi26, wheat-a0a3b6at77 Abstract Bread wheat (Triticum aestivum, AABBDD) is one of the most widely cultivated and consumed food crops in the world. However, the complex polyploid nature of its genome makes genetic and functional analyses extremely challenging. The A genome, as a basic genome of bread wheat and other polyploid wheats, for example, T. turgidum (AABB), T. timopheevii (AAGG) and T. zhukovskyi (AAGGA(m)A(m)), is central to wheat evolution, domestication and genetic improvement. The progenitor species of the A genome is the diploid wild einkorn wheat T. urartu, which resembles cultivated wheat more extensively than do Aegilops speltoides (the ancestor of the B genome) and Ae. tauschii (the donor of the D genome), especially in the morphology and development of spike and seed. Here we present the generation, assembly and analysis of a whole-genome shotgun draft sequence of the T. urartu genome. We identified protein-coding gene models, performed genome structure analyses and assessed its utility for analysing agronomically important genes and for developing molecular markers. Our T. urartu genome assembly provides a diploid reference for analysis of polyploid wheat genomes and is a valuable resource for the genetic improvement of wheat. Title: Potential tumor-suppressive role of monoglyceride lipase in human colorectal cancer Sun H, Jiang L, Luo X, Jin W, He Q, An J, Lui K, Shi J, Rong R and Huang Y <4 more author(s)> Sun H, Jiang L, Luo X, Jin W, He Q, An J, Lui K, Shi J, Rong R, Su W, Lucchesi C, Liu Y, Sheikh MS, Huang Y (- 4) Ref: Oncogene, 32:234, 2013 : PubMed ESTHER: Sun_2013_Oncogene_32_234 PubMedSearch: Sun 2013 Oncogene 32 234 PubMedID: 22349814 Abstract Human monoglyceride lipase (MGL) is a recently identified lipase and very little is known about its regulation and function in cellular regulatory processes, particularly in context to human malignancy. In this study, we investigated the regulation and function of MGL in human cancer(s) and report that MGL expression was either absent or reduced in the majority of primary colorectal cancers. Immunohistochemical studies showed that reduction of MGL expression in the colorectal tumor tissues predominantly occurred in the cancerous epithelial cells. MGL was found to reside in the core surface of a cellular organelle named 'lipid body'. Furthermore, it was found to interact selectively with a number of phospholipids, including phosphatidic acid and phosphoinositol(3,4,5)P3, phosphoinositol(3,5)P2, phosphoinositol(3,4)P2 and several other phosphoinositides, and among all phosphoinositides analyzed, its interaction with PI(3,4,5)P3 was found to be the strongest. In addition, overexpression of MGL suppressed colony formation in tumor cell lines and knockdown of MGL resulted in increased Akt phosphorylation. Taken together, our results suggest that MGL plays a negative regulatory role in phosphatidylinositol-3 kinase/Akt signaling and tumor cell growth. Title: The Paleozoic origin of enzymatic lignin decomposition reconstructed from 31 fungal genomes Floudas D, Binder M, Riley R, Barry K, Blanchette RA, Henrissat B, Martinez AT, Otillar R, Spatafora JW and Hibbett DS <61 more author(s)> Floudas D, Binder M, Riley R, Barry K, Blanchette RA, Henrissat B, Martinez AT, Otillar R, Spatafora JW, Yadav JS, Aerts A, Benoit I, Boyd A, Carlson A, Copeland A, Coutinho PM, de Vries RP, Ferreira P, Findley K, Foster B, Gaskell J, Glotzer D, Gorecki P, Heitman J, Hesse C, Hori C, Igarashi K, Jurgens JA, Kallen N, Kersten P, Kohler A, Kues U, Kumar TK, Kuo A, LaButti K, Larrondo LF, Lindquist E, Ling A, Lombard V, Lucas S, Lundell T, Martin R, McLaughlin DJ, Morgenstern I, Morin E, Murat C, Nagy LG, Nolan M, Ohm RA, Patyshakuliyeva A, Rokas A, Ruiz-Duenas FJ, Sabat G, Salamov A, Samejima M, Schmutz J, Slot JC, St John F, Stenlid J, Sun H, Sun S, Syed K, Tsang A, Wiebenga A, Young D, Pisabarro A, Eastwood DC, Martin F, Cullen D, Grigoriev IV, Hibbett DS (- 61) Ref: Science, 336:1715, 2012 : PubMed ESTHER: Floudas_2012_Science_336_1715 PubMedSearch: Floudas 2012 Science 336 1715 PubMedID: 22745431 Gene_locus related to this paper: aurde-j0d098, aurde-j0dc31, glota-s7rlc1, fompi-s8f7s4, dacsp-m5fpg2, dicsq-r7sm16, dacsp-m5g7q5, dacsp-m5fr12, glota-s7q5w3, fompi-s8f826.1, fompi-s8f826.2, dicsq-r7sy09, glota-s7rt87, dicsq-r7t032, glota-s7rym7, fompi-s8fiv2, dacsp-m5gda3.2, dicsq-r7swi6, dacsp-m5frf2, fompi-s8ebb6, dicsq-r7sln3, dicsq-r7sya6, dacsp-m5g7g1, dicsq-r7syx7, dicsq-r7sx57, dacsp-m5fps7, glota-s7pwi7, dicsq-r7swj6, fompi-s8ejq6, dicsq-r7spc3, glota-s7q258, dacsp-m5ft65, glota-s7q3m7, fompi-s8dkc7, glota-s7q1z1, fompi-s8eqi2, glota-s7q1z8, fompi-s8du50, dacsp-m5gg33, dacsp-m5g3a7, fompi-s8ecd7, fompi-s8dps1, dacsp-m5fwr0, dicsq-r7sub7, glota-s7q8k9, fompi-s8ffc3, dacsp-m5g2f9, fompi-s8ecc2, dacsp-m5g868, fompi-s8f890, dicsq-r7t1a8, fompi-s8ebx4, fompi-s8eb97, glota-s7q222, glota-s7puf0, fompi-s8f6v9, dacsp-m5g0z2, dacsp-m5gdh9, fompi-s8fb37, dacsp-m5fy91, glota-s7q5v6, fompi-s8fl44, dicsq-r7stv9, dicsq-r7szk3, fompi-s8epq9, glota-s7rh56, dacsp-m5gbt1, punst-r7s3x9, punst-r7s0t5, glota-s7q312, glota-s7rhh6, dicsq-r7t117, dicsq-r7slz3 Abstract Wood is a major pool of organic carbon that is highly resistant to decay, owing largely to the presence of lignin. The only organisms capable of substantial lignin decay are white rot fungi in the Agaricomycetes, which also contains non-lignin-degrading brown rot and ectomycorrhizal species. Comparative analyses of 31 fungal genomes (12 generated for this study) suggest that lignin-degrading peroxidases expanded in the lineage leading to the ancestor of the Agaricomycetes, which is reconstructed as a white rot species, and then contracted in parallel lineages leading to brown rot and mycorrhizal species. Molecular clock analyses suggest that the origin of lignin degradation might have coincided with the sharp decrease in the rate of organic carbon burial around the end of the Carboniferous period. Title: Crystal structure of the acyltransferase domain of the iterative polyketide synthase in enediyne biosynthesis Liew CW, Nilsson M, Chen MW, Sun H, Cornvik T, Liang ZX, Lescar J Ref: Journal of Biological Chemistry, 287:23203, 2012 : PubMed ESTHER: Liew_2012_J.Biol.Chem_287_23203 PubMedSearch: Liew 2012 J.Biol.Chem 287 23203 PubMedID: 22589546 Abstract Biosynthesis of the enediyne natural product dynemicin in Micromonospora chersina is initiated by DynE8, a highly reducing iterative type I polyketide synthase that assembles polyketide intermediates from the acetate units derived solely from malonyl-CoA. To understand the substrate specificity and the evolutionary relationship between the acyltransferase (AT) domains of DynE8, fatty acid synthase, and modular polyketide synthases, we overexpressed a 44-kDa fragment of DynE8 (hereafter named AT(DYN10)) encompassing its entire AT domain and the adjacent linker domain. The crystal structure at 1.4 A resolution unveils a alpha/beta hydrolase and a ferredoxin-like subdomain with the Ser-His catalytic dyad located in the cleft between the two subdomains. The linker domain also adopts a alpha/beta fold abutting the AT catalytic domain. Co-crystallization with malonyl-CoA yielded a malonyl-enzyme covalent complex that most likely represents the acyl-enzyme intermediate. The structure explains the preference for malonyl-CoA with a conserved arginine orienting the carboxylate group of malonate and several nonpolar residues that preclude alpha-alkyl malonyl-CoA binding. Co-crystallization with acetyl-CoA revealed two noncovalently bound acetates generated by the enzymatic hydrolysis of acetyl-CoA that acts as an inhibitor for DynE8. This suggests that the AT domain can upload the acyl groups from either malonyl-CoA or acetyl-CoA onto the catalytic Ser(651) residue. However, although the malonyl group can be transferred to the acyl carrier protein domain, transfer of the acetyl group to the acyl carrier protein domain is suppressed. Local structural differences may account for the different stability of the acyl-enzyme intermediates. Title: A novel Escherichia coli O157:H7 clone causing a major hemolytic uremic syndrome outbreak in China Xiong Y, Wang P, Lan R, Ye C, Wang H, Ren J, Jing H, Wang Y, Zhou Z and Xu J <7 more author(s)> Xiong Y, Wang P, Lan R, Ye C, Wang H, Ren J, Jing H, Wang Y, Zhou Z, Bai X, Cui Z, Luo X, Zhao A, Zhang S, Sun H, Wang L, Xu J (- 7) Ref: PLoS ONE, 7:e36144, 2012 : PubMed ESTHER: Xiong_2012_PLoS.ONE_7_E36144 PubMedSearch: Xiong 2012 PLoS.ONE 7 E36144 PubMedID: 22558360 Gene_locus related to this paper: ecoli-ycfp, ecoli-YFBB, ecoli-yqia, ecoli-Z1341 Abstract An Escherichia coli O157:H7 outbreak in China in 1999 caused 177 deaths due to hemolytic uremic syndrome. Sixteen outbreak associated isolates were found to belong to a new clone, sequence type 96 (ST96), based on multilocus sequence typing of 15 housekeeping genes. Whole genome sequencing of an outbreak isolate, Xuzhou21, showed that the isolate is phylogenetically closely related to the Japan 1996 outbreak isolate Sakai, both of which share the most recent common ancestor with the US outbreak isolate EDL933. The levels of IL-6 and IL-8 of peripheral blood mononuclear cells induced by Xuzhou21 and Sakai were significantly higher than that induced by EDL933. Xuzhou21 also induced a significantly higher level of IL-8 than Sakai while both induced similar levels of IL-6. The expression level of Shiga toxin 2 in Xuzhou21 induced by mitomycin C was 68.6 times of that under non-inducing conditions, twice of that induced in Sakai (32.7 times) and 15 times higher than that induced in EDL933 (4.5 times). Our study shows that ST96 is a novel clone and provided significant new insights into the evolution of virulence of E. coli O157:H7. Title: The genomes of the fungal plant pathogens Cladosporium fulvum and Dothistroma septosporum reveal adaptation to different hosts and lifestyles but also signatures of common ancestry de Wit PJ, van der Burgt A, Okmen B, Stergiopoulos I, Abd-Elsalam KA, Aerts AL, Bahkali AH, Beenen HG, Chettri P and Bradshaw RE <29 more author(s)> de Wit PJ, van der Burgt A, Okmen B, Stergiopoulos I, Abd-Elsalam KA, Aerts AL, Bahkali AH, Beenen HG, Chettri P, Cox MP, Datema E, de Vries RP, Dhillon B, Ganley AR, Griffiths SA, Guo Y, Hamelin RC, Henrissat B, Kabir MS, Jashni MK, Kema G, Klaubauf S, Lapidus A, Levasseur A, Lindquist E, Mehrabi R, Ohm RA, Owen TJ, Salamov A, Schwelm A, Schijlen E, Sun H, van den Burg HA, van Ham RC, Zhang S, Goodwin SB, Grigoriev IV, Collemare J, Bradshaw RE (- 29) Ref: PLoS Genet, 8:e1003088, 2012 : PubMed ESTHER: de Wit_2012_PLoS.Genet_8_E1003088 PubMedSearch: de Wit 2012 PLoS.Genet 8 E1003088 PubMedID: 23209441 Gene_locus related to this paper: mycpj-q30dw8, mycp1-n1pnd6, mycp1-n1per0, mycp1-n1pg49, mycp1-n1pwj1, mycp1-n1pcl8, mycp1-m2y2b1, mycp1-n1pwu7, mycp1-n1ppa8, mycp1-m2yk59, mycp1-n1pps5, mycp1-n1pw13, mycp1-n1pe19, mycp1-m2xhl1, mycp1-n1pnh6, mycp1-n1psn5, mycp1-n1puh9, mycp1-n1phf7, mycp1-m2y2h4, mycp1-n1q523, dotsn-n1q1b1, dotsn-n1q415, dotsn-est1 Abstract We sequenced and compared the genomes of the Dothideomycete fungal plant pathogens Cladosporium fulvum (Cfu) (syn. Passalora fulva) and Dothistroma septosporum (Dse) that are closely related phylogenetically, but have different lifestyles and hosts. Although both fungi grow extracellularly in close contact with host mesophyll cells, Cfu is a biotroph infecting tomato, while Dse is a hemibiotroph infecting pine. The genomes of these fungi have a similar set of genes (70% of gene content in both genomes are homologs), but differ significantly in size (Cfu >61.1-Mb; Dse 31.2-Mb), which is mainly due to the difference in repeat content (47.2% in Cfu versus 3.2% in Dse). Recent adaptation to different lifestyles and hosts is suggested by diverged sets of genes. Cfu contains an alpha-tomatinase gene that we predict might be required for detoxification of tomatine, while this gene is absent in Dse. Many genes encoding secreted proteins are unique to each species and the repeat-rich areas in Cfu are enriched for these species-specific genes. In contrast, conserved genes suggest common host ancestry. Homologs of Cfu effector genes, including Ecp2 and Avr4, are present in Dse and induce a Cf-Ecp2- and Cf-4-mediated hypersensitive response, respectively. Strikingly, genes involved in production of the toxin dothistromin, a likely virulence factor for Dse, are conserved in Cfu, but their expression differs markedly with essentially no expression by Cfu in planta. Likewise, Cfu has a carbohydrate-degrading enzyme catalog that is more similar to that of necrotrophs or hemibiotrophs and a larger pectinolytic gene arsenal than Dse, but many of these genes are not expressed in planta or are pseudogenized. Overall, comparison of their genomes suggests that these closely related plant pathogens had a common ancestral host but since adapted to different hosts and lifestyles by a combination of differentiated gene content, pseudogenization, and gene regulation. Title: Comparative genomics of xylose-fermenting fungi for enhanced biofuel production Wohlbach DJ, Kuo A, Sato TK, Potts KM, Salamov AA, LaButti KM, Sun H, Clum A, Pangilinan JL and Gasch AP <11 more author(s)> Wohlbach DJ, Kuo A, Sato TK, Potts KM, Salamov AA, LaButti KM, Sun H, Clum A, Pangilinan JL, Lindquist EA, Lucas S, Lapidus A, Jin M, Gunawan C, Balan V, Dale BE, Jeffries TW, Zinkel R, Barry KW, Grigoriev IV, Gasch AP (- 11) Ref: Proc Natl Acad Sci U S A, 108:13212, 2011 : PubMed ESTHER: Wohlbach_2011_Proc.Natl.Acad.Sci.U.S.A_108_13212 PubMedSearch: Wohlbach 2011 Proc.Natl.Acad.Sci.U.S.A 108 13212 PubMedID: 21788494 Gene_locus related to this paper: cantc-g3b3r0, spapn-g3ap60, spapn-g3aif9, cantc-g3axw7 Abstract Cellulosic biomass is an abundant and underused substrate for biofuel production. The inability of many microbes to metabolize the pentose sugars abundant within hemicellulose creates specific challenges for microbial biofuel production from cellulosic material. Although engineered strains of Saccharomyces cerevisiae can use the pentose xylose, the fermentative capacity pales in comparison with glucose, limiting the economic feasibility of industrial fermentations. To better understand xylose utilization for subsequent microbial engineering, we sequenced the genomes of two xylose-fermenting, beetle-associated fungi, Spathaspora passalidarum and Candida tenuis. To identify genes involved in xylose metabolism, we applied a comparative genomic approach across 14 Ascomycete genomes, mapping phenotypes and genotypes onto the fungal phylogeny, and measured genomic expression across five Hemiascomycete species with different xylose-consumption phenotypes. This approach implicated many genes and processes involved in xylose assimilation. Several of these genes significantly improved xylose utilization when engineered into S. cerevisiae, demonstrating the power of comparative methods in rapidly identifying genes for biomass conversion while reflecting on fungal ecology. Title: Genome sequence of the verrucomicrobium Opitutus terrae PB90-1, an abundant inhabitant of rice paddy soil ecosystems van Passel MW, Kant R, Palva A, Copeland A, Lucas S, Lapidus A, Glavina Del Rio T, Pitluck S, Goltsman E and Smidt H <11 more author(s)> van Passel MW, Kant R, Palva A, Copeland A, Lucas S, Lapidus A, Glavina Del Rio T, Pitluck S, Goltsman E, Clum A, Sun H, Schmutz J, Larimer FW, Land ML, Hauser L, Kyrpides N, Mikhailova N, Richardson PP, Janssen PH, de Vos WM, Smidt H (- 11) Ref: Journal of Bacteriology, 193:2367, 2011 : PubMed ESTHER: van Passel_2011_J.Bacteriol_193_2367 PubMedSearch: van Passel 2011 J.Bacteriol 193 2367 PubMedID: 21398538 Gene_locus related to this paper: opitp-b1zrm2 Abstract Bacteria of the deeply branching phylum Verrucomicrobia are rarely cultured yet commonly detected in metagenomic libraries from aquatic, terrestrial, and intestinal environments. We have sequenced the genome of Opitutus terrae PB90-1, a fermentative anaerobe within this phylum, isolated from rice paddy soil and capable of propionate production from plant-derived polysaccharides. Title: Complete genome sequence of Cellulomonas flavigena type strain (134) Abt B, Foster B, Lapidus A, Clum A, Sun H, Pukall R, Lucas S, Glavina Del Rio T, Nolan M and Klenk HP <23 more author(s)> Abt B, Foster B, Lapidus A, Clum A, Sun H, Pukall R, Lucas S, Glavina Del Rio T, Nolan M, Tice H, Cheng JF, Pitluck S, Liolios K, Ivanova N, Mavromatis K, Ovchinnikova G, Pati A, Goodwin L, Chen A, Palaniappan K, Land M, Hauser L, Chang YJ, Jeffries CD, Rohde M, Goker M, Woyke T, Bristow J, Eisen JA, Markowitz V, Hugenholtz P, Kyrpides NC, Klenk HP (- 23) Ref: Stand Genomic Sci, 3:15, 2010 : PubMed ESTHER: Abt_2010_Stand.Genomic.Sci_3_15 PubMedSearch: Abt 2010 Stand.Genomic.Sci 3 15 PubMedID: 21304688 Gene_locus related to this paper: celfn-d5uif8, celfn-d5uil9, celfn-d5ukl6, celfn-d5ulu1, celfn-d5ulp3, celfn-d5ul75, celfn-d5ufu5, celfn-d5ugh8 Abstract Cellulomonas flavigena (Kellerman and McBeth 1912) Bergey et al. 1923 is the type species of the genus Cellulomonas of the actinobacterial family Cellulomonadaceae. Members of the genus Cellulomonas are of special interest for their ability to degrade cellulose and hemicellulose, particularly with regard to the use of biomass as an alternative energy source. Here we describe the features of this organism, together with the complete genome sequence, and annotation. This is the first complete genome sequence of a member of the genus Cellulomonas, and next to the human pathogen Tropheryma whipplei the second complete genome sequence within the actinobacterial family Cellulomonadaceae. The 4,123,179 bp long single replicon genome with its 3,735 protein-coding and 53 RNA genes is part of the Genomic Encyclopedia of Bacteria and Archaea project. Title: Complete genome sequence of Nocardiopsis dassonvillei type strain (IMRU 509) Sun H, Lapidus A, Nolan M, Lucas S, Del Rio TG, Tice H, Cheng JF, Tapia R, Han C and Klenk HP <23 more author(s)> Sun H, Lapidus A, Nolan M, Lucas S, Del Rio TG, Tice H, Cheng JF, Tapia R, Han C, Goodwin L, Pitluck S, Pagani I, Ivanova N, Mavromatis K, Mikhailova N, Pati A, Chen A, Palaniappan K, Land M, Hauser L, Chang YJ, Jeffries CD, Djao OD, Rohde M, Sikorski J, Goker M, Woyke T, Bristow J, Eisen JA, Markowitz V, Hugenholtz P, Kyrpides NC, Klenk HP (- 23) Ref: Stand Genomic Sci, 3:325, 2010 : PubMed ESTHER: Sun_2010_Stand.Genomic.Sci_3_325 PubMedSearch: Sun 2010 Stand.Genomic.Sci 3 325 PubMedID: 21304737 Gene_locus related to this paper: nocdd-d7auf1, nocdd-d7avl6, nocdd-d7b2j7, nocdd-d7b3b3, nocdd-d7b6l9, nocdd-d7b210, nocdd-d7b279, nocdd-d7b3k0, nocdd-d7awb2 Abstract Nocardiopsis dassonvillei (Brocq-Rousseau 1904) Meyer 1976 is the type species of the genus Nocardiopsis, which in turn is the type genus of the family Nocardiopsaceae. This species is of interest because of its ecological versatility. Members of N. dassonvillei have been isolated from a large variety of natural habitats such as soil and marine sediments, from different plant and animal materials as well as from human patients. Moreover, representatives of the genus Nocardiopsis participate actively in biopolymer degradation. This is the first complete genome sequence in the family Nocardiopsaceae. Here we describe the features of this organism, together with the complete genome sequence and annotation. The 6,543,312 bp long genome consist of a 5.77 Mbp chromosome and a 0.78 Mbp plasmid and with its 5,570 protein-coding and 77 RNA genes is a part of the Genomic Encyclopedia of Bacteria and Archaea project. Title: Complete genome sequence of Desulfarculus baarsii type strain (2st14) Sun H, Spring S, Lapidus A, Davenport K, Del Rio TG, Tice H, Nolan M, Copeland A, Cheng JF and Land M <26 more author(s)> Sun H, Spring S, Lapidus A, Davenport K, Del Rio TG, Tice H, Nolan M, Copeland A, Cheng JF, Lucas S, Tapia R, Goodwin L, Pitluck S, Ivanova N, Pagani I, Mavromatis K, Ovchinnikova G, Pati A, Chen A, Palaniappan K, Hauser L, Chang YJ, Jeffries CD, Detter JC, Han C, Rohde M, Brambilla E, Goker M, Woyke T, Bristow J, Eisen JA, Markowitz V, Hugenholtz P, Kyrpides NC, Klenk HP, Land M (- 26) Ref: Stand Genomic Sci, 3:276, 2010 : PubMed ESTHER: Sun_2010_Stand.Genomic.Sci_3_276 PubMedSearch: Sun 2010 Stand.Genomic.Sci 3 276 PubMedID: 21304732 Gene_locus related to this paper: desb2-e1qfv0, desb2-e1qiq4, desb2-e1qd85 Abstract Desulfarculus baarsii (Widdel 1981) Kuever et al. 2006 is the type and only species of the genus Desulfarculus, which represents the family Desulfarculaceae and the order Desulfarculales. This species is a mesophilic sulfate-reducing bacterium with the capability to oxidize acetate and fatty acids of up to 18 carbon atoms completely to CO(2). The acetyl-CoA/CODH (Wood-Ljungdahl) pathway is used by this species for the complete oxidation of carbon sources and autotrophic growth on formate. The type strain 2st14(T) was isolated from a ditch sediment collected near the University of Konstanz, Germany. This is the first completed genome sequence of a member of the order Desulfarculales. The 3,655,731 bp long single replicon genome with its 3,303 protein-coding and 52 RNA genes is a part of the Genomic Encyclopedia of Bacteria and Archaea project. Title: Genomic characterization of the Guillain-Barre syndrome-associated Campylobacter jejuni ICDCCJ07001 Isolate Zhang M, He L, Li Q, Sun H, Gu Y, You Y, Meng F, Zhang J Ref: PLoS ONE, 5:e15060, 2010 : PubMed ESTHER: Zhang_2010_PLoS.ONE_5_E15060 PubMedSearch: Zhang 2010 PLoS.ONE 5 E15060 PubMedID: 21124772 Gene_locus related to this paper: camjr-q5ht69 Abstract Campylobacter jejuni ICDCCJ07001 (HS:41, ST2993) was isolated from a Guillain-Barre syndrome (GBS) patient during a 36-case GBS outbreak triggered by C. jejuni infections in north China in 2007. Sequence analysis revealed that the ICDCCJ07001 genome consisted of 1,664,840 base pairs (bp) and one tetracycline resistance plasmid of 44,084 bp. The GC content was 59.29% and 1,579 and 37 CDSs were identified on the chromosome and plasmid, respectively. The ICDCCJ07001 genome was compared to C. jejuni subsp. jejuni strains 81-176, 81116, NCTC11168, RM1221 and C. jejuni subsp. doylei 269.97. The length and organization of ICDCCJ07001 was similar to that of NCTC11168, 81-176 and 81-116 except that CMLP1 had a reverse orientation in strain ICDCCJ07001. Comparative genomic analyses were also carried out between GBS-associated C. jejuni strains. Thirteen common genes were present in four GBS-associated strains and 9 genes mapped to the LOS cluster and the ICDCCJ07001_pTet (44 kb) plasmid was mosaic in structure. Thirty-seven predicted CDS in ICDCCJ07001_pTet were homologous to genes present in three virulence-associated plasmids in Campylobacter: 81-176_pTet, pCC31 and 81-176_pVir. Comparative analysis of virulence loci and virulence-associated genes indicated that the LOS biosynthesis loci of ICDCCJ07001 belonged to type A, previously reported to be associated with cases of GBS. The polysaccharide capsular biosynthesis (CPS) loci and the flagella modification (FM) loci of ICDCCJ07001 were similar to corresponding sequences of strain 260.94 of similar serotype as strain ICDCCJ07001. Other virulence-associated genes including cadF, peb1, jlpA, cdt and ciaB were conserved between the C. jejuni strains examined. Title: The complete genome sequence of Staphylothermus marinus reveals differences in sulfur metabolism among heterotrophic Crenarchaeota Anderson IJ, Dharmarajan L, Rodriguez J, Hooper S, Porat I, Ulrich LE, Elkins JG, Mavromatis K, Sun H and Kyrpides N <10 more author(s)> Anderson IJ, Dharmarajan L, Rodriguez J, Hooper S, Porat I, Ulrich LE, Elkins JG, Mavromatis K, Sun H, Land M, Lapidus A, Lucas S, Barry K, Huber H, Zhulin IB, Whitman WB, Mukhopadhyay B, Woese C, Bristow J, Kyrpides N (- 10) Ref: BMC Genomics, 10:145, 2009 : PubMed ESTHER: Anderson_2009_BMC.Genomics_10_145 PubMedSearch: Anderson 2009 BMC.Genomics 10 145 PubMedID: 19341479 Abstract BACKGROUND: Staphylothermus marinus is an anaerobic, sulfur-reducing peptide fermenter of the archaeal phylum Crenarchaeota. It is the third heterotrophic, obligate sulfur reducing crenarchaeote to be sequenced and provides an opportunity for comparative analysis of the three genomes. Title: Complete genome sequence of Staphylothermus marinus Stetter and Fiala 1986 type strain F1 Anderson IJ, Sun H, Lapidus A, Copeland A, Glavina Del Rio T, Tice H, Dalin E, Lucas S, Barry K and Kyrpides NC <3 more author(s)> Anderson IJ, Sun H, Lapidus A, Copeland A, Glavina Del Rio T, Tice H, Dalin E, Lucas S, Barry K, Land M, Richardson P, Huber H, Kyrpides NC (- 3) Ref: Stand Genomic Sci, 1:183, 2009 : PubMed ESTHER: Anderson_2009_Stand.Genomic.Sci_1_183 PubMedSearch: Anderson 2009 Stand.Genomic.Sci 1 183 PubMedID: 21304655 Abstract Staphylothermus marinus Fiala and Stetter 1986 belongs to the order Desulfurococcales within the archaeal phylum Crenarchaeota. S. marinus is a hyperthermophilic, sulfur-dependent, anaerobic heterotroph. Strain F1 was isolated from geothermally heated sediments at Vulcano, Italy, but S. marinus has also been isolated from a hydrothermal vent on the East Pacific Rise. We report the complete genome of S. marinus strain F1, the type strain of the species. This is the fifth reported complete genome sequence from the order Desulfurococcales. Title: Genomic analysis of Elusimicrobium minutum, the first cultivated representative of the phylum Elusimicrobia (formerly termite group 1) Herlemann DP, Geissinger O, Ikeda-Ohtsubo W, Kunin V, Sun H, Lapidus A, Hugenholtz P, Brune A Ref: Applied Environmental Microbiology, 75:2841, 2009 : PubMed ESTHER: Herlemann_2009_Appl.Environ.Microbiol_75_2841 PubMedSearch: Herlemann 2009 Appl.Environ.Microbiol 75 2841 PubMedID: 19270133 Abstract Organisms of the candidate phylum termite group 1 (TG1) are regularly encountered in termite hindguts but are present also in many other habitats. Here, we report the complete genome sequence (1.64 Mbp) of "Elusimicrobium minutum" strain Pei191(T), the first cultured representative of the TG1 phylum. We reconstructed the metabolism of this strictly anaerobic bacterium isolated from a beetle larva gut, and we discuss the findings in light of physiological data. E. minutum has all genes required for uptake and fermentation of sugars via the Embden-Meyerhof pathway, including several hydrogenases, and an unusual peptide degradation pathway comprising transamination reactions and leading to the formation of alanine, which is excreted in substantial amounts. The presence of genes encoding lipopolysaccharide biosynthesis and the presence of a pathway for peptidoglycan formation are consistent with ultrastructural evidence of a gram-negative cell envelope. Even though electron micrographs showed no cell appendages, the genome encodes many genes putatively involved in pilus assembly. We assigned some to a type II secretion system, but the function of 60 pilE-like genes remains unknown. Numerous genes with hypothetical functions, e.g., polyketide synthesis, nonribosomal peptide synthesis, antibiotic transport, and oxygen stress protection, indicate the presence of hitherto undiscovered physiological traits. Comparative analysis of 22 concatenated single-copy marker genes corroborated the status of "Elusimicrobia" (formerly TG1) as a separate phylum in the bacterial domain, which was so far based only on 16S rRNA sequence analysis. Title: Genome analysis of the anaerobic thermohalophilic bacterium Halothermothrix orenii Mavromatis K, Ivanova N, Anderson I, Lykidis A, Hooper SD, Sun H, Kunin V, Lapidus A, Hugenholtz P and Kyrpides NC <1 more author(s)> Mavromatis K, Ivanova N, Anderson I, Lykidis A, Hooper SD, Sun H, Kunin V, Lapidus A, Hugenholtz P, Patel B, Kyrpides NC (- 1) Ref: PLoS ONE, 4:e4192, 2009 : PubMed ESTHER: Mavromatis_2009_PLoS.ONE_4_E4192 PubMedSearch: Mavromatis 2009 PLoS.ONE 4 E4192 PubMedID: 19145256 Gene_locus related to this paper: haloh-b8cwa6, haloh-b8czv0 Abstract Halothermothirx orenii is a strictly anaerobic thermohalophilic bacterium isolated from sediment of a Tunisian salt lake. It belongs to the order Halanaerobiales in the phylum Firmicutes. The complete sequence revealed that the genome consists of one circular chromosome of 2578146 bps encoding 2451 predicted genes. This is the first genome sequence of an organism belonging to the Haloanaerobiales. Features of both Gram positive and Gram negative bacteria were identified with the presence of both a sporulating mechanism typical of Firmicutes and a characteristic Gram negative lipopolysaccharide being the most prominent. Protein sequence analyses and metabolic reconstruction reveal a unique combination of strategies for thermophilic and halophilic adaptation. H. orenii can serve as a model organism for the study of the evolution of the Gram negative phenotype as well as the adaptation under thermohalophilic conditions and the development of biotechnological applications under conditions that require high temperatures and high salt concentrations. Title: A glimpse of streptococcal toxic shock syndrome from comparative genomics of S. suis 2 Chinese isolates Chen C, Tang J, Dong W, Wang C, Feng Y, Wang J, Zheng F, Pan X, Liu D and Yu J <16 more author(s)> Chen C, Tang J, Dong W, Wang C, Feng Y, Wang J, Zheng F, Pan X, Liu D, Li M, Song Y, Zhu X, Sun H, Feng T, Guo Z, Ju A, Ge J, Dong Y, Sun W, Jiang Y, Yan J, Yang H, Wang X, Gao GF, Yang R, Yu J (- 16) Ref: PLoS ONE, 2:e315, 2007 : PubMed ESTHER: Chen_2007_PLoS.ONE_2_E315 PubMedSearch: Chen 2007 PLoS.ONE 2 E315 PubMedID: 17375201 Gene_locus related to this paper: strsu-a4vws4, strsu-q302y4, strsy-a4vus4, strsy-a4vwf6 Abstract BACKGROUND: Streptococcus suis serotype 2 (SS2) is an important zoonotic pathogen, causing more than 200 cases of severe human infection worldwide, with the hallmarks of meningitis, septicemia, arthritis, etc. Very recently, SS2 has been recognized as an etiological agent for streptococcal toxic shock syndrome (STSS), which was originally associated with Streptococcus pyogenes (GAS) in Streptococci. However, the molecular mechanisms underlying STSS are poorly understood. METHODS AND FINDINGS: To elucidate the genetic determinants of STSS caused by SS2, whole genome sequencing of 3 different Chinese SS2 strains was undertaken. Comparative genomics accompanied by several lines of experiments, including experimental animal infection, PCR assay, and expression analysis, were utilized to further dissect a candidate pathogenicity island (PAI). Here we show, for the first time, a novel molecular insight into Chinese isolates of highly invasive SS2, which caused two large-scale human STSS outbreaks in China. A candidate PAI of approximately 89 kb in length, which is designated 89K and specific for Chinese SS2 virulent isolates, was investigated at the genomic level. It shares the universal properties of PAIs such as distinct GC content, consistent with its pivotal role in STSS and high virulence. CONCLUSIONS: To our knowledge, this is the first PAI candidate from S. suis worldwide. Our finding thus sheds light on STSS triggered by SS2 at the genomic level, facilitates further understanding of its pathogenesis and points to directions of development on some effective strategies to combat highly pathogenic SS2 infections. Title: Investigation of differentially expressed proteins in rat gastrocnemius muscle during denervation-reinnervation Sun H, Liu J, Ding F, Wang X, Liu M, Gu X Ref: J Muscle Res Cell Motil, 27:241, 2006 : PubMed ESTHER: Sun_2006_J.Muscle.Res.Cell.Motil_27_241 PubMedSearch: Sun 2006 J.Muscle.Res.Cell.Motil 27 241 PubMedID: 16752196 Abstract To have a better insight into the molecular events involved in denervation-induced atrophy and reinnervation-induced regeneration of skeletal muscles, it is important to investigate the changes in expression levels of a great multitude of muscle proteins during the process of denervation-reinnervation. In this study, we employed an experimental model of rat sciatic nerve crush to examine the differentially expressed proteins in the rat gastrocnemius muscle at different time points (0, 1, 2, 3, 4 weeks) after sciatic nerve crush by using two-dimensional gel electrophoresis (2-DE) followed by matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF-MS), collectively referred to as the modern proteomic analysis. The results showed that 16 proteins in the rat gastrocnemius muscle exhibited two distinct types of change pattern in their relative abundance: (1) The relative expression levels of 11 proteins (including alpha actin, myosin heavy chain, etc.) were decreased either within 1 or 2 weeks post-sciatic nerve injury, followed by restoration during the ensuing days until 4 weeks. (2) The other 5 proteins (including alpha enolase, beta enolase, signal peptide peptidase-like 3, etc.) displayed an up-regulation in their relative expression levels within 1 week following sciatic nerve injury, and a subsequent gradual decrease in their relative expression levels until 4 weeks. Moreover, the significance of the changes in expression levels of the 16 proteins during denervation-reinnervation has been selectively discussed. Title: Generation and annotation of the DNA sequences of human chromosomes 2 and 4 Hillier LW, Graves TA, Fulton RS, Fulton LA, Pepin KH, Minx P, Wagner-McPherson C, Layman D, Wylie K and Wilson RK <111 more author(s)> Hillier LW, Graves TA, Fulton RS, Fulton LA, Pepin KH, Minx P, Wagner-McPherson C, Layman D, Wylie K, Sekhon M, Becker MC, Fewell GA, Delehaunty KD, Miner TL, Nash WE, Kremitzki C, Oddy L, Du H, Sun H, Bradshaw-Cordum H, Ali J, Carter J, Cordes M, Harris A, Isak A, Van Brunt A, Nguyen C, Du F, Courtney L, Kalicki J, Ozersky P, Abbott S, Armstrong J, Belter EA, Caruso L, Cedroni M, Cotton M, Davidson T, Desai A, Elliott G, Erb T, Fronick C, Gaige T, Haakenson W, Haglund K, Holmes A, Harkins R, Kim K, Kruchowski SS, Strong CM, Grewal N, Goyea E, Hou S, Levy A, Martinka S, Mead K, McLellan MD, Meyer R, Randall-Maher J, Tomlinson C, Dauphin-Kohlberg S, Kozlowicz-Reilly A, Shah N, Swearengen-Shahid S, Snider J, Strong JT, Thompson J, Yoakum M, Leonard S, Pearman C, Trani L, Radionenko M, Waligorski JE, Wang C, Rock SM, Tin-Wollam AM, Maupin R, Latreille P, Wendl MC, Yang SP, Pohl C, Wallis JW, Spieth J, Bieri TA, Berkowicz N, Nelson JO, Osborne J, Ding L, Sabo A, Shotland Y, Sinha P, Wohldmann PE, Cook LL, Hickenbotham MT, Eldred J, Williams D, Jones TA, She X, Ciccarelli FD, Izaurralde E, Taylor J, Schmutz J, Myers RM, Cox DR, Huang X, McPherson JD, Mardis ER, Clifton SW, Warren WC, Chinwalla AT, Eddy SR, Marra MA, Ovcharenko I, Furey TS, Miller W, Eichler EE, Bork P, Suyama M, Torrents D, Waterston RH, Wilson RK (- 111) Ref: Nature, 434:724, 2005 : PubMed ESTHER: Hillier_2005_Nature_434_724 PubMedSearch: Hillier 2005 Nature 434 724 PubMedID: 15815621 Gene_locus related to this paper: human-ABHD1, human-LDAH, human-ABHD18, human-KANSL3, human-PGAP1, human-PREPL Abstract Human chromosome 2 is unique to the human lineage in being the product of a head-to-head fusion of two intermediate-sized ancestral chromosomes. Chromosome 4 has received attention primarily related to the search for the Huntington's disease gene, but also for genes associated with Wolf-Hirschhorn syndrome, polycystic kidney disease and a form of muscular dystrophy. Here we present approximately 237 million base pairs of sequence for chromosome 2, and 186 million base pairs for chromosome 4, representing more than 99.6% of their euchromatic sequences. Our initial analyses have identified 1,346 protein-coding genes and 1,239 pseudogenes on chromosome 2, and 796 protein-coding genes and 778 pseudogenes on chromosome 4. Extensive analyses confirm the underlying construction of the sequence, and expand our understanding of the structure and evolution of mammalian chromosomes, including gene deserts, segmental duplications and highly variant regions. Title: Macrophage-derived lipoprotein lipase increases aortic atherosclerosis in cholesterol-fed Tg rabbits Ichikawa T, Liang J, Kitajima S, Koike T, Wang X, Sun H, Morimoto M, Shikama H, Watanabe T and Fan J <1 more author(s)> Ichikawa T, Liang J, Kitajima S, Koike T, Wang X, Sun H, Morimoto M, Shikama H, Watanabe T, Yamada N, Fan J (- 1) Ref: Atherosclerosis, 179:87, 2005 : PubMed ESTHER: Ichikawa_2005_Atherosclerosis_179_87 PubMedSearch: Ichikawa 2005 Atherosclerosis 179 87 PubMedID: 15721013 Abstract Lipoprotein lipase (LPL) produced by macrophages is upregulated in the atherosclerotic lesions; however, it is not fully understood whether increased macrophage-derived LPL is pro-atherogenic. To examine the hypothesis that macrophage-derived LPL in the arterial wall enhances atherosclerotic lesion formation, we generated transgenic (Tg) rabbits that express the human LPL transgene under the control of the human scavenger receptor enhancer/promoter, which drives macrophage-specific expression of the human LPL gene. We fed Tg and non-Tg littermate rabbits a diet containing 0.3% cholesterol for 16 weeks and compared their lipoproteins and aortic atherosclerosis. We found that there was no difference in plasma lipid or lipoprotein profiles between Tg and non-Tg rabbits; however, atherosclerotic lesions were significantly increased in Tg compared to non-Tg rabbits. There was a 1.4-fold increase in total aortic en face lesions and a 2-fold increase in intimal lesions evaluated by image analysis system. Furthermore, immunohistochemical staining revealed that the increased atherosclerotic lesions present in Tg rabbits were characterized by marked accumulation of macrophage-derived foam cells and frequently associated with the deposition of oxidized LDL. These results support the notion that macrophage-derived LPL in the arterial wall is pro-atherogenic, possibly via the enhancement of foam cell formation during atherogenesis. Title: Enhanced aortic atherosclerosis in transgenic Watanabe heritable hyperlipidemic rabbits expressing lipoprotein lipase Koike T, Liang J, Wang X, Ichikawa T, Shiomi M, Sun H, Watanabe T, Liu G, Fan J Ref: Cardiovascular Research, 65:524, 2005 : PubMed ESTHER: Koike_2005_Cardiovasc.Res_65_524 PubMedSearch: Koike 2005 Cardiovasc.Res 65 524 PubMedID: 15639492 Abstract OBJECTIVE: This study was designed to address the effects of increased lipoprotein lipase (LPL) activity on atherosclerosis in the setting of LDL receptor deficiency. Title: High lipoprotein lipase activity increases insulin sensitivity in transgenic rabbits Liu E, Kitajima S, Higaki Y, Morimoto M, Sun H, Watanabe T, Yamada N, Fan J Ref: Metabolism, 54:132, 2005 : PubMed ESTHER: Liu_2005_Metabolism_54_132 PubMedSearch: Liu 2005 Metabolism 54 132 PubMedID: 15562391 Abstract Lipoprotein lipase (LPL) is the rate-limiting enzyme in the hydrolysis of triglyceride-rich lipoproteins and plays an important role in glucose metabolism. To examine the hypothesis that increased LPL activity may alter insulin sensitivity, we investigated glucose metabolism and insulin sensitivity in transgenic (Tg) rabbits expressing the human LPL gene under the control of a I(2) -actin promoter. An intravenous glucose tolerance test showed that the plasma glucose clearance rate was not significantly different between Tg and non-Tg rabbits; however, the area under the curve for insulin and free fatty acids in Tg rabbits was significantly reduced compared with that of non-Tg rabbits (P < .05). Using the intravenous insulin tolerance test, we found that the area of under the curve of glucose of Tg rabbits was also significantly reduced (P < .01). Furthermore, euglycemic-hyperinsulinemic clamp test revealed that the mean glucose infusion rate in Tg rabbits was significantly higher than in non-Tg rabbits (P < .05). These results demonstrate that systemic overexpression of LPL increases whole-body insulin sensitivity and genetic manipulation of LPL genes may be a potential target for the treatment of diabetic patients. Title: Overexpression of lipoprotein lipase in transgenic rabbits leads to increased small dense LDL in plasma and promotes atherosclerosis Ichikawa T, Kitajima S, Liang J, Koike T, Wang X, Sun H, Okazaki M, Morimoto M, Shikama H and Fan J <2 more author(s)> Ichikawa T, Kitajima S, Liang J, Koike T, Wang X, Sun H, Okazaki M, Morimoto M, Shikama H, Watanabe T, Yamada N, Fan J (- 2) Ref: Lab Invest, 84:715, 2004 : PubMed ESTHER: Ichikawa_2004_Lab.Invest_84_715 PubMedSearch: Ichikawa 2004 Lab.Invest 84 715 PubMedID: 15122303 Abstract Lipoprotein lipase (LPL) is a key enzyme in the hydrolysis of triglyceride-rich lipoproteins. Previous studies using transgenic mice and rabbits have demonstrated that high level of LPL activity in adipose and skeletal muscle protects against diet-induced hypercholesterolemia and subsequently prevents aortic atherosclerosis. However, it is unknown, per se, whether increased LPL activity itself is antiatherogenic, or whether the antiatherogenic effect of LPL is dependent upon the LPL lipid-lowering effect. To address this issue, we fed LPL transgenic and littermate rabbits diets containing different amounts of cholesterol (0.3-0.6%) adjusted to maintain their plasma cholesterol concentrations at similarly high levels for 16 weeks. We analyzed their lipoprotein profiles and compared their susceptibility to atherosclerosis. The results showed that the overexpression of LPL in transgenic rabbits reduced remnant lipoproteins (beta-VLDL, d<1.006 g/ml) but concomitantly led to a significant increase of the large (d=1.02-1.04 g/ml) and small LDLs (d=1.04-1.06 g/ml) compared to the amounts in control rabbits. Furthermore, we found that with equally high hypercholesterolemia, transgenic rabbits developed 1.8-fold more extensive aortic atherosclerosis than control rabbits. To examine the hypothesis that altered lipoprotein profiles may be responsible for the enhanced atherosclerosis in transgenic rabbits, we studied the atherogenic properties of apoB-containing lipoproteins in vitro. These studies revealed that small-sized LDLs of transgenic rabbits were more susceptible to copper-induced oxidation and had higher affinity to biglycan than large remnant lipoproteins. We conclude, therefore, that LPL exerts a dual function in terms of its atherogenicity, namely antiatherogenicity, through enhancing receptor-mediated remnant lipoprotein catabolism and proatherogenicity via the generation of a large amount of small-sized LDLs. At an equal atherogenic-cholesterol level, small and dense LDLs are more atherogenic than large remnant lipoproteins. Title: Comparison of genome degradation in Paratyphi A and Typhi, human-restricted serovars of Salmonella enterica that cause typhoid McClelland M, Sanderson KE, Clifton SW, Latreille P, Porwollik S, Sabo A, Meyer R, Bieri T, Ozersky P and Wilson RK <25 more author(s)> McClelland M, Sanderson KE, Clifton SW, Latreille P, Porwollik S, Sabo A, Meyer R, Bieri T, Ozersky P, McLellan M, Harkins CR, Wang C, Nguyen C, Berghoff A, Elliott G, Kohlberg S, Strong C, Du F, Carter J, Kremizki C, Layman D, Leonard S, Sun H, Fulton L, Nash W, Miner T, Minx P, Delehaunty K, Fronick C, Magrini V, Nhan M, Warren W, Florea L, Spieth J, Wilson RK (- 25) Ref: Nat Genet, 36:1268, 2004 : PubMed ESTHER: McClelland_2004_Nat.Genet_36_1268 PubMedSearch: McClelland 2004 Nat.Genet 36 1268 PubMedID: 15531882 Gene_locus related to this paper: salen-OPDB, salty-AES, salty-BIOH, salty-DLHH, salty-ENTF, salty-FES, salty-IROD, salty-IROE, salty-P74847, salty-PLDB, salty-STM2547, salty-STM4506, salty-STY1441, salty-STY2428, salty-STY3846, salty-yafa, salty-YBFF, salty-ycfp, salty-YFBB, salty-YHET, salty-YQIA Abstract Salmonella enterica serovars often have a broad host range, and some cause both gastrointestinal and systemic disease. But the serovars Paratyphi A and Typhi are restricted to humans and cause only systemic disease. It has been estimated that Typhi arose in the last few thousand years. The sequence and microarray analysis of the Paratyphi A genome indicates that it is similar to the Typhi genome but suggests that it has a more recent evolutionary origin. Both genomes have independently accumulated many pseudogenes among their approximately 4,400 protein coding sequences: 173 in Paratyphi A and approximately 210 in Typhi. The recent convergence of these two similar genomes on a similar phenotype is subtly reflected in their genotypes: only 30 genes are degraded in both serovars. Nevertheless, these 30 genes include three known to be important in gastroenteritis, which does not occur in these serovars, and four for Salmonella-translocated effectors, which are normally secreted into host cells to subvert host functions. Loss of function also occurs by mutation in different genes in the same pathway (e.g., in chemotaxis and in the production of fimbriae). Title: The DNA sequence of human chromosome 7 Hillier LW, Fulton RS, Fulton LA, Graves TA, Pepin KH, Wagner-McPherson C, Layman D, Maas J, Jaeger S and Wilson RK <97 more author(s)> Hillier LW, Fulton RS, Fulton LA, Graves TA, Pepin KH, Wagner-McPherson C, Layman D, Maas J, Jaeger S, Walker R, Wylie K, Sekhon M, Becker MC, O'Laughlin MD, Schaller ME, Fewell GA, Delehaunty KD, Miner TL, Nash WE, Cordes M, Du H, Sun H, Edwards J, Bradshaw-Cordum H, Ali J, Andrews S, Isak A, Vanbrunt A, Nguyen C, Du F, Lamar B, Courtney L, Kalicki J, Ozersky P, Bielicki L, Scott K, Holmes A, Harkins R, Harris A, Strong CM, Hou S, Tomlinson C, Dauphin-Kohlberg S, Kozlowicz-Reilly A, Leonard S, Rohlfing T, Rock SM, Tin-Wollam AM, Abbott A, Minx P, Maupin R, Strowmatt C, Latreille P, Miller N, Johnson D, Murray J, Woessner JP, Wendl MC, Yang SP, Schultz BR, Wallis JW, Spieth J, Bieri TA, Nelson JO, Berkowicz N, Wohldmann PE, Cook LL, Hickenbotham MT, Eldred J, Williams D, Bedell JA, Mardis ER, Clifton SW, Chissoe SL, Marra MA, Raymond C, Haugen E, Gillett W, Zhou Y, James R, Phelps K, Iadanoto S, Bubb K, Simms E, Levy R, Clendenning J, Kaul R, Kent WJ, Furey TS, Baertsch RA, Brent MR, Keibler E, Flicek P, Bork P, Suyama M, Bailey JA, Portnoy ME, Torrents D, Chinwalla AT, Gish WR, Eddy SR, McPherson JD, Olson MV, Eichler EE, Green ED, Waterston RH, Wilson RK (- 97) Ref: Nature, 424:157, 2003 : PubMed ESTHER: Hillier_2003_Nature_424_157 PubMedSearch: Hillier 2003 Nature 424 157 PubMedID: 12853948 Gene_locus related to this paper: human-ABHD11, human-ACHE, human-CPVL, human-DPP6, human-MEST Abstract Human chromosome 7 has historically received prominent attention in the human genetics community, primarily related to the search for the cystic fibrosis gene and the frequent cytogenetic changes associated with various forms of cancer. Here we present more than 153 million base pairs representing 99.4% of the euchromatic sequence of chromosome 7, the first metacentric chromosome completed so far. The sequence has excellent concordance with previously established physical and genetic maps, and it exhibits an unusual amount of segmentally duplicated sequence (8.2%), with marked differences between the two arms. Our initial analyses have identified 1,150 protein-coding genes, 605 of which have been confirmed by complementary DNA sequences, and an additional 941 pseudogenes. Of genes confirmed by transcript sequences, some are polymorphic for mutations that disrupt the reading frame. Title: Cocaine metabolism accelerated by a re-engineered human butyrylcholinesterase Sun H, Shen ML, Pang YP, Lockridge O, Brimijoin S Ref: Journal of Pharmacology & Experimental Therapeutics, 302:710, 2002 : PubMed ESTHER: Sun_2002_J.Pharmacol.Exp.Ther_302_710 PubMedSearch: Sun 2002 J.Pharmacol.Exp.Ther 302 710 PubMedID: 12130735 Gene_locus related to this paper: human-BCHE Inhibitor(s) related to this paper: Cocaine Abstract Plasma butyrylcholinesterase (BChE) is important in the metabolism of cocaine, but natural human BChE has limited therapeutic potential for detoxication because of low catalytic efficiency with cocaine. Here we report pharmacokinetics of cocaine in rats treated with A328W/Y332A BChE, an excellent cocaine hydrolase designed with the aid of molecular modeling. Compared with wild-type BChE, this enzyme hydrolyzes cocaine with 40-fold improved k(cat) (154 min(-1) versus 4.1 min(-1)) and only slightly increased K(M) (18 microM versus 4.5 microM). In rats given this hydrolase (3 mg/kg i.v.) 10 min before cocaine challenge (6.8 mg/kg i.v.), cocaine half-life was reduced from 52 min to 18 min. Mirroring the reductions of plasma cocaine were large increases in benzoic acid, a product of BChE-mediated cocaine hydrolysis. All other pharmacokinetic parameters confirmed a large, dose-dependent acceleration of cocaine removal by the injected cocaine hydrolase. These results show that A328W/Y332A, an efficient cocaine hydrolase in vivo as well as in vitro, might promote cocaine detoxication in a clinical setting. Title: Re-engineering butyrylcholinesterase as a cocaine hydrolase Sun H, Pang YP, Lockridge O, Brimijoin S Ref: Molecular Pharmacology, 62:220, 2002 : PubMed ESTHER: Sun_2002_Mol.Pharmacol_62_220 PubMedSearch: Sun 2002 Mol.Pharmacol 62 220 PubMedID: 12130672 Gene_locus related to this paper: human-BCHE Inhibitor(s) related to this paper: Cocaine Abstract To address the problem of acute cocaine overdose, we undertook molecular engineering of butyrylcholinesterase (BChE) as a cocaine hydrolase so that modest doses could be used to accelerate metabolic clearance of this drug. Molecular modeling of BChE complexed with cocaine suggested that the inefficient hydrolysis (k(cat) = 4 min(-1)) involves a rotation toward the catalytic triad, hindered by Tyr332. To eliminate rotational hindrance and retain substrate affinity, we introduced two amino acid substitutions (Ala328Trp/Tyr332Ala). The resulting mutant BChE reduced cocaine burden in tissues, accelerated plasma clearance by 20-fold, and prevented cocaine-induced hyperactivity in mice. The enzyme's kinetic properties (k(cat) = 154 min(-1), K(M) = 18 microM) satisfy criteria suggested previously for treating cocaine overdose (k(cat) >120 min(-1), K(M) < 30 microM). This success demonstrates that computationally guided mutagenesis can generate functionally novel enzymes with clinical potential. Title: Complete genome sequence of Salmonella enterica serovar Typhimurium LT2 McClelland M, Sanderson KE, Spieth J, Clifton SW, Latreille P, Courtney L, Porwollik S, Ali J, Dante M and Wilson RK <16 more author(s)> McClelland M, Sanderson KE, Spieth J, Clifton SW, Latreille P, Courtney L, Porwollik S, Ali J, Dante M, Du F, Hou S, Layman D, Leonard S, Nguyen C, Scott K, Holmes A, Grewal N, Mulvaney E, Ryan E, Sun H, Florea L, Miller W, Stoneking T, Nhan M, Waterston R, Wilson RK (- 16) Ref: Nature, 413:852, 2001 : PubMed ESTHER: McClelland_2001_Nature_413_852 PubMedSearch: McClelland 2001 Nature 413 852 PubMedID: 11677609 Gene_locus related to this paper: salen-OPDB, salti-q8z717, salty-AES, salty-BIOH, salty-ENTF, salty-FES, salty-IROD, salty-IROE, salty-P74847, salty-PLDB, salty-STM0332, salty-STM2547, salty-STM3079, salty-STM4506, salty-STY1441, salty-STY2428, salty-STY3846, salty-yafa, salty-YBFF, salty-ycfp, salty-YFBB, salty-YHET, salty-YJFP, salty-YQIA Abstract Salmonella enterica subspecies I, serovar Typhimurium (S. typhimurium), is a leading cause of human gastroenteritis, and is used as a mouse model of human typhoid fever. The incidence of non-typhoid salmonellosis is increasing worldwide, causing millions of infections and many deaths in the human population each year. Here we sequenced the 4,857-kilobase (kb) chromosome and 94-kb virulence plasmid of S. typhimurium strain LT2. The distribution of close homologues of S. typhimurium LT2 genes in eight related enterobacteria was determined using previously completed genomes of three related bacteria, sample sequencing of both S. enterica serovar Paratyphi A (S. paratyphi A) and Klebsiella pneumoniae, and hybridization of three unsequenced genomes to a microarray of S. typhimurium LT2 genes. Lateral transfer of genes is frequent, with 11% of the S. typhimurium LT2 genes missing from S. enterica serovar Typhi (S. typhi), and 29% missing from Escherichia coli K12. The 352 gene homologues of S. typhimurium LT2 confined to subspecies I of S. enterica-containing most mammalian and bird pathogens-are useful for studies of epidemiology, host specificity and pathogenesis. Most of these homologues were previously unknown, and 50 may be exported to the periplasm or outer membrane, rendering them accessible as therapeutic or vaccine targets. Title: Predicted Michaelis-Menten complexes of cocaine-butyrylcholinesterase. Engineering effective butyrylcholinesterase mutants for cocaine detoxication. Sun H, El Yazal J, Lockridge O, Schopfer LM, Brimijoin S, Pang YP Ref: Journal of Biological Chemistry, 276:9330, 2001 : PubMed ESTHER: Sun_2001_J.Biol.Chem_276_9330 PubMedSearch: Sun 2001 J.Biol.Chem 276 9330 PubMedID: 11104759 Inhibitor(s) related to this paper: Cocaine Abstract Butyrylcholinesterase (BChE) is important in cocaine metabolism, but it hydrolyzes (-)-cocaine only one-two thousandth as fast as the unnatural (+)-stereoisomer. A starting point in engineering BChE mutants that rapidly clear cocaine from the bloodstream, for overdose treatment, is to elucidate structural factors underlying the stereochemical difference in catalysis. Here, we report two three-dimensional Michaelis-Menten complexes of BChE liganded with natural and unnatural cocaine molecules, respectively, that were derived from molecular modeling and supported by experimental studies. Such complexes revealed that the benzoic ester group of both cocaine stereoisomers must rotate toward the catalytic Ser(198) for hydrolysis. Rotation of (-)-cocaine appears to be hindered by interactions of its phenyl ring with Phe(329) and Trp(430). These interactions do not occur with (+)-cocaine. Because the rate of (-)-cocaine hydrolysis is predicted to be determined mainly by the re-orientation step, it should not be greatly influenced by pH. In fact, measured rates of this reaction were nearly constant over the pH range from 5.5 to 8.5, despite large rate changes in hydrolysis of (+)-cocaine. Our models can explain why BChE hydrolyzes (+)-cocaine faster than (-)-cocaine, and they suggest that mutations of certain residues in the catalytic site could greatly improve catalytic efficiency and the potential for detoxication. Title: Sequence and analysis of chromosome 1 of the plant Arabidopsis thaliana Theologis A, Ecker JR, Palm CJ, Federspiel NA, Kaul S, White O, Alonso J, Altafi H, Araujo R and Davis RW <79 more author(s)> Theologis A, Ecker JR, Palm CJ, Federspiel NA, Kaul S, White O, Alonso J, Altafi H, Araujo R, Bowman CL, Brooks SY, Buehler E, Chan A, Chao Q, Chen H, Cheuk RF, Chin CW, Chung MK, Conn L, Conway AB, Conway AR, Creasy TH, Dewar K, Dunn P, Etgu P, Feldblyum TV, Feng J, Fong B, Fujii CY, Gill JE, Goldsmith AD, Haas B, Hansen NF, Hughes B, Huizar L, Hunter JL, Jenkins J, Johnson-Hopson C, Khan S, Khaykin E, Kim CJ, Koo HL, Kremenetskaia I, Kurtz DB, Kwan A, Lam B, Langin-Hooper S, Lee A, Lee JM, Lenz CA, Li JH, Li Y, Lin X, Liu SX, Liu ZA, Luros JS, Maiti R, Marziali A, Militscher J, Miranda M, Nguyen M, Nierman WC, Osborne BI, Pai G, Peterson J, Pham PK, Rizzo M, Rooney T, Rowley D, Sakano H, Salzberg SL, Schwartz JR, Shinn P, Southwick AM, Sun H, Tallon LJ, Tambunga G, Toriumi MJ, Town CD, Utterback T, Van Aken S, Vaysberg M, Vysotskaia VS, Walker M, Wu D, Yu G, Fraser CM, Venter JC, Davis RW (- 79) Ref: Nature, 408:816, 2000 : PubMed ESTHER: Theologis_2000_Nature_408_816 PubMedSearch: Theologis 2000 Nature 408 816 PubMedID: 11130712 Gene_locus related to this paper: arath-At1g05790, arath-At1g09280, arath-At1g09980, arath-AT1G29120, arath-AT1G52695, arath-AT1G66900, arath-At1g73750, arath-AT1G73920, arath-AT1G74640, arath-AT1G76140, arath-AT1G78210, arath-clh1, arath-F1O17.3, arath-F1O17.4, arath-F1O17.5, arath-F5I6.3, arath-At1g52700, arath-F6D8.27, arath-F6D8.32, arath-F9L1.44, arath-F9P14.11, arath-F12A4.4, arath-MES11, arath-F14G24.2, arath-F14G24.3, arath-F14I3.4, arath-F14O10.2, arath-F16N3.25, arath-LCAT2, arath-At1g34340, arath-MES15, arath-CXE6, arath-ICML1, arath-At1g72620, arath-LCAT1, arath-PLA12, arath-PLA15, arath-PLA17, arath-Q8L7S1, arath-At1g15070, arath-SCP2, arath-SCP4, arath-SCP5, arath-SCP18, arath-SCP32, arath-SCP44, arath-SCP45, arath-SCPL6, arath-F4IE65, arath-At1g30370, arath-T6L1.8, arath-T6L1.20, arath-T14P4.6, arath-MES14, arath-SCP3, arath-AXR4, arath-At1g10040, arath-ZW18, arath-pae2, arath-pae1, arath-a0a1p8awg3 Abstract The genome of the flowering plant Arabidopsis thaliana has five chromosomes. Here we report the sequence of the largest, chromosome 1, in two contigs of around 14.2 and 14.6 megabases. The contigs extend from the telomeres to the centromeric borders, regions rich in transposons, retrotransposons and repetitive elements such as the 180-base-pair repeat. The chromosome represents 25% of the genome and contains about 6,850 open reading frames, 236 transfer RNAs (tRNAs) and 12 small nuclear RNAs. There are two clusters of tRNA genes at different places on the chromosome. One consists of 27 tRNA(Pro) genes and the other contains 27 tandem repeats of tRNA(Tyr)-tRNA(Tyr)-tRNA(Ser) genes. Chromosome 1 contains about 300 gene families with clustered duplications. There are also many repeat elements, representing 8% of the sequence. Title: Sequence and analysis of chromosome 4 of the plant Arabidopsis thaliana Mayer K, Schuller C, Wambutt R, Murphy G, Volckaert G, Pohl T, Dusterhoft A, Stiekema W, Entian KD and McCombie WR <220 more author(s)> Mayer K, Schuller C, Wambutt R, Murphy G, Volckaert G, Pohl T, Dusterhoft A, Stiekema W, Entian KD, Terryn N, Harris B, Ansorge W, Brandt P, Grivell L, Rieger M, Weichselgartner M, de Simone V, Obermaier B, Mache R, Muller M, Kreis M, Delseny M, Puigdomenech P, Watson M, Schmidtheini T, Reichert B, Portatelle D, Perez-Alonso M, Boutry M, Bancroft I, Vos P, Hoheisel J, Zimmermann W, Wedler H, Ridley P, Langham SA, McCullagh B, Bilham L, Robben J, Van der Schueren J, Grymonprez B, Chuang YJ, Vandenbussche F, Braeken M, Weltjens I, Voet M, Bastiaens I, Aert R, Defoor E, Weitzenegger T, Bothe G, Ramsperger U, Hilbert H, Braun M, Holzer E, Brandt A, Peters S, van Staveren M, Dirske W, Mooijman P, Klein Lankhorst R, Rose M, Hauf J, Kotter P, Berneiser S, Hempel S, Feldpausch M, Lamberth S, Van den Daele H, De Keyser A, Buysshaert C, Gielen J, Villarroel R, De Clercq R, van Montagu M, Rogers J, Cronin A, Quail M, Bray-Allen S, Clark L, Doggett J, Hall S, Kay M, Lennard N, McLay K, Mayes R, Pettett A, Rajandream MA, Lyne M, Benes V, Rechmann S, Borkova D, Blocker H, Scharfe M, Grimm M, Lohnert TH, Dose S, de Haan M, Maarse A, Schafer M, Muller-Auer S, Gabel C, Fuchs M, Fartmann B, Granderath K, Dauner D, Herzl A, Neumann S, Argiriou A, Vitale D, Liguori R, Piravandi E, Massenet O, Quigley F, Clabauld G, Mundlein A, Felber R, Schnabl S, Hiller R, Schmidt W, Lecharny A, Aubourg S, Chefdor F, Cooke R, Berger C, Montfort A, Casacuberta E, Gibbons T, Weber N, Vandenbol M, Bargues M, Terol J, Torres A, Perez-Perez A, Purnelle B, Bent E, Johnson S, Tacon D, Jesse T, Heijnen L, Schwarz S, Scholler P, Heber S, Francs P, Bielke C, Frishman D, Haase D, Lemcke K, Mewes HW, Stocker S, Zaccaria P, Bevan M, Wilson RK, de la Bastide M, Habermann K, Parnell L, Dedhia N, Gnoj L, Schutz K, Huang E, Spiegel L, Sehkon M, Murray J, Sheet P, Cordes M, Abu-Threideh J, Stoneking T, Kalicki J, Graves T, Harmon G, Edwards J, Latreille P, Courtney L, Cloud J, Abbott A, Scott K, Johnson D, Minx P, Bentley D, Fulton B, Miller N, Greco T, Kemp K, Kramer J, Fulton L, Mardis E, Dante M, Pepin K, Hillier L, Nelson J, Spieth J, Ryan E, Andrews S, Geisel C, Layman D, Du H, Ali J, Berghoff A, Jones K, Drone K, Cotton M, Joshu C, Antonoiu B, Zidanic M, Strong C, Sun H, Lamar B, Yordan C, Ma P, Zhong J, Preston R, Vil D, Shekher M, Matero A, Shah R, Swaby IK, O'Shaughnessy A, Rodriguez M, Hoffmann J, Till S, Granat S, Shohdy N, Hasegawa A, Hameed A, Lodhi M, Johnson A, Chen E, Marra M, Martienssen R, McCombie WR (- 220) Ref: Nature, 402:769, 1999 : PubMed ESTHER: Mayer_1999_Nature_402_769 PubMedSearch: Mayer 1999 Nature 402 769 PubMedID: 10617198 Gene_locus related to this paper: arath-AT4G00500, arath-AT4G16690, arath-AT4G17480, arath-AT4G24380, arath-AT4g30610, arath-o65513, arath-o65713, arath-LPAAT, arath-f4jt64 Abstract The higher plant Arabidopsis thaliana (Arabidopsis) is an important model for identifying plant genes and determining their function. To assist biological investigations and to define chromosome structure, a coordinated effort to sequence the Arabidopsis genome was initiated in late 1996. Here we report one of the first milestones of this project, the sequence of chromosome 4. Analysis of 17.38 megabases of unique sequence, representing about 17% of the genome, reveals 3,744 protein coding genes, 81 transfer RNAs and numerous repeat elements. Heterochromatic regions surrounding the putative centromere, which has not yet been completely sequenced, are characterized by an increased frequency of a variety of repeats, new repeats, reduced recombination, lowered gene density and lowered gene expression. Roughly 60% of the predicted protein-coding genes have been functionally characterized on the basis of their homology to known genes. Many genes encode predicted proteins that are homologous to human and Caenorhabditis elegans proteins. | |||||||
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