Author Report for: Wu DNo contact information in database for Wu D
Lei K, Liang R, Tan B, Li L, Lyu Y, Wang K, Wang W, Hu X, Wu D and Wang M <1 more author(s)> Lei K, Liang R, Tan B, Li L, Lyu Y, Wang K, Wang W, Hu X, Wu D, Lin H, Wang M (- 1) Ref: Oxid Med Cell Longev, 2023:6811625, 2023 : PubMed ESTHER: Lei_2023_Oxid.Med.Cell.Longev_2023_6811625 PubMedSearch: Lei 2023 Oxid.Med.Cell.Longev 2023 6811625 PubMedID: 36703911 Abstract BACKGROUND: Lipid metabolism reprogramming played an important role in cancer occurrence, development, and immune regulation. The aim of this study was to identify and validate lipid metabolism-related genes (LMRGs) associated with the phenotype, prognosis, and immunological characteristics of lung squamous cell carcinoma (LUSC). METHODS: In the TCGA cohort, bioinformatics and survival analysis were used to identify lipid metabolism-related differentially expressed genes (DEGs) associated with the prognosis of LUSC. PTGIS/HRASLS knockdown and overexpression effects on the LUSC phenotype were analyzed in vitro experiments. Based on the expression distribution of PTGIS/HRASLS, LUSC patients were divided into two clusters by consensus clustering. Clinical information, prognosis, immune infiltration, expression of immune checkpoints, and tumor mutation burden (TMB) level were compared between the TCGA and GSE4573 cohorts. The genes related to clustering and tumor immunity were screened by weighted gene coexpression network analysis (WGCNA), and the target module genes were analyzed by functional enrichment analysis, protein-protein interaction (PPI) analysis, and immune correlation analysis. RESULTS: 191 lipid metabolism-related DEGs were identified, of which 5 genes were independent prognostic genes of LUSC. PTGIS/HRASLS were most closely related to LUSC prognosis and immunity. RT-qPCR, western blot (WB) analysis, and immunohistochemistry (IHC) showed that the expression of PTGIS was low in LUSC, while HRASLS was high. Functionally, PTGIS promoted LUSC proliferation, migration, and invasion, while HRASLS inhibited LUSC proliferation, migration, and invasion. The two clusters' expression and distribution of PTGIS/HRASLS had the opposite trend. Cluster 1 was associated with lower pathological staging (pT, pN, and pTNM stages), better prognosis, stronger immune infiltration, higher expression of immune checkpoints, and higher TMB level than cluster 2. WGCNA found that 28 genes including CD4 and IL10RA were related to the expression of PTGIS/HRASLS and tumor immune infiltration. PTGIS/HRASLS in the GSE4573 cohort had the same effect on LUSC prognosis and tumor immunity as the TCGA cohort. CONCLUSIONS: PTGIS and HRASLS can be used as new therapeutic targets for LUSC as well as biomarkers for prognosis and tumor immunity, which has positive significance for guiding the immunotherapy of LUSC. Title: Design, synthesis and biological evaluation of new multi-target scutellarein hybrids for treatment of Alzheimer's disease Luo K, Chen J, Li H, Wu D, Du Y, Zhao S, Liu T, Li L, Dai Z and Fu X <3 more author(s)> Luo K, Chen J, Li H, Wu D, Du Y, Zhao S, Liu T, Li L, Dai Z, Li Y, Zhao Y, Tang L, Fu X (- 3) Ref: Bioorg Chem, 138:106596, 2023 : PubMed ESTHER: Luo_2023_Bioorg.Chem_138_106596 PubMedSearch: Luo 2023 Bioorg.Chem 138 106596 PubMedID: 37186997 Abstract Scutellarein hybrids were designed, synthesized and evaluated as multifunctional therapeutic agents for the treatment of Alzheimer's disease (AD). Compounds 11a-i, containing a 2-hydroxymethyl-3,5,6-trimethylpyrazine fragment at the 7-position of scutellarein, were found to have balanced and effective multi-target potencies against AD. Among them, compound 11e exhibited the most potent inhibition of electric eel and human acetylcholinesterase enzymes with IC(50) values of 6.72 +/- 0.09 and 8.91 +/- 0.08 microM, respectively. In addition, compound 11e displayed not only excellent inhibition of self- and Cu(2+)-induced Abeta(1-42) aggregation (91.85% and 85.62%, respectively) but also induced disassembly of self- and Cu(2+)-induced Abeta fibrils (84.54% and 83.49% disaggregation, respectively). Moreover, 11e significantly reduced tau protein hyperphosphorylation induced by Abeta(25-35), and also exhibited good inhibition of platelet aggregation. A neuroprotective assay demonstrated that pre-treatment of PC12 cells with 11e significantly decreased lactate dehydrogenase levels, increased cell viability, enhanced expression of relevant apoptotic proteins (Bcl-2, Bax and caspase-3) and inhibited RSL3-induced PC12 cell ferroptosis. Furthermore, hCMEC/D3 and hPepT1-MDCK cell line permeability assays indicated that 11e would have optimal blood-brain barrier and intestinal absorption characteristics. In addition, in vivo studies revealed that compound 11e significantly attenuated learning and memory impairment in an AD mice model. Toxicity experiments with the compound did not reveal any safety concerns. Notably, 11e significantly reduced beta-amyloid precursor protein (APP) and beta-site APP cleaving enzyme-1 (BACE-1) protein expression in brain tissue of scopolamine-treated mice. Taken together, these outstanding properties qualified compound 11e as a promising multi-target candidate for AD therapy, worthy of further studies. Title: Exploring the binding effects and inhibiting mechanism of hyperoside to lipase using multi-spectroscopic approaches, isothermal titration calorimetry, inhibition kinetics and molecular dynamics Zeng Z, Wu D, Tang L, Hu X, Zhang J, Geng F Ref: RSC Adv, 13:6507, 2023 : PubMed ESTHER: Zeng_2023_RSC.Adv_13_6507 PubMedSearch: Zeng 2023 RSC.Adv 13 6507 PubMedID: 36845588 Abstract Hyperoside (HYP) is a flavonoid with various physiological activities. The present study examined the interaction mechanism between HYP and lipase using multi-spectrum and computer-aided techniques. Results demonstrated that the force type of HYP on lipase was mainly hydrogen bond, hydrophobic interaction force, and van der Waals force, and HYP had an excellent binding affinity with lipase at 1.576 x 10(5) M(-1). HYP dose-dependently inhibited lipase in the inhibition experiment, and its IC(50) value was 1.92 x 10(-3) M. Moreover, the results suggested that HYP could inhibit the activity by binding to essential groups. Conformational studies indicated that the conformation and microenvironment of lipase were slightly changed after the addition of HYP. Computational simulations further confirmed the structural relationships of HYP to lipase. The interaction between HYP and lipase can provide ideas for the development of functional foods related to weight loss. The results of this study help comprehend the pathological significance of HYP in biological systems, as well as its mechanism. Title: Genome-wide association identifies a missing hydrolase for tocopherol synthesis in plants Albert E, Kim S, Magallanes-Lundback M, Bao Y, Deason N, Danilo B, Wu D, Li X, Wood JC and DellaPenna D <3 more author(s)> Albert E, Kim S, Magallanes-Lundback M, Bao Y, Deason N, Danilo B, Wu D, Li X, Wood JC, Bornowski N, Gore MA, Buell CR, DellaPenna D (- 3) Ref: Proc Natl Acad Sci U S A, 119:e2113488119, 2022 : PubMed ESTHER: Albert_2022_Proc.Natl.Acad.Sci.U.S.A_119_e2113488119 PubMedSearch: Albert 2022 Proc.Natl.Acad.Sci.U.S.A 119 e2113488119 PubMedID: 35639691 Gene_locus related to this paper: maize-b6u1c6, arath-AT5G39220 Abstract SignificanceTocopherols (vitamin E) are plant-synthesized, lipid-soluble antioxidants whose dietary intake, primarily from seed oils, is essential for human health. Tocopherols contain a phytol-derived hydrophobic tail whose in vivo source has been elusive. The most significant genome-wide association signal for Arabidopsis seed tocopherols identified an uncharacterized, seed-specific esterase (VTE7) localized to the chloroplast envelope, where tocopherol synthesis occurs. VTE7 disruption and overexpression had large impacts on tissue tocopherol contents with metabolic phenotypes consistent with release of prenyl alcohols, including phytol, during chlorophyll synthesis, rather than from the bulk degradation of thylakoid chlorophylls as has long been assumed. Understanding the source of phytol for tocopherols will enable breeding and engineering plants for vitamin E biofortification and enhanced stress resilience. Title: Protective effect of Monarda didymaL. essential oil and its main component thymol on learning and memory impairment in aging mice Guo Y, Qu Y, Li W, Shen H, Cui J, Liu J, Li J, Wu D Ref: Front Pharmacol, 13:992269, 2022 : PubMed ESTHER: Guo_2022_Front.Pharmacol_13_992269 PubMedSearch: Guo 2022 Front.Pharmacol 13 992269 PubMedID: 36105199 Abstract The aging process of human beings is accompanied by the decline of learning and memory ability and progressive decline of brain function, which induces Alzheimer's Disease (AD) in serious cases and seriously affects the quality of patient's life. In recent years, more and more studies have found that natural plant antioxidants can help to improve the learning and memory impairment, reduce oxidative stress injury and aging lesions in tissues. This study aimed to investigate the effect of Monarda didymaL. essential oil and its main component thymol on learning and memory impairment in D-galactose-induced aging mice and its molecular mechanism. The composition of Monarda didymaL. essential oil was analyzed by Gas Chromatography-Mass Spectrometer (GC-MS). A mouse aging model was established by the subcutaneous injection of D-galactose in mice. The behavior changes of the mice were observed by feeding the model mice with essential oil, thymol and donepezil, and the histopathological changes of the hippocampus were observed by HE staining. And the changes of acetylcholinesterase (AchE), superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) activities, and the content of malondialdehyde (MDA) in hippocampal tissues were detected by corresponding kits. The expression of mitogen activated protein kinase (MAPK) and nuclear factor E2 related factor 2 (Nrf2) pathways related proteins were detected by western blot. Animal experimental results showed that compared with model group, the above indexes in Monarda didymaL. essential oil and thymol groups improved significantly in a dose-dependent manner. Monarda didymaL. essential oil and its main active component thymol can improve the learning and memory impairment of aging mice to some extent, and Nrf2 and MAPK pathways may be involved in its action process. Title: Maternal Low-Protein Diet during Puberty and Adulthood Aggravates Lipid Metabolism of Their Offspring Fed a High-Fat Diet in Mice Huang X, Zhuo Y, Jiang D, Zhu Y, Fang Z, Che L, Lin Y, Xu S, Hua L and Feng B <4 more author(s)> Huang X, Zhuo Y, Jiang D, Zhu Y, Fang Z, Che L, Lin Y, Xu S, Hua L, Zou Y, Huang C, Li L, Wu D, Feng B (- 4) Ref: Nutrients, 14:, 2022 : PubMed ESTHER: Huang_2022_Nutrients_14_ PubMedSearch: Huang 2022 Nutrients 14 PubMedID: 36235710 Abstract A maternal low-protein (LP) diet during gestation and/or lactation results in metabolic syndrome in their offspring. Here, we investigated the effect of maternal LP diet during puberty and adulthood on the metabolic homeostasis of glucose and lipids in offspring. Female mice were fed with normal-protein (NP) diet or a LP diet for 11 weeks. Male offspring were then fed with a high-fat diet (NP-HFD and LP-HFD groups) or standard chow diet (NP-Chow and LP-Chow groups) for 4 months. Results showed that maternal LP diet during puberty and adulthood did not alter the insulin sensitivity and hepatic lipid homeostasis of their offspring under chow diet, but aggravated insulin resistance, hepatic steatosis, and hypercholesterolemia of offspring in response to a post-weaning HFD. Accordingly, transcriptomics study with offspring's liver indicated that several genes related to glucose and lipid metabolism, including lipoprotein lipase (Lpl), long-chain acyl-CoA synthetase 1 (Acsl1), Apoprotein A1 (Apoa1), major urinary protein 19 (Mup19), cholesterol 7alpha hydroxylase (Cyp7a1) and fibroblast growth factor 1 (Fgf1), were changed by maternal LP diet. Taken together, maternal LP diet during puberty and adulthood could disarrange the expression of metabolic genes in the liver of offspring and aggravate insulin resistance and hepatic steatosis in offspring fed a HFD. Title: Enrichment of polystyrene microplastics induces histological damage, oxidative stress, Keap1-Nrf2 signaling pathway-related gene expression in loach juveniles (Paramisgurnus dabryanus) Wang X, Jian S, Zhang S, Wu D, Wang J, Gao M, Sheng J, Hong Y Ref: Ecotoxicology & Environmental Safety, 237:113540, 2022 : PubMed ESTHER: Wang_2022_Ecotoxicol.Environ.Saf_237_113540 PubMedSearch: Wang 2022 Ecotoxicol.Environ.Saf 237 113540 PubMedID: 35453027 Abstract Polystyrene microplastics (PS-MPs, particle size<5 mm) cause great harm to aquatic organisms. However, their precise effects are not completely understood. In China, placing plastic film at the pond bottom has become an important loach aquaculture mode. In this mode, MPs will affect loach health. This study investigated the enrichment of PS-MPs and its effects on the growth, liver histomorphology, antioxidant enzymes, and Keap1-Nrf2 signaling pathway-related gene expression in loach juveniles (Paramisgurnus dabryanus). The loach juveniles were raised at the concentration of 1000 microg/L fluorescent polystyrene microplastics (PS-MPs) with particle size of 0.5 microm or 5 microm for seven days, the results showed that fluorescent PS-MPs were found to be enriched in liver, intestine, and gill, and the enrichment amount was higher in liver than in gill and intestine (P < 0.05). Furthermore, the enrichment amount of different-sized PS-MPs was different in liver, gill, and intestine. The loach juveniles were cultured for 21 days in the water of the concentration of 100 or 1000 microg/L PS-MPs with particle size of 0.5 microm or 5 microm, the results showed that the survival rate, weight gain rate, and specific growth rate of loach juveniles were significantly reduced. The histological analysis revealed that PS-MPs caused liver damage. The activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-PX), and acetylcholinesterase (AChE) were decreased with the extended exposure to PS-MPs. Generally, the expressions of Nrf2 and Keap1 showed the similar change trend. From 7-14 day, the expression trend of oxidative stressed-related genes was not completely consistent with that of Nrf2 gene, but on day 21, the gene expression trend of oxidative stress-related SOD, CAT, and GSH-PX in the downstream of Keap1-Nrf2 signaling pathway was roughly consistent with that of Nrf2 gene. Basically, the change trends of these three gene expression were similar to those of their corresponding enzyme activities. This study provides theoretical basis for the toxicological effects of PS-MPs on freshwater fish. Title: Design, synthesis and evaluation of novel scutellarin and scutellarein-N,N-bis-substituted carbamate-l-amino acid derivatives as potential multifunctional therapeutics for Alzheimer's disease Wu D, Chen J, Luo K, Li H, Liu T, Li L, Dai Z, Li Y, Zhao Y, Fu X Ref: Bioorg Chem, 122:105760, 2022 : PubMed ESTHER: Wu_2022_Bioorg.Chem_122_105760 PubMedSearch: Wu 2022 Bioorg.Chem 122 105760 PubMedID: 35349945 Abstract In this study, we designed, synthesized and evaluated a series of scutellarin and scutellarein-N,N-bis-substituted carbamate-l-amino acid derivatives as multifunctional therapeutic agents for the treatment of Alzheimer's disease (AD). Compounds containing scutellarein as the parent nucleus (6a-l) had good inhibitory activity against acetyl cholinesterase (AChE), with compound 6 h exhibiting the most potent inhibition of electric eel AChE and human AChE enzymes with IC(50) values of 6.01 +/- 1.66 and 7.91 +/- 0.49 microM, respectively. In addition, compound 6 h displayed not only excellent inhibition of self- and Cu(2+)-induced Abeta(1-42) aggregation (89.17% and 86.19% inhibition) but also induced disassembly of self- and Cu(2+)-induced Abeta fibrils (84.25% and 78.73% disaggregation). Moreover, a neuroprotective assay demonstrated that pre-treatment of PC12 cells with 6 h significantly decreased lactate dehydrogenase levels, increased cell viability, enhanced expression of relevant apoptotic proteins (Bcl-2, Bax, and caspase-3) and inhibited RSL3 induced PC12 cell ferroptosis. Furthermore, hCMEC/D3 and hPepT1-MDCK cell line permeability assays indicated that 6 h would have optimal blood-brain barrier and intestinal absorption characteristics. The in vivo experimental data suggested that 6 h ameliorated learning and memory impairment in mice by decreasing AChE activity, increasing ACh levels and alleviating pathological damage of hippocampal tissue cells. These multifunctional properties highlight compound 6 h as a promising candidate for development as a multifunctional drug against AD. Title: Binding mechanism and functional evaluation of quercetin 3-rhamnoside on lipase Wu D, Duan R, Tang L, Hu X, Geng F, Sun Q, Zhang Y, Li H Ref: Food Chem, 359:129960, 2021 : PubMed ESTHER: Wu_2021_Food.Chem_359_129960 PubMedSearch: Wu 2021 Food.Chem 359 129960 PubMedID: 33945987 Abstract The interaction between lipase and quercetin 3-rhamnoside was studied by fluorescence spectroscopy, enzyme kinetics, and molecular dynamics simulation. The results showed that quercetin 3-rhamnoside had a strong quenching effect on the intrinsic fluorescence of lipase. The binding constant decreased with increasing temperature, and the number of binding sites approached 1. Thermodynamic parameters indicated that hydrogen bonding and van der Waals forces are the dominant forces when the interaction occurs. Circular dichroism spectroscopy and infrared spectroscopy proved that the ligand perturbed the structure of lipase. Enzyme kinetics results showed that quercetin 3-rhamnoside inhibited lipase, and the inhibitory effect was dose-dependent. Molecular dynamics simulation further explained the interaction mechanism and inhibitory effect. This study confirmed the inhibitory effect of quercetin 3-rhamnoside on lipase explained their binding mechanism, which will contribute to guiding the development of fat-reducing functional foods. Title: Medial septum tau accumulation induces spatial memory deficit via disrupting medial septum-hippocampus cholinergic pathway Wu D, Gao D, Yu H, Pi G, Xiong R, Lei H, Wang X, Liu E, Ye J and Wang JZ <8 more author(s)> Wu D, Gao D, Yu H, Pi G, Xiong R, Lei H, Wang X, Liu E, Ye J, Gao Y, He T, Jiang T, Sun F, Su J, Song G, Peng W, Yang Y, Wang JZ (- 8) Ref: Clin Transl Med, 11:e428, 2021 : PubMed ESTHER: Wu_2021_Clin.Transl.Med_11_e428 PubMedSearch: Wu 2021 Clin.Transl.Med 11 e428 PubMedID: 34185417 Abstract Tau accumulation and cholinergic impairment are characteristic pathologies in Alzheimer's disease (AD). However, the causal role of tau accumulation in cholinergic lesion is elusive. Here, we observed an aberrant tau accumulation in the medial septum (MS) of 3xTg and 5xFAD mice, especially in their cholinergic neurons. Overexpressing hTau in mouse MS (MS(hTau) ) for 6 months but not 3 months induced spatial memory impairment without changing object recognition and anxiety-like behavior, indicating a specific and time-dependent effect of MS-hTau accumulation on spatial cognitive functions. With increasing hTau accumulation, the MS(hTau) mice showed a time-dependent cholinergic neuron loss with reduced cholinergic projections to the hippocampus. Intraperitoneal administration of donepezil, a cholinesterase inhibitor, for 1 month ameliorated the MS-hTau-induced spatial memory deficits with preservation of MS-hippocampal cholinergic pathway and removal of tau load; and the beneficial effects of donepezil was more prominent at low dose. Proteomics revealed that MS-hTau accumulation deregulated multiple signaling pathways with numerous differentially expressed proteins (DEPs). Among them, the vacuolar protein sorting-associated protein 37D (VP37D), an autophagy-related protein, was significantly reduced in MS(hTau) mice; the reduction of VP37D was restored by donepezil, and the effect was more significant at low dose than high dose. These novel evidences reveal a causal role of tau accumulation in linking MS cholinergic lesion to hippocampus-dependent spatial cognitive damages as seen in the AD patients, and the new tau-removal and autophagy-promoting effects of donepezil may extend its application beyond simple symptom amelioration to potential disease modification. Title: Deep cerebral microbleeds are associated with poor cholinesterase inhibitor treatment response in people with Alzheimer disease Chiu WT, Lee TY, Chan L, Wu D, Huang LK, Chen DY, Lee YT, Hu CJ, Hong CT Ref: Clin Neurol Neurosurg, 195:105959, 2020 : PubMed ESTHER: Chiu_2020_Clin.Neurol.Neurosurg_195_105959 PubMedSearch: Chiu 2020 Clin.Neurol.Neurosurg 195 105959 PubMedID: 32480198 Abstract OBJECTIVES: Cholinesterase inhibitors (ChEIs) are the most effective treatment for Alzheimer disease (AD), but the response to treatment varies. Vascular lesions are associated with the pathogenesis of AD, and cerebral microbleeds (CMBs) are an indicator of hemorrhagic vascular pathology, which can be detected through susceptibility-weighted magnetic resonance imaging (SWMRI). This study investigated the association between CMBs and ChEI treatment response in patients with AD. PATIENTS AND METHODS: We reviewed the medical records of 112 Taiwanese people with mild to moderate AD and at least 2 years of ChEI treatment between 2009 and 2016. Their baseline CMBs were quantified using the Microbleed Anatomical Rating Scale on SWMRI. Cognitive function of the patients was assessed using the Mini-Mental State Examination (MMSE) and Cognitive Abilities Screening Instrument (CASI). Student t test and multivariable logistic regression were used to analyze the association between cognitive decline and CMBs. RESULTS: The mean age of the study population was 76.0+/-8.0 years. In total, 79 out of 112 patients were women. The presence of deep, but not lobar CMBs at baseline was associated with a significant cognitive decline according to the MMSE and CASI, particularly in long-term memory, attention, orientation, mental manipulation, and verbal fluency. Among deep CMBs, those in the basal ganglia and thalamus were significantly associated with cognitive decline. CONCLUSIONS: Deep CMBs, particularly those in the basal ganglia and thalamus, but not lobar CMBs, are associated with poor response to ChEI treatment in people with AD. This can serve as a biomarker for predicting ChEI treatment response. Title: Neuroprotective function of a novel hexapeptide QMDDQ from shrimp via activation of PKA/CREB/BNDF signaling pathway and its structure-activity relationship Wu D, Zhang S, Sun N, Zhu B, Lin S Ref: Journal of Agricultural and Food Chemistry, :, 2020 : PubMed ESTHER: Wu_2020_J.Agric.Food.Chem__ PubMedSearch: Wu 2020 J.Agric.Food.Chem PubMedID: 32452680 Abstract This study aimed to evaluate the neuroprotective function of shrimp-derived peptides QMDDQ and KMDDQ. Biochemical results revealed that both peptides exerted neuroprotective effects by increasing acetylcholine (ACh) content and inhibiting acetylcholinesterase (AChE) activity in PC12 cells; QMDDQ was more active than KMDDQ. COSY-NOESY spectroscopic data showed that the superior neuroprotective function of QMDDQ might be attributed to its N-terminal glutamine as it exhibited an extended spatial conformation, facilitating its interactions with AChE. QMDDQ can promote the basic energy metabolism of cells more than KMDDQ. The peptides showed neuroprotective ability due to activating the anti-apoptosis and PKA/CREB/BNDF signaling pathway. QMDDQ was selected to investigate its memory-enhancing activity in scopolamine-induced amnesic mice, revealing memory protection in mice, as it improved their performance in the Morris water maze experiment. In addition, QMDDQ increased ACh content (4.98+/-0.51 mug/mg prot) and decreased AChE activity (4.72+/-0.11 U/mg prot) in the mouse hippocampus. These data indicate the systemic mechanism through which naturally derived QMDDQ improved neuroprotection and memory ability. Title: Effect of a Novel Alpha/Beta Hydrolase Domain Protein on Tolerance of K. marxianus to Lignocellulosic Biomass Derived Inhibitors Wu D, Wang D, Hong J Ref: Front Bioeng Biotechnol, 8:844, 2020 : PubMed ESTHER: Wu_2020_Front.Bioeng.Biotechnol_8_844 PubMedSearch: Wu 2020 Front.Bioeng.Biotechnol 8 844 PubMedID: 32850717 Gene_locus related to this paper: kluma-w0t4a7 Abstract The multiple inhibitors tolerance of microorganism is important in bioconversion of lignocellulosic biomass which is a promising renewable and sustainable source for biofuels and other chemicals. The disruption of an unknown alpha/beta hydrolase, which was termed KmYME and located in mitochondria in this study, resulted in the yeast more susceptible to lignocellulose-derived inhibitors, particularly to acetic acid, furfural and 5-HMF. The KmYME disrupted strain lost more mitochondrial membrane potential, showed increased plasma membrane permeability, severer redox ratio imbalance, and increased ROS accumulation, compared with those of the non-disrupted strain in the presence of the same inhibitors. The intracellular concentration of ATP, NAD and NADP in the KmYME disrupted strain was decreased. However, disruption of KmYME did not result in a significant change of gene expression at the transcriptional level. The KmYME possessed esterase/thioesterase activity which was necessary for the resistance to inhibitors. In addition, KmYME was also required for the resistance to other stresses including ethanol, temperature, and osmotic pressure. Disruption of two possible homologous genes in S. cerevisiae also reduced its tolerance to inhibitors. Title: AGLPM and QMDDQ peptides exert a synergistic action on memory improvement against scopolamine-induced amnesiac mice Wu D, Xu X, Sun N, Li D, Zhu B, Lin S Ref: Food Funct, 11:10925, 2020 : PubMed ESTHER: Wu_2020_Food.Funct_11_10925 PubMedSearch: Wu 2020 Food.Funct 11 10925 PubMedID: 33242042 Abstract This study aimed to explore the synergistic action of pentapeptides Gln-Met-Asp-Asp-Gln (QMDDQ) and Ala-Gly-Leu-Pro-Met (AGLPM) on memory improvement against scopolamine-induced impairment in mice compared to those of either peptide alone. In behavioral tests, the codelivery of QMDDQ and AGLPM was superior to the individual supplements of either peptide alone not only in enhancing the memory ability at training trials but also in recovering the memory impairment in scopolamine-induced amnesiac mice in test trials. Furthermore, combination treatment with QMDDQ and AGLPM could significantly reduce the acetylcholinesterase (AChE) level and increase the acetylcholine (ACh) level in the hippocampus, and noticeably improve the pathological morphology of the neuron cells in hippocampal regions CA1 and CA2 and dentate gyrus (DG). The findings indicated that the combination treatment with QMDDQ and AGLPM could improve the memory function by regulating the cholinergic system. Title: Chemical composition, antioxidant, antibacterial and cholinesterase inhibitory activities of three Juniperus species Zhang Y, Wu D, Kuang S, Qing M, Ma Y, Yang T, Wang T, Li D Ref: Nat Prod Res, 34:3531, 2020 : PubMed ESTHER: Zhang_2020_Nat.Prod.Res_34_3531 PubMedSearch: Zhang 2020 Nat.Prod.Res 34 3531 PubMedID: 30822132 Abstract The chemical composition, antioxidant, antibacterial and cholinesterase inhibitory activities of three Juniperus species were studied. The contents of total phenolic and 10 phenolic compounds were highest in Juniperus rigida Sieb.et Zucc., of which catechin and cumaric acid were the predominant phenolic compounds, but were lowest in Juniperus sibirica Burgsd. GC-MS analysis showed the highest contents of essential oils were in J. rigida (92.61%), followed by Juniperus formosana Hayata (87.30%) and J. sibirica (84.89%). The a-pinene was the most dominant compound in J. rigida (23.99%) and J. formosana (9.71%), however, it has not been detected in J. sibirica. Ethanol extracts showed the higher radical scavenging capacity in ABTS, FRAP and DPPH assays than essential oils. The essential oils and ethanol extracts of J.sibirica showed the strong antibacterial activity against Salmonella typhimurium and Escherichia coli. Three Juniperus species showed certain acetylcholinesterase and butyrylcholinesterase inhibitions and J. formosana showed better cholinesterase inhibitory. Title: Identifying genes for resistant starch, slowly digestible starch, and rapidly digestible starch in rice using genome-wide association studies Zhang N, Wang M, Fu J, Shen Y, Ding Y, Wu D, Shu X, Song W Ref: Genes Genomics, 42:1227, 2020 : PubMed ESTHER: Zhang_2020_Genes.Genomics_42_1227 PubMedSearch: Zhang 2020 Genes.Genomics 42 1227 PubMedID: 32901332 Abstract BACKGROUND: The digestibility of starch is important for the nutritive value of staple food. Although several genes are responsible for resistant starch (RS) and slowly digestible starch (SDS), gaps persist concerning the molecular basis of RS and SDS formation due to the complex genetic mechanisms of starch digestibility. OBJECTIVES: The objective of this study was to identify new genes for starch digestibility in rice and interprete the genetic mechanisms of RS and SDS by GWAS. METHODS: Genome-wide association studies were conducted by associating the RS and SDS phenotypes of 104 re-sequenced rice lines to an SNP dataset of 2,288,867 sites using a compressed mixed linear model. Candidate genes were identified according to the position of the SNPs based on data from the MSU Rice Genome Annotation Project. RESULTS: Seven quantitative trait loci (QTLs) were detected to be associated with the RS content, among which the SNP 6 m1765761 was located on Waxy. Starch branching enzymes IIa (BEIIa) close to QTL qRS-I4 was detected and further identified as a specific candidate gene for RS in INDICA. Two QTLs were associated with SDS, and the LOC_Os09g09360 encoding lipase was identified as a causal gene for SDS. CONCLUSIONS: GWAS is a valid strategy to genetically dissect the formation of starch digestion properties in rice. RS formation in grains is dependent on the rice type; lipid might also contribute to starch digestibility and should be an alternative factor to improve rice starch digestibility. Title: The relationship of lipoprotein-associated phospholipase A2 activity with the seriousness of coronary artery disease Zhang H, Gao Y, Wu D, Zhang D Ref: BMC Cardiovasc Disord, 20:295, 2020 : PubMed ESTHER: Zhang_2020_BMC.Cardiovasc.Disord_20_295 PubMedSearch: Zhang 2020 BMC.Cardiovasc.Disord 20 295 PubMedID: 32546193 Abstract BACKGROUND: The level of lipoprotein-associated phospholipase A2 (LP-PLA2) in serum is independently correlated to coronary artery diseases (CAD). The aim of the study was to determine whether LP-PLA2 activity is positively associated with the seriousness of CAD. METHODS: Amount to 1056 patients suspected of having CAD underwent coronary angiography (CAG) to determine the seriousness of CAD. According to the amount of diseased coronary branches, the 1056 patients were split into three groups: single-vessel stenosis group, multiple-vessels stenosis group (> or = 2 diseased coronary branches),and control group (no diseased coronary branches). According to CAG results, electrocardiography, cardiac biomarker, and clinical presentation, all patients were split into four groups: acute myocardial infarction (AMI), unstable angina (UA), stable angina (SA), and control groups (excluding CAD). The activity of LP-PLA2 was compared statistically among the subgroups. Receiver operating characteristic analysis was applied to investigate the role of LP-PLA2 in evaluating the presence and seriousness of CAD. RESULTS: The level of LP-PLA2 increased in line with the number of diseased coronary branches. The levels of LP-PLA2 in the AMI and UA groups were observably higher when compared with the control and SA groups. LP-PLA2 had 75.6% sensitivity and 67.3% specificity for recognizing CAD, and 53.0% sensitivity and 80.3% specificity for recognizing severe coronary artery lesions. CONCLUSION: The activity of LP-PLA2 is positively correlated to the seriousness of CAD. Title: MKK6 Functions in Two Parallel MAP Kinase Cascades in Immune Signaling Lian K, Gao F, Sun T, van Wersch R, Ao K, Kong Q, Nitta Y, Wu D, Krysan P, Zhang Y Ref: Plant Physiol, 178:1284, 2018 : PubMed ESTHER: Lian_2018_Plant.Physiol_178_1284 PubMedSearch: Lian 2018 Plant.Physiol 178 1284 PubMedID: 30185442 Abstract Arabidopsis (Arabidopsis thaliana) MAP KINASE (MPK) proteins can function in multiple MAP kinase cascades and physiological processes. For instance, MPK4 functions in regulating development as well as in plant defense by participating in two independent MAP kinase cascades: the MEKK1-MKK1/MKK2-MPK4 cascade promotes basal resistance against pathogens and is guarded by the NB-LRR protein SUMM2, whereas the ANPs-MKK6-MPK4 cascade plays an essential role in cytokinesis. Here, we report a novel role for MKK6 in regulating plant immune responses. We found that MKK6 functions similarly to MKK1/MKK2 and works together with MEKK1 and MPK4 to prevent autoactivation of SUMM2-mediated defense responses. Interestingly, loss of MKK6 or ANP2/ANP3 results in constitutive activation of plant defense responses. The autoimmune phenotypes of mkk6 and anp2 anp3 mutant plants can be largely suppressed by a constitutively active mpk4 mutant. Further analysis showed that the constitutive defense response in anp2 anp3 is dependent on the defense regulators PAD4 and EDS1, but not on SUMM2, suggesting that the ANP2/ANP3-MKK6-MPK4 cascade may be guarded by a TIR-NB-LRR protein. Our study shows that MKK6 has multiple functions in plant defense responses in addition to cytokinesis. Title: Modification-free carbon dots as turn-on fluorescence probe for detection of organophosphorus pesticides Lin B, Yan Y, Guo M, Cao Y, Yu Y, Zhang T, Huang Y, Wu D Ref: Food Chem, 245:1176, 2018 : PubMed ESTHER: Lin_2018_Food.Chem_245_1176 PubMedSearch: Lin 2018 Food.Chem 245 1176 PubMedID: 29287338 Abstract It is important to detect pesticides residues due to the concern over food safety. In this work, the burning ash of waste paper was used as carbon source to synthesize carbon dots (C-dots). The fluorescence of obtained C-dots could been turn off by Fe(3+) which was from Fe(2+) oxidized by H2O2, organophosphorus pesticides could effectively inhibit the production of H2O2 by destroying the acetylcholinesterase activity, so the fluorescence of C-dots hold turning on in the presence of organophosphorus pesticides. Based on above principle that the fluorescence intensity of C-dots was proportional to the pesticides concentration, take chlorpyrifos for example, a universal method for pesticides detection was established. The linear range was 0.01-1.0mug/mL with detection limit of 3ng/mL. The method was reliable and sensitive to actual samples. The imaging of chlorpyrifos on cabbages leaves indicated this method could be used for visualization detection of organophosphorus pesticides in vegetables. Title: Antitumor potential of a novel camptothecin derivative, ZBH-ZM-06 Wu D, Zhao DW, Li YQ, Shi WG, Yin QL, Tu ZK, Yu YY, Zhong BH, Yu H, Bao WG Ref: Oncol Rep, 39:871, 2018 : PubMed ESTHER: Wu_2018_Oncol.Rep_39_871 PubMedSearch: Wu 2018 Oncol.Rep 39 871 PubMedID: 29251321 Abstract Camptothecin (CPT) is a cytotoxic quinoline alkaloid that is used clinically as an anticancer drug. However, the clinical application of CPT is limited due to its low solubility as well as serious and unfathomable side-effects. In the present study, we created a novel 10-hydroxy CPT prodrug, ZBH-ZM06. Its cellular cytotoxic activity was analyzed in terms of cellular viability, acetylcholinesterase (AchE) inhibition, DNA relaxation, cellular cycling and apoptosis properties. Our results showed that the AchE inhibition rate of 10 micromol/l ZBH-ZM-06 was 12.5%, compared to 96.5% for carbonyl-oxycamptothecin (CPT-11). In a chemical stability assay, only 4.9% of ZBH-ZM-06 remained after 4 h at pH 7.4. In addition, 10 micromol/l ZBH-ZM-06 significantly inhibited the tumor cell viability of nine tumor cell lines, compared to CPT-11 and the CPT active ingredient, 7-ethyl-10-hydroxy-camptothecin (SN38) (p<0.01-0.05). In the apoptosis assay, ZBH-ZM-06 increased the ratio of annexin V+/propidium iodide (PI)-/+ cells by flow cytometric analysis (p<0.05). Moreover, ZBH-ZM-06 activated caspase-3 and poly(ADP-ribose)polymerase (PARP) expression by immunoblotting. Furthermore, ZBH-ZM-06 induced a greater G2/M phase arrest ratio, compared to CPT-11 and SN38. These results indicated that ZBH-ZM-06 had higher antitumor activity than CPT-11 and SN38, which was shown by its: i) release of the effective ingredient; ii) growth inhibition of a broad spectrum of tumor cells; iii) inhibition of DNA topoisomerase (Topo-1); and iv) promotion of apoptosis through an intrinsic signaling pathway. Thus, ZBH-ZM-06 may be applied in the preclinic study for cancer treatment. Title: The Associations between Paraoxonase 1 L55M/Q192R Genetic Polymorphisms and the Susceptibilities of Diabetic Macroangiopathy and Diabetic Microangiopathy: A Meta-Analysis Wu C, Wu D, Lin M, Zhong Y Ref: Diabetes Ther, 9:1669, 2018 : PubMed ESTHER: Wu_2018_Diabetes.Ther_9_1669 PubMedSearch: Wu 2018 Diabetes.Ther 9 1669 PubMedID: 29987647 Abstract INTRODUCTION: Plenty of studies have focused on the associations of paraoxonase 1 Q192R and L55M genetic polymorphisms with diabetic macroangiopathy and microangiopathy susceptibility, but these associations remain controversial. Therefore, this meta-analysis was conducted to demonstrate these relationships. METHODS: Relevant studies published in English or Chinese were identified in PubMed, Embase, Wanfang Database, and CNKI by applying specific inclusion and exclusion criteria. Statistical analyses were performed using the STATA 12.0 statistical software. RESULTS: 25 Case-control studies were included in the meta-analyses: six on the association between paraoxonase 1 L55M genetic polymorphism and diabetic macroangiopathy risk, nine on the association between L55M and diabetic microangiopathy risk, 12 on the association between Q192R and diabetic macroangiopathy risk, and 12 on the association between Q192R and diabetic microangiopathy risk. Paraoxonase 1 L55M genetic polymorphism was significantly associated with diabetic microangiopathy susceptibility in the dominant model [odds ratio (OR) 0.53, 95% confidence interval (CI) 0.33-0.83, P = 0.006], the homozygous model (OR 0.37, 95% CI 0.16-0.86, P = 0.021), the allelic contrast model (OR 0.62, 95% CI 0.43-0.90, P = 0.011), the recessive model (OR 12.04, 95% CI 8.02-18.06, P = 0.000), and the heterozygous model (OR 0.57, 95% CI 0.38-0.85, P = 0.006), but L55M was not significantly associated with macroangiopathy susceptibility. Paraoxonase 1 Q192R genetic polymorphism was significantly associated with diabetic macroangiopathy susceptibility in the homozygous model (OR 1.88, 95% CI 1.06-3.32, P = 0.030), the allelic contrast model (OR 1.31, 95% CI 1.02-1.69, P = 0.038), and the recessive model (OR 1.55, 95% CI 1.11-2.16, P = 0.010), but not in the dominant and heterozygous models. Meanwhile, there was no significant association between paraoxonase 1 Q192R genetic polymorphism and diabetic microangiopathy susceptibility. CONCLUSION: Paraoxonase 1 L55M and Q192R genetic polymorphisms play important roles in diabetic macroangiopathy and microangiopathy susceptibility. Further well-designed studies based on large samples are needed to confirm these results. Title: Development and validation of a novel score for fibrosis staging in patients with chronic hepatitis B Wu D, Rao Q, Chen W, Ji F, Xie Z, Huang K, Chen E, Zhao Y, Ouyang X and Li L <5 more author(s)> Wu D, Rao Q, Chen W, Ji F, Xie Z, Huang K, Chen E, Zhao Y, Ouyang X, Zhang S, Jiang Z, Zhang L, Xu L, Gao H, Li L (- 5) Ref: Liver Int, 38:1930, 2018 : PubMed ESTHER: Wu_2018_Liver.Int_38_1930 PubMedSearch: Wu 2018 Liver.Int 38 1930 PubMedID: 29654711 Abstract BACKGROUND & AIMS: Non-invasive assessment methods for liver fibrosis are urgently needed. The present study aimed to develop a novel diagnostic model for fibrosis staging in patients with chronic hepatitis B. METHODS: A cross-sectional set of 417 chronic hepatitis B patients who underwent liver biopsy was enrolled and the METAVIR score was adopted as the reference of fibrosis staging. RESULTS: Among thyroid hormones, only the level of free tetraiodothyronine (FT4) decreased gradually with the METAVIR fibrosis score (P < .001). FibroStage, a novel diagnosis model that incorporates data on FT4, platelets, cholinesterase, gamma-glutamyl transpeptidase, and age, was developed using the deriving set (n = 219). For the diagnosis of significant fibrosis, the FibroStage model had a significantly higher area under the receiver operating curve than did the FibroIndex, Forn, and Lok models (all of P < .01) and tended to better than the fibrosis-4 (P = .0791) but comparable with the aspartate transaminase-to-platelet ratio index model (P = .1694). For the diagnosis of advanced fibrosis, FibroStage had a higher area under the receiver operating curve than did the aspartate transaminase-to-platelet ratio index, FibroIndex, Forn, and Lok models (all of P < .05) and had a comparable area under the receiver operating curve with the fibrosis-4 model (P = .2109). For the diagnosis of cirrhosis, the area under the receiver operating curve of FibroStage was higher than those of the aspartate transaminase-to-platelet ratio index, fibrosis-4, FibroIndex, and Lok (all of P < .05) models and was comparable with Forn (P = .1649). These results was validated by a validation set (n = 198). CONCLUSION: FT4 may be an indicator for fibrosis staging in chronic hepatitis B patients. FibroStage is a better model than aspartate transaminase-to-platelet ratio index, fibrosis-4, FibroIndex, Forn, and Lok for the comprehensively diagnosis of significant and advanced fibrosis and cirrhosis. Title: Novel Phosphodiesterase Inhibitors for Cognitive Improvement in Alzheimer's Disease Wu Y, Li Z, Huang YY, Wu D, Luo HB Ref: Journal of Medicinal Chemistry, 61:5467, 2018 : PubMed ESTHER: Wu_2018_J.Med.Chem_61_5467 PubMedSearch: Wu 2018 J.Med.Chem 61 5467 PubMedID: 29363967 Abstract Alzheimer's disease (AD) is one of the greatest public health challenges. Phosphodiesterases (PDEs) are a superenzyme family responsible for the hydrolysis of two second messengers: cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP). Since several PDE subfamilies are highly expressed in the human brain, the inhibition of PDEs is involved in neurodegenerative processes by regulating the concentration of cAMP and/or cGMP. Currently, PDEs are considered as promising targets for the treatment of AD since many PDE inhibitors have exhibited remarkable cognitive improvement effects in preclinical studies and over 15 of them have been subjected to clinical trials. The aim of this review is to summarize the outstanding progress that has been made by PDE inhibitors as anti-AD agents with encouraging results in preclinical studies and clinical trials. The binding affinity, pharmacokinetics, underlying mechanisms, and limitations of these PDE inhibitors in the treatment of AD are also reviewed and discussed. Title: Naringenin induces laxative effects by upregulating the expression levels of c-Kit and SCF, as well as those of aquaporin 3 in mice with loperamide-induced constipation Yin J, Liang Y, Wang D, Yan Z, Yin H, Wu D, Su Q Ref: Int J Mol Med, 41:649, 2018 : PubMed ESTHER: Yin_2018_Int.J.Mol.Med_41_649 PubMedSearch: Yin 2018 Int.J.Mol.Med 41 649 PubMedID: 29207043 Abstract Constipation is a common affliction which causes discomfort and affects the quality of life of affected individuals. Naringenin (NAR), a natural flavonoid widely found in citrus fruits and tomatoes, has been reported to exhibit various pharmacological effects, such as anti-inflammatory, anti-atherogenic, anti-mutagenic, hepatoprotective and anticancer effects. Increasing evidence has indicated that NAR has potential for use in the treatment of constipation. Thus, the aim of this study was to evaluate the laxative effects of NAR in mice with loperamide-induced (Lop-induced) constipation. The data indicated that NAR relieved Lop-induced constipation in mice based on the changes of fecal parameters (numbers, weight and water content), the intestinal charcoal transit ratio and the histological alteration. ELISA revealed that NAR regulated the production levels of gastrointestinal metabolic components, such as motilin (MTL), gastrin (Gas), endothelin (ET), substance P (SP), acetylcholinesterase (AChE) and vasoactive intestinal peptide (VIP) in serum. The expression levels of enteric nerve-related factors, glial cell line-derived neurotrophic factor (GDNF), transient receptor potential vanilloid 1 (TRPV1), nitric oxide synthase (NOS), c-Kit, stem cell factor (SCF) and aquaporin 3 (AQP3) were examined by western blot analysis and RT-PCR analysis. The results of this study suggest that NAR relieves Lop-induced constipation by increasing the levels of interstitial cells of Cajal markers (c-Kit and SCF), as well as AQP3. Thus, NAR may be effective as a candidate in patients suffering from lifestyle-induced constipation. Title: Accumulation of polystyrene microplastics in juvenile Eriocheir sinensis and oxidative stress effects in the liver Yu P, Liu Z, Wu D, Chen M, Lv W, Zhao Y Ref: Aquat Toxicol, 200:28, 2018 : PubMed ESTHER: Yu_2018_Aquat.Toxicol_200_28 PubMedSearch: Yu 2018 Aquat.Toxicol 200 28 PubMedID: 29709883 Abstract As a widespread and ubiquitous pollutant of marine ecosystems, microplastic has the potential to become an emerging global threat for aquatic organisms. The present study aims to elucidate the effects of microplastics on the growth, accumulation and oxidative stress response in the liver of Eriocheir sinensis. Fluorescent microplastic particles (diameter=0.5mum) accumulated in the gill, liver and gut tissues of E. sinensis were investigated when crabs were exposed to a concentration of 40000mug/L for 7days. A 21day toxicity test suggested that the rate of weight gain, specific growth rate, and hepatosomatic index of E. sinensis decreased with increasing microplastic concentration (0mug/L, 40mug/L, 400mug/L, 4000mug/L and 40000mug/L). The activities of AChE and GPT in crabs exposed to microplastics were lower than those in control group. GOT activity increased significantly after exposure to a low concentration of microplastics and then decreased continuously with increasing microplastic concentrations. The activities of superoxide dismutase (SOD), aspartate transaminase (GOT), glutathione (GSH), and glutathione peroxidase (GPx) increased in specimens exposed to low concentrations of microplastics (40 and 400mug/L) compared to the control and decreased in organisms exposed to high concentrations (4000 and 40000mug/L). In contrast, the activities of acetylcholinesterase, catalase (CAT), and alanine aminotransferase were significantly lower in the organisms exposed to microplastics compared to control animals. Upon exposure to increasing microplastic concentrations, the expression of genes encoding the antioxidants SOD, CAT, GPx and glutathione S-transferase in the liver decreased after first increasing. Exposure to microplastics increased the expression of the gene encoding p38 in the MAPK signaling pathway and significantly decreased the expressions of genes encoding ERK, AKT, and MEK. The results of this study demonstrate that microplastics can accumulate in the tissues of E. sinensis and negatively affect growth. In addition, exposure to microplastics causes damage and induces oxidative stress in the hepatopancreas of E. sinensis. The findings provide basic biological data for environmental and human risk assessments of microplastics of high concern. Title: Protein-mimicking nanowire-inspired electro-catalytic biosensor for probing acetylcholinesterase activity and its inhibitors Zhang Q, Hu Y, Wu D, Ma S, Wang J, Rao J, Xu L, Xu H, Shao H and Wang S <1 more author(s)> Zhang Q, Hu Y, Wu D, Ma S, Wang J, Rao J, Xu L, Xu H, Shao H, Guo Z, Wang S (- 1) Ref: Talanta, 183:258, 2018 : PubMed ESTHER: Zhang_2018_Talanta_183_258 PubMedSearch: Zhang 2018 Talanta 183 258 PubMedID: 29567174 Abstract A highly sensitive electrochemical biosensor based on the synthetized L-Cysteine-Ag(I) coordination polymer (L-Cys-Ag(I) CP), which looks like a protein-mimicking nanowire, was constructed to detect acetylcholinesterase (AChE) activity and screen its inhibitors. This sensing strategy involves the reaction of acetylcholine chloride (ACh) with acetylcholinesterase (AChE) to form choline that is in turn catalytically oxidized by choline oxidase (ChOx) to produce hydrogen peroxide (H2O2), thus L-Cys-Ag(I) CP possesses the electro-catalytic property to H2O2 reduction. Herein, the protein-mimicking nanowire-based platform was capable of investigating successive of H2O2 effectively by amperometric i-t (current-time) response, and was further applied for the turn-on electrochemical detection of AChE activity. The proposed sensor is highly sensitive (limit of detection is 0.0006 U/L) and is feasible for screening inhibitors of AChE. The model for AChE inhibition was further established and two traditional AChE inhibitors (donepezil and tacrine) were employed to verify the feasibility of the system. The IC50 of donepezil and tacrine were estimated to be 1.4nM and 3.5nM, respectively. The developed protocol provides a new and promising platform for probing AChE activity and screening its inhibitors with low cost, high sensitivity and selectivity. Title: Trefoil Factor 3, Cholinesterase and Homocysteine: Potential Predictors for Parkinson's Disease Dementia and Vascular Parkinsonism Dementia in Advanced Stage Zou J, Chen Z, Liang C, Fu Y, Wei X, Lu J, Pan M, Guo Y, Liao X and Wang Q <5 more author(s)> Zou J, Chen Z, Liang C, Fu Y, Wei X, Lu J, Pan M, Guo Y, Liao X, Xie H, Wu D, Li M, Liang L, Wang P, Wang Q (- 5) Ref: Aging Dis, 9:51, 2018 : PubMed ESTHER: Zou_2018_Aging.Dis_9_51 PubMedSearch: Zou 2018 Aging.Dis 9 51 PubMedID: 29392081 Abstract Trefoil factor 3 (TFF3), cholinesterase activity (ChE activity) and homocysteine (Hcy) play critical roles in modulating recognition, learning and memory in neurodegenerative diseases, such as Parkinson's disease dementia (PDD) and vascular parkinsonism with dementia (VPD). However, whether they can be used as reliable predictors to evaluate the severity and progression of PDD and VPD remains largely unknown. METHODS: We performed a cross-sectional study that included 92 patients with PDD, 82 patients with VPD and 80 healthy controls. Serum levels of TFF3, ChE activity and Hcy were measured. Several scales were used to rate the severity of PDD and VPD. Receivers operating characteristic (ROC) curves were applied to map the diagnostic accuracy of PDD and VPD patients compared to healthy subjects. RESULTS: Compared with healthy subjects, the serum levels of TFF3 and ChE activity were lower, while Hcy was higher in the PDD and VPD patients. These findings were especially prominent in male patients. The three biomarkers displayed differences between PDD and VPD sub-groups based on genders and UPDRS (III) scores' distribution. Interestingly, these increased serum Hcy levels were significantly and inversely correlated with decreased TFF3/ChE activity levels. There were significant correlations between TFF3/ChE activity/Hcy levels and PDD/VPD severities, including motor dysfunction, declining cognition and mood/gastrointestinal symptoms. Additionally, ROC curves for the combination of TFF3, ChE activity and Hcy showed potential diagnostic value in discriminating PDD and VPD patients from healthy controls. CONCLUSIONS: Our findings suggest that serum TFF3, ChE activity and Hcy levels may underlie the pathophysiological mechanisms of PDD and VPD. As the race to find biomarkers or predictors for these diseases intensifies, a better understanding of the roles of TFF3, ChE activity and Hcy may yield insights into the pathogenesis of PDD and VPD. Title: Interaction of erythromycin and ketoconazole on the neurological, biochemical and behavioral responses in crucian carp Liu J, Cai Y, Lu G, Dan X, Wu D, Yan Z Ref: Environ Toxicol Pharmacol, 55:14, 2017 : PubMed ESTHER: Liu_2017_Environ.Toxicol.Pharmacol_55_14 PubMedSearch: Liu 2017 Environ.Toxicol.Pharmacol 55 14 PubMedID: 28802958 Abstract The presence of pharmaceuticals in the aquatic environment has received great attention due to their potential impacts on public health. The single, as well as the combined toxicities of erythromycin (ERY) and ketoconazole (KCZ) on the bioaccumulation, biochemical and behavioral responses, were examined in crucian carp. This study focused on the uptake of contaminants, acetylcholinesterase (AChE) activity in the brain, swimming and shoaling behavior of fish. After 14days of binary exposure, the addition of KCZ at nominal concentrations of 0.2, 2 and 20mug/L significantly increased the accumulation of ERY in the brain of the fish and the bioconcentration factor of 2.08 was 2.6-fold higher than that calculated from the ERY-alone exposure. The brain AChE activity was significantly inhibited by ERY and KCZ with a significant correlation with respect to the accumulative concentration of the contaminants. The inhibition rates of swimming activity to KCZ were increased with a corresponding increase in the exposure concentration of KCZ in the single exposure. However, this manner was altered by the combined exposure. In addition, shoaling was significantly enhanced by KCZ-alone exposure, which was significantly correlated with the swimming activity. This study indicates that the mixture of the contaminants may cause endocrine disrupting effects and behavior modification especially in fish with known ecological and evolutionary consequences. Title: Toxic effects of glyphosate on diploid and triploid fin cell lines from Misgurnus anguillicaudatus Qin Y, Li X, Xiang Y, Wu D, Bai L, Li Z, Liang Y Ref: Chemosphere, 180:356, 2017 : PubMed ESTHER: Qin_2017_Chemosphere_180_356 PubMedSearch: Qin 2017 Chemosphere 180 356 PubMedID: 28415036 Abstract We examined the toxic effects of glyphosate on diploid (DIMF) and triploid (TRMF) fin cell lines from the Oriental Weather Loach Misgurnus anguillicaudatus. The LC50 values of glyphosate estimated by methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay were 315.34 and 371.77 mg/L for DIMF and TRMF, respectively. Superoxide dismutase (SOD) and glutathione-S-transferase (GST) activities in DIMF and TRMF cells gradually increased and then decreased with increasing glyphosate concentrations, reaching a maximum at 240 mg/L glyphosate. In contrast, acetylcholinesterase (AChE) activities in DIMF and TRMF decreased with increasing concentrations of glyphosate in a concentration-dependent manner. SOD and AChE activities were generally significantly higher in TRMF compared with DIMF cells (P < 0.05). The rates of micronucleus and abnormal nuclei were significantly higher in DIMF and TRMF groups treated with 80-560 mg/L glyphosate compared with the control groups (P < 0.01). The highest micronuclei rates in both DIMF and TRMF cells (both 4.30 per thousand) occurred at 400 mg/L glyphosate. There were no differences in the rates of micronuclei and abnormal nuclei between DIMF and TRMF cells at any glyphosate concentration. Cell damage, including chromatin condensation, nucleus distortion, and broken and reduced endoplasmic reticulum, mitochondria, and ribosomes, were found in both cells treated with the LC50 concentration of glyphosate. Moreover, vacuolization and apoptotic bodies occurred in glyphosate-exposed DIMF and TRMF cells, indicating apoptosis. These results indicate that glyphosate in the range of tested concentrations represent a potential risk to loach through inhibiting proliferation of diploid and triploid cell lines and induces micronuclei and apoptosis. Title: Discovery of Novel Pyrazolopyrimidinone Derivatives as Phosphodiesterase 9A Inhibitors Capable of Inhibiting Butyrylcholinesterase for Treatment of Alzheimer's Disease Yu YF, Huang YD, Zhang C, Wu XN, Zhou Q, Wu D, Wu Y, Luo HB Ref: ACS Chem Neurosci, 8:2522, 2017 : PubMed ESTHER: Yu_2017_ACS.Chem.Neurosci_8_2522 PubMedSearch: Yu 2017 ACS.Chem.Neurosci 8 2522 PubMedID: 28783948 Abstract Discovery of multitarget-directed ligands (MTDLs), targeting different factors simultaneously to control the complicated pathogenesis of Alzheimer's disease (AD), has become an important research area in recent years. Both phosphodiesterase 9A (PDE9A) and butyrylcholinesterase (BuChE) inhibitors could participate in different processes of AD to attenuate neuronal injuries and improve cognitive impairments. However, research on MTDLs combining the inhibition of PDE9A and BuChE simultaneously has not been reported yet. In this study, a series of novel pyrazolopyrimidinone-rivastigmine hybrids were designed, synthesized, and evaluated in vitro. Most compounds exhibited remarkable inhibitory activities against both PDE9A and BuChE. Compounds 6c and 6f showed the best IC(50) values against PDE9A (6c, 14 nM; 6f, 17 nM) together with the considerable inhibition against BuChE (IC(50), 6c, 3.3 microM; 6f, 0.97 microM). Their inhibitory potencies against BuChE were even higher than the anti-AD drug rivastigmine. It is worthy mentioning that both showed moderate selectivity for BuChE over acetylcholinesterase (AChE). Molecular docking studies revealed their binding patterns and explained the influence of configuration and substitutions on the inhibition of PDE9A and BuChE. Furthermore, compounds 6c and 6f exhibited negligible toxicity, which made them suitable for the further study of AD in vivo. Title: Enriched environment improves post-stroke cognitive impairment in mice by potential regulation of acetylation homeostasis in cholinergic circuits Wang X, Chen A, Wu H, Ye M, Cheng H, Jiang X, Zhang X, Wu D, Gu X and Yu D <2 more author(s)> Wang X, Chen A, Wu H, Ye M, Cheng H, Jiang X, Zhang X, Wu D, Gu X, Shen F, Shan C, Yu D (- 2) Ref: Brain Research, 1650:232, 2016 : PubMed ESTHER: Wang_2016_Brain.Res_1650_232 PubMedSearch: Wang 2016 Brain.Res 1650 232 PubMedID: 27637156 Abstract Post-stroke cognitive impairment (PSCI), commonly seen in the clinical practice, is a major factor impeding patient rehabilitation. Enriched environment (EE) intervention is a simple and effective way to improve cognitive impairment, partially due to the rebalancing of the basal forebrain-hippocampus cholinergic signaling pathway. Epigenetic changes have been identified in many cognitive disorders. However, studies on the effects of EE on epigenetic regulation of cholinergic circuits in PSCI animal models have not yet been reported. In this study, we established a photothrombotic mouse PSCI model and showed that after EE intervention, mice with PSCI had significantly improved water maze performance, better induction of hippocampal long-term potentiation (LTP), enhanced function of the basal forebrain-hippocampus cholinergic circuits of contralateral side of stroke and relatively balanced acetylation homeostasis compared to those of PSCI mice in standard environments (SE). In addition, PSCI mice in EE expressed much higher levels of p-CREB and CBP than in SE, and the chromatins bound to M-type promoter of ChAT gene were more acetylated. These results demonstrate that EE plays an important role in the improvement of PSCI and the underlying mechanism may involve in the acetylation of histones bound to the ChAT gene promoter in cholinergic circuits. Title: Phylogenetically driven sequencing of extremely halophilic archaea reveals strategies for static and dynamic osmo-response Becker EA, Seitzer PM, Tritt A, Larsen D, Krusor M, Yao AI, Wu D, Madern D, Eisen JA and Facciotti MT <1 more author(s)> Becker EA, Seitzer PM, Tritt A, Larsen D, Krusor M, Yao AI, Wu D, Madern D, Eisen JA, Darling AE, Facciotti MT (- 1) Ref: PLoS Genet, 10:e1004784, 2014 : PubMed ESTHER: Becker_2014_PLoS.Genet_10_E1004784 PubMedSearch: Becker 2014 PLoS.Genet 10 E1004784 PubMedID: 25393412 Gene_locus related to this paper: 9eury-m0a9w6, 9eury-m0c9s2, 9eury-m0cx66, 9eury-m0fpi4, halpt-m0fxy0, 9eury-m0jb87, halvd-metxa Abstract Organisms across the tree of life use a variety of mechanisms to respond to stress-inducing fluctuations in osmotic conditions. Cellular response mechanisms and phenotypes associated with osmoadaptation also play important roles in bacterial virulence, human health, agricultural production and many other biological systems. To improve understanding of osmoadaptive strategies, we have generated 59 high-quality draft genomes for the haloarchaea (a euryarchaeal clade whose members thrive in hypersaline environments and routinely experience drastic changes in environmental salinity) and analyzed these new genomes in combination with those from 21 previously sequenced haloarchaeal isolates. We propose a generalized model for haloarchaeal management of cytoplasmic osmolarity in response to osmotic shifts, where potassium accumulation and sodium expulsion during osmotic upshock are accomplished via secondary transport using the proton gradient as an energy source, and potassium loss during downshock is via a combination of secondary transport and non-specific ion loss through mechanosensitive channels. We also propose new mechanisms for magnesium and chloride accumulation. We describe the expansion and differentiation of haloarchaeal general transcription factor families, including two novel expansions of the TATA-binding protein family, and discuss their potential for enabling rapid adaptation to environmental fluxes. We challenge a recent high-profile proposal regarding the evolutionary origins of the haloarchaea by showing that inclusion of additional genomes significantly reduces support for a proposed large-scale horizontal gene transfer into the ancestral haloarchaeon from the bacterial domain. The combination of broad (17 genera) and deep (>/=5 species in four genera) sampling of a phenotypically unified clade has enabled us to uncover both highly conserved and specialized features of osmoadaptation. Finally, we demonstrate the broad utility of such datasets, for metagenomics, improvements to automated gene annotation and investigations of evolutionary processes. Title: A new monoclonal antibody, 4-1a, that binds to the amino terminus of human lipoprotein lipase Bensadoun A, Mottler CD, Pelletier C, Wu D, Seo JJ, Leung CS, Adeyo O, Goulbourne CN, Gin P and Beigneux AP <2 more author(s)> Bensadoun A, Mottler CD, Pelletier C, Wu D, Seo JJ, Leung CS, Adeyo O, Goulbourne CN, Gin P, Fong LG, Young SG, Beigneux AP (- 2) Ref: Biochimica & Biophysica Acta, 1841:970, 2014 : PubMed ESTHER: Bensadoun_2014_Biochim.Biophys.Acta_1841_970 PubMedSearch: Bensadoun 2014 Biochim.Biophys.Acta 1841 970 PubMedID: 24681165 Abstract Lipoprotein lipase (LPL) has been highly conserved through vertebrate evolution, making it challenging to generate useful antibodies. Some polyclonal antibodies against LPL have turned out to be nonspecific, and the available monoclonal antibodies (Mabs) against LPL, all of which bind to LPL's carboxyl terminus, have drawbacks for some purposes. We report a new LPL-specific monoclonal antibody, Mab 4-1a, which binds to the amino terminus of LPL (residues 5-25). Mab 4-1a binds human and bovine LPL avidly; it does not inhibit LPL catalytic activity nor does it interfere with the binding of LPL to heparin. Mab 4-1a does not bind to human hepatic lipase. Mab 4-1a binds to GPIHBP1-bound LPL and does not interfere with the ability of the LPL-GPIHBP1 complex to bind triglyceride-rich lipoproteins. Mab 4-1a will be a useful reagent for both biochemists and clinical laboratories. Title: A multi-biomarker assessment of single and combined effects of norfloxacin and sulfamethoxazole on male goldfish (Carassius auratus) Liu J, Lu G, Wu D, Yan Z Ref: Ecotoxicology & Environmental Safety, 102:12, 2014 : PubMed ESTHER: Liu_2014_Ecotoxicol.Environ.Saf_102_12 PubMedSearch: Liu 2014 Ecotoxicol.Environ.Saf 102 12 PubMedID: 24580816 Abstract In the present study, the sublethal effects of norfloxacin alone and in combination with sulfamethoxazole in goldfish (Carassius auratus) were investigated, the biomarkers including acetylcholinesterase (AChE) in brain, 7-ethoxyresorufin O-deethylase (EROD), glutathione S-transferase (GST), and superoxides dismutase (SOD) activities in liver, vitellogenin (Vtg) in serum and DNA damage in gonad were determined after 1, 2, 4 and 7 days of exposure. Brain AChE activity was significantly inhibited by norfloxacin (>/=0.4mg/L) after 4 and 7 days and the mixtures with sulfamethoxazole (>/=0.24mg/L) after 4 days of exposure, and significant concentration-response relationships were obtained. Liver EROD, GST and SOD activities were significantly increased by the individual and mixed pharmaceuticals in most cases and exhibited analogously bell-shaped concentration-response curves. Serum Vtg was increased by the highest concentration of norfloxacin and two higher concentrations of the mixtures. Higher concentrations of the test antibiotics induced significant DNA damage in a concentration- and time-dependent manner. The results indicated that selected antibiotics possesses cytotoxic and genotoxic potential against the non-target organism C. auratus. Title: Synthesis and Biological Evaluation of Novel 10-Substituted-7-ethyl-10-hydroxycamptothecin (SN-38) Prodrugs Zhou M, Liu M, He X, Yu H, Wu D, Yao Y, Fan S, Zhang P, Shi W, Zhong B Ref: Molecules, 19:19718, 2014 : PubMed ESTHER: Zhou_2014_Molecules_19_19718 PubMedSearch: Zhou 2014 Molecules 19 19718 PubMedID: 25438082 Inhibitor(s) related to this paper: SN-38 Abstract In an attempt to improve the antitumor activity and reduce the side effects of irinotecan (2), novel prodrugs of SN-38 (3) were prepared by conjugating amino acids or dipeptides to the 10-hydroxyl group of SN-38 via a carbamate linkage. The synthesized compounds completely generated SN-38 in pH 7.4 buffer or in human plasma, while remaining stable under acidic conditions. All prodrug compounds demonstrated much greater in vitro antitumor activities against HeLa cells and SGC-7901 cells than irinotecan. The most active compounds, 5h, 7c, 7d, and 7f, exhibited IC50 values that were 1000 times lower against HeLa cells and 30 times lower against SGC-7901 cells than those of irinotecan, and the inhibitory activities of these prodrugs against acetylcholinesterase (AchE) were significantly reduced, with IC50 values more than 6.8 times greater than that of irinotecan. In addition, compound 5e exhibited the same level of tumor growth inhibitory activity as irinotecan (CPT-11) in a human colon xenograft model in vivo. 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: Improving the coverage of the cyanobacterial phylum using diversity-driven genome sequencing Shih PM, Wu D, Latifi A, Axen SD, Fewer DP, Talla E, Calteau A, Cai F, Tandeau de Marsac N and Kerfeld CA <13 more author(s)> Shih PM, Wu D, Latifi A, Axen SD, Fewer DP, Talla E, Calteau A, Cai F, Tandeau de Marsac N, Rippka R, Herdman M, Sivonen K, Coursin T, Laurent T, Goodwin L, Nolan M, Davenport KW, Han CS, Rubin EM, Eisen JA, Woyke T, Gugger M, Kerfeld CA (- 13) Ref: Proc Natl Acad Sci U S A, 110:1053, 2013 : PubMed ESTHER: Shih_2013_Proc.Natl.Acad.Sci.U.S.A_110_1053 PubMedSearch: Shih 2013 Proc.Natl.Acad.Sci.U.S.A 110 1053 PubMedID: 23277585 Gene_locus related to this paper: 9cyan-k9et81, cyagp-k9p8h6, noss7-k9r280, cyaap-k9z9m7, synp3-k9ryw0, anacc-k9zr49, 9chro-l8lle9, 9cyan-l8m3q8, 9cyan-l8mv15, stac7-k9xpe1, 9cyan-k9f0z6, synp3-k9rq00, noss7-k9qm01, stac7-k9xsv0 Abstract The cyanobacterial phylum encompasses oxygenic photosynthetic prokaryotes of a great breadth of morphologies and ecologies; they play key roles in global carbon and nitrogen cycles. The chloroplasts of all photosynthetic eukaryotes can trace their ancestry to cyanobacteria. Cyanobacteria also attract considerable interest as platforms for "green" biotechnology and biofuels. To explore the molecular basis of their different phenotypes and biochemical capabilities, we sequenced the genomes of 54 phylogenetically and phenotypically diverse cyanobacterial strains. Comparison of cyanobacterial genomes reveals the molecular basis for many aspects of cyanobacterial ecophysiological diversity, as well as the convergence of complex morphologies without the acquisition of novel proteins. This phylum-wide study highlights the benefits of diversity-driven genome sequencing, identifying more than 21,000 cyanobacterial proteins with no detectable similarity to known proteins, and foregrounds the diversity of light-harvesting proteins and gene clusters for secondary metabolite biosynthesis. Additionally, our results provide insight into the distribution of genes of cyanobacterial origin in eukaryotic nuclear genomes. Moreover, this study doubles both the amount and the phylogenetic diversity of cyanobacterial genome sequence data. Given the exponentially growing number of sequenced genomes, this diversity-driven study demonstrates the perspective gained by comparing disparate yet related genomes in a phylum-wide context and the insights that are gained from it. Title: Draft genome sequence of Rahnella aquatilis strain HX2, a plant growth-promoting rhizobacterium isolated from vineyard soil in Beijing, China Guo Y, Jiao Z, Li L, Wu D, Crowley DE, Wang Y, Wu W Ref: Journal of Bacteriology, 194:6646, 2012 : PubMed ESTHER: Guo_2012_J.Bacteriol_194_6646 PubMedSearch: Guo 2012 J.Bacteriol 194 6646 PubMedID: 23144397 Gene_locus related to this paper: rahaq-h8nn14, rahac-h2iui7, rahaq-h8nx59 Abstract Rahnella aquatilis strain HX2 is a plant growth-promoting, disease-suppressive rhizobacterium that was isolated from a vineyard soil in Beijing, China. Here, we report the genome sequence of this strain, which provides a valuable resource for future research examining the mechanisms of traits associated with plant growth promotion and biocontrol. Title: Synthesis, structure-activity relationship, and pharmacophore modeling studies of pyrazole-3-carbohydrazone derivatives as dipeptidyl peptidase IV inhibitors Wu D, Jin F, Lu W, Zhu J, Li C, Wang W, Tang Y, Jiang H, Huang J and Li J <1 more author(s)> Wu D, Jin F, Lu W, Zhu J, Li C, Wang W, Tang Y, Jiang H, Huang J, Liu G, Li J (- 1) Ref: Chemical Biology Drug Des, 79:897, 2012 : PubMed ESTHER: Wu_2012_Chem.Biol.Drug.Des_79_897 PubMedSearch: Wu 2012 Chem.Biol.Drug.Des 79 897 PubMedID: 22381062 Abstract Type 2 diabetes mellitus (T2DM) is a metabolic disease and a major challenge to healthcare systems around the world. Dipeptidyl peptidase IV (DPP-4), a serine protease, has been rapidly emerging as an effective therapeutic target for the treatment for T2DM. In this study, a series of novel DPP-4 inhibitors, featuring the pyrazole-3-carbohydrazone scaffold, have been discovered using an integrated approach of structure-based virtual screening, chemical synthesis, and bioassay. Virtual screening of SPECS Database, followed by enzymatic activity assay, resulted in five micromolar or low-to-mid-micromolar inhibitory level compounds (1-5) with different scaffold. Compound 1 was selected for the further structure modifications in considering inhibitory activity, structural variability, and synthetic accessibility. Seventeen new compounds were synthesized and tested with biological assays. Nine compounds (6e, 6g, 6k-l, and 7a-e) were found to show inhibitory effects against DPP-4. Molecular docking models give rational explanation about structure-activity relationships. Based on eight DPP-4 inhibitors (1-5, 6e, 6k, and 7d), the best pharmacophore model hypo1 was obtained, consisting of one hydrogen bond donor (HBD), one hydrogen bond acceptor (HBA), and two hydrophobic (HY) features. Both docking models and pharmacophore mapping results are in agreement with pharmacological results. The present studies give some guiding information for further structural optimization and are helpful for future DPP-4 inhibitors design. Title: Theoretical study of the mechanism of proton transfer in the esterase EstB from Burkholderia gladioli Chen L, Kong X, Liang Z, Ye F, Yu K, Dai W, Wu D, Luo C, Jiang H Ref: J Phys Chem B, 115:13019, 2011 : PubMed ESTHER: Chen_2011_J.Phys.Chem.B_115_13019 PubMedSearch: Chen 2011 J.Phys.Chem.B 115 13019 PubMedID: 21910435 Abstract Esterase EstB from Burkholderia gladioli belongs to a novel class of esterases homologous to penicillin binding proteins, notably DD-peptidase and class C beta-lactamases. It can cleave the side chain acetyl ester group from cephalosporins leaving the beta-lactam ring intact, which is a feature of relevance to industrial biocatalytic applications in the production of semisynthetic cephalosporin derivatives. Due to its important role as a potential biocatalyst in industry, the significance of EstB has been greatly appreciated. However, the molecular basis for those residues involving catalysis of EstB remains elusive. By analyzing the crystal structure of EstB, we identified a conserved water molecule in active-site cavity which might mediate an intramolecular proton transfer (PT) from Lys78 to Asp186 via Tyr133. Then a combined computational approach including molecular dynamics (MD) simulations and quantum mechanics/molecular mechanics (QM/MM) calculations was employed to explore this presumable PT mode in the native enzyme. A 30 ns MD simulation of the enzyme highlights the conserved H-bond network involving Lys78, Tyr133, Asp186, and the conserved water molecule in the active site. In particular, the water molecule did not exchange with bulk solvent, indicating its structural and functional relevance. The energy profile calculated by QM/MM approach displayed a notably low PT barrier (2.2 kcal/mol) and a dramatic energy difference (14.1 kcal/mol) in reactants versus immediate products, which implies that the proposed proton shuttle is concerted and energetically favorable. Our studies offer a reasonable pathway to yield a free base by assisting Lys78 deprotonation, thereby paving the way for future studies on Ser75 activation that is a critical step in catalysis by EstB, as well as biocatalyst development by rational attempts. This PT mode would also afford clues for the forthcoming investigation on acyltransferase LovD that is homologous to EstB. Title: Rapid eye movement sleep atonia in patients with cognitive impairment Chen PC, Wu D, Chen CC, Chi NF, Kang JH, Hu CJ Ref: Journal of Neurology Sci, 305:34, 2011 : PubMed ESTHER: Chen_2011_J.Neurol.Sci_305_34 PubMedSearch: Chen 2011 J.Neurol.Sci 305 34 PubMedID: 21470640 Abstract Acetylcholine (ACh) plays an important role in cognitive function and muscle atonia in rapid eye movement (REM) sleep. This quantitative study used surface electromyography (sEMG) to investigate changes in muscular activity, which may indicate a deficiency of ACh among patients with cognitive impairment. We recruited 9 controls without dementia, 6 patients with mild cognitive impairment (MCI), and 6 patients with mild Alzheimer's disease (AD). None of the participants had sleep complaints, and all AD patients were receiving cholinesterase inhibitors. Subjects underwent polysomnography (PSG), including sEMG of the leg muscles, which was analyzed using root mean square (rms), mean frequency, and peak frequency. The average rms values during REM sleep among the control, MCI, and AD patients were 0.553 +/- 0.177, 2.886 +/- 2.865, and 0.909 +/- 0.822, respectively. The average peak frequencies during REM sleep in control, MCI, and AD patients were 0.402 +/- 0.758, 30.524 +/- 32.237, and 0.566 +/- 1.153, respectively. The average mean frequencies during REM sleep in control, MCI, and AD patients were 8.849 +/- 6.071, 34.530 +/- 25.564, and 9.553 +/- 6.308, respectively. All rms, mean frequencies, and peak frequencies increased significantly (p<0.05) in MCI patients. A deficiency of ACh may result in an increase of sEMG activity in MCI patients. Because cholinesterase inhibitors are capable of suppressing sEMG activity in AD patients, we speculate that an increase in sEMG activity is associated with a deficiency of Ach, which could be an early indicator of dementia. Title: Effects of galantamine on beta-amyloid release and beta-site cleaving enzyme 1 expression in differentiated human neuroblastoma SH-SY5Y cells Li Q, Wu D, Zhang L, Zhang Y Ref: Experimental Gerontology, 45:842, 2010 : PubMed ESTHER: Li_2010_Exp.Gerontol_45_842 PubMedSearch: Li 2010 Exp.Gerontol 45 842 PubMedID: 20600777 Abstract Galantamine (Gal) is an acetylcholinesterase inhibitor and used to treat the symptoms of Alzheimer's disease (AD). Recent studies show that Gal may affect amyloid precursor protein (APP) metabolism and increase release of secretory APPalpha (sAPPalpha). However the effect of Gal on amyloid-beta peptide (Abeta) release and beta-site cleaving enzyme 1 (BACE1) expression is still unknown. Consequently, we investigated the effect of Gal on the level of Abeta and BACE1. In a differentiated human neuroblastoma cell line (SH-SY5Y), Gal (0.3 muM) was found to significantly decrease Abeta release and BACE1 expression following treatment for 6, 12, and 24h. Increasing Gal to 0.9 muM or 10 muM had no further effect. The effect of Gal (0.3 muM for 18h) was maximal on BACE1 expression but not on Abeta secretion. At higher concentration (0.9 muM and 10 muM), Gal had no effect on the level of full-length APP but could still stimulate further decrease in Abeta secretion and release of sAPPalpha. These observations suggested that 0.3 muM Gal exerts its effect on Abeta production by inhibiting BACE1 expression, while 0.9 muM or 10 muM Gal mainly reduces Abeta production by stimulating the non-amyloidogenic pathway to decrease the amount of APP substrate available for beta-secretase cleavage. In addition, alpha7 nicotinic acetylcholine receptor (alpha7nAChR) and multiple second messengers (including PKC, MEK, and p38MAPK) were found to be involved in the regulation of Gal-inhibited Abeta release and BACE1 expression. Title: Adaptations to submarine hydrothermal environments exemplified by the genome of Nautilia profundicola Campbell BJ, Smith JL, Hanson TE, Klotz MG, Stein LY, Lee CK, Wu D, Robinson JM, Khouri HM and Cary SC <1 more author(s)> Campbell BJ, Smith JL, Hanson TE, Klotz MG, Stein LY, Lee CK, Wu D, Robinson JM, Khouri HM, Eisen JA, Cary SC (- 1) Ref: PLoS Genet, 5:e1000362, 2009 : PubMed ESTHER: Campbell_2009_PLoS.Genet_5_E1000362 PubMedSearch: Campbell 2009 PLoS.Genet 5 E1000362 PubMedID: 19197347 Gene_locus related to this paper: naupa-b9l8q7, naupa-b9l9g8, naupa-metxa Abstract Submarine hydrothermal vents are model systems for the Archaean Earth environment, and some sites maintain conditions that may have favored the formation and evolution of cellular life. Vents are typified by rapid fluctuations in temperature and redox potential that impose a strong selective pressure on resident microbial communities. Nautilia profundicola strain Am-H is a moderately thermophilic, deeply-branching Epsilonproteobacterium found free-living at hydrothermal vents and is a member of the microbial mass on the dorsal surface of vent polychaete, Alvinella pompejana. Analysis of the 1.7-Mbp genome of N. profundicola uncovered adaptations to the vent environment--some unique and some shared with other Epsilonproteobacterial genomes. The major findings included: (1) a diverse suite of hydrogenases coupled to a relatively simple electron transport chain, (2) numerous stress response systems, (3) a novel predicted nitrate assimilation pathway with hydroxylamine as a key intermediate, and (4) a gene (rgy) encoding the hallmark protein for hyperthermophilic growth, reverse gyrase. Additional experiments indicated that expression of rgy in strain Am-H was induced over 100-fold with a 20 degrees C increase above the optimal growth temperature of this bacterium and that closely related rgy genes are present and expressed in bacterial communities residing in geographically distinct thermophilic environments. N. profundicola, therefore, is a model Epsilonproteobacterium that contains all the genes necessary for life in the extreme conditions widely believed to reflect those in the Archaean biosphere--anaerobic, sulfur, H2- and CO2-rich, with fluctuating redox potentials and temperatures. In addition, reverse gyrase appears to be an important and common adaptation for mesophiles and moderate thermophiles that inhabit ecological niches characterized by rapid and frequent temperature fluctuations and, as such, can no longer be considered a unique feature of hyperthermophiles. Title: [Protective effect of glial cell line-derived neurotrophic factor infused into the tube setted into cavitas subarachnoidealis on spinal front corner motor neurons] Pan SP, Liu Q, Wu D Ref: Zhongguo Gu Shang, 22:122, 2009 : PubMed ESTHER: Pan_2009_Zhongguo.Gu.Shang_22_122 PubMedSearch: Pan 2009 Zhongguo.Gu.Shang 22 122 PubMedID: 19281023 Abstract OBJECTIVE: To investigate the effect of exogenous glial cell line-derived neurotrophic factor (GDNF) infused into the cavitas subarachnoidealis on cornu anterius medullae spinalis motor neurons after sciatic nerve axotomy. METHODS: Forty-eight healthy SD rats were divided into 2 groups randomly: GDNF group and NS group. The left sciatic nerve in rats were cut off. And then 0.9% saline (6 microl) and GDNF solution (6 microl) were injected into cavitas subarachnoidealis at L4-L6 in NS group and GDNF group,respectively. The rats were sacrificed on postoperative 1, 2, 4 and 8 weeks respectively. Their specimen of L4-L6 spinal cord were taken at different time and sectioned. The HE staining, Nissl staining and cholinesterase (ChE) staining in motor neurons were used for counting of motor neurons. RESULTS: In GDNF group the number of motor neurons in cornu anterius medullae spinalis and the ChE activity were higher than that of NS group. CONCLUSION: The exogenous GDNF infused into the cavitas subarachnoidealis are supposed to protect the degenerated spinal motor neuron from death after sciatic nerve injury. Title: Crystal structure of human esterase D: a potential genetic marker of retinoblastoma Wu D, Li Y, Song G, Zhang D, Shaw N, Liu ZJ Ref: FASEB Journal, 23:1441, 2009 : PubMed ESTHER: Wu_2009_Faseb.J_23_1441 PubMedSearch: Wu 2009 Faseb.J 23 1441 PubMedID: 19126594 Gene_locus related to this paper: human-ESD Abstract Retinoblastoma (RB), a carcinoma of the retina, is caused by mutations in the long arm of chromosome 13, band 13q14. The esterase D (ESD) gene maps at a similar location as the RB gene locus and therefore serves as a potential marker for the prognosis of retinoblastoma. Because very little is known about the structure and function of ESD, we determined the 3-dimensional structure of the enzyme at 1.5 A resolution using X-ray crystallography. ESD shows a single domain with an alpha/beta-hydrolase fold. A number of insertions are observed in the canonical alpha/beta-hydrolase fold. The active site is located in a positively charged, shallow cleft on the surface lined by a number of aromatic residues. Superimposition studies helped identify the typical catalytic triad residues--Ser-153, His264, and Asp230--involved in catalysis. Mutagenesis of any of the catalytic triad residues to alanine abolished the enzyme activity. Backbone amides of Leu54 and Met150 are involved in the formation of the oxyanion hole. Interestingly, a M150A mutation increased the enzyme activity by 62%. The structure of human ESD determined in this study will aid the elucidation of the physiological role of the enzyme in the human body and will assist in the early diagnosis of retinoblastoma. Title: Complete genome sequence of the aerobic CO-oxidizing thermophile Thermomicrobium roseum Wu D, Raymond J, Wu M, Chatterji S, Ren Q, Graham JE, Bryant DA, Robb F, Colman A and Eisen JA <4 more author(s)> Wu D, Raymond J, Wu M, Chatterji S, Ren Q, Graham JE, Bryant DA, Robb F, Colman A, Tallon LJ, Badger JH, Madupu R, Ward NL, Eisen JA (- 4) Ref: PLoS ONE, 4:e4207, 2009 : PubMed ESTHER: Wu_2009_PLoS.ONE_4_E4207 PubMedSearch: Wu 2009 PLoS.ONE 4 E4207 PubMedID: 19148287 Gene_locus related to this paper: therp-b9kxz7, therp-b9l2i8, therp-b9l396 Abstract In order to enrich the phylogenetic diversity represented in the available sequenced bacterial genomes and as part of an "Assembling the Tree of Life" project, we determined the genome sequence of Thermomicrobium roseum DSM 5159. T. roseum DSM 5159 is a red-pigmented, rod-shaped, Gram-negative extreme thermophile isolated from a hot spring that possesses both an atypical cell wall composition and an unusual cell membrane that is composed entirely of long-chain 1,2-diols. Its genome is composed of two circular DNA elements, one of 2,006,217 bp (referred to as the chromosome) and one of 919,596 bp (referred to as the megaplasmid). Strikingly, though few standard housekeeping genes are found on the megaplasmid, it does encode a complete system for chemotaxis including both chemosensory components and an entire flagellar apparatus. This is the first known example of a complete flagellar system being encoded on a plasmid and suggests a straightforward means for lateral transfer of flagellum-based motility. Phylogenomic analyses support the recent rRNA-based analyses that led to T. roseum being removed from the phylum Thermomicrobia and assigned to the phylum Chloroflexi. Because T. roseum is a deep-branching member of this phylum, analysis of its genome provides insights into the evolution of the Chloroflexi. In addition, even though this species is not photosynthetic, analysis of the genome provides some insight into the origins of photosynthesis in the Chloroflexi. Metabolic pathway reconstructions and experimental studies revealed new aspects of the biology of this species. For example, we present evidence that T. roseum oxidizes CO aerobically, making it the first thermophile known to do so. In addition, we propose that glycosylation of its carotenoids plays a crucial role in the adaptation of the cell membrane to this bacterium's thermophilic lifestyle. Analyses of published metagenomic sequences from two hot springs similar to the one from which this strain was isolated, show that close relatives of T. roseum DSM 5159 are present but have some key differences from the strain sequenced. Title: The Calyptogena magnifica chemoautotrophic symbiont genome Newton IL, Woyke T, Auchtung TA, Dilly GF, Dutton RJ, Fisher MC, Fontanez KM, Lau E, Stewart FJ and Cavanaugh CM <6 more author(s)> Newton IL, Woyke T, Auchtung TA, Dilly GF, Dutton RJ, Fisher MC, Fontanez KM, Lau E, Stewart FJ, Richardson PM, Barry KW, Saunders E, Detter JC, Wu D, Eisen JA, Cavanaugh CM (- 6) Ref: Science, 315:998, 2007 : PubMed ESTHER: Newton_2007_Science_315_998 PubMedSearch: Newton 2007 Science 315 998 PubMedID: 17303757 Gene_locus related to this paper: rutmc-a1aw39, rutmc-a1ax96 Abstract Chemoautotrophic endosymbionts are the metabolic cornerstone of hydrothermal vent communities, providing invertebrate hosts with nearly all of their nutrition. The Calyptogena magnifica (Bivalvia: Vesicomyidae) symbiont, Candidatus Ruthia magnifica, is the first intracellular sulfur-oxidizing endosymbiont to have its genome sequenced, revealing a suite of metabolic capabilities. The genome encodes major chemoautotrophic pathways as well as pathways for biosynthesis of vitamins, cofactors, and all 20 amino acids required by the clam. Title: Effect of molecular sieves on lipase-catalyzed esterification of rutin with stearic acid Duan Y, Du Z, Yao Y, Li R, Wu D Ref: Journal of Agricultural and Food Chemistry, 54:6219, 2006 : PubMed ESTHER: Duan_2006_J.Agric.Food.Chem_54_6219 PubMedSearch: Duan 2006 J.Agric.Food.Chem 54 6219 PubMedID: 16910711 Abstract Rutin was acylated with stearic acid in the esterification reaction catalyzed by immobilized Candida antarctica lipase B (Novozym 435) in tert-amyl alcohol with and without molecular sieves. The lipophilic rutin stearate was synthesized by this method, which had a potential use in food, cosmetics, and pharmacy. The structure of rutin stearate was characterized by spectral methods of 1H NMR and 13C NMR, Fourier transform infrared, and UV-vis. The results suggested that the regioselectivity of the lipase-catalyzed esterification of rutin was specific at the C(4''')-position of the rhamnose moiety. It was found that the addition of molecular sieves increased both the reaction rate and the yield. The time effect of adding molecular sieves in the reaction system on the conversion of rutin stearate was further examined. Instead of adding molecular sieves at the beginning of the reaction, the addition of molecular sieves at 5, 18, 24, 31, and 44 h after the beginning of the reaction was also applied. The final conversion for the case to add molecular sieves at 24 h after the beginning of reaction was the highest, with the conversion yield about 46%. Title: Macronuclear genome sequence of the ciliate Tetrahymena thermophila, a model eukaryote Eisen JA, Coyne RS, Wu M, Wu D, Thiagarajan M, Wortman JR, Badger JH, Ren Q, Amedeo P and Orias E <43 more author(s)> Eisen JA, Coyne RS, Wu M, Wu D, Thiagarajan M, Wortman JR, Badger JH, Ren Q, Amedeo P, Jones KM, Tallon LJ, Delcher AL, Salzberg SL, Silva JC, Haas BJ, Majoros WH, Farzad M, Carlton JM, Smith RK, Jr., Garg J, Pearlman RE, Karrer KM, Sun L, Manning G, Elde NC, Turkewitz AP, Asai DJ, Wilkes DE, Wang Y, Cai H, Collins K, Stewart BA, Lee SR, Wilamowska K, Weinberg Z, Ruzzo WL, Wloga D, Gaertig J, Frankel J, Tsao CC, Gorovsky MA, Keeling PJ, Waller RF, Patron NJ, Cherry JM, Stover NA, Krieger CJ, del Toro C, Ryder HF, Williamson SC, Barbeau RA, Hamilton EP, Orias E (- 43) Ref: PLoS Biol, 4:e286, 2006 : PubMed ESTHER: Eisen_2006_PLoS.Biol_4_e286 PubMedSearch: Eisen 2006 PLoS.Biol 4 e286 PubMedID: 16933976 Gene_locus related to this paper: tetts-i7mam3, tetts-i7ml33 Abstract The ciliate Tetrahymena thermophila is a model organism for molecular and cellular biology. Like other ciliates, this species has separate germline and soma functions that are embodied by distinct nuclei within a single cell. The germline-like micronucleus (MIC) has its genome held in reserve for sexual reproduction. The soma-like macronucleus (MAC), which possesses a genome processed from that of the MIC, is the center of gene expression and does not directly contribute DNA to sexual progeny. We report here the shotgun sequencing, assembly, and analysis of the MAC genome of T. thermophila, which is approximately 104 Mb in length and composed of approximately 225 chromosomes. Overall, the gene set is robust, with more than 27,000 predicted protein-coding genes, 15,000 of which have strong matches to genes in other organisms. The functional diversity encoded by these genes is substantial and reflects the complexity of processes required for a free-living, predatory, single-celled organism. This is highlighted by the abundance of lineage-specific duplications of genes with predicted roles in sensing and responding to environmental conditions (e.g., kinases), using diverse resources (e.g., proteases and transporters), and generating structural complexity (e.g., kinesins and dyneins). In contrast to the other lineages of alveolates (apicomplexans and dinoflagellates), no compelling evidence could be found for plastid-derived genes in the genome. UGA, the only T. thermophila stop codon, is used in some genes to encode selenocysteine, thus making this organism the first known with the potential to translate all 64 codons in nuclear genes into amino acids. We present genomic evidence supporting the hypothesis that the excision of DNA from the MIC to generate the MAC specifically targets foreign DNA as a form of genome self-defense. The combination of the genome sequence, the functional diversity encoded therein, and the presence of some pathways missing from other model organisms makes T. thermophila an ideal model for functional genomic studies to address biological, biomedical, and biotechnological questions of fundamental importance. Title: Metabolic complementarity and genomics of the dual bacterial symbiosis of sharpshooters Wu D, Daugherty SC, Van Aken SE, Pai GH, Watkins KL, Khouri H, Tallon LJ, Zaborsky JM, Dunbar HE and Eisen JA <2 more author(s)> Wu D, Daugherty SC, Van Aken SE, Pai GH, Watkins KL, Khouri H, Tallon LJ, Zaborsky JM, Dunbar HE, Tran PL, Moran NA, Eisen JA (- 2) Ref: PLoS Biol, 4:e188, 2006 : PubMed ESTHER: Wu_2006_PLoS.Biol_4_E188 PubMedSearch: Wu 2006 PLoS.Biol 4 E188 PubMedID: 16729848 Gene_locus related to this paper: bauch-q1lsz2 Abstract Mutualistic intracellular symbiosis between bacteria and insects is a widespread phenomenon that has contributed to the global success of insects. The symbionts, by provisioning nutrients lacking from diets, allow various insects to occupy or dominate ecological niches that might otherwise be unavailable. One such insect is the glassy-winged sharpshooter (Homalodisca coagulata), which feeds on xylem fluid, a diet exceptionally poor in organic nutrients. Phylogenetic studies based on rRNA have shown two types of bacterial symbionts to be coevolving with sharpshooters: the gamma-proteobacterium Baumannia cicadellinicola and the Bacteroidetes species Sulcia muelleri. We report here the sequencing and analysis of the 686,192-base pair genome of B. cicadellinicola and approximately 150 kilobase pairs of the small genome of S. muelleri, both isolated from H. coagulata. Our study, which to our knowledge is the first genomic analysis of an obligate symbiosis involving multiple partners, suggests striking complementarity in the biosynthetic capabilities of the two symbionts: B. cicadellinicola devotes a substantial portion of its genome to the biosynthesis of vitamins and cofactors required by animals and lacks most amino acid biosynthetic pathways, whereas S. muelleri apparently produces most or all of the essential amino acids needed by its host. This finding, along with other results of our genome analysis, suggests the existence of metabolic codependency among the two unrelated endosymbionts and their insect host. This dual symbiosis provides a model case for studying correlated genome evolution and genome reduction involving multiple organisms in an intimate, obligate mutualistic relationship. In addition, our analysis provides insight for the first time into the differences in symbionts between insects (e.g., aphids) that feed on phloem versus those like H. coagulata that feed on xylem. Finally, the genomes of these two symbionts provide potential targets for controlling plant pathogens such as Xylella fastidiosa, a major agroeconomic problem, for which H. coagulata and other sharpshooters serve as vectors of transmission. Title: Structural insights and functional implications of choline acetyltransferase Govindasamy L, Pedersen B, Lian W, Kukar T, Gu Y, Jin S, Agbandje-McKenna M, Wu D, McKenna R Ref: J Struct Biol, 148:226, 2004 : PubMed ESTHER: Govindasamy_2004_J.Struct.Biol_148_226 PubMedSearch: Govindasamy 2004 J.Struct.Biol 148 226 PubMedID: 15477102 Abstract The biosynthetic enzyme for the neurotransmitter acetylcholine, choline acetyltransferase (ChAT) (E.C. 2.3.1.6), is essential for the development and neuronal activities of cholinergic systems involved in many fundamental brain functions. ChAT catalyzes the transfer of an acetyl group from acetyl-coenzyme A to choline to form the neurotransmitter acetylcholine. Since its discovery more than 60 years ago much research has been devoted to the kinetic studies of this enzyme. For the first time we report the crystal structure of rat ChAT (rChAT) to 1.55 A resolution. The structure of rChAT is a monomer and consists of two domains with an interfacial active site tunnel. This structure, with the modeled substrate binding, provides critical insights into the molecular basis for the production of acetylcholine and may further our understanding of disease causing mutations. Title: Crystallization and preliminary X-ray crystallographic studies on recombinant rat choline acetyltransferase Lian W, Gu Y, Pedersen B, Kukar T, Govindasamy L, Agbandje-McKenna M, Jin S, McKenna R, Wu D Ref: Acta Crystallographica D Biol Crystallogr, 60:374, 2004 : PubMed ESTHER: Lian_2004_Acta.Crystallogr.D.Biol.Crystallogr_60_374 PubMedSearch: Lian 2004 Acta.Crystallogr.D.Biol.Crystallogr 60 374 PubMedID: 14747730 Abstract Choline acetyltransferase (ChAT) catalyzes the biosynthesis of the neurotransmitter acetylcholine from acetyl-CoA and choline in cholinergic neurons. Rat ChAT (rChAT) was overexpressed in Escherichia coli, purified by affinity chromatography and crystallized. Diffraction data were collected from a single crystal under cryoconditions at the F1 beamline at the Cornell High Energy Synchrotron Source, with a maximal useful diffraction pattern to 1.55 A resolution. The crystals were shown to belong to the orthorhombic space group P2(1)2(1)2(1), with unit-cell parameters a = 138.97, b = 77.67, c = 59.67 A and a scaling R(sym) of 0.054 for 72 446 unique reflections. Packing considerations indicate there to be one molecule per asymmetric unit. It is expected that in the near future the structure of rChAT will be obtained using molecular-replacement methods. Elucidation of the structure of rChAT will aid in the development of therapeutic agents for Alzheimer's disease. Title: Genome of Geobacter sulfurreducens: metal reduction in subsurface environments Methe BA, Nelson KE, Eisen JA, Paulsen IT, Nelson W, Heidelberg JF, Wu D, Wu M, Ward N and Fraser CM <24 more author(s)> Methe BA, Nelson KE, Eisen JA, Paulsen IT, Nelson W, Heidelberg JF, Wu D, Wu M, Ward N, Beanan MJ, Dodson RJ, Madupu R, Brinkac LM, Daugherty SC, DeBoy RT, Durkin AS, Gwinn M, Kolonay JF, Sullivan SA, Haft DH, Selengut J, Davidsen TM, Zafar N, White O, Tran B, Romero C, Forberger HA, Weidman J, Khouri H, Feldblyum TV, Utterback TR, Van Aken SE, Lovley DR, Fraser CM (- 24) Ref: Science, 302:1967, 2003 : PubMed ESTHER: Methe_2003_Science_302_1967 PubMedSearch: Methe 2003 Science 302 1967 PubMedID: 14671304 Gene_locus related to this paper: geosl-q74a54, geosl-q74ac8, geosl-q74eb1, geosl-q747u4, geosl-q747v8, geosl-q749w4 Abstract The complete genome sequence of Geobacter sulfurreducens, a delta-proteobacterium, reveals unsuspected capabilities, including evidence of aerobic metabolism, one-carbon and complex carbon metabolism, motility, and chemotactic behavior. These characteristics, coupled with the possession of many two-component sensors and many c-type cytochromes, reveal an ability to create alternative, redundant, electron transport networks and offer insights into the process of metal ion reduction in subsurface environments. As well as playing roles in the global cycling of metals and carbon, this organism clearly has the potential for use in bioremediation of radioactive metals and in the generation of electricity. Title: The sequence of the human genome Venter JC, Adams MD, Myers EW, Li PW, Mural RJ, Sutton GG, Smith HO, Yandell M, Evans CA and Zhu X <264 more author(s)> Venter JC, Adams MD, Myers EW, Li PW, Mural RJ, Sutton GG, Smith HO, Yandell M, Evans CA, Holt RA, Gocayne JD, Amanatides P, Ballew RM, Huson DH, Wortman JR, Zhang Q, Kodira CD, Zheng XH, Chen L, Skupski M, Subramanian G, Thomas PD, Zhang J, Gabor Miklos GL, Nelson C, Broder S, Clark AG, Nadeau J, McKusick VA, Zinder N, Levine AJ, Roberts RJ, Simon M, Slayman C, Hunkapiller M, Bolanos R, Delcher A, Dew I, Fasulo D, Flanigan M, Florea L, Halpern A, Hannenhalli S, Kravitz S, Levy S, Mobarry C, Reinert K, Remington K, Abu-Threideh J, Beasley E, Biddick K, Bonazzi V, Brandon R, Cargill M, Chandramouliswaran I, Charlab R, Chaturvedi K, Deng Z, Di Francesco V, Dunn P, Eilbeck K, Evangelista C, Gabrielian AE, Gan W, Ge W, Gong F, Gu Z, Guan P, Heiman TJ, Higgins ME, Ji RR, Ke Z, Ketchum KA, Lai Z, Lei Y, Li Z, Li J, Liang Y, Lin X, Lu F, Merkulov GV, Milshina N, Moore HM, Naik AK, Narayan VA, Neelam B, Nusskern D, Rusch DB, Salzberg S, Shao W, Shue B, Sun J, Wang Z, Wang A, Wang X, Wang J, Wei M, Wides R, Xiao C, Yan C, Yao A, Ye J, Zhan M, Zhang W, Zhang H, Zhao Q, Zheng L, Zhong F, Zhong W, Zhu S, Zhao S, Gilbert D, Baumhueter S, Spier G, Carter C, Cravchik A, Woodage T, Ali F, An H, Awe A, Baldwin D, Baden H, Barnstead M, Barrow I, Beeson K, Busam D, Carver A, Center A, Cheng ML, Curry L, Danaher S, Davenport L, Desilets R, Dietz S, Dodson K, Doup L, Ferriera S, Garg N, Gluecksmann A, Hart B, Haynes J, Haynes C, Heiner C, Hladun S, Hostin D, Houck J, Howland T, Ibegwam C, Johnson J, Kalush F, Kline L, Koduru S, Love A, Mann F, May D, McCawley S, McIntosh T, McMullen I, Moy M, Moy L, Murphy B, Nelson K, Pfannkoch C, Pratts E, Puri V, Qureshi H, Reardon M, Rodriguez R, Rogers YH, Romblad D, Ruhfel B, Scott R, Sitter C, Smallwood M, Stewart E, Strong R, Suh E, Thomas R, Tint NN, Tse S, Vech C, Wang G, Wetter J, Williams S, Williams M, Windsor S, Winn-Deen E, Wolfe K, Zaveri J, Zaveri K, Abril JF, Guigo R, Campbell MJ, Sjolander KV, Karlak B, Kejariwal A, Mi H, Lazareva B, Hatton T, Narechania A, Diemer K, Muruganujan A, Guo N, Sato S, Bafna V, Istrail S, Lippert R, Schwartz R, Walenz B, Yooseph S, Allen D, Basu A, Baxendale J, Blick L, Caminha M, Carnes-Stine J, Caulk P, Chiang YH, Coyne M, Dahlke C, Mays A, Dombroski M, Donnelly M, Ely D, Esparham S, Fosler C, Gire H, Glanowski S, Glasser K, Glodek A, Gorokhov M, Graham K, Gropman B, Harris M, Heil J, Henderson S, Hoover J, Jennings D, Jordan C, Jordan J, Kasha J, Kagan L, Kraft C, Levitsky A, Lewis M, Liu X, Lopez J, Ma D, Majoros W, McDaniel J, Murphy S, Newman M, Nguyen T, Nguyen N, Nodell M, Pan S, Peck J, Peterson M, Rowe W, Sanders R, Scott J, Simpson M, Smith T, Sprague A, Stockwell T, Turner R, Venter E, Wang M, Wen M, Wu D, Wu M, Xia A, Zandieh A, Zhu X (- 264) Ref: Science, 291:1304, 2001 : PubMed ESTHER: Venter_2001_Science_291_1304 PubMedSearch: Venter 2001 Science 291 1304 PubMedID: 11181995 Gene_locus related to this paper: human-AADAC, human-ABHD1, human-ABHD10, human-ABHD11, human-ACHE, human-BCHE, human-LDAH, human-ABHD18, human-CMBL, human-ABHD17A, human-KANSL3, human-LIPA, human-LYPLAL1, human-NDRG2, human-NLGN3, human-NLGN4X, human-NLGN4Y, human-PAFAH2, human-PREPL, human-RBBP9, human-SPG21 Abstract A 2.91-billion base pair (bp) consensus sequence of the euchromatic portion of the human genome was generated by the whole-genome shotgun sequencing method. The 14.8-billion bp DNA sequence was generated over 9 months from 27,271,853 high-quality sequence reads (5.11-fold coverage of the genome) from both ends of plasmid clones made from the DNA of five individuals. Two assembly strategies-a whole-genome assembly and a regional chromosome assembly-were used, each combining sequence data from Celera and the publicly funded genome effort. The public data were shredded into 550-bp segments to create a 2.9-fold coverage of those genome regions that had been sequenced, without including biases inherent in the cloning and assembly procedure used by the publicly funded group. This brought the effective coverage in the assemblies to eightfold, reducing the number and size of gaps in the final assembly over what would be obtained with 5.11-fold coverage. The two assembly strategies yielded very similar results that largely agree with independent mapping data. The assemblies effectively cover the euchromatic regions of the human chromosomes. More than 90% of the genome is in scaffold assemblies of 100,000 bp or more, and 25% of the genome is in scaffolds of 10 million bp or larger. Analysis of the genome sequence revealed 26,588 protein-encoding transcripts for which there was strong corroborating evidence and an additional approximately 12,000 computationally derived genes with mouse matches or other weak supporting evidence. Although gene-dense clusters are obvious, almost half the genes are dispersed in low G+C sequence separated by large tracts of apparently noncoding sequence. Only 1.1% of the genome is spanned by exons, whereas 24% is in introns, with 75% of the genome being intergenic DNA. Duplications of segmental blocks, ranging in size up to chromosomal lengths, are abundant throughout the genome and reveal a complex evolutionary history. Comparative genomic analysis indicates vertebrate expansions of genes associated with neuronal function, with tissue-specific developmental regulation, and with the hemostasis and immune systems. DNA sequence comparisons between the consensus sequence and publicly funded genome data provided locations of 2.1 million single-nucleotide polymorphisms (SNPs). A random pair of human haploid genomes differed at a rate of 1 bp per 1250 on average, but there was marked heterogeneity in the level of polymorphism across the genome. Less than 1% of all SNPs resulted in variation in proteins, but the task of determining which SNPs have functional consequences remains an open challenge. Title: [Analysis of association between gene polymorphisms of microsomal epoxide hydrolase (EPHX1) and infant birthweight] Wu D, Zhang XQ, Yang F, Hong XM, Ju F, Chen DF Ref: Yi Chuan Xue Bao, 28:595, 2001 : PubMed ESTHER: Wu_2001_Yi.Chuan.Xue.Bao_28_595 PubMedSearch: Wu 2001 Yi.Chuan.Xue.Bao 28 595 PubMedID: 11480169 Abstract We investigated association between genetic polymorphisms of EPHX1 in mother and infant birthweight. Data of 342 female workers were collected in textile mill. A total of 342 mothers were genotyped for the His139Arg polymorphism of EPHX1 by a polymerase chain reaction-restriction fragment length polymorphism assay. Using multiple linear regression models, we estimated the adjusted association between polymorphisms of EPHX1 and birthweight, with adjusted for potential confounders. We found that polymorphisms of EPHX1 were closely associated with reduced birthweight (beta +/- SE = -149 g +/- 56, P = 0.0083) after adjustment for major cofounders. In subgroup of passive smoking analysis, the polymorphisms of EPHX1 were highly associted with birthweight for those with passive smoking (beta +/- SE = -234 g +/- 88, P = 0.0088); The significant association of EPHX1 polymorphisms with reduced birthweight were showed for those with working stress (beta +/- SE = -157 g +/- 59, P = 0.0079). Our data provide polymorphisms of EPHX1 in mothers were significant association with birthweight of their infant, and showed gene-environmental interaction in relation to birthweight. Title: The genome sequence of Drosophila melanogaster Adams MD, Celniker SE, Holt RA, Evans CA, Gocayne JD, Amanatides PG, Scherer SE, Li PW, Hoskins RA and Venter JC <185 more author(s)> Adams MD, Celniker SE, Holt RA, Evans CA, Gocayne JD, Amanatides PG, Scherer SE, Li PW, Hoskins RA, Galle RF, George RA, Lewis SE, Richards S, Ashburner M, Henderson SN, Sutton GG, Wortman JR, Yandell MD, Zhang Q, Chen LX, Brandon RC, Rogers YH, Blazej RG, Champe M, Pfeiffer BD, Wan KH, Doyle C, Baxter EG, Helt G, Nelson CR, Gabor GL, Abril JF, Agbayani A, An HJ, Andrews-Pfannkoch C, Baldwin D, Ballew RM, Basu A, Baxendale J, Bayraktaroglu L, Beasley EM, Beeson KY, Benos PV, Berman BP, Bhandari D, Bolshakov S, Borkova D, Botchan MR, Bouck J, Brokstein P, Brottier P, Burtis KC, Busam DA, Butler H, Cadieu E, Center A, Chandra I, Cherry JM, Cawley S, Dahlke C, Davenport LB, Davies P, de Pablos B, Delcher A, Deng Z, Mays AD, Dew I, Dietz SM, Dodson K, Doup LE, Downes M, Dugan-Rocha S, Dunkov BC, Dunn P, Durbin KJ, Evangelista CC, Ferraz C, Ferriera S, Fleischmann W, Fosler C, Gabrielian AE, Garg NS, Gelbart WM, Glasser K, Glodek A, Gong F, Gorrell JH, Gu Z, Guan P, Harris M, Harris NL, Harvey D, Heiman TJ, Hernandez JR, Houck J, Hostin D, Houston KA, Howland TJ, Wei MH, Ibegwam C, Jalali M, Kalush F, Karpen GH, Ke Z, Kennison JA, Ketchum KA, Kimmel BE, Kodira CD, Kraft C, Kravitz S, Kulp D, Lai Z, Lasko P, Lei Y, Levitsky AA, Li J, Li Z, Liang Y, Lin X, Liu X, Mattei B, McIntosh TC, McLeod MP, McPherson D, Merkulov G, Milshina NV, Mobarry C, Morris J, Moshrefi A, Mount SM, Moy M, Murphy B, Murphy L, Muzny DM, Nelson DL, Nelson DR, Nelson KA, Nixon K, Nusskern DR, Pacleb JM, Palazzolo M, Pittman GS, Pan S, Pollard J, Puri V, Reese MG, Reinert K, Remington K, Saunders RD, Scheeler F, Shen H, Shue BC, Siden-Kiamos I, Simpson M, Skupski MP, Smith T, Spier E, Spradling AC, Stapleton M, Strong R, Sun E, Svirskas R, Tector C, Turner R, Venter E, Wang AH, Wang X, Wang ZY, Wassarman DA, Weinstock GM, Weissenbach J, Williams SM, WoodageT, Worley KC, Wu D, Yang S, Yao QA, Ye J, Yeh RF, Zaveri JS, Zhan M, Zhang G, Zhao Q, Zheng L, Zheng XH, Zhong FN, Zhong W, Zhou X, Zhu S, Zhu X, Smith HO, Gibbs RA, Myers EW, Rubin GM, Venter JC (- 185) Ref: Science, 287:2185, 2000 : PubMed ESTHER: Adams_2000_Science_287_2185 PubMedSearch: Adams 2000 Science 287 2185 PubMedID: 10731132 Gene_locus related to this paper: drome-1vite, drome-2vite, drome-3vite, drome-a1z6g9, drome-abhd2, drome-ACHE, drome-b6idz4, drome-BEM46, drome-CG5707, drome-CG5704, drome-CG1309, drome-CG1882, drome-CG1986, drome-CG2059, drome-CG2493, drome-CG2528, drome-CG2772, drome-CG3160, drome-CG3344, drome-CG3523, drome-CG3524, drome-CG3734, drome-CG3739, drome-CG3744, drome-CG3841, drome-CG4267, drome-CG4382, drome-CG4390, drome-CG4572, drome-CG4582, drome-CG4851, drome-CG4979, drome-CG5068, drome-CG5162, drome-CG5355, drome-CG5377, drome-CG5397, drome-CG5412, drome-CG5665, drome-CG5932, drome-CG5966, drome-CG6018, drome-CG6113, drome-CG6271, drome-CG6283, drome-CG6295, drome-CG6296, drome-CG6414, drome-CG6431, drome-CG6472, drome-CG6567, drome-CG6675, drome-CG6753, drome-CG6847, drome-CG7329, drome-CG7367, drome-CG7529, drome-CG7632, drome-CG8058, drome-CG8093, drome-CG8233, drome-CG8424, drome-CG8425, drome-CG9059, drome-CG9186, drome-CG9287, drome-CG9289, drome-CG9542, drome-CG9858, drome-CG9953, drome-CG9966, drome-CG10116, drome-CG10163, drome-CG10175, drome-CG10339, drome-CG10357, drome-CG10982, drome-CG11034, drome-CG11055, drome-CG11309, drome-CG11319, drome-CG11406, drome-CG11598, drome-CG11600, drome-CG11608, drome-CG11626, drome-CG11935, drome-CG12108, drome-CG12869, drome-CG13282, drome-CG13562, drome-CG13772, drome-CG14034, drome-nlg3, drome-CG14717, drome-CG15101, drome-CG15102, drome-CG15106, drome-CG15111, drome-CG15820, drome-CG15821, drome-CG15879, drome-CG17097, drome-CG17099, drome-CG17101, drome-CG17191, drome-CG17192, drome-CG17292, drome-CG18258, drome-CG18284, drome-CG18301, drome-CG18302, drome-CG18493, drome-CG18530, drome-CG18641, drome-CG18815, drome-CG31089, drome-CG31091, drome-CG32333, drome-CG32483, drome-CG33174, drome-dnlg1, drome-este4, drome-este6, drome-GH02384, drome-GH02439, drome-glita, drome-KRAKEN, drome-lip1, drome-LIP2, drome-lip3, drome-MESK2, drome-nrtac, drome-OME, drome-q7k274, drome-Q9VJN0, drome-Q8IP31, drome-q9vux3 Abstract The fly Drosophila melanogaster is one of the most intensively studied organisms in biology and serves as a model system for the investigation of many developmental and cellular processes common to higher eukaryotes, including humans. We have determined the nucleotide sequence of nearly all of the approximately 120-megabase euchromatic portion of the Drosophila genome using a whole-genome shotgun sequencing strategy supported by extensive clone-based sequence and a high-quality bacterial artificial chromosome physical map. Efforts are under way to close the remaining gaps; however, the sequence is of sufficient accuracy and contiguity to be declared substantially complete and to support an initial analysis of genome structure and preliminary gene annotation and interpretation. The genome encodes approximately 13,600 genes, somewhat fewer than the smaller Caenorhabditis elegans genome, but with comparable functional diversity. Title: Sequence and analysis of chromosome 3 of the plant Arabidopsis thaliana Salanoubat M, Lemcke K, Rieger M, Ansorge W, Unseld M, Fartmann B, Valle G, Blocker H, Perez-Alonso M and Tabata S <127 more author(s)> Salanoubat M, Lemcke K, Rieger M, Ansorge W, Unseld M, Fartmann B, Valle G, Blocker H, Perez-Alonso M, Obermaier B, Delseny M, Boutry M, Grivell LA, Mache R, Puigdomenech P, de Simone V, Choisne N, Artiguenave F, Robert C, Brottier P, Wincker P, Cattolico L, Weissenbach J, Saurin W, Quetier F, Schafer M, Muller-Auer S, Gabel C, Fuchs M, Benes V, Wurmbach E, Drzonek H, Erfle H, Jordan N, Bangert S, Wiedelmann R, Kranz H, Voss H, Holland R, Brandt P, Nyakatura G, Vezzi A, D'Angelo M, Pallavicini A, Toppo S, Simionati B, Conrad A, Hornischer K, Kauer G, Lohnert TH, Nordsiek G, Reichelt J, Scharfe M, Schon O, Bargues M, Terol J, Climent J, Navarro P, Collado C, Perez-Perez A, Ottenwalder B, Duchemin D, Cooke R, Laudie M, Berger-Llauro C, Purnelle B, Masuy D, de Haan M, Maarse AC, Alcaraz JP, Cottet A, Casacuberta E, Monfort A, Argiriou A, Flores M, Liguori R, Vitale D, Mannhaupt G, Haase D, Schoof H, Rudd S, Zaccaria P, Mewes HW, Mayer KF, Kaul S, Town CD, Koo HL, Tallon LJ, Jenkins J, Rooney T, Rizzo M, Walts A, Utterback T, Fujii CY, Shea TP, Creasy TH, Haas B, Maiti R, Wu D, Peterson J, Van Aken S, Pai G, Militscher J, Sellers P, Gill JE, Feldblyum TV, Preuss D, Lin X, Nierman WC, Salzberg SL, White O, Venter JC, Fraser CM, Kaneko T, Nakamura Y, Sato S, Kato T, Asamizu E, Sasamoto S, Kimura T, Idesawa K, Kawashima K, Kishida Y, Kiyokawa C, Kohara M, Matsumoto M, Matsuno A, Muraki A, Nakayama S, Nakazaki N, Shinpo S, Takeuchi C, Wada T, Watanabe A, Yamada M, Yasuda M, Tabata S (- 127) Ref: Nature, 408:820, 2000 : PubMed ESTHER: Salanoubat_2000_Nature_408_820 PubMedSearch: Salanoubat 2000 Nature 408 820 PubMedID: 11130713 Gene_locus related to this paper: arath-MES17, arath-AT3G12150, arath-At3g61680, arath-AT3g62590, arath-CXE12, arath-eds1, arath-SCP25, arath-F1P2.110, arath-F1P2.140, arath-F11F8.28, arath-F14D17.80, arath-F16B3.4, arath-SCP27, arath-At3g50790, arath-At3g05600, arath-PAD4, arath-At3g51000, arath-SCP16, arath-gid1, arath-GID1B, arath-Q9LUG8, arath-Q84JS1, arath-Q9SFF6, arath-q9m236, arath-q9sr22, arath-q9sr23, arath-SCP7, arath-SCP14, arath-SCP15, arath-SCP17, arath-SCP36, arath-SCP37, arath-SCP39, arath-SCP40, arath-SCP49, arath-T19F11.2 Abstract Arabidopsis thaliana is an important model system for plant biologists. In 1996 an international collaboration (the Arabidopsis Genome Initiative) was formed to sequence the whole genome of Arabidopsis and in 1999 the sequence of the first two chromosomes was reported. The sequence of the last three chromosomes and an analysis of the whole genome are reported in this issue. Here we present the sequence of chromosome 3, organized into four sequence segments (contigs). The two largest (13.5 and 9.2 Mb) correspond to the top (long) and the bottom (short) arms of chromosome 3, and the two small contigs are located in the genetically defined centromere. This chromosome encodes 5,220 of the roughly 25,500 predicted protein-coding genes in the genome. About 20% of the predicted proteins have significant homology to proteins in eukaryotic genomes for which the complete sequence is available, pointing to important conserved cellular functions among eukaryotes. 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: Corrigendum to 'Protection against ischemic injury in primary cultured mouse astrocytes by bis(7)-tacrine, a novel acetylcholinesterase inhibitor' Wu D, Xiao X, Ng AK, Chen PM, Chung W, Lee NT, Carlier PR, Pang Y, Yu AC, Han Y Ref: Neuroscience Letters, 290:84, 2000 : PubMed ESTHER: Wu_2000_Neurosci.Lett_290_84 PubMedSearch: Wu 2000 Neurosci.Lett 290 84 PubMedID: 10925180 Inhibitor(s) related to this paper: Bis7-tacrine Title: Mesopontine cholinergic and non-cholinergic neurons in schizophrenia German DC, Manaye KF, Wu D, Hersh LB, Zweig RM Ref: Neuroscience, 94:33, 1999 : PubMed ESTHER: German_1999_Neurosci_94_33 PubMedSearch: German 1999 Neurosci 94 33 PubMedID: 10613494 Abstract Mesopontine cholinergic neurons influence midbrain dopaminergic neurons, and thalamic and cerebellar structures which have been implicated in the neuroanatomy of schizophrenia. It has been reported that there are approximately twice as many mesopontine cholinergic neurons in schizophrenics than in normals, using nicotinomide adenosine dinucleotide phosphatediaphorase histochemistry to identify the cholinergic neurons. The present study sought to replicate this finding by analysing mesopontine cholinergic neurons using an antibody against choline acetyltransferase. The mesopontine cholinergic neurons are located in the pars compacta and pars dissipata of the pedunculopontine nucleus, and in the laterodorsal tegmental nucleus. Quantitative computer imaging techniques were used to map the distribution of mesopontine cholinergic neurons. In addition, all medium-sized and large neurons in a region of interest containing the middle portion of the pedunculopontine nucleus pars compacta were counted in Nissl-stained sections. There was no difference between schizophrenic and normal brains in terms of: (i) the rostral-caudal length of the cholinergic cell complex, approximately 10 mm; (ii) the estimated total number of cholinergic neurons in the combined pedunculopontine nucleus and laterodorsal tegmental nucleus, approximately 20,000 cells unilaterally; and (iii) the combined number of cholinergic and non-cholinergic Nissl-stained neurons in the middle portion of the pedunculopontine nucleus. The present data do not support the previous observation of increased numbers of mesopontine cholinergic neurons in schizophrenia. Title: Mechanisms of Fenvalerate Resistance in the German Cockroach, Blattella germanica(L.) Wu D, Scharf ME, Neal JJ, Suiter DR, Bennett GW Ref: Pesticide Biochemistry and Physiology, 61:53, 1998 : PubMed ESTHER: Wu_1998_Pestic.Biochem.Physiol_61_53 PubMedSearch: Wu 1998 Pestic.Biochem.Physiol 61 53 Abstract The Munsyana strain of German cockroach, originally collected in Muncie, Indana, was found to have high-level resistance to fenvalerate, displaying 825-fold levels of resistance by topical application compared to a susceptible laboratory strain (Johnson Wax). Pretreatment with the cytochrome P450 monooxygenase inhibitors piperonyl butoxide (PBO) or MGK-264, or the esterase inhibitorS,S,S-tributyl phosphorotrithioate (DEF), reduced fenvalerate LD50resistance ratios by 12-fold, 55-fold, and 10-fold, respectively. Detoxication enzyme assays revealed elevated activity of microsomal oxidases (N-demethylation), esterases (PNPA hydrolysis), and glutathione-S-transferases (CDNB conjugation).In vivopenetration studies employing [14C]fenvalerate indicated reduced accumulation in the resistant strain relative to the susceptible strain.In vitrometabolism of [14C]fenvalerate by 105,000-g supernatant fractions with and without DEF inhibition suggested that hydrolysis was occurring. In the microsomal fraction, PBO also reduced the quantity of metabolitesin vitro. Overall, results suggest that monooxygenase, hydrolase, glutathione-S-transferase and decreased cuticular penetration are involved in fenvalerate resistance in the Munsyana strain. However, resistance to fenvalerate was not completely eliminated by either PBO, MGK-246, or DEF, suggesting that additional mechanisms, possibly including sodium channel insensitivity, are involved in this resistance. | |||||||
|
