Author Report for: Xu JNo contact information in database for Xu J
Ding Y, Xing L, Xu J, Jiang T, Tang X, Wang Y, Huang S, Hao W, Zhou X and Xie CG <1 more author(s)> Ding Y, Xing L, Xu J, Jiang T, Tang X, Wang Y, Huang S, Hao W, Zhou X, Zhang Y, Xie CG (- 1) Ref: Front Plant Sci, 14:1139972, 2023 : PubMed ESTHER: Ding_2023_Front.Plant.Sci_14_1139972 PubMedSearch: Ding 2023 Front.Plant.Sci 14 1139972 PubMedID: 37008509 Abstract The Gly-Asp-Ser-Leu (GDSL)-type esterase/lipase proteins (GELP) are one of the most important families of lipolytic enzymes and play prominent roles in seed germination and early seedling establishment through mobilizing the lipids stored in seeds. However, there are no comprehensive studies systematically investigating the GELP gene family in Brassica napus (BnGELP), and their biological significance to these physiological processes are far from understood. In the present study, a total of 240 BnGELP genes were identified in B. napus cultivar "Zhongshuang 11" (ZS11), which is nearly 2.3-fold more GELP genes than in Arabidopsis thaliana. The BnGELP genes clustered into 5 clades based on phylogenetic analysis. Ten BnGELPs were identified through zymogram analysis of esterase activity followed by mass spectrometry, among which five clustered into the clade 5. Gene and protein architecture, gene expression, and cis-element analyses of BnGELP genes in clade 5 suggested that they may play different roles in different tissues and in response to different abiotic stresses. BnGELP99 and BnGELP159 were slightly induced by cold, which may be attributed to two low-temperature responsive cis-acting regulatory elements present in their promoters. An increased activity of esterase isozymes by cold was also observed, which may reflect other cold inducible esterases/lipases in addition to the ten identified BnGELPs. This study provides a systemic view of the BnGELP gene family and offers a strategy for researchers to identify candidate esterase/lipase genes responsible for lipid mobilization during seed germination and early seedling establishment. Title: A Turn-On Lipid Droplet-Targeted Near-Infrared Fluorescent Probe with a Large Stokes Shift for Detection of Intracellular Carboxylesterases and Cell Viability Imaging Li C, Li S, Li X, Yuan T, Xu J, Gu X, Hua J Ref: Molecules, 28:, 2023 : PubMed ESTHER: Li_2023_Molecules_28_ PubMedSearch: Li 2023 Molecules 28 PubMedID: 36903562 Abstract Carboxylesterases (CEs) play important physiological roles in the human body and are involved in numerous cellular processes. Monitoring CEs activity has great potential for the rapid diagnosis of malignant tumors and multiple diseases. Herein, we developed a new phenazine-based "turn-on" fluorescent probe DBPpys by introducing 4-bromomethyl-phenyl acetate to DBPpy, which can selectively detect CEs with a low detection limit (9.38 x 10(-5) U/mL) and a large Stokes shift (more than 250 nm) in vitro. In addition, DBPpys can also be converted into DBPpy by carboxylesterase in HeLa cells and localized in lipid droplets (LDs), emitting bright near-infrared fluorescence under the irradiation of white light. Moreover, we achieved the detection of cell health status by measuring the intensity of NIR fluorescence after co-incubation of DBPpys with H(2)O(2)-pretreated HeLa cells, indicating that DBPpys has great potential applications for assessing CEs activity and cellular health. Title: Systematic assessment of cyflumetofen toxicity in soil-earthworm (Eisenia fetida) microcosms Shi L, Zhang P, Xu J, Wu X, Pan X, He L, Dong F, Zheng Y Ref: J Hazard Mater, 452:131300, 2023 : PubMed ESTHER: Shi_2023_J.Hazard.Mater_452_131300 PubMedSearch: Shi 2023 J.Hazard.Mater 452 131300 PubMedID: 37002996 Abstract Cyflumetofen was widely applied in agriculture with its excellent acaricidal effect. However, the impact of cyflumetofen on the soil non-target organism earthworm (Eisenia fetida) is unclear. This study aimed to elucidate the bioaccumulation of cyflumetofen in soil-earthworm systems and the ecotoxicity of earthworms. The highest concentration of cyflumetofen enriched by earthworms was found on the 7th day. Long-term exposure of earthworms to the cyflumetofen (10 mg/kg) could suppress protein content and increases Malondialdehyde content leading to severe peroxidation. Transcriptome sequencing analysis demonstrated that catalase and superoxide-dismutase activities were significantly activated while genes involved in related signaling pathways were significantly upregulated. In terms of detoxification metabolic pathways, high concentrations of cyflumetofen stimulated the number of Differentially-Expressed-Genes involved in the detoxification pathway of the metabolism of glutathione. Identification of three detoxification genes (LOC100376457, LOC114329378, and JGIBGZA-33J12) had synergistic detoxification. Additionally, cyflumetofen promoted disease-related signaling pathways leading to higher disease risk, affecting the transmembrane capacity and cell membrane composition, ultimately causing cytotoxicity. Superoxide-Dismutase in oxidative stress enzyme activity contributed more to detoxification. Carboxylesterase and glutathione-S-transferase activation play a major detoxification role in high-concentration treatment. Altogether, these results contribute to a better understanding of toxicity and defense mechanisms involved in long-term cyflumetofen exposure in earthworms. Title: Toxic effects of isofenphos-methyl on zebrafish embryonic development Wu Y, Wang J, Xia Y, Tang K, Xu J, Wang A, Hu S, Wen L, Wang B, Yao W Ref: Ecotoxicology & Environmental Safety, 254:114723, 2023 : PubMed ESTHER: Wu_2023_Ecotoxicol.Environ.Saf_254_114723 PubMedSearch: Wu 2023 Ecotoxicol.Environ.Saf 254 114723 PubMedID: 36871354 Inhibitor(s) related to this paper: Isofenphos-methyl Abstract Isofenphos-methyl (IFP) is widely used as an organophosphorus for controlling underground insects and nematodes. However, excessive use of IFP may pose potential risks to the environment and humans, but little information is available on its sublethal toxicity to aquatic organisms. To address this knowledge gap, the current study exposed zebrafish embryos to 2, 4, and 8 mg/L IFP within 6-96 h past fertilization (hpf) and measured mortality, hatching, developmental abnormalities, oxidative stress, gene expressions, and locomotor activity. The results showed that IFP exposure reduced the rates of heart and survival rate, hatchability, and body length of embryos and induced uninflated swim bladder and developmental malformations. Reduction in locomotive behavior and inhibition of AChE activity indicated that IFP exposure may induce behavioral defects and neurotoxicity in zebrafish larvae. IFP exposure also led to pericardial edema, longer venous sinus-arterial bulb (SV-BA) distance, and apoptosis of the heart cells. Moreover, IFP exposure increased the accumulation of reactive oxygen species (ROS) and the content of malonaldehyde (MDA), also elevated the levels of antioxidant enzymes of superoxide dismutase (SOD) and catalase (CAT), but decreased glutathione (GSH) levels in zebrafish embryos. The relative expressions of heart development-related genes (nkx2.5, nppa, gata4, and tbx2b), apoptosis-related genes (bcl2, p53, bax, and puma), and swim bladder development-related genes (foxA3, anxa5b, mnx1, and has2) were significantly altered by IFP exposure. Collectively, our results indicated that IFP induced developmental toxicity and neurotoxicity to zebrafish embryos and the mechanisms may be relevant to the activation of oxidative stress and reduction of acetylcholinesterase (AChE) content. Title: Exploration of Synergistic Pesticidal Activities, Control Effects and Toxicology Study of a Monoterpene Essential Oil with Two Natural Alkaloids Xu J, Lv M, Fang S, Wang Y, Wen H, Zhang S, Xu H Ref: Toxins (Basel), 15:, 2023 : PubMed ESTHER: Xu_2023_Toxins.(Basel)_15_ PubMedSearch: Xu 2023 Toxins.(Basel) 15 PubMedID: 37104178 Abstract With the increasing development of pest resistances, it is not easy to achieve satisfactory control effects by using only one agrochemical. Additionally, although the alkaloid matrine (MT) isolated from Sophora flavescens is now utilized as a botanical pesticide in China, in fact, its pesticidal activities are much lower in magnitude than those of commercially agrochemicals. To improve its pesticidal activities, here, the joint pesticidal effects of MT with another alkaloid oxymatrine (OMT) (isolated from S. flavescens) and the monoterpene essential oil 1,8-cineole (CN) (isolated from the eucalyptus leaves) were investigated in the laboratory and greenhouse conditions. Moreover, their toxicological properties were also studied. Against Plutella xylostella, when the mass ratio of MT and OMT was 8/2, good larvicidal activity was obtained; against Tetranychus urticae, when the mass ratio of MT and OMT was 3/7, good acaricidal activity was obtained. Especially when MT and OMT were combined with CN, the significant synergistic effects were observed: against P. xylostella, the co-toxicity coefficient (CTC) of MT/OMT (8/2)/CN was 213; against T. urticae, the CTC of MT/OMT (3/7)/CN was 252. Moreover, the activity changes over time of two detoxification enzymes, carboxylesterase (CarE) and glutathione S-transferase (GST) of P. xylostella treated with MT/OMT (8/2)/CN, were observed. In addition, by scanning electron microscope (SEM), the toxicological study suggested that the acaricidal activity of MT/OMT (3/7)/CN may be related to the damage of the cuticle layer crest of T. urticae. Title: Strigolactones positively regulate Verticillium wilt resistance in cotton via crosstalk with other hormones Yi F, An G, Song A, Cheng K, Liu J, Wang C, Wu S, Wang P, Zhu J and Cai Y <11 more author(s)> Yi F, An G, Song A, Cheng K, Liu J, Wang C, Wu S, Wang P, Zhu J, Liang Z, Chang Y, Chu Z, Cai C, Zhang X, Chen A, Xu J, Burritt DJ, Herrera-Estrella L, Tran LP, Li W, Cai Y (- 11) Ref: Plant Physiol, :, 2023 : PubMed ESTHER: Yi_2023_Plant.Physiol__ PubMedSearch: Yi 2023 Plant.Physiol PubMedID: 36718522 Abstract Verticillium wilt caused by Verticillium dahliae is a serious vascular disease in cotton (Gossypium spp.). V. dahliae induces the expression of the CAROTENOID CLEAVAGE DIOXYGENASE 7 (GauCCD7) gene involved in strigolactone (SL) biosynthesis in Gossypium australe, suggesting a role for SLs in Verticillium wilt resistance. We found that the SL analog rac-GR24 enhanced while the SL biosynthesis inhibitor TIS108 decreased cotton resistance to Verticillium wilt. Knock-down of GbCCD7 and GbCCD8b genes in island cotton (Gossypium barbadense) decreased resistance, whereas overexpression of GbCCD8b in upland cotton (Gossypium hirsutum) increased resistance to Verticillium wilt. Additionally, Arabidopsis (Arabidopsis thaliana) SL mutants defective in CCD7 and CCD8 putative orthologs were susceptible, whereas both Arabidopsis GbCCD7- and GbCCD8b-overexpressing plants were more resistant to Verticillium wilt than wild-type (WT) plants. Transcriptome analyses showed that several genes related to the jasmonic acid (JA)- and abscisic acid (ABA)-signaling pathways, such as MYELOCYTOMATOSIS 2 (GbMYC2) and ABA-INSENSITIVE 5, respectively, were up-regulated in the roots of WT cotton plants in responses to rac-GR24 and V. dahliae infection but down-regulated in the roots of both GbCCD7- and GbCCD8b-silenced cotton plants. Furthermore, GbMYC2 suppressed the expression of GbCCD7 and GbCCD8b by binding to their promoters, which might regulate the homeostasis of SLs in cotton through a negative feedback loop. We also found that GbCCD7- and GbCCD8b-silenced cotton plants were impaired in V. dahliae-induced reactive oxygen species (ROS) accumulation. Taken together, our results suggest that SLs positively regulate cotton resistance to Verticillium wilt through crosstalk with the JA and ABA-signaling pathways and by inducing ROS accumulation. Title: NMDA receptor hypofunction underlies deficits in parvalbumin interneurons and social behavior in neuroligin 3 R451C knockin mice Cao W, Li JH, Lin S, Xia QQ, Du YL, Yang Q, Ye YZ, Zeng LH, Li XY and Luo JH <1 more author(s)> Cao W, Li JH, Lin S, Xia QQ, Du YL, Yang Q, Ye YZ, Zeng LH, Li XY, Xu J, Luo JH (- 1) Ref: Cell Rep, 41:111771, 2022 : PubMed ESTHER: Cao_2022_Cell.Rep_41_111771 PubMedSearch: Cao 2022 Cell.Rep 41 111771 PubMedID: 36476879 Abstract Neuroligins (NLs), a family of postsynaptic cell-adhesion molecules, have been associated with autism spectrum disorder. We have reported that dysfunction of the medial prefrontal cortex (mPFC) leads to social deficits in an NL3 R451C knockin (KI) mouse model of autism. However, the underlying molecular mechanism remains unclear. Here, we find that N-methyl-D-aspartate receptor (NMDAR) function and parvalbumin-positive (PV+) interneuron number and expression are reduced in the mPFC of the KI mice. Selective knockdown of NMDAR subunit GluN1 in the mPFC PV+ interneuron decreases its intrinsic excitability. Restoring NMDAR function by its partial agonist D-cycloserine rescues the PV+ interneuron dysfunction and social deficits in the KI mice. Interestingly, early D-cycloserine administration at adolescence prevents adult KI mice from social deficits. Together, our results suggest that NMDAR hypofunction and the resultant PV+ interneuron dysfunction in the mPFC may constitute a central node in the pathogenesis of social deficits in the KI mice. Title: Construction, Pesticidal Activities, Control Effects, and Detoxification Enzyme Activities of Osthole Ester/Amide Derivatives Hao M, Lv M, Zhou L, Li H, Xu J, Xu H Ref: Journal of Agricultural and Food Chemistry, 70:9337, 2022 : PubMed ESTHER: Hao_2022_J.Agric.Food.Chem_70_9337 PubMedSearch: Hao 2022 J.Agric.Food.Chem 70 9337 PubMedID: 35857419 Abstract Pesticide research and development has entered an era of safety, efficiency, and environmental friendliness. Discovery of effective active products directly or indirectly from plant secondary metabolites as pesticide candidates has been one of the current research focuses. Herein, two series of new ester and amide derivatives were prepared by structural modifications of a natural coumarin-type product osthole at its C-4' position. Their structures were characterized by IR, mp, (1)H NMR, and HRMS. Confirmation of steric configuration of seven compounds was based on single-crystal analysis. Against Tetranychus cinnabarinus Boisduval (Acari: Tetranychidae), (2'E)-3'-ethoxycarbonylosthole (4b) and (2'E)-3'-(n)hexyloxycarbonylosthole (4e) exhibited 3.2 and 3.1 times acaricidal activity of osthole, and particularly, they also showed 2.4 and 2.2 times control efficiency on the 5th day of osthole. Against Aphis citricola Van der Goot (Homoptera: Aphididae), (2'E)-3'-(p-CF(3))benzyloxycarbonylosthole (4w), (2'E)-3'-benzylaminocarbonylosthole (5f), and (2'E)-3'-phenylethylaminocarbonylosthole (5g) showed 1.9-2.1-fold aphicidal activity of osthole. Furthermore, the changes in two detoxification enzyme [carboxylesterase (CarE) and glutathione S-transferase (GST)] activities over time in treated T. cinnabarinus were investigated. These results can pave the foundation for future design and preparation of osthole derivatives as botanical agrochemicals. Title: Preparation and Characterization of Magnetic Metal-Organic Frameworks Functionalized by Ionic Liquid as Supports for Immobilization of Pancreatic Lipase Li X, Jia Y, Li J, Zhang P, Li T, Lu L, Yao H, Liu J, Zhu Z and Xu L <24 more author(s)> Li X, Jia Y, Li J, Zhang P, Li T, Lu L, Yao H, Liu J, Zhu Z, Xu J, Morita S, Yamada H, Koga K, Ota W, Furuta T, Yamatsu A, Kim M, Li C, Tang W, Chen S, He J, Zhu X, Li H, Peng Y, Li M, Dai X, Li A, Qi Q, Wang W, Cao J, Jiang Z, Liu R, Suo H, Xu L (- 24) Ref: Molecules, 27:, 2022 : PubMed ESTHER: Li_2022_Molecules_27_ PubMedSearch: Li 2022 Molecules 27 PubMedID: 35630563 35956860 36234873 36296392 Abstract Enzymes are difficult to recycle, which limits their large-scale industrial applications. In this work, an ionic liquid-modified magnetic metal-organic framework composite, IL-Fe(3)O(4)@UiO-66-NH(2), was prepared and used as a support for enzyme immobilization. The properties of the support were characterized with X-ray powder diffraction (XRD), Fourier-transform infrared (FTIR) spectra, transmission electron microscopy (TEM), scanning electronic microscopy (SEM), and so on. The catalytic performance of the immobilized enzyme was also investigated in the hydrolysis reaction of glyceryl triacetate. Compared with soluble porcine pancreatic lipase (PPL), immobilized lipase (PPL-IL-Fe(3)O(4)@UiO-66-NH(2)) had greater catalytic activity under reaction conditions. It also showed better thermal stability and anti-denaturant properties. The specific activity of PPL-IL-Fe(3)O(4)@UiO-66-NH(2) was 2.3 times higher than that of soluble PPL. After 10 repeated catalytic cycles, the residual activity of PPL-IL-Fe(3)O(4)@UiO-66-NH(2) reached 74.4%, which was higher than that of PPL-Fe(3)O(4)@UiO-66-NH(2) (62.3%). In addition, kinetic parameter tests revealed that PPL-IL-Fe(3)O(4)@UiO-66-NH(2) had a stronger affinity to the substrate and, thus, exhibited higher catalytic efficiency. The results demonstrated that Fe(3)O(4)@UiO-66-NH(2) modified by ionic liquids has great potential for immobilized enzymes. Title: Discovery of novel hybrids containing clioquinol-1-benzyl-1,2,3,6-tetrahydropyridine as multi-target-directed ligands (MTDLs) against Alzheimer's disease Li X, Li T, Zhang P, Lu L, Sun Y, Zhang B, Allen S, White L, Phillips J and Xu J <2 more author(s)> Li X, Li T, Zhang P, Lu L, Sun Y, Zhang B, Allen S, White L, Phillips J, Zhu Z, Yao H, Xu J (- 2) Ref: Eur Journal of Medicinal Chemistry, 244:114841, 2022 : PubMed ESTHER: Li_2022_Eur.J.Med.Chem_244_114841 PubMedSearch: Li 2022 Eur.J.Med.Chem 244 114841 PubMedID: 36257284 Inhibitor(s) related to this paper: Compound19n-quinolinol Abstract Based on the multitarget strategy, a series of novel clioquinol-1-benzyl-1,2,3,6-tetrahydropyridine hybrids were identified for the potential treatment of Alzheimer's disease (AD). Biological evaluation in vitro revealed that these hybrids exhibited significant inhibitory activities toward acetylcholinesterase (AChE). The optimal compound, 19n, exhibited excellent AChE inhibitory potency (IC(50) = 0.11 microM), appropriate metal chelating functions, modulation of AChE- and metal-induced Abeta aggregation, neuroprotection against okadaic acid-induced mitochondrial dysfunction and ROS damage, and interesting properties that reduced p-Tau levels in addition to no toxicity on SH-SY5Y cells observed at a concentration up to 50 microM. Most importantly, compound 19n was more well tolerated (>1200 mg/kg) than donepezil (LD(50) = 28.124 mg/kg) in vivo. Moreover, compound 19n demonstrated marked improvements in cognitive and spatial memory in two AD mice models (scopolamine-induced and Abeta(1-42)-induced) and suppressed inflammation induced by Abeta(1-42) in the cortex. The multifunctional profiles of compound 19n demonstrate that it deserves further investigation as a promising lead in the development of innovatively multifunctional drugs for Alzheimer's disease. Title: Design, Synthesis, and Biological Evaluation of Novel Chromanone Derivatives as Multifunctional Agents for the Treatment of Alzheimer's Disease Li X, Li T, Zhan F, Cheng F, Lu L, Zhang B, Li J, Hu Z, Zhou S and Yao H <6 more author(s)> Li X, Li T, Zhan F, Cheng F, Lu L, Zhang B, Li J, Hu Z, Zhou S, Jia Y, Allen S, White L, Phillips J, Zhu Z, Xu J, Yao H (- 6) Ref: ACS Chem Neurosci, :, 2022 : PubMed ESTHER: Li_2022_ACS.Chem.Neurosci__ PubMedSearch: Li 2022 ACS.Chem.Neurosci PubMedID: 36383455 Abstract Based on a multitarget strategy, a series of novel chromanone-1-benzyl-1,2,3,6-tetrahydropyridin hybrids were identified for the potential treatment of Alzheimer's disease (AD). Biological evaluation demonstrated that these hybrids exhibited significant inhibitory activities toward acetylcholinesterase (AChE) and monoamine oxidase B (MAO-B). The optimal compound C10 possessed excellent dual AChE/MAO-B inhibition both in terms of potency and equilibrium (AChE: IC(50) = 0.58 0.05 M; MAO-B: IC(50) = 0.41 0.04 M). Further molecular modeling and kinetic investigations revealed that compound C10 was a dual-binding inhibitor bound to both the catalytic anionic site and peripheral anionic site of AChE. In addition, compound C10 exhibited low neurotoxicity and potently inhibited AChE enzymatic activity. Furthermore, compound C10 more effectively protected against mitochondrial dysfunction and oxidation than donepezil, strongly inhibited AChE-induced amyloid aggregation, and moderately reduced glutaraldehyde-induced phosphorylation of tau protein in SH-SY5Y cells. Moreover, compound C10 displayed largely enhanced improvements in cognitive behaviors and spatial memory in a scopolamine-induced AD mice model with better efficacy than donepezil. Overall, the multifunctional profiles of compound C10 suggest that it deserves further investigation as a promising lead for the prospective treatment of AD. Title: Novel inhibitors of AChE and Abeta aggregation with neuroprotective properties as lead compounds for the treatment of Alzheimer's disease Liu Y, Uras G, Onuwaje I, Li W, Yao H, Xu S, Li X, Phillips J, Allen S and Xu J <4 more author(s)> Liu Y, Uras G, Onuwaje I, Li W, Yao H, Xu S, Li X, Phillips J, Allen S, Gong Q, Zhang H, Zhu Z, Liu J, Xu J (- 4) Ref: Eur Journal of Medicinal Chemistry, 235:114305, 2022 : PubMed ESTHER: Liu_2022_Eur.J.Med.Chem_235_114305 PubMedSearch: Liu 2022 Eur.J.Med.Chem 235 114305 PubMedID: 35339839 Inhibitor(s) related to this paper: Fluoropezil Abstract A series of sulfone analogs of donepezil were designed and synthesized as novel acetylcholinesterase (AChE) inhibitors with the potent inhibiting Abeta aggregation and providing neuroprotective effects as potential modalities for Alzheimer's disease (AD). Most of the target compounds displayed effective inhibition of AChE, especially compound 24r which displayed powerful inhibitory activity (IC(50) = 2.4 nM). Kinetic and docking studies indicated that compound 24r was a mixed-type inhibitor. Furthermore, in glyceraldehyde (GA)-exposed SH-SY5Y differentiated neuronal cells, compound 24r could potently inhibit AChE, reduce tau phosphorylation at S396 residue, provide neuroprotection by rescuing neuronal morphology and increasing cell viability. It was also found to reduce amyloid aggregation in the presence of AChE. In addition, compound 24r showed evident protections from mitochondrial membrane dysfunction and oxidative stress in okadaic acid-induced pharmacological models. Moreover, compound 24r exhibited more effective treatment prospects in vivo than donepezil, including a moderate blood-brain barrier permeability, a more potent AChE inhibitory activity and behavioral improvement in scopolamine-induced cognition-impaired mice model at a much lower dose. Collectively, compound 24r is a promising lead compound for further investigation to discovery and development of new anti-AD agents. Title: Development of p-Tau Differentiated Cell Model of Alzheimer's Disease to Screen Novel Acetylcholinesterase Inhibitors Uras G, Li X, Manca A, Pantaleo A, Bo M, Xu J, Allen S, Zhu Z Ref: Int J Mol Sci, 23:, 2022 : PubMed ESTHER: Uras_2022_Int.J.Mol.Sci_23_ PubMedSearch: Uras 2022 Int.J.Mol.Sci 23 PubMedID: 36499118 Abstract Alzheimer's disease (AD) is characterized by an initial accumulation of amyloid plaques and neurofibrillary tangles, along with the depletion of cholinergic markers. The currently available therapies for AD do not present any disease-modifying effects, with the available in vitro platforms to study either AD drug candidates or basic biology not fully recapitulating the main features of the disease or being extremely costly, such as iPSC-derived neurons. In the present work, we developed and validated a novel cell-based AD model featuring Tau hyperphosphorylation and degenerative neuronal morphology. Using the model, we evaluated the efficacy of three different groups of newly synthesized acetylcholinesterase (AChE) inhibitors, along with a new dual acetylcholinesterase/glycogen synthase kinase 3 inhibitor, as potential AD treatment on differentiated SH-SY5Y cells treated with glyceraldehyde to induce Tau hyperphosphorylation, and subsequently neurite degeneration and cell death. Testing of such compounds on the newly developed model revealed an overall improvement of the induced defects by inhibition of AChE alone, showing a reduction of S396 aberrant phosphorylation along with a moderate amelioration of the neuron-like morphology. Finally, simultaneous AChE/GSK3 inhibition further enhanced the limited effects observed by AChE inhibition alone, resulting in an improvement of all the key parameters, such as cell viability, morphology, and Tau abnormal phosphorylation. Title: Rapid Mining of Novel alpha-Glucosidase and Lipase Inhibitors from Streptomyces sp. HO1518 Using UPLC-QTOF-MS/MS Xu J, Liu Z, Feng Z, Ren Y, Liu H, Wang Y Ref: Mar Drugs, 20:, 2022 : PubMed ESTHER: Xu_2022_Mar.Drugs_20_ PubMedSearch: Xu 2022 Mar.Drugs 20 PubMedID: 35323488 Abstract A rapid and sensitive method using ultra-high performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS/MS) was applied for the analysis of the metabolic profile of acarviostatin-containing aminooligosaccharides derived from Streptomyces sp. HO1518. A total of ninety-eight aminooligosaccharides, including eighty potential new compounds, were detected mainly based on the characteristic fragment ions originating from quinovosidic bond cleavages in their molecules. Following an LC-MS-guided separation technique, seven new aminooligosaccharides (10-16) along with four known related compounds (17-20) were obtained directly from the crude extract of strain HO1518. Compounds 10-13 represent the first examples of aminooligosaccharides with a rare acarviostatin II02-type structure. In addition, all isolates displayed considerable inhibitory effects on three digestive enzymes, which revealed that the number of the pseudo-trisaccharide core(s), the feasible length of the oligosaccharides, and acyl side chain exerted a crucial influence on their bioactivities. These results demonstrated that the UPLC-QTOF-MS/MS-based metabolomics approach could be applied for the rapid identification of aminooligosaccharides and other similar structures in complex samples. Furthermore, this study highlights the potential of acylated aminooligosaccharides with conspicuous alpha-glucosidase and lipase inhibition for the future development of multi-target anti-diabetic drugs. Title: Lipase-Catalyzed Phospha-Michael Addition Reactions under Mild Conditions Xu J, Cao P, Fan Z, Luo X, Yang G, Qu T, Gao J, Xu Y, Li F and Wang L <5 more author(s)> Xu J, Cao P, Fan Z, Luo X, Yang G, Qu T, Gao J, Xu Y, Li F, Ma J, Li J, Xie H, Wang C, Chen P, Wang L (- 5) Ref: Molecules, 27:, 2022 : PubMed ESTHER: Xu_2022_Molecules_27_ PubMedSearch: Xu 2022 Molecules 27 PubMedID: 35684413 36431898 Abstract Organophosphorus compounds are the core structure of many active natural products. The synthesis of these compounds is generally achieved by metal catalysis requiring specifically functionalized substrates or harsh conditions. Herein, we disclose the phospha-Michael addition reaction of biphenyphosphine oxide with various substituted beta-nitrostyrenes or benzylidene malononitriles. This biocatalytic strategy provides a direct route for the synthesis of C-P bonds with good functional group compatibility and simple and practical operation. Under the optimal conditions (styrene (0.5 mmol), biphenyphosphine oxide (0.5 mmol), Novozym 435 (300 U), and EtOH (1 mL)), lipase leads to the formation of organophosphorus compounds in yields up to 94% at room temperature. Furthermore, we confirm the role of the catalytic triad of lipase in this phospha-Michael addition reaction. This new biocatalytic system will have broad applications in organic synthesis. Title: Efficacy and safety of DBPR108 (prusogliptin) as an add-on to metformin therapy in patients with type 2 diabetes mellitus: A 24-week, multi-center, randomized, double-blind, placebo-controlled, superiority, phase III clinical trial Xu J, Ling H, Geng J, Huang Y, Xie Y, Zheng H, Niu H, Zhang T, Yuan J, Xiao X Ref: Diabetes Obes Metab, :, 2022 : PubMed ESTHER: Xu_2022_Diabetes.Obes.Metab__ PubMedSearch: Xu 2022 Diabetes.Obes.Metab PubMedID: 35791646 Inhibitor(s) related to this paper: Prusogliptin Abstract AIMS: To evaluate the efficacy and safety of DBPR108 (prusogliptin), a novel dipeptidyl-peptidase-4 (DPP-4) inhibitor, as an add-on therapy in patients with type 2 diabetes mellitus (T2DM) that is inadequately controlled with metformin. MATERIALS AND METHODS: In this 24-week, multi-center, randomized, double-blind, placebo-controlled, superiority, phase III study, adult T2DM patients with glycated hemoglobin A1c (HbA1c) levels ranging from 7.0-9.5% on stable metformin were enrolled and randomized (2:1) into the DBPR108+metformin and placebo+metformin groups. The primary endpoint was the change from baseline in HbA1c at week 24 of DBPR108 versus placebo as an add-on therapy to metformin. RESULTS: At week 24, the least-square (LS) mean (standard error [SE]) change from baseline in HbA1c was significantly greater in the DBPR108 group (-0.70% [0.09%]) than that in the placebo group (-0.07% [0.11%]) (P-value <0.001), with a treatment difference of -0.63% (95% confidence interval [CI]: -0.87, -0.39) on full analysis set. A higher proportion of patients achieved an HbA1c >=6.5% (19.7% vs. 8.5%) and HbA1c >=7.0% (50.0% vs. 21.1%) at week 24 in the DBPR108+metformin group. Furthermore, add-on DBPR108 produced greater reductions from baseline in fasting plasma glucose and 2-hour postprandial plasma glucose (2-h PPG) without causing weight gain. The overall frequency of adverse events (AEs) was similar between the two groups. CONCLUSIONS: DBPR108 as add-on therapy to metformin offered a significant improvement in glycemic control, was superior to metformin monotherapy (placebo), and was safe and well-tolerated in T2DM patients that is inadequately controlled with metformin. This article is protected by copyright. All rights reserved. Title: Comparative genomics of Sarcoptes scabiei provide new insights into adaptation to permanent parasitism and within-host species divergence Xu J, Wang Q, Wang S, Huang W, Xie Y, Gu X, He R, Peng X, Wu S, Yang G Ref: Transbound Emerg Dis, :, 2022 : PubMed ESTHER: Xu_2022_Transbound.Emerg.Dis__ PubMedSearch: Xu 2022 Transbound.Emerg.Dis PubMedID: 36134513 Abstract Sarcoptic scabiei is the causative agent of a highly contagious skin disease in humans and more than 100 mammals. Here, we report the first chromosome-level reference genome of S. scabiei isolated from rabbits, with a contig N50 size of 5.92 Mb, a total assembled length of 57.30 Mb, -12.65% repetitive sequences, and 9,333 predicted protein-coding genes. The phylogenetic tree based on 1,338 shared high-confidence single-copy orthologous genes estimated that the mammalian ectoparasite S. scabiei and the plant-feeding mite Tetranychus urticae separated approximately 340 million years ago. Both neighbor-joining tree and principal component analysis of 20 mite populations isolated from four hosts (humans, pigs, dogs and rabbits) distributed in three countries (China, Australia and the US) consistently supported the genetic subdivisions according to host species rather than geographical location. The demographic history of S. scabiei reconstructed by multiple sequentially Markovian coalescent analysis suggested that S. scabiei isolated from rabbits, humans, dogs, and pigs diverged -5,000 years ago. Investigation of the homeobox (Hox) genes revealed that S. scabiei contains eight of 10 canonical Hox genes that are present in the arthropod ancestor, and the absence of the Abd-A gene may correlate with the long gap between their front and back legs. Comparative genomics demonstrated that genes specific to scabies mites were mainly enriched in nutrition digestive systems and genes in the families that involved detoxification (cytochrome P450, carboxyl/cholinesterases, and the ATP-binding cassette transporter C group) were extremely contracted compared with that of other mites analyzed in this study. Selective sweep analysis of mite populations from either two of the four host species revealed that the strongest selective sweep signals were mainly enriched in cysteine-type peptidase activity and apoptosis. The results provided clues for the mechanisms of S. scabiei adaptation to a permanent parasitic lifestyle and knowledge that would enable further control of this highly contagious skin disease. This article is protected by copyright. All rights reserved. Title: The monoacylglycerol lipase inhibitor, JZL184, has comparable effects to therapeutic hypothermia, attenuating global cerebral injury in a rat model of cardiac arrest Xu J, Zheng G, Hu J, Ge W, Bradley JL, Ornato JP, Tang W Ref: Biomed Pharmacother, 156:113847, 2022 : PubMed ESTHER: Xu_2022_Biomed.Pharmacother_156_113847 PubMedSearch: Xu 2022 Biomed.Pharmacother 156 113847 PubMedID: 36252353 Abstract Post-resuscitation cerebral ischemia-reperfusion injury (IRI) is a vital contributor to poor neurological prognosis. Exploring novel therapeutics that attenuate cerebral IRI is of great significance. Inflammation plays a role in the development of cerebral IRI after successful cardiopulmonary resuscitation (CPR). Monoacylglycerol lipase (MAGL) is an enzyme that is predominantly responsible for the metabolism of endocannabinoid 2-arachidonoylglycerol (2-AG) to arachidonic acid (AA) metabolites, which are associated with inflammation. Therefore, we investigated the efficacy of the MAGL inhibitor, JZL184, on cerebral IRI and further compared the effects to therapeutic hypothermia (TH). Thirty-six rats were randomized into three groups: 1) JZL184; 2) Control; 3) TH (N = 12 for each group). Animals underwent 6 min of ventricular fibrillation (VF) followed with 8 min of CPR. After return of spontaneous circulation (ROSC), rats received an intraperitoneal injection of JZL184 (16 mg/kg) or DMSO (20 mg/ml) or body cooling was initiated. Cerebral microcirculation, brain edema, blood brain barrier (BBB) permeability, serum neuron-specific enolase (NSE), S-100beta, interleukin-6 (IL-6) and interleukin-10 (IL-10) were quantified at 6 h post ROSC. Compared to control, treatment with JZL184 or TH was associated with significantly ameliorated cerebral microcirculation, mitigated brain edema, attenuated BBB permeability, decreased serum levels of NSE, S-100beta and IL-6, and increased serum IL-10 levels (p < 0.05). There was no significant difference in the above measurements between JZL184 and TH. JZL184 has comparable neuroprotective effects to therapeutic hypothermia on global cerebral IRI in a rat model of cardiac arrest (CA). Title: Identification of Host Molecules Involved in the Proliferation of Nucleopolyhedrovirus in Bombyx mori Xu J, Xie X, Ma Q, Zhang L, Li Y, Chen Y, Li K, Xiao Y, Tettamanti G and Tian L <1 more author(s)> Xu J, Xie X, Ma Q, Zhang L, Li Y, Chen Y, Li K, Xiao Y, Tettamanti G, Xu H, Tian L (- 1) Ref: Journal of Agricultural and Food Chemistry, :, 2022 : PubMed ESTHER: Xu_2022_J.Agric.Food.Chem__ PubMedSearch: Xu 2022 J.Agric.Food.Chem PubMedID: 36321811 Abstract The Bombyx mori nucleopolyhedrovirus (BmNPV), a foodborne infectious virus, is the pathogen causing nuclear polyhedrosis and high lethality in the silkworm. In this study, we characterized the molecules involved in BmNPV-silkworm interaction by RNA sequencing of the fat body isolated from the virus-susceptible strain P50. Kyoto Encyclopedia of Genes and Genomes (KEGG) annotation showed that the upregulated differentially expressed genes (DEGs) were mainly involved in translation, signal transduction, folding, sorting, and degradation, as well as transport and catabolism, while the downregulated DEGs were predominantly enriched in the metabolism of carbohydrates, amino acids, and lipids at 72 h post BmNPV infection. Knockout of the upregulated somatomedin-B and thrombospondin type-1 domain-containing protein, probable allantoicase, trifunctional purine biosynthetic protein adenosine-3, and Psl and pyoverdine operon regulator inhibited the proliferation of BmNPV, while knockout of the downregulated clip domain serine protease 3 and carboxylesterase clade H, member 1 promoted it. The molecules herein identified provide a foundation for developing strategies and designing drugs against BmNPV. Title: Effect of thiamethoxam on the behavioral profile alteration and toxicity of adult zebrafish at environmentally relevant concentrations Yang J, Guo C, Luo Y, Fan J, Wang W, Yin X, Xu J Ref: Sci Total Environ, 858:159883, 2022 : PubMed ESTHER: Yang_2022_Sci.Total.Environ_858_159883 PubMedSearch: Yang 2022 Sci.Total.Environ 858 159883 PubMedID: 36356732 Abstract Thiamethoxam (THM) is a commercial neonicotinoid insecticide with broad-spectrum insecticidal activity. It has been widely detected in the aquatic environment, but its behavioral toxicity on aquatic organisms received limited attention. In this study, adult zebrafish were exposed to THM at three levels (0.1, 10, and 1000 g/L) for 45 days to investigate its effect on their ecological behavior, histopathology, bioaccumulation, and stress response. The bioconcentration factor in zebrafish brain was significantly higher (p < 0.05) at low concentration of THM (0.1 g/L) than in other treatment groups. In terms of individual behavior, the locomotor activity, aggregation, and social activity of fish were enhanced after THM exposure, but the memory of the food zone was disturbed and abnormal swimming behavior was observed. THM exposure caused brain tissue necrosis, erythrocyte infiltration, cloudy swelling, and other pathological changes in brain tissue and affected the concentrations of acetylcholinesterase and cortisol related to neurotoxicity. The condition factor and organ coefficients (brain, heart, and intestine) of zebrafish were markedly impacted by THM treatment at 0.1 and 1000 g/L, respectively. This finding showed that THM was more harmful to fish behavior than lethality, reproduction, and growth, and a behavioral study can be a useful tool for ecological risk assessment. Title: Genome-wide analysis of the strigolactone biosynthetic and signaling genes in grapevine and their response to salt and drought stresses Yu Y, Xu J, Wang C, Pang Y, Li L, Tang X, Li B, Sun Q Ref: PeerJ, 10:e13551, 2022 : PubMed ESTHER: Yu_2022_PeerJ_10_e13551 PubMedSearch: Yu 2022 PeerJ 10 e13551 PubMedID: 35712547 Abstract Strigolactones (SLs) are a novel class of plant hormones that play critical roles in regulating various developmental processes and stress tolerance. Although the SL biosynthetic and signaling genes were already determined in some plants such as Arabidopsis and rice, the information of SL-related genes in grapevine (Vitis vinifera L.) remains largely unknown. In this study, the SL-related genes were identified from the whole grapevine genome, and their expression patterns under salt and drought stresses were determined. The results indicated that the five genes that involved in the SL biosynthesis included one each of the D27, CCD7, CCD8, MAX1 and LBO genes, as well as the three genes that involved in the SL signaling included one each of the D14, MAX2, D53 genes. Phylogenetic analysis suggested that these SL-related proteins are highly conserved among different plant species. Promoter analysis showed that the prevalence of a variety of cis-acting elements associated with hormones and abiotic stress existed in the promoter regions of these SL-related genes. Furthermore, the transcription expression analysis demonstrated that most SL-related genes are involved in the salt and drought stresses response in grapevine. These findings provided valuable information for further investigation and functional analysis of SL biosynthetic and signaling genes in response to salt and drought stresses in grapevine. Title: Chemical profile, anti-hepatoma activity, anti-acetylcholinesterase and antioxidant activity of aerial part of Aconitum carmichaeli Debx Yu J, Xia J, Xu J, Chen S, Zhang Y, Yin F, Fang J, Cai L, Zhang B and Liang Z <3 more author(s)> Yu J, Xia J, Xu J, Chen S, Zhang Y, Yin F, Fang J, Cai L, Zhang B, Zhan Y, Zhang X, Zeng Z, Liang Z (- 3) Ref: Nat Prod Res, :1, 2022 : PubMed ESTHER: Yu_2022_Nat.Prod.Res__1 PubMedSearch: Yu 2022 Nat.Prod.Res 1 PubMedID: 36503283 Abstract Five extracts of the aerial parts of Aconitum carmichaeli were obtained by different solvent extraction or macroporous adsorption resin purification: ethyl acetate layer extract (EAE), n-butanol layer extract (BuE), water layer extract (WE), extract eluted by 10% ethanol from macroporous resin (10%EE), extract eluted by 80% ethanol from macroporous resin (80%EE). Antioxidant activities of the five extracts were determined by ABTS, DPPH, FRAP assays, anti-AChE activities by modified Ellman's method, insvitro anti-hepatoma activities by CCK-8 assay, and chemical constituents of 80%EE were identified by UPLC-QE-Orbitrap-MS. The results demonstrated that the 80%EE showed the best insvitro anti-hepatoma activity on Huh-7 cell line with an IC(50) of 103.91 +/- 11.02 microg/mL. 10%EE and 80%EE gave the highest antioxidant activity. Furthermore, current findings demonstrated that the aerial part of Aconitum carmichaeli Debx. has high medicinal value and may be a good natural medicine. Title: Analysis of virulence proteins in pathogenic Acinetobacter baumannii to provide early warning of zoonotic risk Zou D, Chang J, Lu S, Xu J, Hu P, Zhang K, Sun X, Guo W, Li Y and Ren H <1 more author(s)> Zou D, Chang J, Lu S, Xu J, Hu P, Zhang K, Sun X, Guo W, Li Y, Liu Z, Ren H (- 1) Ref: Microbiol Res, 266:127222, 2022 : PubMed ESTHER: Zou_2022_Microbiol.Res_266_127222 PubMedSearch: Zou 2022 Microbiol.Res 266 127222 PubMedID: 36306681 Gene_locus related to this paper: aciba-YdeN Abstract Acinetobacter baumannii is a ubiquitous opportunistic pathogen usually with low virulence. In recent years, reports of increased pathogenicity of A. baumannii in livestock due to the migratory behaviour of wildlife have attracted public health attention. Our previous study reported that an A. baumannii strain isolated from dead chicks, CCGGD201101, showed enhanced pathogenicity, but the mechanism for increased virulence is not understood. Here, to screen potential virulence factors, the proteomes of the isolated strain CCGGD201101 and the standard strain ATCC19606 of A. baumannii were compared, and the possible virulence-enhancing mechanisms were further analysed. The 50 % lethal dose (LD(50)) values of CCGGD201101 and standard strain ATCC19606 in ICR mice were determined to verify their bacterial toxicity. 2D fluorescence difference gel electrophoresis (2D-DIGE) combined with matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF/TOF-MS) and quantitative real-time PCR (RTqPCR) were applied to screen and identify differentially expressed proteins or genes that may be related to virulence enhancement. Bioinformatics analyses based on proteinprotein interaction (PPI) networks were used to explore the function of potential virulence proteins. The pathogenicity of potential virulence factors was assessed by phylogenetic analyses and an animal infection model. The results showed that the LD(50) of CCGGD201101 for mice was 1.186 x 10(6) CFU/mL, and the virulence was increased by 180.5-fold compared to ATCC19606. Forty-seven protein spots were significantly upregulated for the A. baumannii CCGGD201101 strain (fold change <=1.5, p < 0.05). In total, 14 upregulated proteins were identified using proteomic analysis, and the mRNA expression levels of these proteins were nearly identical, with few exceptions. According to the PPI network and phylogenetic analyses, the I78 family peptidase inhibitor, 3-oxoacyl-ACP reductase FabG, and glycine zipper were screened as being closely related to the pathogenicity of bacteria. Furthermore, the I78 overexpression strains exhibited higher lethality in mouse infection models, which indicated that the I78 family peptidase inhibitor was a potential new virulence factor to enhance the pathogenicity of the A. baumannii CCGGD201101 strain. The present study helped us to better understand the mechanisms of virulence enhancement and provided a scientific basis for establishing an early warning system for enhanced virulence of A. baumannii from animals. Title: Evolution of Ycf54-independent chlorophyll biosynthesis in cyanobacteria Chen GE, Hitchcock A, Mares J, Gong Y, Tichy M, Pilny J, Kovarova L, Zdvihalova B, Xu J and Sobotka R <1 more author(s)> Chen GE, Hitchcock A, Mares J, Gong Y, Tichy M, Pilny J, Kovarova L, Zdvihalova B, Xu J, Hunter CN, Sobotka R (- 1) Ref: Proc Natl Acad Sci U S A, 118:, 2021 : PubMed ESTHER: Chen_2021_Proc.Natl.Acad.Sci.U.S.A_118_ PubMedSearch: Chen 2021 Proc.Natl.Acad.Sci.U.S.A 118 PubMedID: 33649240 Gene_locus related to this paper: synsp-slr1916 Abstract Chlorophylls (Chls) are essential cofactors for photosynthesis. One of the least understood steps of Chl biosynthesis is formation of the fifth (E) ring, where the red substrate, magnesium protoporphyrin IX monomethyl ester, is converted to the green product, 3,8-divinyl protochlorophyllide a In oxygenic phototrophs, this reaction is catalyzed by an oxygen-dependent cyclase, consisting of a catalytic subunit (AcsF/CycI) and an auxiliary protein, Ycf54. Deletion of Ycf54 impairs cyclase activity and results in severe Chl deficiency, but its exact role is not clear. Here, we used a deltaycf54 mutant of the model cyanobacterium Synechocystis sp. PCC 6803 to generate suppressor mutations that restore normal levels of Chl. Sequencing deltaycf54 revertants identified a single D219G amino acid substitution in CycI and frameshifts in slr1916, which encodes a putative esterase. Introduction of these mutations to the original deltaycf54 mutant validated the suppressor effect, especially in combination. However, comprehensive analysis of the deltaycf54 suppressor strains revealed that the D219G-substituted CycI is only partially active and its accumulation is misregulated, suggesting that Ycf54 controls both the level and activity of CycI. We also show that Slr1916 has Chl dephytylase activity in vitro and its inactivation up-regulates the entire Chl biosynthetic pathway, resulting in improved cyclase activity. Finally, large-scale bioinformatic analysis indicates that our laboratory evolution of Ycf54-independent CycI mimics natural evolution of AcsF in low-light-adapted ecotypes of the oceanic cyanobacteria Prochlorococcus, which lack Ycf54, providing insight into the evolutionary history of the cyclase enzyme. Title: A Neuroligin Isoform Translated by circNlgn Contributes to Cardiac Remodeling Du WW, Xu J, Yang W, Wu N, Li F, Zhou L, Wang S, Li X, He AT and Yang BB <7 more author(s)> Du WW, Xu J, Yang W, Wu N, Li F, Zhou L, Wang S, Li X, He AT, Du KY, Zeng K, Ma J, Lyu J, Zhang C, Zhou C, Maksimovic K, Yang BB (- 7) Ref: Circulation Research, :, 2021 : PubMed ESTHER: Du_2021_Circ.Res__ PubMedSearch: Du 2021 Circ.Res PubMedID: 34261347 Abstract Rationale: Fibrotic cardiac remodeling is a maladaptive response to acute or chronic injury that leads to arrythmia and progressive heart failure. The underlying mechanisms remain unclear.Objective: We performed high-throughput RNA sequencing to analyze circular RNA (circRNA) profile in human cardiac disease and developed transgenic mice to explore the roles of circNlgn. Methods and Results: Using RNA sequencing, we found that circular neuroligin RNA (circNlgn) was highly upregulated in myocardial tissues of patients with selected congenital heart defects with cardiac overload. Back-splicing of the neuroligin gene led to the translation of a circular RNA-derived peptide (Nlgn173) with a 9-amino-acid nuclear localization motif. Binding of this motif to the structural protein LaminB1 facilitated the nuclear localization of Nlgn173. CHIP analysis demonstrated subsequent binding of Nlgn173 to both ING4 and C8orf44-SGK3 promoters, resulting in aberrant collagen deposition, cardiac fibroblast proliferation, and reduced cardiomyocyte viability. Three-dimensional ultrasound imaging of circNlgn transgenic mice showed impaired left ventricular function, with further impairment when subjected to left ventricular pressure overload compared to wild type mice. Nuclear translocation of Nlgn173, dysregulated expression of ING4 and C8orf44-SGK3, and immunohistochemical markers of cardiac fibrosis were detected in a panel of 145 patient specimens. Phenotypic changes observed in left ventricular pressure overload and transgenic mice were abrogated with silencing of circNlgn or its targets ING4 and SGK3. Conclusions: We show that a circular RNA can be translated into a novel protein isoform. Dysregulation of this process contributes to fibrosis and heart failure in cardiac overload-induced remodeling. This mechanism may hold therapeutic implications for cardiac disease. Title: Discovery of 2-(cyclopropanecarboxamido)-N-(5-((1-(4-fluorobenzyl)piperidin-4-yl)methoxy)pyridin-3-yl)isonicotinamide as a potent dual AChE/GSK3beta inhibitor for the treatment of Alzheimer's disease: Significantly increasing the level of acetylcholine in the brain without affecting that in intestine Jiang X, Liu C, Zou M, Xie H, Lin T, Lyu W, Xu J, Li Y, Feng F and Liu W <1 more author(s)> Jiang X, Liu C, Zou M, Xie H, Lin T, Lyu W, Xu J, Li Y, Feng F, Sun H, Liu W (- 1) Ref: Eur Journal of Medicinal Chemistry, 223:113663, 2021 : PubMed ESTHER: Jiang_2021_Eur.J.Med.Chem_223_113663 PubMedSearch: Jiang 2021 Eur.J.Med.Chem 223 113663 PubMedID: 34198150 Abstract Acetylcholinesterase (AChE) inhibitors are currently the first-line drugs approved by the FDA for the treatment of Alzheimer's disease (AD). However, a short effective-window limits their therapeutic benefits. Clinical studies have confirmed that the combination of AChE inhibitors and neuroprotective agents exhibits better anti-AD effects. We have previously reported that the dual AChE/GSK3beta (Glycogen synthase kinase 3beta) modulators have both neuroprotective effects and cognitive impairment-improvement effects. In this study, we characterized a new backbone of the AChE/GSK3beta inhibitor 11c. It was identified as a highly potent AChE inhibitor and was found superior to donepezil, the first-line drug for the treatment of AD. In vivo studies confirmed that 11c significantly inhibited the activity of AChE in the brain but had little effect on the activity of AChE in the intestine. This advantage of 11c was expected to reduce the peripheral side effects caused by donepezil. Furthermore, biomarker studies have shown that 11c also improved the levels of acetylcholine and synaptophysin in the brain and exhibited neuroprotective effects. Preliminary in vivo and in vitro research results underline the exciting potential of compound 11c in the treatment of AD. Title: Glycerol is Released from a New Path in MGL Lipase Catalytic Process Lan D, Li S, Tang W, Zhao Z, Luo M, Yuan S, Xu J, Wang Y Ref: J Chem Inf Model, :, 2021 : PubMed ESTHER: Lan_2021_J.Chem.Inf.Model__ PubMedSearch: Lan 2021 J.Chem.Inf.Model PubMedID: 34873908 Abstract Traditionally, it is believed that the substrate and products of a monoacylglycerol lipase (MGL) share the same path to enter and exit the catalytic site. Glycerol (a product of MGL), however, was recently hypothesized to be released through a different path. In order to improve the catalytic efficacy and thermo-stability of MGL, it is important to articulate the pathways of a MGL products releasing. In this study, with structure biological approaches, biochemical experiments, and in silico methods, we prove that glycerol is released from a different path in the catalytic site indeed. The fatty acid (another product of MGL) does share the same binding path with the substrate. This discovery paves a new road to design MGL inhibitors or optimize MGL catalytic efficacy. Title: One-Step Synthesis of 4-Octyl Itaconate through the Structure Control of Lipase Liu C, Wang Y, Liu J, Chen A, Xu J, Zhang R, Wang F, Nie K, Deng L Ref: J Org Chem, :, 2021 : PubMed ESTHER: Liu_2021_J.Org.Chem__ PubMedSearch: Liu 2021 J.Org.Chem PubMedID: 34085515 Abstract 4-Octyl itaconate is a novel antiviral and immunoregulatory small molecule showing great potential in the treatment of various autoimmune diseases and viral infections. It is difficult to selectively esterify the C4 carboxyl group of itaconate acid via one-step direct esterification using chemical catalysts, while the two-step route with itaconic anhydride as an intermediate is environmentally unfriendly and costly. This research investigated the one-step and green synthesis of 4-octyl itaconate through the structure control of lipase, obtaining 4-octyl itaconate with over 98% yield and over 99% selectivity. Multiscale molecular dynamics simulations were applied to investigate the reaction mechanism. The cavity pocket of lipases resulted in a 4-octyl itaconate selectivity by affecting distribution of substrates toward the catalytic site. Toluene could enhance monoesterification in the C4 carboxyl group and contribute to a nearly 100% conversion from itaconate acid into 4-octyl itaconate by adjusting the catalytic microenvironment around the lipase, producing a shrinkage effect on the channel. Title: Repeated low-dose exposures to sarin disrupted the homeostasis of phospholipid and sphingolipid metabolism in guinea pig hippocampus Shi M, Deng S, Cui Y, Chen X, Shi T, Song L, Zhang R, Zhang Y, Xu J and Li L <2 more author(s)> Shi M, Deng S, Cui Y, Chen X, Shi T, Song L, Zhang R, Zhang Y, Xu J, Shi J, Wang C, Li L (- 2) Ref: Toxicol Lett, 338:32, 2021 : PubMed ESTHER: Shi_2021_Toxicol.Lett_338_32 PubMedSearch: Shi 2021 Toxicol.Lett 338 32 PubMedID: 33253782 Abstract Repeated low-level exposure to sarin results to hippocampus dysfunction. Metabonomics involves a holistic analysis of a set of metabolites in an organism in the search for a relationship between these metabolites and physiological or pathological changes. The objective of the present study was to evaluate the effects of repeated exposure to low-level sarin on the metabonomics in hippocampus of a guinea pig model. Guinea pigs were divided randomly into control and sarin treated groups (n = 14). Guinea pigs in the control group received saline; while the sarin-treated group received 0.4xLD(50) (16.8 microg/kg) sarin. Daily injections (a total of 14 days) were administered sc between the shoulder blades in a volume of 1.0 ml/kg body weight. At the end of the final injection, 6 animals in each group were chosen for Morris water maze test. The rest guinea pigs (n = 8 for each group) were sacrificed by decapitation, and hippocampus were dissected for analysis. Compared with the control-group, the escape latency in sarin-group was significantly (p < 0.05) longer while the crossing times were significantly decreased in the Morris water task (p < 0.05). Sarin inhibited activities of acetylcholinesterase (AChE) and neuropathy target esterase (NTE) in hippocampus. The AChE activity of hippocampus from sarin-treated groups is equivalent to 59.9 +/- 6.4 %, and the NTE activity of hippocampus from sarin-groups is equivalent to 78.1 +/- 8.3 % of that from control-group. Metabolites were identified and validated. A total of 14 variables were selected as potential biomarkers. Phospholipids [phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidic acid (PA), phosphatidylglycerol (PG), phosphatidylinositol (PI), Lysophosphatidylethanolamine (LysoPE or LPE)] and sphingolipids (SPs) [sphinganine (SA), phytosphingosine (PSO) and sphinganine-1-phosphate (SA1P)] were clearly modified. In conclusion, repeated low-dose exposures to sarin disrupted the homeostasis of phospholipid and sphingolipid metabolism in guinea pig hippocampus and may lead to a neuronal-specific function disorders. Identified metabolites such as SA1P need to be studied more deeply on their biological function that against sarin lesions. In future research, we should pay more attention to characterize the physiological roles of lipid metabolism enzymes as well as their involvement in pathologies induced by repeated low-level sarin exposure. Title: In vivo Evaluation of a Newly Synthesized Acetylcholinesterase Inhibitor in a Transgenic Drosophila Model of Alzheimer's Disease Uras G, Manca A, Zhang P, Markus Z, Mack N, Allen S, Bo M, Xu S, Xu J and Zhu Z <1 more author(s)> Uras G, Manca A, Zhang P, Markus Z, Mack N, Allen S, Bo M, Xu S, Xu J, Georgiou M, Zhu Z (- 1) Ref: Front Neurosci, 15:691222, 2021 : PubMed ESTHER: Uras_2021_Front.Neurosci_15_691222 PubMedSearch: Uras 2021 Front.Neurosci 15 691222 PubMedID: 34276297 Abstract Alzheimer's disease is a neurodegenerative disease characterized by disrupted memory, learning functions, reduced life expectancy, and locomotor dysfunction, as a result of the accumulation and aggregation of amyloid peptides that cause neuronal damage in neuronal circuits. In the current study, we exploited a transgenic Drosophila melanogaster line, expressing amyloid-beta peptides to investigate the efficacy of a newly synthesized acetylcholinesterase inhibitor, named XJP-1, as a potential AD therapy. Behavioral assays and confocal microscopy were used to characterize the drug effect on AD symptomatology and amyloid peptide deposition. The symptomatology induced in this particular transgenic model recapitulates the scenario observed in human AD patients, showing a shortened lifespan and reduced locomotor functions, along with a significant accumulation of amyloid plaques in the brain. XJP-1 treatment resulted in a significant improvement of AD symptoms and a reduction of amyloid plaques by diminishing the amyloid aggregation rate. In comparison with clinically effective AD drugs, our results demonstrated that XJP-1 has similar effects on AD symptomatology, but at 10 times lower drug concentration than donepezil. It also showed an earlier beneficial effect on the reduction of amyloid plaques at 10 days after drug treatment, as observed for donepezil at 20 days, while the other drugs tested have no such effect. As a novel and potent AChE inhibitor, our study demonstrates that inhibition of the enzyme AChE by XJP-1 treatment improves the amyloid-induced symptomatology in Drosophila, by reducing the number of amyloid plaques within the fruit fly CNS. Thus, compound XJP-1 has the therapeutic potential to be further investigated for the treatment of AD. Title: PbCSE1 promotes lignification during stone cell development in pear (Pyrus bretschneideri) fruit Xu J, Tao X, Xie Z, Gong X, Qi K, Zhang S, Shiratake K, Tao S Ref: Sci Rep, 11:9450, 2021 : PubMed ESTHER: Xu_2021_Sci.Rep_11_9450 PubMedSearch: Xu 2021 Sci.Rep 11 9450 PubMedID: 33941813 Abstract Pear [Pyrus bretschneideri cv. Dangshan Su] fruit quality is not always satisfactory owing to the presence of stone cells, and lignin is the main component of stone cells in pear fruits. Caffeoyl shikimate esterase (CSE) is a key enzyme in the lignin biosynthesis. Although CSE-like genes have been isolated from a variety of plant species, their orthologs are not characterized in pear. In this study, the CSE gene family (PbCSE) from P. bretschneideri was identified. According to the physiological data and quantitative RT-PCR (qRT-PCR), PbCSE1 was associated with lignin deposition and stone cell formation. The overexpression of PbCSE1 increased the lignin content in pear fruits. Relative to wild-type (WT) Arabidopsis, the overexpression of PbCSE1 delayed growth, increased the lignin deposition and lignin content in stems. Simultaneously, the expression of lignin biosynthetic genes were also increased in pear fruits and Arabidopsis. These results demonstrated that PbCSE1 plays an important role in cell lignification and will provide a potential molecular strategy to improve the quality of pear fruits. Title: Discovery of Novel Tacrine-Pyrimidone Hybrids as Potent Dual AChE/GSK-3 Inhibitors for the Treatment of Alzheimer's Disease Yao H, Uras G, Zhang P, Xu S, Yin Y, Liu J, Qin S, Li X, Allen S and Xu J <4 more author(s)> Yao H, Uras G, Zhang P, Xu S, Yin Y, Liu J, Qin S, Li X, Allen S, Bai R, Gong Q, Zhang H, Zhu Z, Xu J (- 4) Ref: Journal of Medicinal Chemistry, :, 2021 : PubMed ESTHER: Yao_2021_J.Med.Chem__ PubMedSearch: Yao 2021 J.Med.Chem PubMedID: 34024109 Inhibitor(s) related to this paper: ACHE-GSK-3-27g Abstract Based on a multitarget strategy, a series of novel tacrine-pyrimidone hybrids were identified for the potential treatment of Alzheimer's disease (AD). Biological evaluation results demonstrated that these hybrids exhibited significant inhibitory activities toward acetylcholinesterase (AChE) and glycogen synthase kinase 3 (GSK-3). The optimal compound 27g possessed excellent dual AChE/GSK-3 inhibition both in terms of potency and equilibrium (AChE: IC(50) = 51.1 nM; GSK-3beta: IC(50) = 89.3 nM) and displayed significant amelioration on cognitive deficits in scopolamine-induced amnesia mice and efficient reduction against phosphorylation of tau protein on Ser-199 and Ser-396 sites in glyceraldehyde (GA)-stimulated differentiated SH-SY5Y cells. Furthermore, compound 27g exhibited eligible pharmacokinetic properties, good kinase selectivity, and moderate neuroprotection against GA-induced reduction in cell viability and neurite damage in SH-SY5Y-derived neurons. The multifunctional profiles of compound 27g suggest that it deserves further investigation as a promising lead for the prospective treatment of AD. Title: Effect of Chitosan Coatings with Cinnamon Essential Oil on Postharvest Quality of Mangoes Yu K, Xu J, Zhou L, Zou L, Liu W Ref: Foods, 10:, 2021 : PubMed ESTHER: Yu_2021_Foods_10_ PubMedSearch: Yu 2021 Foods 10 PubMedID: 34945553 Abstract Mango (Mangifera indica Linn.) is a famous climacteric fruit containing abundant flavor and nutrients in the tropics, but it is prone to decay without suitable postharvest preservation measures. In this study, the chitosan (CH)-cinnamon essential oil (CEO) Pickering emulsion (CH-PE) coating was prepared, with cellulose nanocrystals as the emulsifier, and applied to harvested mangoes at the green stage of maturity. It was compared with a pure CH coating and a CH-CEO emulsion (CH-E) coating, prepared with the emulsifier Tween 80. Results showed that the CH-PE coating had a lower water solubility and water vapor permeability than the other coatings, which was mainly due to electrostatic interactions, and had a better sustained-release performance for CEO than the CH-E coating. During mango storage, the CH-PE coating effectively improved the appearance of mangoes at 25 degreesC for 12 d by reducing yellowing and dark spots, and delayed water loss. Hardness was maintained and membrane lipid peroxidation was reduced by regulating the activities of pectin methyl esterase, polygalacturonase, and peroxidase. In addition, the nutrient quality was improved by the CH-PE coating, with higher contents of total soluble solid, titratable acid, and ascorbic acid. Therefore, the CH-PE coating is promising to comprehensively maintain the postharvest quality of mangoes, due to its enhanced physical and sustained-release properties. Title: Discovery of Three New Monoterpenoid Indole Alkaloids from the Leaves of Gardneria multiflora and Their Vasorelaxant and AChE Inhibitory Activities Zhang SY, Li ZW, Xu J, Chen QL, Song M, Zhang QW Ref: Molecules, 26:, 2021 : PubMed ESTHER: Zhang_2021_Molecules_26_ PubMedSearch: Zhang 2021 Molecules 26 PubMedID: 34885772 Abstract Three novel monoterpenoid indole alkaloids gardflorine A (1), gardflorine B (2), and gardflorine C (3) were isolated from the leaves of Gardneria multiflora. Their structures, including absolute configurations, were established on the basis of spectroscopic methods (MS, UV, IR, 1D and 2D NMR) and circular dichroism experiments. All the compounds were evaluated for their vasorelaxant and acetylcholinesterase (AChE) inhibitory activities. Compound 1 exhibited potent vasorelaxant activity, with an EC(50) value of 8.7 microM, and compounds 2 and 3 showed moderate acetylcholinesterase (AChE) inhibitory activities, with IC(50) values of 26.8 and 29.2 microM, respectively. Title: Multivalent butyrylcholinesterase inhibitor discovered by exploiting dynamic combinatorial chemistry Zhao S, Xu J, Zhang S, Han M, Wu Y, Li Y, Hu L Ref: Bioorg Chem, 108:104656, 2021 : PubMed ESTHER: Zhao_2021_Bioorg.Chem_108_104656 PubMedSearch: Zhao 2021 Bioorg.Chem 108 104656 PubMedID: 33548731 Abstract In this study, we report the generation of a polymer-based dynamic combinatorial library (DCL) incorporating exchangeable side chains using acylhydrazone formation reaction. In combination with tetrameric butyrylcholinesterase (BChE), the most potent binding side chain was identified, and the information obtained was further used for the synthesis of a multivalent BChE inhibitor. In the in vitro biological evaluation, this multivalent inhibitor exhibited not only better inhibitory effect than the commercial reference but also high selectivity on BChE over acetylcholinesterase (AChE). Title: miR-140-3p Inhibits Cutaneous Melanoma Progression by Disrupting AKT/p70S6K and JNK Pathways through ABHD2 He Y, Yang Y, Liao Y, Xu J, Liu L, Li C, Xiong X Ref: Mol Ther Oncolytics, 17:83, 2020 : PubMed ESTHER: He_2020_Mol.Ther.Oncolytics_17_83 PubMedSearch: He 2020 Mol.Ther.Oncolytics 17 83 PubMedID: 32322665 Gene_locus related to this paper: human-ABHD2 Abstract Because cutaneous melanoma (CM) is one of the most lethal human tumors, major treatment advances are vital. miR-140-3p has been suggested to act as a suppressor in a range of malignant tumors, implying its possible use as a biomarker for effective antineoplastic treatment. However, the potential role of miR-140-3p in CM and the underlying mechanism remain unclear. In the present study, we identified lower levels of miR-140-3p in both CM tissues and cell lines; this downregulation was strongly associated with worse CM survival. Additionally, overexpression of miR-140-3p significantly inhibited cell proliferation, migration, and invasion in CM cells with different cell line origins. Importantly, by means of both bioinformatics analysis and luciferase reporter assay, we revealed abhydrolase domain containing 2 (ABHD2) to be a target of miR-140-3p in CM cells. Upregulation of ABHD2 reversed the tumor-suppressive effects of miR-140-3p in CM cells. Furthermore, miR-140-3p-targeted ABHD2 played a role in both activation of JNK signaling and inhibition of the AKT/p70S6K pathway in CM cells. Finally, in vivo results strongly suggested the suppressive effects of miR-140-3p on CM growth and metastasis. Collectively, our findings highlight a novel antineoplastic function for miR-140-3p in CM through ABHD2. Title: Discovery of small-molecule enzyme activators by activity-based protein profiling Kok BP, Ghimire S, Kim W, Chatterjee S, Johns T, Kitamura S, Eberhardt J, Ogasawara D, Xu J and Saez E <10 more author(s)> Kok BP, Ghimire S, Kim W, Chatterjee S, Johns T, Kitamura S, Eberhardt J, Ogasawara D, Xu J, Sukiasyan A, Kim SM, Godio C, Bittencourt JM, Cameron M, Galmozzi A, Forli S, Wolan DW, Cravatt BF, Boger DL, Saez E (- 10) Ref: Nat Chemical Biology, 16:997, 2020 : PubMed ESTHER: Kok_2020_Nat.Chem.Biol_16_997 PubMedSearch: Kok 2020 Nat.Chem.Biol 16 997 PubMedID: 32514184 Gene_locus related to this paper: human-LYPLAL1 Abstract Activity-based protein profiling (ABPP) has been used extensively to discover and optimize selective inhibitors of enzymes. Here, we show that ABPP can also be implemented to identify the converse-small-molecule enzyme activators. Using a kinetically controlled, fluorescence polarization-ABPP assay, we identify compounds that stimulate the activity of LYPLAL1-a poorly characterized serine hydrolase with complex genetic links to human metabolic traits. We apply ABPP-guided medicinal chemistry to advance a lead into a selective LYPLAL1 activator suitable for use in vivo. Structural simulations coupled to mutational, biochemical and biophysical analyses indicate that this compound increases LYPLAL1's catalytic activity likely by enhancing the efficiency of the catalytic triad charge-relay system. Treatment with this LYPLAL1 activator confers beneficial effects in a mouse model of diet-induced obesity. These findings reveal a new mode of pharmacological regulation for this large enzyme family and suggest that ABPP may aid discovery of activators for additional enzyme classes. Title: Functional Characterization of two Carboxylesterase Genes Involved in Pyrethroid Detoxification in Helicoverpa armigera Li Y, Bai L, Zhao C, Xu J, Sun Z, Dong Y, Li D, Liu XL, Ma ZQ Ref: Journal of Agricultural and Food Chemistry, 68:3390, 2020 : PubMed ESTHER: Li_2020_J.Agric.Food.Chem_68_3390 PubMedSearch: Li 2020 J.Agric.Food.Chem 68 3390 PubMedID: 32096985 Gene_locus related to this paper: helam-d5g3d5, helam-d9iv61 Abstract Insect carboxylesterases are major enzymes involved in metabolism of xenobiotics including insecticides. Two carboxylesterase genes, CarE001A and CarE001H, were cloned from the destructive agricultural pest Helicoverpa armigera. Quantitative Real-Time PCR showed that CarE001A and CarE001H were predominantly expressed in fat body and midgut, respectively; developmental expression analyses found that the expression levels of both CarEs were significantly higher in fifth- instar larvae than in other life stages. Recombinant CarE001A and CarE001H expressed in the Escherichia coli exhibited high enzymatic activity toward alpha-naphthyl acetate. Inhibition assays showed that organophosphates had strong inhibition on CarEs activity compared to pyrethroids. Metabolism assays indicated that CarE001A and CarE001H were able to metabolize beta-cypermethrin and lambda-cyhalothrin. Homology modeling and molecular docking analyses demonstrated that beta-cypermethrin could fit nicely into the active pocket of both carboxylesterases. These results suggested that CarE001A and CarE001H could play important roles in the detoxification of pyrehtroids in H. armigera. Title: Lemon essential oil ameliorates age-associated cognitive dysfunction via modulating hippocampal synaptic density and inhibiting acetylcholinesterase Liu B, Kou J, Li F, Huo D, Xu J, Zhou X, Meng D, Ghulam M, Artyom B and Han D <2 more author(s)> Liu B, Kou J, Li F, Huo D, Xu J, Zhou X, Meng D, Ghulam M, Artyom B, Gao X, Ma N, Han D (- 2) Ref: Aging (Albany NY), 12:, 2020 : PubMed ESTHER: Liu_2020_Aging.(Albany.NY)_12_ PubMedSearch: Liu 2020 Aging.(Albany.NY) 12 PubMedID: 32392535 Abstract The lemon essential oil (LEO), extracted from the fruit of lemon, has been used to treat multiple pathological diseases, such as diabetes, inflammation, cardiovascular diseases, depression and hepatobiliary dysfunction. The study was designed to study the effects of LEO on cognitive dysfunction induced by Alzheimer's disease (AD). We used APP/PS1 double transgene (APP/PS1) AD mice in the experiment; these mice exhibit significant deficits in synaptic density and hippocampal-dependent spatial related memory. The effects of LEO on learning and memory were examined using the Morris Water Maze (MWM) test, Novel object recognition test, and correlative indicators, including a neurotransmitter (acetylcholinesterase, AChE), a nerve growth factor (brain-derived neurotrophic factor, BDNF), a postsynaptic marker (PSD95), and presynaptic markers (synapsin-1, and synaptophysin), in APP/PS1 mice. Histopathology was performed to estimate the effects of LEO on AD mice. A significantly lowered brain AChE depression in APP/PS1 and wild-type C57BL/6L (WT) mice. PSD95/ Synaptophysin, the index of synaptic density, was noticeably improved in histopathologic changes. Hence, it can be summarized that memory-enhancing activity might be associated with a reduction in the AChE levels and is elevated by BDNF, PSD95, and synaptophysin through enhancing synaptic plasticity. Title: LPL deletion is associated with poorer response to ibrutinib-based treatments and overall survival in TP53-deleted chronic lymphocytic leukemia Liu W, Burger JA, Xu J, Tang Z, Toruner G, Khanlari M, Medeiros LJ, Tang G Ref: Ann Hematol, 99:2343, 2020 : PubMed ESTHER: Liu_2020_Ann.Hematol_99_2343 PubMedSearch: Liu 2020 Ann.Hematol 99 2343 PubMedID: 32833105 Abstract Ibrutinib-based therapy represents a recent success in managing high-risk CLL patients with 17p/TP53 deletion. However, a subset of CLL patients are resistant to therapy. Deletion of lipoprotein lipase (LPL) has been postulated as a potential evasion mechanism to ibrutinib-based therapy. In this study, we assessed for LPL deletion by fluorescence in situ hybridization in 176 consecutive CLL patients with 17p/TP53 deletion. LPL deletion was detected in 35 (20%) of CLL patients. Patients with LPL deletion (del) showed a higher frequency of CD38 expression but have comparable frequencies of somatic hypermutation and ZAP-70 expression compared with patients with normal (nml) LPL. Gene mutation analysis showed that TP53 was mutated in 68% of LPL-del versus 91% of LPL-nml patients. The overall response to ibrutinib-based therapy was 57%, including 37% complete remission (CR) and 20% partial remission (PR) in patients with LPL-del versus 90% (56% CR and 34% PR) in patients with LPL-nml (p<0.001). LPL-del patients also showed a poorer overall survival (OS) compared with patients with LPL-nml (median OS, 236 months versus undefined, p<0.001). In summary, the data presented establish an association between LPL deletion, resistance to ibrutinib-based therapy, and poorer overall survival in TP53-deleted CLL patients. We suggest that LPL deletion might be utilized as a biomarker for risk stratification and to predict therapeutic response in this high-risk group of CLL patients. Title: Patatin primary structural properties and effects on lipid metabolism Wu J, Wu Q, Yang D, Zhou M, Xu J, Wen Q, Cui Y, Bai Y, Xu S and Wang S <1 more author(s)> Wu J, Wu Q, Yang D, Zhou M, Xu J, Wen Q, Cui Y, Bai Y, Xu S, Wang Z, Wang S (- 1) Ref: Food Chem, :128661, 2020 : PubMed ESTHER: Wu_2020_Food.Chem__128661 PubMedSearch: Wu 2020 Food.Chem 128661 PubMedID: 33272761 Abstract Patatin, the major protein found in potatoes, was purified and shows several isoforms. The essential amino acid content of patatin was ashighas 76%, indicating that it is a valuable protein source. Patatin was an O-linked glycoprotein that contained fucose monosaccharides, as well as mannose, rhamnose, glucose, galactose, xylose, and arabinose. Patatin had a fucosylated glycan structural feature, which strongly bound AAL (Aleuria aurantia Leukoagglutinin), a known fucose binding lectin. Moreover, thelipid metabolism regulatory effects of patatin on the fat catabolism, fat absorption, and inhibition of lipase activity were measured after high-fat feeding of zebrafish larvae. Results revealed that 37.0 g/mL patatin promoted 23% lipid decomposition metabolism. Meanwhile patatin could inhibite lipase activity and fat absorption, whose effects accounted for half that of a positive control drug. Our findings suggest that patatin, a fucosylated glycoprotein, could potentially be used as a naturalactiveconstituent with anti-obesity effects. Title: Pharmacological Mechanisms Underlying the Neuroprotective Effects of Alpinia oxyphylla Miq. on Alzheimer's Disease Xu J, Wang F, Guo J, Xu C, Cao Y, Fang Z, Wang Q Ref: Int J Mol Sci, 21:, 2020 : PubMed ESTHER: Xu_2020_Int.J.Mol.Sci_21_ PubMedSearch: Xu 2020 Int.J.Mol.Sci 21 PubMedID: 32197305 Abstract Alpinia oxyphylla Miq. (i.e., A. oxyphylla), a traditional Chinese medicine, can exert neuroprotective effects in ameliorating mild cognitive impairment and improving the pathological hallmarks of Alzheimer's disease (AD). Here, 50 active compounds and 164 putative targets were collected and identified with 251 clinically tested AD-associated target proteins using network pharmacology approaches. Based on the Gene Ontology/Kyoto Encyclopedia of Genes and Genomes pathway enrichments, the compound-target-pathway-disease/protein-protein interaction network constructions, and the network topological analysis, we concluded that A. oxyphylla may have neuroprotective effects by regulating neurotransmitter function, as well as brain plasticity in neuronal networks. Moreover, closely-related AD proteins, including the amyloid-beta precursor protein, the estrogen receptor 1, acetylcholinesterase, and nitric oxide synthase 2, were selected as the bottleneck nodes of network for further verification by molecular docking. Our analytical results demonstrated that terpene, as the main compound of A. oxyphylla extract, exerts neuroprotective effects, providing new insights into the development of a natural therapy for the prevention and treatment of AD. Title: Development of a multivalent acetylcholinesterase inhibitor via dynamic combinatorial chemistry Xu J, Zhao S, Zhang S, Pei J, Li Y, Zhang Y, He X, Hu L Ref: Int J Biol Macromol, 150:1184, 2020 : PubMed ESTHER: Xu_2020_Int.J.Biol.Macromol_150_1184 PubMedSearch: Xu 2020 Int.J.Biol.Macromol 150 1184 PubMedID: 31758986 Abstract In this study, we report the generation of a polymer based dynamic combinatorial library (DCL) using aldehyde-functionalized linear poly(glycidol) and hydrazide derivatives as initial building blocks. In combination with tetrameric acetylcholinesterase (AChE), a certain type of amplified acylhydrazone side chain is identified and further used for the synthesis of a multivalent AChE inhibitor. The cytotoxicity and inhibition properties of the multivalent inhibitor are evaluated, and the results indicate superior bioactivity compared to the commercial reference Edrophonium chloride. Title: JZL184 protects hippocampal neurons from oxygen-glucose deprivation-induced injury via activating Nrf2/ARE signaling pathway Xu J, Guo Q, Huo K, Song Y, Li N, Du J Ref: Hum Exp Toxicol, :960327120984220, 2020 : PubMed ESTHER: Xu_2020_Hum.Exp.Toxicol__960327120984220 PubMedSearch: Xu 2020 Hum.Exp.Toxicol 960327120984220 PubMedID: 33375871 Abstract JZL184 is a selective inhibitor of monoacylglycerol lipase (MAGL) that has neuroprotective effect. However, the role of JZL184 in cerebral ischemia/reperfusion (I/R) injury and the exact mechanism have not been fully understood. This study was designed to elucidate the role of JZL184 in cerebral I/R injury induced by oxygen-glucose deprivation/reoxygenation (OGD/R) in hippocampal neurons. Hippocampal neurons were pretreated with various concentrations of JZL184 for 2 h, followed by OGD for 3 h and reoxygen for 24 h. Our results showed that JZL184 improved cell viability in hippocampal neurons in response to OGD/R. JZL184 treatment significantly inhibited the production of reactive oxygen species (ROS) and malondialdehyde (MDA), as well as increased superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities in OGD/R-induced hippocampal neurons. The increased TNF-alpha, IL-1beta, and IL-6 productions in OGD/R-induced hippocampal neurons were decreased after treatment with JZL184. Moreover, the OGD/R-caused intense TUNEL staining in hippocampal neurons was attenuated by JZL184. JZL184 treatment prevented OGD/R-caused increases in bax and cleaved caspase-3 expression and a decrease in bcl-2 expression. Furthermore, JZL184 treatment significantly promoted the activation of Nrf2/ARE signaling pathway in OGD/R-induced hippocampal neurons. Additionally, silencing of Nrf2 reversed the protective effect of JZL184 on hippocampal neurons under OGD/R condition. Taken together, these findings suggested that JZL184 exerted protective effect against OGD/R-induced injury in hippocampal neurons via activating Nrf2/ARE signaling pathway, which provided in vitro experimental support for the therapeutic benefit of JZL184 in cerebral ischemia. Title: [Proteolytic cleavage of neuroligins and functions of their cleavage products] Yu J, Xu J Ref: Zhejiang Da Xue Xue Bao Yi Xue Ban, 49:514, 2020 : PubMed ESTHER: Yu_2020_Zhejiang.Da.Xue.Xue.Bao.Yi.Xue.Ban_49_514 PubMedSearch: Yu 2020 Zhejiang.Da.Xue.Xue.Bao.Yi.Xue.Ban 49 514 PubMedID: 32985166 Abstract Neuroligin is a key protein that mediates synaptic development and maturation, and is closely related to neurodevelopmental diseases such as autism. In recent years, researchers have found that neuroligin can be hydrolyzed by various proteases at different stages of development, neuronal activities or pathological states of some neuropsychiatric diseases, thus affecting synaptic activity and participating in the occurrence and development of neurological diseases. The hydrolysates may have different physiological functions from the whole protein, and play different functions in neural activities, such as regulating synaptic plasticity, increasing synaptic strength and number, affecting amyloid-beta polymerization, promoting glioma proliferation and growth, activating related signaling pathways, and so on. In this article, on the basis of elaborating the structure and function of neuroligin as a whole protein, the conditions and products of its hydrolysis are summarized and analyzed, and the functional consequences and physiological significance of its hydrolysis are discussed. Title: High-efficiency expression of the thermophilic lipase from Geobacillus thermocatenulatus in Escherichia coli and its application in the enzymatic hydrolysis of rapeseed oil Zhang J, Tian M, Lv P, Luo W, Wang Z, Xu J Ref: 3 Biotech, 10:523, 2020 : PubMed ESTHER: Zhang_2020_3.Biotech_10_523 PubMedSearch: Zhang 2020 3.Biotech 10 523 PubMedID: 33194527 Abstract Long-chain fatty acids are widely used in food and chemical industries, and the enzymatic preparation of fatty acids is considered an environmentally friendly process. In the present study, long-chain fatty acids were prepared by the enzymatic hydrolysis of rapeseed oil with a genetically engineered lipase. Because thermophilic lipase has strong stability at higher temperatures, it was more suitable for the industrial production of long-chain fatty acids. Therefore, the thermophilic lipase BTL2 from Geobacillus thermocatenulatus was efficiently expressed in E. coli BL21(DE3) cells with an enzyme activity of 39.50 U/mg followed by gene codon optimisation. Experimental results showed that the recombinant lipase BTL2 exhibited excellent resistance to certain organic solvents (n-hexane, benzene, ethanol, and butanol). The metal cation Ca(2+) and the non-ionic surfactant Triton-100X enhanced enzyme activity by 7.36% and 56.21% respectively. Moreover, the acid value of the liberated long-chain fatty acids by hydrolysing rapeseed oil was approximately 161.64 mg KOH/g at 50 degreeC in 24 h, the hydrolytic conversion rate was 91.45%, and the productivity was approximately 6.735 mg KOH/g h. These results suggested that the recombinant lipase BTL2 has excellent hydrolytic performance for rapeseed oil and showed great potential for the enzymatic preparation of long-chain fatty acids. Title: Thiol-ene click reaction-induced fluorescence enhancement by altering the radiative rate for assaying butyrylcholinesterase activity Chen G, Feng H, Xi W, Xu J, Pan S, Qian Z Ref: Analyst, 144:559, 2019 : PubMed ESTHER: Chen_2019_Analyst_144_559 PubMedSearch: Chen 2019 Analyst 144 559 PubMedID: 30417195 Abstract Butyrylcholinesterase (BChE) generally acts as an important plasma biomarker for clinical diagnosis due to its major contribution to human plasma cholinesterase levels, but its current fluorometric assay relying on fluorogenic substrates frequently suffers from the lack of sufficiently fast response time and specific recognition of substrates relative to the traditional Ellman's method. In this work, we report a fluorescent molecular probe for assaying BChE activity based on thiol-triggered fluorescence enhancement via thiol-ene click reactions. A low-temperature experiment and theoretical analysis exclude the possibility of weak fluorescence of the probe caused by an intramolecular photoinduced electron transfer process and support the main cause of an ultraslow radiative rate due to the introduction of two acrylyl groups. This probe has sensitive fluorescence responses to thiols via thiol-ene click chemistry, and it can distinguish between glutathione and cysteine or homocysteine in different emission colors. The rapid reaction kinetics of this probe enables it to monitor hydrolysis reactions catalyzed by butyrylcholinesterase (BChE) in a real-time manner. This probe is used to develop the first fluorometric assay of BChE activity based on fluorescence enhancement triggered by thiol-ene click chemistry using butyrylthiocholine as the substrate. The established BChE assay shows excellent sensitivity, and is capable of avoiding the interference from glutathione and acetylcholinesterase (AChE) in a complex matrix. The inhibition test of tacrine on BChE with this assay substantiates its feasibility in screening potential inhibitors of BChE. This work demonstrates a design strategy of fluorescent probes lighted up by thiol-ene click reactions, reveals the main cause of thiol-triggered fluorescence enhancement by altering the radiative rate, and provides the first fluorometric assay of BChE based on rapid thiol-ene click reactions. Title: Effects of Picrasma quassioides and its active constituents on Alzheimer's disease in vitro and in vivo Guo E, Hu Y, Du T, Zhu H, Chen L, Qu W, Zhang J, Xie N, Liu W and Xu J <1 more author(s)> Guo E, Hu Y, Du T, Zhu H, Chen L, Qu W, Zhang J, Xie N, Liu W, Feng F, Xu J (- 1) Ref: Bioorg Chem, 92:103258, 2019 : PubMed ESTHER: Guo_2019_Bioorg.Chem_92_103258 PubMedSearch: Guo 2019 Bioorg.Chem 92 103258 PubMedID: 31520892 Abstract Alzheimer disease (AD), a prevalent neurodegenerative disorder, is one of the leading causes of dementia. However, there is no effective drug for this disease to date. Picrasma quassioides (D.Don) Benn, a Chinese traditional medicine, was used mainly for the treatment of inflammation, fever, microbial infection and dysentery. In this paper, we reported that the EtOAc extract of Picrasma quassioides stems showed potential neuroprotective activities in l-glutamate-stimulated PC12 and Abeta25-35-stimulated SH-SY5Y cell models, as well as improved memory and cognitive abilities in AD mice induced by amyloid-beta peptide. Moreover, it was revealed that the anti-AD mechanism was related to suppressing neuroinflammatory and reducing Abeta1-42 deposition using ELISA assay kits. To clarify the active components of the EtOAc extract of Picrasma quassioides stems, a systematic phytochemistry study led to isolate and identify six beta-carboline alkaloids (1-6), seven canthin-6-one alkaloids (7-13), and five quassinoids (14-18). Among them, four beta-carbolines (1-3, and 6) and six canthin-6-ones (7-11, and 13) exhibited potential neuroprotective activities in vitro. Based on these date, the structure-activity relationships of alkaloids were discussed. Furthermore, molecular docking experiments showed that compounds 2 and 3 have high affinity for both of dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYPKIA) and butyrylcholinesterase (BuChE). Title: Visual detection of mixed organophosphorous pesticide using QD-AChE aerogel based microfluidic arrays sensor Hu T, Xu J, Ye Y, Han Y, Li X, Wang Z, Sun D, Zhou Y, Ni Z Ref: Biosensors & Bioelectronics, 136:112, 2019 : PubMed ESTHER: Hu_2019_Biosens.Bioelectron_136_112 PubMedSearch: Hu 2019 Biosens.Bioelectron 136 112 PubMedID: 31054518 Abstract In this paper, we present a simple strategy to fabricate a sensitive fluorescence microfluidic sensor based on quantum dots (QDs) aerogel and acetylcholinesterase enzyme (AChE) for organophosphate pesticides (OPs) detection The detection is based on the change of fluorescence intensity of QDs aerogel, which will be partly quenched as a consequence of the hydrolytic reaction of acetylthiocholine (ATCh) catalyzed by the AChE, and then the fluorescence of QDs aerogel is recovered due to decreasing of the enzymatic activity in the presence of OPs. The QDs-AChE aerogel based microfluidic arrays sensor provided good sensitivity for rapid detection of OPs with a detection limit of 0.38 pM, while the detection range is from 10(-5) to 10(-12)M. Due to the result of random orientations of AChE in the 3D porous aerogel nano-structure, the sensor presents similar calibration curves to difference pesticides, which promises the ability of the sensor to monitor total OPs of mixture. This determination sensor shows a low detection limit, wide linear range, and highly accurate determination of total OPs and carbamate content. Finally, we show the proposed sensor can be used to monitor of simple OPs and mixture in spiked fruit samples. This novel QDs-AChE aerogel sensor has an extremely high sensitivity and large detection range, it is a promising tool for accurate, rapid and cost-effective detection of various OP residues on agricultural products. Title: Single intranasal immunization with chimpanzee adenovirus-based vaccine induces sustained and protective immunity against MERS-CoV infection Jia W, Channappanavar R, Zhang C, Li M, Zhou H, Zhang S, Zhou P, Xu J, Shan S and Zhang L <5 more author(s)> Jia W, Channappanavar R, Zhang C, Li M, Zhou H, Zhang S, Zhou P, Xu J, Shan S, Shi X, Wang X, Zhao J, Zhou D, Perlman S, Zhang L (- 5) Ref: Emerg Microbes Infect, 8:760, 2019 : PubMed ESTHER: Jia_2019_Emerg.Microbes.Infect_8_760 PubMedSearch: Jia 2019 Emerg.Microbes.Infect 8 760 PubMedID: 31130102 Abstract The recently identified Middle East Respiratory Syndrome Coronavirus (MERS-CoV) causes severe and fatal acute respiratory illness in humans. However, no approved prophylactic and therapeutic interventions are currently available. The MERS-CoV envelope spike protein serves as a crucial target for neutralizing antibodies and vaccine development, as it plays a critical role in mediating viral entry through interactions with the cellular receptor, dipeptidyl peptidase 4 (DPP4). Here, we constructed a recombinant rare serotype of the chimpanzee adenovirus 68 (AdC68) that expresses full-length MERS-CoV S protein (AdC68-S). Single intranasal immunization with AdC68-S induced robust and sustained neutralizing antibody and T cell responses in BALB/c mice. In a human DPP4 knock-in (hDPP4-KI) mouse model, it completely protected against lethal challenge with a mouse-adapted MERS-CoV (MERS-CoV-MA). Passive transfer of immune sera to naive hDPP4-KI mice also provided survival advantages from lethal MERS-CoV-MA challenge. Analysis of sera absorption and isolated monoclonal antibodies from immunized mice demonstrated that the potent and broad neutralizing activity was largely attributed to antibodies targeting the receptor binding domain (RBD) of the S protein. These results show that AdC68-S can induce protective immune responses in mice and represent a promising candidate for further development against MERS-CoV infection in both dromedaries and humans. Title: Ratiometric two-photon fluorescent probe for in situ imaging of carboxylesterase (CE)-mediated mitochondrial acidification during medication Jiang A, Chen G, Xu J, Liu Y, Zhao G, Liu Z, Chen T, Li Y, James TD Ref: Chem Commun (Camb), 55:11358, 2019 : PubMed ESTHER: Jiang_2019_Chem.Commun.(Camb)_55_11358 PubMedSearch: Jiang 2019 Chem.Commun.(Camb) 55 11358 PubMedID: 31482158 Abstract We report on a dual ratiometric two-photon fluorescent probe for in situ sensing of mitochondrial CE activity and pH. Using the probe it is possible to visualize the CE-mediated acidification of hepatoma cells and hepatic tissues during medication with antipyretic anti-inflammatory drugs. Title: A Compound Heterozygous Mutation of Lipase Maturation Factor 1 is Responsible for Hypertriglyceridemia of a Patient Liu Y, Xu J, Tao W, Yu R, Zhang X Ref: J Atheroscler Thromb, 26:136, 2019 : PubMed ESTHER: Liu_2019_J.Atheroscler.Thromb_26_136 PubMedSearch: Liu 2019 J.Atheroscler.Thromb 26 136 PubMedID: 29910226 Abstract AIM: Dyslipidemia is the most common lipid metabolism disorder in humans, and its etiology remains elusive. Hypertriglyceridemia (HTG) is a type of dyslipidemia that contributes to atherosclerosis and coronary heart disease. Previous studies have demonstrated that mutations in lipoprotein lipase (LPL), apolipoprotein CII (APOC2), apolipoprotein AV (APOA5), glycosylphosphatidylinositol anchored high-density lipoprotein-binding protein 1 (GPIHBP1), lipase maturation factor 1(LMF1), and glycerol-3 phosphate dehydrogenase 1 (GPD1) are responsible for HTG by using genomic microarrays and next-generation sequencing. The aim of this study was to identify genetic lesions in patients with HTG. METHOD: Our study included a family of seven members from Jiangsu province across three generations. The proband was diagnosed with severe HTG, with a plasma triglyceride level of 38.70 mmol/L. Polymerase chain reaction (PCR) and Sanger sequencing were performed to explore the possible causative gene mutations for this patient. Furthermore, we measured the post-heparin LPL and hepatic lipase (HL) activities using an antiserum inhibition method. RESULTS: A compound heterozygous mutation in the LMF1 gene (c.257CT/p.P86L and c.1184CT/p.T395I) was identified and co-segregated with the affected patient in this family. Both mutations were predicted to be deleterious by three bioinformatics programs (Polymorphism Phenotyping-2, Sorting Intolerant From Tolerant, and MutationTaster). The levels of the plasma post-heparin LPL and HL activities in the proband (57 and 177 mU/mL) were reduced to 24% and 75%, respectively, compared with those assayed in the control subject with normal plasma triglycerides. CONCLUSION: A compound heterozygous mutation of LMF1 was identified in the presenting patient with severe HTG. These findings expand on the spectrum of LMF1 mutations and contribute to the genetic diagnosis and counseling of families with HTG. Title: Royal Jelly Ameliorates Behavioral Deficits, Cholinergic System Deficiency, and Autonomic Nervous Dysfunction in Ovariectomized Cholesterol-Fed Rabbits Pan Y, Xu J, Jin P, Yang Q, Zhu K, You M, Chen M, Hu F Ref: Molecules, 24:, 2019 : PubMed ESTHER: Pan_2019_Molecules_24_ PubMedSearch: Pan 2019 Molecules 24 PubMedID: 30909491 Abstract Estrogen deficiency after menopause is associated with autonomic nervous changes, leading to memory impairment and increased susceptibility to Alzheimer's disease (AD). Royal jelly (RJ) from honeybees (Apis mellifera) has estrogenic activity. Here, we investigated whether RJ can improve behavior, cholinergic and autonomic nervous function in ovariectomized (OVX) cholesterol-fed rabbits. OVX rabbits on high-cholesterol diet were administered with RJ for 12 weeks. The results showed that RJ could significantly improve the behavioral deficits of OVX cholesterol-fed rabbits and image structure of the brain. RJ reduced body weight, blood lipid, as well as the levels of amyloid-beta (Abeta), acetylcholinesterase (AchE), and malonaldehyde (MDA) in the brain. Moreover, RJ also increased the activities of choline acetyltransferase (ChAT) and superoxide dismutase (SOD) in the brain, and enhanced heart rate variability (HRV) and Baroreflex sensitivity (BRS) in OVX cholesterol-fed rabbits. Furthermore, RJ was also shown to reduce the content of Evans blue and the expression levels of Abeta, beta-site APP cleaving enzyme 1(BACE1), and receptor for advanced glycation end products (RAGE), and increase the expression level of LDL(low density lipoprotein) receptor-related protein 1 (LRP-1) in the brain. Our findings suggested that RJ has beneficial effects in neurological disorders of postmenopausal women, which were associated with reducing cholesterol and Abeta deposition, enhancing the estrogen levels and the activities of cholinergic and antioxidant systems, and ameliorating the blood(-)brain barrier (BBB) permeability and restoring autonomic nervous system. Title: Acetylcholinesterase-functionalized two-dimensional photonic crystal for the sensing of G-series nerve agents Qi F, Yan C, Meng Z, Li S, Xu J, Hu X, Xue M Ref: Anal Bioanal Chem, 411:2577, 2019 : PubMed ESTHER: Qi_2019_Anal.Bioanal.Chem_411_2577 PubMedSearch: Qi 2019 Anal.Bioanal.Chem 411 2577 PubMedID: 30847569 Abstract G-series nerve agents, such as sarin, tabun, and soman, would cause tremendous harm in military and terrorist attacks, so it is necessary to develop a simple method for the rapid and efficient detection of these hazardous substances. We have developed a tunable acetylcholinesterase (AChE)-functionalized two-dimensional photonic crystal (2D PhC) for the detection of a real nerve agent, sarin. In accordance with the 2D PhC previously prepared by our group, the AChE-functionalized 2D PhC was optimized by adjustment of the amount of monomer in the hydrogel, which not only increased the sensitivity of the 2D PhC, with the detection limit decreasing by two orders of magnitude, but also ensured the structural color spanned the whole visible region in the detection range. A linear relationship between the logarithm of the sarin concentration and the particle spacing of the AChE-functionalized 2D PhC was observed from 7.1 x 10(-17) to 7.1 x 10(-4) mol/L. The AChE-functionalized 2D PhC also responded to mimics of G-series nerve agents, including dimethyl methylphosphonate, diisopropyl methylphosphonate, and isodipropyl methylphosphonate, to various degrees. The proposed 2D-PhC hydrogel has potential for low-cost, trace-level, and on-site monitoring of other G-series nerve agents. Graphical abstract. Title: Design, synthesis and molecular modeling of isothiochromanone derivatives as acetylcholinesterase inhibitors Shuai W, Li W, Yin Y, Yang L, Xu F, Xu S, Yao H, Zhu Z, Xu J Ref: Future Med Chem, 11:2687, 2019 : PubMed ESTHER: Shuai_2019_Future.Med.Chem_11_2687 PubMedSearch: Shuai 2019 Future.Med.Chem 11 2687 PubMedID: 31596141 Abstract Aim: A series of novel isothio- and isoselenochromanone derivatives bearing N-benzyl pyridinium moiety were designed, synthesized and evaluated as acetylcholinesterase (AChE) inhibitors. Results: Most of the target compounds exhibited potent anti-AChE activities with IC50 values in nanomolar ranges. Among them, compound 15a exhibited the most potent anti-AChE activity (IC50 = 2.7 nM), moderate antioxidant activity and low neurotoxicity. Moreover, the kinetic and docking studies revealed that compound 15a was a mixed-type inhibitor, which bounds to peripheral anionic site and catalytic active site of AChE. Conclusion: Those results suggested that compound 15a might be a potential candidate for AD treatment. Title: Fast emerging insecticide resistance in Aedes albopictus in Guangzhou, China: Alarm to the dengue epidemic Su X, Guo Y, Deng J, Xu J, Zhou G, Zhou T, Li Y, Zhong D, Kong L and Chen XG <4 more author(s)> Su X, Guo Y, Deng J, Xu J, Zhou G, Zhou T, Li Y, Zhong D, Kong L, Wang X, Liu M, Wu K, Yan G, Chen XG (- 4) Ref: PLoS Negl Trop Dis, 13:e0007665, 2019 : PubMed ESTHER: Su_2019_PLoS.Negl.Trop.Dis_13_e0007665 PubMedSearch: Su 2019 PLoS.Negl.Trop.Dis 13 e0007665 PubMedID: 31525199 Abstract Dengue is one of the most serious mosquito-borne infectious diseases in the world. Aedes albopictus is the most invasive mosquito and one of the primary vectors of dengue. Vector control using insecticides is the only viable strategy to prevent dengue virus transmission. In Guangzhou, after the 2014 pandemic, massive insecticides have been implemented. Massive insecticide use may lead to the development of resistance, but few reports are available on the status of insecticide resistance in Guangzhou after 2014. In this study, Ae. albopictus were collected from four districts with varied dengue virus transmission intensity in Guangzhou from 2015 to 2017. Adult Ae. albopictus insecticide susceptibility to deltamethrin (0.03%), permethrin(0.25%), DDT(4%), malathion (0.8%) and bendiocarb (0.1%) was determined by the standard WHO tube test, and larval resistance bioassays were conducted using temephos, Bacillus thuringiensis israelensis (Bti), pyriproxyfen (PPF) and hexaflumuron. Mutations at the voltage-gated sodium channel (VGSC) gene and acetylcholinesterase (AChE) gene were analyzed. The effect of cytochrome P450s on the resistance of Ae. albopictus to deltamethrin was tested using the synergistic agent piperonyl butoxide (PBO). The results showed that Ae. albopictus populations have rapidly developed very high resistances to multiple commonly used insecticides at all study areas except malathion, Bti and hexaflumuron. We found 1534 codon mutations in the VGSC gene that were significantly correlated with the resistance to pyrethroids and DDT, and 11 synonymous mutations were also found in the gene. The resistance to deltamethrin can be significantly reduced by PBO but may generated cross-resistance to PPF. Fast emerging resistance in Ae. albopictus may affect mosquito management and threaten the prevention and control of dengue, similar to the resistance in Anopheles mosquitoes has prevented the elimination of malaria and call for timely and guided insecticide management. Title: Effects of BIS-MEP on Reversing Amyloid Plaque Deposition and Spatial Learning and Memory Impairments in a Mouse Model of beta-Amyloid Peptide- and Ibotenic Acid-Induced Alzheimer's Disease Wang Y, Xia J, Shen M, Zhou Y, Wu Z, Shi Y, Xu J, Hou L, Zhang R and Wang H <4 more author(s)> Wang Y, Xia J, Shen M, Zhou Y, Wu Z, Shi Y, Xu J, Hou L, Zhang R, Qiu Z, Xie Q, Chen H, Zhang Y, Wang H (- 4) Ref: Front Aging Neurosci, 11:3, 2019 : PubMed ESTHER: Wang_2019_Front.Aging.Neurosci_11_3 PubMedSearch: Wang 2019 Front.Aging.Neurosci 11 3 PubMedID: 30723404 Inhibitor(s) related to this paper: bis9-(-)-nor-meptazinol Abstract Alzheimer's disease (AD) is the main type of dementia and is characterized by progressive memory loss and a notable decrease in cholinergic neuron activity. As classic drugs currently used in the clinic, acetylcholinesterase inhibitors (AChEIs) restore acetylcholine levels and relieve the symptoms of AD, but are insufficient at delaying the onset of AD. Based on the multi-target-directed ligand (MTDL) strategy, bis-(-)-nor-meptazinol (BIS-MEP) was developed as a multi-target AChEI that mainly targets AChE catalysis and the beta-amyloid (Abeta) aggregation process. In this study, we bilaterally injected Abeta oligomers and ibotenic acid (IBO) into the hippocampus of ICR mice and then subcutaneously injected mice with BIS-MEP to investigate its therapeutic effects and underlying mechanisms. According to the results from the Morris water maze test, BIS-MEP significantly improved the spatial learning and memory impairments in AD model mice. Compared with the vehicle control, the BIS-MEP treatment obviously inhibited the AChE activity in the mouse brain, consistent with the findings from the behavioral tests. The BIS-MEP treatment also significantly reduced the Abeta plaque area in both the hippocampus and cortex, suggesting that BIS-MEP represents a direct intervention for AD pathology. Additionally, the immunohistochemistry and ELISA results revealed that microglia (ionized calcium-binding adapter molecule 1, IBA1) and astrocyte (Glial fibrillary acidic protein, GFAP) activation and the secretion of relevant inflammatory factors (TNFalpha and IL-6) induced by Abeta were decreased by the BIS-MEP treatment. Furthermore, BIS-MEP showed more advantages than donepezil (an approved AChEI) as an Abeta intervention. Based on our findings, BIS-MEP improved spatial learning and memory deficits in AD mice by regulating acetylcholinesterase activity, Abeta deposition and the inflammatory response in the brain. Title: Neuroligins Differentially Mediate Subtype-Specific Synapse Formation in Pyramidal Neurons and Interneurons Xia QQ, Xu J, Liao TL, Yu J, Shi L, Xia J, Luo JH Ref: Neurosci Bull, 35:497, 2019 : PubMed ESTHER: Xia_2019_Neurosci.Bull_35_497 PubMedSearch: Xia 2019 Neurosci.Bull 35 497 PubMedID: 30790215 Abstract Neuroligins (NLs) are postsynaptic cell-adhesion proteins that play important roles in synapse formation and the excitatory-inhibitory balance. They have been associated with autism in both human genetic and animal model studies, and affect synaptic connections and synaptic plasticity in several brain regions. Yet current research mainly focuses on pyramidal neurons, while the function of NLs in interneurons remains to be understood. To explore the functional difference among NLs in the subtype-specific synapse formation of both pyramidal neurons and interneurons, we performed viral-mediated shRNA knockdown of NLs in cultured rat cortical neurons and examined the synapses in the two major types of neurons. Our results showed that in both types of neurons, NL1 and NL3 were involved in excitatory synapse formation, and NL2 in GABAergic synapse formation. Interestingly, NL1 affected GABAergic synapse formation more specifically than NL3, and NL2 affected excitatory synapse density preferentially in pyramidal neurons. In summary, our results demonstrated that different NLs play distinct roles in regulating the development and balance of excitatory and inhibitory synapses in pyramidal neurons and interneurons. Title: Converting solution viscosity to distance-readout on paper substrates based on enzyme-mediated alginate hydrogelation: Quantitative determination of organophosphorus pesticides Xu J, Hu X, Khan H, Tian M, Yang L Ref: Anal Chim Acta, 1071:1, 2019 : PubMed ESTHER: Xu_2019_Anal.Chim.Acta_1071_1 PubMedSearch: Xu 2019 Anal.Chim.Acta 1071 1 PubMedID: 31128750 Abstract Quantitatively paper-based senor is performed with simple distance-readout on mixed cellulose ester (MCE) filter paper based on acetylcholinesterase (AChE)-mediated alginate hydrogel. The method is accomplished with the aid of the inhibition effect of target samples on the AChE enzyme-catalyzed hydrolysis of acetylcholine, which changes the pH value of the solution to release Ca(2+) and trigger alginate hydrogelation. The viscosity of the solution is thus regulated with the presence of target samples in the reaction mixture, leading to a significant change in the diffusion diameter of the solution spotted on the filter paper. The concentration in the sample is quantitatively determined by ruler-measureable diffusion diameter of the spot on the paper. With successfully application for quantitatively sensing of organophosphorus pesticides (OPs), we show that the method exhibits excellent reproducibility with RSD (n=5) as low as 0.09% and good selectivity for detection of OPs. The dynamic range of the method is up to 66.7ng/mL with the limit-of-detection (LOD) of 3.3ng/mL. The present study provides a new approach for developing paper-based sensors with quantitative distance-readout, by utilizing enzymatic inhibition to modulate liquid viscosity, which would be of value for target detection in complex samples. Title: Potential Pharmacokinetic Herb-Drug Interactions: Have we Overlooked the Importance of Human Carboxylesterases 1 and 2? Xu J, Qiu JC, Ji X, Guo HL, Wang X, Zhang B, Wang T, Chen F Ref: Curr Drug Metab, 20:130, 2019 : PubMed ESTHER: Xu_2019_Curr.Drug.Metab_20_130 PubMedSearch: Xu 2019 Curr.Drug.Metab 20 130 PubMedID: 29600756 Abstract BACKGROUND: Herbal products have grown steadily across the globe and have increasingly been incorporated into western medicine for healthcare aims, thereby causing potential pharmacokinetic Herb-drug Interactions (HDIs) through the inhibition or induction of drug-metabolizing enzymes and transporters. Human Carboxylesterases 1 (CES1) and 2 (CES2) metabolize endogenous and exogenous chemicals including many important therapeutic medications. The growing number of CES substrate drugs also underscores the importance of the enzymes. Herein, we summarized those potential inhibitors and inducers coming from herbal constituents toward CES1 and CES2. We also reviewed the reported HDI studies focusing on herbal products and therapeutic agents metabolized by CES1 or CES2. METHODS: We searched in PubMed for manuscript published in English after Jan 1, 2000 combining terms "carboxylesterase 1", "carboxylesterase 2", "inhibitor", "inducer", "herb-drug interaction", "inhibitory", and "herbal supplement". We also searched specific websites including FDA and EMA. The data of screened papers were analyzed and summarized. RESULTS: The results showed that more than 50 natural inhibitors of CES1 or CES2, including phenolic chemicals, triterpenoids, and tanshinones were found from herbs, whereas only few inducers of CES1 and CES2 were reported. Systemic exposure to some commonly used drugs including oseltamivir, irinotecan, and clopidogrel were changed when they were co-administered with herb products such as goldenseal, black cohosh, ginger, St. John's Wort, curcumin, and some Chinese compound formula in animals. CONCLUSION: Nonclinical and clinical studies on HDIs are warranted in the future to provide safety information toward better clinical outcomes for the combination of herbal products and conventional drugs. Title: Stereodivergent Protein Engineering of a Lipase To Access All Possible Stereoisomers of Chiral Esters with Two Stereocenters Xu J, Cen Y, Singh W, Fan J, Wu L, Lin X, Zhou J, Huang M, Reetz MT, Wu Q Ref: Journal of the American Chemical Society, 141:7934, 2019 : PubMed ESTHER: Xu_2019_J.Am.Chem.Soc_141_7934 PubMedSearch: Xu 2019 J.Am.Chem.Soc 141 7934 PubMedID: 31023008 Gene_locus related to this paper: canar-LipB Inhibitor(s) related to this paper: 6J1T-B7U Abstract Enzymatic stereodivergent synthesis to access all possible product stereoisomers bearing multiple stereocenters is relatively undeveloped, although enzymes are being increasingly used in both academic and industrial areas. When two stereocenters and thus four stereoisomeric products are involved, obtaining stereodivergent enzyme mutants for individually accessing all four stereoisomers would be ideal. Although significant success has been achieved in directed evolution of enzymes in general, stereodivergent engineering of one enzyme into four highly stereocomplementary variants for obtaining the full complement of stereoisomers bearing multiple stereocenters remains a challenge. Using Candida antarctica lipase B (CALB) as a model, we report the protein engineering of this enzyme into four highly stereocomplementary variants needed for obtaining all four stereoisomers in transesterification reactions between racemic acids and racemic alcohols in organic solvents. By generating and screening less than 25 variants of each isomer, we achieved >90% selectivity for all of the four possible stereoisomers in the model reaction. This difficult feat was accomplished by developing a strategy dubbed "focused rational iterative site-specific mutagenesis" (FRISM) at sites lining the enzyme's binding pocket. The accumulation of single mutations by iterative site-specific mutagenesis using a restricted set of rationally chosen amino acids allows the formation of ultrasmall mutant libraries requiring minimal screening for stereoselectivity. The crystal structure of all stereodivergent CALB variants, flanked by MD simulations, uncovered the source of selectivity. Title: Neuroligin 3 Regulates Dendritic Outgrowth by Modulating Akt/mTOR Signaling Xu J, Du YL, Xu JW, Hu XG, Gu LF, Li XM, Hu PH, Liao TL, Xia QQ and Wang Z <4 more author(s)> Xu J, Du YL, Xu JW, Hu XG, Gu LF, Li XM, Hu PH, Liao TL, Xia QQ, Sun Q, Shi L, Luo JH, Xia J, Wang Z (- 4) Ref: Front Cell Neurosci, 13:518, 2019 : PubMed ESTHER: Xu_2019_Front.Cell.Neurosci_13_518 PubMedSearch: Xu 2019 Front.Cell.Neurosci 13 518 PubMedID: 31849609 Abstract Neuroligins (NLs) are a group of postsynaptic cell adhesion molecules that function in synaptogenesis and synaptic transmission. Genetic defects in neuroligin 3 (NL3), a member of the NL protein family, are associated with autism. Studies in rodents have revealed that mutations of NL3 gene lead to increased growth and complexity in dendrites in the central nervous system. However, the detailed mechanism is still unclear. In our study, we found that deficiency of NL3 led to morphological changes of the pyramidal neurons in layer II/III somatosensory cortex in mice, including enlarged somata, elongated dendritic length, and increased dendritic complexity. Knockdown of NL3 in cultured rat neurons upregulated Akt/mTOR signaling, resulting in both increased protein synthesis and dendritic growth. Treating neurons with either rapamycin to inhibit the mTOR or LY294002 to inhibit the PI3K/Akt activity rescued the morphological abnormalities resulting from either NL3 knockdown or knockout (KO). In addition, we found that the hyperactivated Akt/mTOR signaling associated with NL3 defects was mediated by a reduction in phosphatase and tensin (PTEN) expression, and that MAGI-2, a scaffold protein, interacted with both NL3 and PTEN and could be a linker between NL3 and Akt/mTOR signaling pathway. In conclusion, our results suggest that NL3 regulates neuronal morphology, especially dendritic outgrowth, by modulating the PTEN/Akt/mTOR signaling pathway, probably via MAGI-2. Thereby, this study provides a new link between NL3 and neuronal morphology. Title: Multi-target design strategies for the improved treatment of Alzheimer's disease Zhang P, Xu S, Zhu Z, Xu J Ref: Eur Journal of Medicinal Chemistry, 176:228, 2019 : PubMed ESTHER: Zhang_2019_Eur.J.Med.Chem_176_228 PubMedSearch: Zhang 2019 Eur.J.Med.Chem 176 228 PubMedID: 31103902 Abstract Alzheimer's disease (AD) is a multifactorial syndrome resulting in profound misery and poses a substantial burden on human health, economy, and society throughout the world. Based on the numerous AD-related targets in the disease network, multi-target design strategy is a crucial direction to seek for enhanced therapy, and multi-target drugs have the ability to regulate more targets than single-target drugs, affecting the disease network with more potency. Herein, we highlight nine major targets associated with AD, which are acetylcholine esterase (AChE), beta-site amyloid precursor protein cleaving enzyme 1 (beta-secretase, BACE-1), glycogen synthase kinase 3 beta (GSK-3beta), monoamine oxidases (MAOs), metal ions in the brain, N-methyl-D-aspartate (NMDA) receptor, 5-hydroxytryptamine (5-HT) receptors, the third subtype of histamine receptor (H3 receptor), and phosphodiesterases (PDEs), and their respective relationship to the disease network. Furthermore, eleven multi-target design strategies classified by the involvement of AChE and related promising compounds for improved therapy of AD in recent years are described based on the nine major targets. Title: Gamma Oscillation Dysfunction in mPFC Leads to Social Deficits in Neuroligin 3 R451C Knockin Mice Cao W, Lin S, Xia QQ, Du YL, Yang Q, Zhang MY, Lu YQ, Xu J, Duan SM and Luo JH <2 more author(s)> Cao W, Lin S, Xia QQ, Du YL, Yang Q, Zhang MY, Lu YQ, Xu J, Duan SM, Xia J, Feng G, Luo JH (- 2) Ref: Neuron, 97:1253, 2018 : PubMed ESTHER: Cao_2018_Neuron_97_1253 PubMedSearch: Cao 2018 Neuron 97 1253 PubMedID: 29503190 Gene_locus related to this paper: mouse-3neur Abstract Neuroligins (NLs) are critical for synapse formation and function. NL3 R451C is an autism-associated mutation. NL3 R451C knockin (KI) mice exhibit autistic behavioral abnormalities, including social novelty deficits. However, neither the brain regions involved in social novelty nor the underlying mechanisms are clearly understood. Here, we found decreased excitability of fast-spiking interneurons and dysfunction of gamma oscillation in the medial prefrontal cortex (mPFC), which contributed to the social novelty deficit in the KI mice. Neuronal firing rates and phase-coding abnormalities were also detected in the KI mice during social interactions. Interestingly, optogenetic stimulation of parvalbumin interneurons in the mPFC at 40 Hz nested at 8 Hz positively modulated the social behaviors of mice and rescued the social novelty deficit in the KI mice. Our findings suggest that gamma oscillation dysfunction in the mPFC leads to social deficits in autism, and manipulating mPFC PV interneurons may reverse the deficits in adulthood. Title: Redox-Controlled Fluorescent Nanoswitch Based on Reversible Disulfide and Its Application in Butyrylcholinesterase Activity Assay Chen G, Feng H, Jiang X, Xu J, Pan S, Qian Z Ref: Analytical Chemistry, 90:1643, 2018 : PubMed ESTHER: Chen_2018_Anal.Chem_90_1643 PubMedSearch: Chen 2018 Anal.Chem 90 1643 PubMedID: 29298486 Abstract Butyrylcholinesterase (BChE) mainly contributing to plasma cholinesterase activity is an important indicator for routinely diagnosing liver function and organophosphorus poisoning in clinical diagnosis, but its current assays are scarce and frequently suffer from some significant interference and instability. Herein, we report a redox-controlled fluorescence nanoswtich based on reversible disulfide bonds, and further develop a fluorometric assay of BChE via thiol-triggered disaggregation-induced emission. Thiol-functionalized carbon quantum dots (thiol-CQDs) with intense fluorescence is found to be responsive to hydrogen peroxide, and their redox reaction transforms thiol-CQDs to nonfluorescent thiol-CQD assembly. The thiols inverse this process by a thiol-exchange reaction to turn on the fluorescence. The fluorescence can be reversibly switched by the formation and breaking of disulfide bonds caused by external redox stimuli. The specific thiol-triggered disaggregation-induced emission enables us to assay BChE activity in a fluorescence turn-on and real-time way using butyrylthiocholine iodide as the substrate. As-established BChE assay achieves sufficient sensitivity for practical determination in human serum, and is capable of avoiding the interference from micromolar glutathione and discriminatively quantifying BChE from its sister enzyme acetylcholinesterase. The first design of reversible redox-controlled nanosiwtch based on disulfide expands the application of disulfide chemistry in sensing and clinical diagnostics, and this novel BChE assay enriches the detection methods for cholinesterase activity. Title: Alterations of drug-metabolizing enzymes and transporters under diabetic conditions: what is the potential clinical significance? Chen F, Li DY, Zhang B, Sun JY, Sun F, Ji X, Qiu JC, Parker RB, Laizure SC, Xu J Ref: Drug Metabolism Reviews, :1, 2018 : PubMed ESTHER: Chen_2018_Drug.Metab.Rev__1 PubMedSearch: Chen 2018 Drug.Metab.Rev 1 PubMedID: 30221555 Abstract There will be 642 million people worldwide by 2040 suffering from diabetes mellitus. Long-term multidrug therapy aims to achieve normal glycemia and minimize complications, and avoid severe hypoglycemic events. The appreciation of the drug-metabolizing enzymes and drug transporters as critical players in the treatment of diabetes has attracted much attention regarding their potential alterations in the pathogenesis of the disease. This review discusses pharmacokinetics-based alterations of cytochrome P450 enzymes, phase-II metabolizing enzymes, and membrane transporter proteins, as well as the potential mechanisms underlying these alterations. We also discuss the potential influences of altered enzymes and transporters on the disposition of commonly prescribed glucose-lowering medicines. Future studies should delve into the impact of altered drug-metabolizing enzymes and transporters on the progression toward abnormal glucose homeostasis. Title: Acetylcholine and necroptosis are players in follicular development in primates Du Y, Bagnjuk K, Lawson MS, Xu J, Mayerhofer A Ref: Sci Rep, 8:6166, 2018 : PubMed ESTHER: Du_2018_Sci.Rep_8_6166 PubMedSearch: Du 2018 Sci.Rep 8 6166 PubMedID: 29670172 Abstract Acetylcholine (ACh) in the ovary and its actions were linked to survival of human granulosa cells in vitro and improved fertility of rats in vivo. These effects were observed upon experimental blockage of the ACh-degrading enzyme (ACH esterase; ACHE), by Huperzine A. We now studied actions of Huperzine A in a three-dimensional culture of macaque follicles. Because a form of programmed necrotic cell death, necroptosis, was previously identified in human granulosa cells in vitro, we also studied actions of necrostatin-1 (necroptosis inhibitor). Blocking the breakdown of ACh by inhibiting ACHE, or interfering with necroptosis, did not improve the overall follicle survival, but promoted the growth of macaque follicles from the secondary to the small antral stage in vitro, which was correlated with oocyte development. The results from this translational model imply that ovarian function and fertility in primates may be improved by pharmacological interference with ACHE actions and necroptosis. Title: Evidence for multiple-insecticide resistance in urban Aedes albopictus populations in southern China Li Y, Xu J, Zhong D, Zhang H, Yang W, Zhou G, Su X, Wu Y, Wu K and Chen XG <2 more author(s)> Li Y, Xu J, Zhong D, Zhang H, Yang W, Zhou G, Su X, Wu Y, Wu K, Cai S, Yan G, Chen XG (- 2) Ref: Parasit Vectors, 11:4, 2018 : PubMed ESTHER: Li_2018_Parasit.Vectors_11_4 PubMedSearch: Li 2018 Parasit.Vectors 11 4 PubMedID: 29298700 Abstract BACKGROUND: Aedes albopictus (Skuse) is an invasive mosquito that has become an important vector of chikungunya, dengue and Zika viruses. In the absence of specific antiviral therapy or a vaccine, vector management is the sole method available for reducing Aedes-induced disease morbidity. Determining the resistance status of Ae. albopictus to insecticides and exploring the resistance mechanisms is essential for future vector control planning. METHODS: Aedes albopictus larvae and pupae were sampled from six sites (two sites each from urban, suburban and rural) in Guangzhou. The resistance bioassays were conducted against Bacillus thuringiensis israelensis (Bti): deltamethrin, propoxur and malathion for larvae; and deltamethrin, DDT, propoxur and malathion for adults. P450 monooxygenase (P450s), glutathione S-transferase (GSTs) and carboxylesterase (COEs) activities of adult mosquitoes were measured. Mutations at the knockdown resistance (kdr) gene were analyzed, and the association between kdr mutations and phenotypic resistance was tested. RESULTS: Adult bioassays revealed varied susceptibility against DDT, deltamethrin and propoxur in the six Ae. albopictus populations. Significantly lower mortality rates were found in urban populations than suburban and rural populations. Urban mosquito populations showed resistance against DDT, deltamethrin and propoxur, while one rural population was resistant to DDT. All populations tested were susceptible to malathion. Larval bioassays results indicated that all populations of Ae. albopictus were sensitive to the larvicide Bti and malathion. Resistance to deltamethrin and propoxur was common in larval populations. The F1534S and F1534 L mutations were found to be significantly associated with deltamethrin resistance. Biochemical assays indicated elevated detoxification enzyme activities in the field mosquito populations. CONCLUSIONS: Aedes albopictus populations in Guangzhou, especially in urban areas, have developed resistance to the commonly used insecticides, primarily DDT and deltamethrin. This finding calls for resistance management and developing counter measures to mitigate the spread of resistance. Title: High expression of NDRG3 associates with unfavorable overall survival in non-small cell lung cancer Luo X, Hou N, Chen X, Xu Z, Xu J, Wang L, Yang S, Liu S, Xu L and Fan W <3 more author(s)> Luo X, Hou N, Chen X, Xu Z, Xu J, Wang L, Yang S, Liu S, Xu L, Chen Y, Xiong L, Wang J, Fan W (- 3) Ref: Cancer Biomark, 21:461, 2018 : PubMed ESTHER: Luo_2018_Cancer.Biomark_21_461 PubMedSearch: Luo 2018 Cancer.Biomark 21 461 PubMedID: 29171988 Abstract BACKGROUND AND OBJECTIVE: N-myc downstream-regulated gene 3 (NDRG3) is one of the important members of the NDRG family which crucially take part in cell proliferation, differentiation and other biological processes. METHODS: In this present study, western-blotting analysis was performed to evaluate NDRG3 expression in NSCLC cell lines. One-step quantitative reverse transcription-polymerase chain reaction (qPCR) with 16 fresh-frozen NSCLC samples and immunohistochemistry (IHC) analysis in 100 NSCLC cases were conducted to explore the relationship between NDRG3 expression and the clinicopathological characteristics of NSCLC. RESULTS: NDRG3 expression levels were statistically higher in NSCLC cell lines and tissue samples, compared with that of in non-cancerous cell line and tissue samples (p< 0.05). The IHC data demonstrated that the NDRG3 expression was significantly correlated with pathological grade (p= 0.038), N (p= 0.020) and TNM stage (p= 0.002). Survival analysis and Kaplan-Meier curve indicated that NDRG3 expression (p= 0.002) and T (p= 0.047) were independently associated with the unfavorable overall survival of patients with NSCLC. CONCLUSIONS: The data implied that NDRG3 expression may be identified as a new predictor in NSCLC prognosis. Title: Bis(9)-(-)-Meptazinol, a novel dual-binding AChE inhibitor, rescues cognitive deficits and pathological changes in APP/PS1 transgenic mice Shi Y, Huang W, Wang Y, Zhang R, Hou L, Xu J, Qiu Z, Xie Q, Chen H and Wang H <1 more author(s)> Shi Y, Huang W, Wang Y, Zhang R, Hou L, Xu J, Qiu Z, Xie Q, Chen H, Zhang Y, Wang H (- 1) Ref: Transl Neurodegener, 7:21, 2018 : PubMed ESTHER: Shi_2018_Transl.Neurodegener_7_21 PubMedSearch: Shi 2018 Transl.Neurodegener 7 21 PubMedID: 30237878 Abstract Background: Alzheimer's disease (AD) is a progressive and irreversible neurodegenerative brain disorder, which is the most common form of dementia. Intensive efforts have been made to find effective and safe treatment against AD. Acetylcholinesterase inhibitors (AChEIs) have been widely used for the treatment of mild to moderate AD. In this study, we investigated the effect of Bis(9)-(-)-Meptazinol (B9M), a novel potential dual-binding acetylcholinesterase (AChE) inhibitor, on learning and memory abilities, as well as the underlying mechanism in the APP/PS1 mouse model of AD. Methods: B9M (0.1 mug/kg, 0.3 mug/kg, and 1 mug/kg) was administered by subcutaneous injection into eight-month-old APP/PS1 transgenic mice for four weeks. Morris water maze, nest-building and novel object recognition were used to examine learning and memory ability. Abeta levels and Abeta plaque were evaluated by ELISA and immunochemistry. Results: Our results showed that chronic treatment with B9M significantly improved the cognitive function of APP/PS1 transgenic mice in the Morris water maze test, nest-building test and novel object recognition test. Moreover, B9M improved cognitive deficits in APP/PS1 mice by a mechanism that may be associated with its inhibition of the AChE activity, Abeta plaque burden, levels of Abeta and the consequent activation of astrocytes and microglia in the brain of APP/PS1 transgenic mice. Most of important, the most effective dose of B9M in the present study is 1 mug/kg, which is one thousand of the dosage of Donepezil acted as the control treatment. Furthermore, B9M reduced Abeta plaque burden better than Donepezil. Conclusion: These results indicate that B9M appears to have potential as an effective AChE inhibitor for the treatment of AD with symptom-relieving and disease-modifying properties. Title: Design, synthesis, biological evaluation, and docking study of 4-isochromanone hybrids bearing N-benzyl pyridinium moiety as dual binding site acetylcholinesterase inhibitors (part II) Wang J, Wang C, Wu Z, Li X, Xu S, Liu J, Lan Q, Zhu Z, Xu J Ref: Chemical Biology Drug Des, 91:756, 2018 : PubMed ESTHER: Wang_2018_Chem.Biol.Drug.Des_91_756 PubMedSearch: Wang 2018 Chem.Biol.Drug.Des 91 756 PubMedID: 29112799 Abstract A series of novel 4-isochromanone compounds bearing N-benzyl pyridinium moiety were designed and synthesized as acetylcholinesterase (AChE) inhibitors. The biological evaluation showed that most of the target compounds exhibited potent inhibitory activities against AChE. Among them, compound 1q possessed the strongest anti-AChE activity with an IC50 value of 0.15 nm and high AChE/BuChE selectivity (SI > 5,000). Moreover, compound 1q had low toxicity in normal nerve cells and was relatively stable in rat plasma. Together, the current finding may provide a new approach for the discovery of novel anti-Alzheimer's disease agents. Title: Sequence analysis and structure prediction of ABHD16A and the roles of the ABHD family members in human disease Xu J, Gu W, Ji K, Xu Z, Zhu H, Zheng W Ref: Open Biol, 8:, 2018 : PubMed ESTHER: Xu_2018_Open.Biol_8_ PubMedSearch: Xu 2018 Open.Biol 8 PubMedID: 29794032 Gene_locus related to this paper: human-ABHD16A, human-ABHD16B Abstract Abhydrolase domain containing 16A (ABHD16A) is a member of the alpha/beta hydrolase domain-containing (ABHD) protein family and is expressed in a variety of animal cells. Studies have shown that ABHD16A has acylglycerol lipase and phosphatidylserine lipase activities. Its gene location in the main histocompatibility complex (MHC) III gene cluster suggests that this protein may participate in the immunomodulation of the body. The results of studies investigating nearly 20 species of ABHDs reveal that the ABHD proteins are key factors in metabolic regulation and disease occurrence and development. In this paper, we summarize the related progress regarding the function of ABHD16A and other ABHD proteins. A prediction of the active sites and structural domains of ABHD16A and an analysis of the amino acid sites are included. Moreover, we analysed the amino acid sequences of the ABHD16A molecules in different species and provide an overview of the related functions and diseases associated with these proteins. The functions and diseases related to ABHD are systematically summarized and highlighted. Future research directions for studies investigating the functions and mechanisms of these proteins are also suggested. Further studies investigating the function of ABHD proteins may further confirm their positions as important determinants of lipid metabolism and related diseases. Title: N-Carbamoylmaleimide-treated carbon dots: stabilizing the electrochemical intermediate and extending it for the ultrasensitive detection of organophosphate pesticides Xu J, Yu C, Feng T, Liu M, Li F, Wang Y Ref: Nanoscale, 10:19390, 2018 : PubMed ESTHER: Xu_2018_Nanoscale_10_19390 PubMedSearch: Xu 2018 Nanoscale 10 19390 PubMedID: 30307023 Abstract To date, numerous methods have been reported for the detection of organophosphorus pesticides (OP) due to their severe potential hazard to the environment, public health and national security. However, very few works have ever found that the signal loss of thiocholine (TCh) during electrochemical processing is a key factor leading to the low sensitivity of acetylcholinesterase (AChE)-based OP electrochemical sensing platforms. Herein, we propose an ultrasensitive detection method for multiple OPs including parathion-methyl, paraoxon, dimethoate and O,O-dimethyl-O-2,2-dichlorovinyl-phosphate using N-carbamoylmaleimide-functionalized carbon dots (N-MAL-CDs) as a nano-stabilizer. For the first time, Michael addition is introduced into an AChE-based OP electrochemical sensing platform to enrich the electrochemical intermediate TCh. The Michael addition between TCh and N-MAL-CDs is demonstrated via XRD, FTIR, SEM and EDS elemental mapping experiments. Due to the stabilization and enhancement of TCh with N-MAL-CDs, the as prepared OP sensing platform achieves ultrahigh sensitivity by detecting the initial electrochemical signals of TCh without signal loss, showing a wide linear range of 3.8 x 10(-15)-3.8 x 10(-10) M for parathion-methyl and 1.8 x 10(-14)-3.6 x 10(-10) M for paraoxon, with a limit of detection of 1.4 x 10(-15) M for parathion-methyl and 4.8 x 10(-15) M for paraoxon. Title: Single-Step In Situ Acetylcholinesterase-Mediated Alginate Hydrogelation for Enzyme Encapsulation in CE Yang J, Hu X, Xu J, Liu X, Yang L Ref: Analytical Chemistry, 90:4071, 2018 : PubMed ESTHER: Yang_2018_Anal.Chem_90_4071 PubMedSearch: Yang 2018 Anal.Chem 90 4071 PubMedID: 29469571 Abstract A novel capillary electrophoresis-integrated immobilized enzyme reactor (CE-integrated IMER) is developed using single-step in situ acetylcholinesterase (AChE)-mediated alginate hydrogelation and enzyme encapsulation. Alginate hydrogelation with "egg-box" structure is triggered inside a capillary with releasing of Ca(2+) by changing the pH of the sol solution, which is accomplished in situ by AChE-catalyzed hydrolysis reaction of acetylthiocholine to produce acetic acid. AChE and any other enzyme initially contained in the sol solution [e.g., xanthine oxidase (XO)] are efficiently encapsulated as the hydrogel network grows, forming CE-integrated IMERs without any additional manipulation process. The proposed method facilitates the analysis of different kinds of enzymes using the same IMER depending on the substrate injected for CE analysis. Approximately 68% of the original enzyme in the sol mixture can be encapsulated, indicating high loading capacity for the CE-integrated IMERs. The IMERs exhibit excellent intraday and interday stability and batch-to-batch reproducibility, and these characteristics imply the reliability of the proposed IMERs for accurate online enzyme assays. Enzymatic activities and inhibition of immobilized AChE and XO are analyzed, and the results are compared with those using free enzymes. The feasibility of the proposed method for potential application in real sample analysis is demonstrated by the successful application of the IMERs in detecting organophosphorus pesticides in apple juice samples using AChE-catalyzed reactions. The proposed method is a simple, efficient, and universal approach for online CE assays with immobilized enzymes, which can be widely applied in bioanalysis. Title: ACE: an efficient and sensitive tool to detect insecticide resistance-associated mutations in insect acetylcholinesterase from RNA-Seq data Guo D, Luo J, Zhou Y, Xiao H, He K, Yin C, Xu J, Li F Ref: BMC Bioinformatics, 18:330, 2017 : PubMed ESTHER: Guo_2017_BMC.Bioinformatics_18_330 PubMedSearch: Guo 2017 BMC.Bioinformatics 18 330 PubMedID: 28693417 Abstract BACKGROUND: Insecticide resistance is a substantial problem in controlling agricultural and medical pests. Detecting target site mutations is crucial to manage insecticide resistance. Though PCR-based methods have been widely used in this field, they are time-consuming and inefficient, and typically have a high false positive rate. Acetylcholinesterases (Ace) is the neural target of the widely used organophosphate (OP) and carbamate insecticides. However, there is not any software available to detect insecticide resistance associated mutations in RNA-Seq data at present. Title: Malassezia globosa MgMDL2 lipase: Crystal structure and rational modification of substrate specificity Lan D, Xu H, Xu J, Dubin G, Liu J, Iqbal Khan F, Wang Y Ref: Biochemical & Biophysical Research Communications, 488:259, 2017 : PubMed ESTHER: Lan_2017_Biochem.Biophys.Res.Commun_488_259 PubMedSearch: Lan 2017 Biochem.Biophys.Res.Commun 488 259 PubMedID: 28433636 Gene_locus related to this paper: malgo-a8puy5 Abstract Lipases play an important role in physiological metabolism and diseases, and also have multiple industrial applications. Rational modification of lipase specificity may increase the commercial utility of this group of enzymes, but is hindered by insufficient mechanistic understanding. Here, we report the 2.0 A resolution crystal structure of a mono- and di-acylglycerols lipase from Malassezia globosa (MgMDL2). Interestingly, residues Phe278 and Glu282 were found to involve in substrate recognition because mutation on each residue led to convert MgMDL2 to a triacylglycerol (TAG) lipase. The Phe278Ala and Glu282Ala mutants also acquired ability to synthesize TAGs by esterification of glycerol and fatty acids. By in silicon analysis, steric hindrance of these residues seemed to be key factors for the altered substrate specificity. Our work may shed light on understanding the unique substrate selectivity mechanism of mono- and di-acylglycerols lipases, and provide a new insight for engineering biocatalysts with desired catalytic behaviors for biotechnological application. Title: A new facet of NDRG1 in pancreatic ductal adenocarcinoma: Suppression of glycolytic metabolism Liu W, Zhang B, Hu Q, Qin Y, Xu W, Shi S, Liang C, Meng Q, Xiang J and Xu J <9 more author(s)> Liu W, Zhang B, Hu Q, Qin Y, Xu W, Shi S, Liang C, Meng Q, Xiang J, Liang D, Ji S, Liu J, Hu P, Liu L, Liu C, Long J, Ni Q, Yu X, Xu J (- 9) Ref: Int J Oncol, 50:1792, 2017 : PubMed ESTHER: Liu_2017_Int.J.Oncol_50_1792 PubMedSearch: Liu 2017 Int.J.Oncol 50 1792 PubMedID: 28350132 Abstract N-myc downstream-regulated gene 1 (NDRG1) is known as tumor/metastasis suppressor in a variety of cancers including pancreas, being involved in angiogenesis, cancer growth and metastasis. However, the precise molecular mechanism how NDRG1 exerts its inhibitory function in pancreatic cancer remains unclear. In this investigation, we demonstrated that K-Ras plays a vital role in modulating NDRG1 protein level in PDAC cancer cells in vitro, which is mediated through ERK signaling. Noteworthy, K-Ras downstream Akt/mTOR signaling is inhibited upon NDRG1 overexpression, resulting in decease of HIF1alpha level. Moreover, NDRG1 has a unique role in modulating cancer metabolism of pancreatic ductal adenocarcinoma (PDAC). The mechanism accounting for NDRG1 in modulating aerobic glycolysis, at least partly, relied on its regulation of glycolysis genes including GLUT1, HK2, LDHA and PDK1. Additionally, NDRG1 is shown to suppress the activity of HIF1alpha, which is responsible for regulation of glycolysis enzymes. The current study is the first to elucidate a unique facet of the potent tumor/metastasis suppressor NDRG1 in the regulation of PDAC glycolysis, leading to important insights into the mechanism by which NDRG1 exert inhibitory function in PDAC. Title: Enzymatic synthesis of lysophosphatidylcholine with n-3 polyunsaturated fatty acid from sn-glycero-3-phosphatidylcholine in a solvent-free system Liu Y, Zhang Q, Guo Y, Liu J, Xu J, Li Z, Wang J, Wang Y, Xue C Ref: Food Chem, 226:165, 2017 : PubMed ESTHER: Liu_2017_Food.Chem_226_165 PubMedSearch: Liu 2017 Food.Chem 226 165 PubMedID: 28254008 Abstract The n-3 polyunsaturated fatty acids (PUFA)-rich lysophosphatidylcholine (LPC) was successfully synthesized by Thermomyces lanuginosus lipase (TL IM)-catalyzed esterification of glycerylphosphorylcholine (GPC) and n-3 PUFA-rich fatty acids in a solvent-free system. Effects of reaction temperature, enzyme loading and substrate mole ratio on the yield of LPC and incorporation of n-3 PUFA were evaluated. The acyl-specificities of five enzymes were tested for direct esterification of n-3 PUFA, and Lipozyme TL IM was found to be more effective than others for production of LPC with n-3 PUFA. Substrate mole ratio and reaction temperature, however, had no significant effect on the incorporation. The maximal yield of LPC was obtained under the following conditions: temperature 45 degC, enzyme loading 15% by weight and substrate mole ratio (GPC/n-3 PUFA) 1:20. Furthermore, the composition of products were further investigated in the study. The 1-acyl-sn-glycero-3-lysophosphatidylcholine (2-LPC) was predominant in the mixtures at early stages of reaction, whereas less increment of 2-acyl-sn-glycero-3-lysophosphatidylcholine (1-LPC) and PC was observed at later stages. Title: Esterase activity inspired selection and characterization of zearalenone degrading bacteria Bacillus pumilus ES-21 Wang G, Yu M, Dong F, Shi J, Xu J Ref: Food Control, 77:57, 2017 : PubMed ESTHER: Wang_2017_Food.Control_77_57 PubMedSearch: Wang 2017 Food.Control 77 57 Abstract Zearalenone (ZEN), mainly produced by Fusarium species, is an estrogenic mycotoxin which causes reproductive disorders in livestock. In this study, we described a simple and rapid method for screening of ZEN-degrading bacteria by esterase activity assay. Soil bacteria strains were first tested for their esterase activities, then active strains were further evaluated for their ZEN-degrading potentials. A bacterial strain named Bacillus pumilus ES-21 was detected to be able to eliminate ZEN in the culture medium. ZEN degradation conditions were optimized through response surface methodology and the result showed that the degradation rate of ZEN by Bacillus pumilus ES-21 was up to 95.7% at the ZEN concentration of 17.9 mug/ml within 24 h. One of the degradation product was proposed to be 1-(3,5-dihydroxyphenyl)-6'-hydroxy-l'-undecen-l0'-one according to LC-TOF-MS/MS analysis. This study provided a strategy for the isolation of ZEN degrading microbes and a promising degrading strain. Title: Stereoselectivity-Tailored, Metal-Free Hydrolytic Dynamic Kinetic Resolution of Morita-Baylis-Hillman Acetates Using an Engineered Lipase-Organic Base Cocatalyst Xia B, Xu J, Xiang Z, Cen Y, Hu Y, Lin X, Wu Q Ref: ACS Catal, 7:4542, 2017 : PubMed ESTHER: Xia_2017_ACS.Catal_7_4542 PubMedSearch: Xia 2017 ACS.Catal 7 4542 Gene_locus related to this paper: canar-LipB Abstract Metal-free enantiocomplementary hydrolytic dynamic kinetic resolution of Morita-Baylis-Hillman (MBH) acetates was developed using triethylamine (TEA) as a racemization catalyst and wild-type or engineered lipase B from Candida antarctica (CALB) as stereoselectivity-determining catalyst, leading to chiral MBH alcohols with tailor-made R or S configurations on an optional basis. In the TEA-WT CALB catalysis system, WT CALB displays excellent S enantioselectivity for a series of MBH acetates tested (up to 96% ee and 98% conversion). Reversal of enantioselectivity in favor of (R)-MBH alcohols (95% ee; 95% conversion) was achieved by generating a focused site-specific mutagenesis library composed of less than 20 variants. Molecular modeling explains the origin of stereoselectivity. Title: Global inactivation of carboxylesterase 1 (Ces1/Ces1g) protects against atherosclerosis in Ldlr (-/-) mice Xu J, Xu Y, Yin L, Zhang Y Ref: Sci Rep, 7:17845, 2017 : PubMed ESTHER: Xu_2017_Sci.Rep_7_17845 PubMedSearch: Xu 2017 Sci.Rep 7 17845 PubMedID: 29259301 Gene_locus related to this paper: mouse-Ces1g Abstract Atherosclerotic cardiovascular disease is a leading cause of death in the western world. Increased plasma triglyceride and cholesterol levels are major risk factors for this disease. Carboxylesterase 1 (Ces1/Ces1g) has been shown to play a role in metabolic control. So far, the role of mouse Ces1/Ces1g deficiency in atherosclerosis is not elucidated. We generated Ces1/Ces1g (-/-) mice. Compared to wild-type mice, Ces1/Ces1g (-/-) mice had reduced plasma cholesterol levels. We then generated Ces1g (-/-) Ldlr (-/-) double knockout (DKO) mice, which were fed a Western diet for 16 weeks. Compared to Ldlr (-/-) mice, DKO mice displayed decreased plasma cholesterol and TG levels and reduced atherosclerotic lesions. Interestingly, knockdown of hepatic Ces1/Ces1g in Apoe (-/-) mice resulted in hyperlipidemia and exacerbated Western diet-induced atherogenesis. Mechanistically, global inactivation of Ces1/Ces1g inhibited intestinal cholesterol and fat absorption and Niemann-Pick C1 like 1 expression, and increased macrophage cholesterol efflux by inducing ATP-binding cassette subfamily A member 1 (ABCA1) and ABCG1. Ces1/Ces1g ablation also promoted M2 macrophage polarization and induced hepatic cholesterol 7alpha-hydroxylase and sterol 12alpha-hydroxylase expression. In conclusion, global loss of Ces1/Ces1g protects against the development of atherosclerosis by inhibiting intestinal cholesterol and triglyceride absorption and promoting macrophage cholesterol efflux. Title: Cholinergic Regulation of hnRNPA2/B1 Translation by M1 Muscarinic Receptors Kolisnyk B, Al-Onaizi MA, Xu J, Parfitt GM, Ostapchenko VG, Hanin G, Soreq H, Prado MAM, Prado VF Ref: Journal of Neuroscience, 36:6287, 2016 : PubMed ESTHER: Kolisnyk_2016_J.Neurosci_36_6287 PubMedSearch: Kolisnyk 2016 J.Neurosci 36 6287 PubMedID: 27277805 Abstract Cholinergic vulnerability, characterized by loss of acetylcholine (ACh), is one of the hallmarks of Alzheimer's disease (AD). Previous work has suggested that decreased ACh activity in AD may contribute to pathological changes through global alterations in alternative splicing. This occurs, at least partially, via the regulation of the expression of a critical protein family in RNA processing, heterogeneous nuclear ribonucleoprotein (hnRNP) A/B proteins. These proteins regulate several steps of RNA metabolism, including alternative splicing, RNA trafficking, miRNA export, and gene expression, providing multilevel surveillance in RNA functions. To investigate the mechanism by which cholinergic tone regulates hnRNPA2/B1 expression, we used a combination of genetic mouse models and in vivo and in vitro techniques. Decreasing cholinergic tone reduced levels of hnRNPA2/B1, whereas increasing cholinergic signaling in vivo increased expression of hnRNPA2/B1. This effect was not due to decreased hnRNPA2/B1 mRNA expression, increased aggregation, or degradation of the protein, but rather to decreased mRNA translation by nonsense-mediated decay regulation of translation. Cell culture and knock-out mice experiments demonstrated that M1 muscarinic signaling is critical for cholinergic control of hnRNPA2/B1 protein levels. Our experiments suggest an intricate regulation of hnRNPA2/B1 levels by cholinergic activity that interferes with alternative splicing in targeted neurons mimicking deficits found in AD. SIGNIFICANCE STATEMENT: In Alzheimer's disease, degeneration of basal forebrain cholinergic neurons is an early event. These neurons communicate with target cells and regulate their long-term activity by poorly understood mechanisms. Recently, the splicing factor hnRNPA2/B, which is decreased in Alzheimer's disease, was implicated as a potential mediator of long-term cholinergic regulation. Here, we demonstrate a mechanism by which cholinergic signaling controls the translation of hnRNPA2/B1 mRNA by activation of M1 muscarinic type receptors. Loss of cholinergic activity can have profound effects in target cells by modulating hnRNPA2/B1 levels. Title: Effects of abhydrolase domain containing 5 gene (ABHD5) expression and variations on chicken fat metabolism Ouyang H, Liu Q, Xu J, Zeng F, Pang X, Jebessa E, Liang S, Nie Q, Zhang X Ref: Poult Sci, 95:99, 2016 : PubMed ESTHER: Ouyang_2016_Poult.Sci_95_99 PubMedSearch: Ouyang 2016 Poult.Sci 95 99 PubMedID: 26574024 Abstract Abhydrolase domain containing 5 gene (ABHD5), also known as comparative gene identification 58 (CGI-58), is a member of the alpha/beta-hydrolase family as a protein cofactor of ATGL stimulating its triacylglycerol hydrolase activity. In this study, we aim to characterize the expression and variations of ABHD5 and to study their functions in chicken fat metabolism. We compared the ABHD5 expression level in various tissues and under different nutrition conditions, identified the variations of ABHD5, and associated them with production traits in an F2 resource population of chickens. Overexpression analysis with two different genotypes and siRNA interfering analysis of ABHD5 were performed in chicken preadipocytes. Chicken ABDH5 was expressed widely and most predominantly in adipose tissue. Five SNPs of the ABHD5 gene were identified and genotyped in the F2 resource population. The c.490C > T SNP was associated with subcutaneous fat thickness (P < 0.01), carcass weight (P < 0.05), body weight (P < 0.05), shank diameter (P < 0.05), and shank length (P < 0.05). The c.423T > C SNP was also associated with chicken body weight (P < 0.05) and shank diameter (P < 0.05). In chicken preadipocytes, overexpression of wild type ABDH5 did not affect the mRNA level of ATGL (adipose triglyceride lipase) but markedly decreased (P < 0.05) the TG (triglyceride) content of the cell, whereas overexpression of mutation type ABHD5 did not affect either ATGL expression or TG content of the cell. The expression of ATGL and TG content of the cell were decreased (P < 0.05) after ABHD5 knockdown in preadipocytes. The mRNA level of ABHD5 was regulated by both feeding and fasting, and by consumption of a high fat diet. It was increased greatly by fasting (P < 0.05) and was returned to control levels after re-feeding in the adipose tissues, and down-regulated in abdominal fat (P < 0.05) and the liver (P < 0.01) of chickens with a high fat diet. These results suggest that expression and variations of ABHD5 may affect fat metabolism through regulating the activity of ATGL in chickens. Title: Carboxylesterase 1 Is Regulated by Hepatocyte Nuclear Factor 4alpha and Protects Against Alcohol- and MCD diet-induced Liver Injury Xu J, Xu Y, Li Y, Jadhav K, You M, Yin L, Zhang Y Ref: Sci Rep, 6:24277, 2016 : PubMed ESTHER: Xu_2016_Sci.Rep_6_24277 PubMedSearch: Xu 2016 Sci.Rep 6 24277 PubMedID: 27075303 Gene_locus related to this paper: human-CES1 Abstract The liver is a major organ that controls hepatic and systemic homeostasis. Dysregulation of liver metabolism may cause liver injury. Previous studies have demonstrated that carboxylesterase 1 (CES1) regulates hepatic triglyceride metabolism and protects against liver steatosis. In the present study, we investigated whether CES1 played a role in the development of alcoholic liver disease (ALD) and methionine and choline-deficient (MCD) diet-induced liver injury. Both hepatocyte nuclear factor 4alpha (HNF4alpha) and CES1 were markedly reduced in patients with alcoholic steatohepatitis. Alcohol repressed both HNF4alpha and CES1 expression in primary hepatocytes. HNF4alpha regulated CES1 expression by directly binding to the proximal promoter of CES1. Global inactivation of CES1 aggravated alcohol- or MCD diet-induced liver inflammation and liver injury, likely as a result of increased production of acetaldehyde and reactive oxygen species and mitochondrial dysfunctions. Knockdown of hepatic CES1 exacerbated ethanol-induced steatohepatitis. These data indicate that CES1 plays a crucial role in protection against alcohol- or MCD diet-induced liver injury. Title: Ingestion of the epoxide hydrolase inhibitor AUDA modulates immune responses of the mosquito, Culex quinquefasciatus during blood feeding Xu J, Morisseau C, Yang J, Lee KS, Kamita SG, Hammock BD Ref: Insect Biochemistry & Molecular Biology, 76:62, 2016 : PubMed ESTHER: Xu_2016_Insect.Biochem.Mol.Biol_76_62 PubMedSearch: Xu 2016 Insect.Biochem.Mol.Biol 76 62 PubMedID: 27369469 Inhibitor(s) related to this paper: AUDA Abstract Epoxide hydrolases (EHs) are enzymes that play roles in metabolizing xenobiotic epoxides from the environment, and in regulating lipid signaling molecules, such as juvenile hormones in insects and epoxy fatty acids in mammals. In this study we fed mosquitoes with an epoxide hydrolase inhibitor AUDA during artificial blood feeding, and we found the inhibitor increased the concentration of epoxy fatty acids in the midgut of female mosquitoes. We also observed ingestion of AUDA triggered early expression of defensin A, cecropin A and cecropin B2 at 6 h after blood feeding. The expression of cecropin B1 and gambicin were not changed more than two fold compared to controls. The changes in gene expression were transient possibly because more than 99% of the inhibitor was metabolized or excreted at 42 h after being ingested. The ingestion of AUDA also affected the growth of bacteria colonizing in the midgut, but did not affect mosquito longevity, fecundity and fertility in our laboratory conditions. When spiked into the blood, EpOMEs and DiHOMEs were as effective as the inhibitor AUDA in reducing the bacterial load in the midgut, while EETs rescued the effects of AUDA. Our data suggest that epoxy fatty acids from host blood are immune response regulators metabolized by epoxide hydrolases in the midgut of female mosquitoes, inhibition of which causes transient changes in immune responses, and affects growth of microbes in the midgut. Title: Differentially expressed lncRNAs and mRNAs identified by microarray analysis in GBS patients vs healthy controls Xu J, Gao C, Zhang F, Ma X, Peng X, Zhang R, Kong D, Simard AR, Hao J Ref: Sci Rep, 6:21819, 2016 : PubMed ESTHER: Xu_2016_Sci.Rep_6_21819 PubMedSearch: Xu 2016 Sci.Rep 6 21819 PubMedID: 26898505 Abstract The aim of our present study was to determine whether message RNAs (mRNAs) and long noncoding RNAs (lncRNAs) are expressed differentially in patients with Guillain-Barre syndrome (GBS) compared with healthy controls. The mRNA and lncRNA profiles of GBS patients and healthy controls were generated by using microarray analysis. From microarray analysis, we listed 310 mRNAs and 114 lncRNAs with the mRMR software classed into two sample groups, GBS patients and healthy controls. KEGG mapping demonstrated that the top seven signal pathways may play important roles in GBS development. Several GO terms, such as cytosol, cellular macromolecular complex assembly, cell cycle, ligase activity, protein catabolic process, etc., were enriched in gene lists, suggesting a potential correlation with GBS development. Co-expression network analysis indicated that 113 lncRNAs and 303 mRNAs were included in the co-expression network. Our present study showed that these differentially expressed mRNAs and lncRNAs may play important roles in GBS development, which provides basic information for defining the mechanism(s) that promote GBS. Title: Functionalized photonic crystal for the sensing of Sarin agents Yan C, Qi F, Li S, Xu J, Liu C, Meng Z, Qiu L, Xue M, Lu W, Yan Z Ref: Talanta, 159:412, 2016 : PubMed ESTHER: Yan_2016_Talanta_159_412 PubMedSearch: Yan 2016 Talanta 159 412 PubMedID: 27474325 Abstract The indiscriminate use of nerve agents by terrorist groups has attracted attention of the scientific communities toward the development of novel sensor technique for these deadly chemicals. A photonic crystal (PhC) hydrogel immobilized with butyrylcholinesterase (BuChE) was firstly prepared for the sensing of Sarin agents. Periodic polystyrene colloidal (240nm) array was embedded inside an acrylamide hydrogel, and then BuChE was immobilized inside the hydrogel matrix via condensation with 3-(diethoxyphosphoryloxy)-1,2,3-benzotriazin-4(3h)-one (DEPBT). It indicated that a total of 3.7 units of BuChE were immobilized onto the PhC hydrogel. The functionalized hydrogel recognized the Sarin agent and then shrunk, thus the diffraction of PhC hydrogel blue shifted significantly, and a limit of detection (LOD) of 10(-15)molL(-1) was achieved. Title: Effects of different fatty acids composition of phosphatidylcholine on brain function of dementia mice induced by scopolamine Zhou MM, Xue Y, Sun SH, Wen M, Li ZJ, Xu J, Wang JF, Yanagita T, Wang YM, Xue CH Ref: Lipids Health Dis, 15:135, 2016 : PubMed ESTHER: Zhou_2016_Lipids.Health.Dis_15_135 PubMedSearch: Zhou 2016 Lipids.Health.Dis 15 135 PubMedID: 27558491 Abstract BACKGROUND: Phosphatidylcholine (PC), the major source of dietary choline, has been demonstrated to improve the capability of learning and memory in rodent and the amelioration of long-chain n-3 polyunsaturated fatty acids (PUFA) on anti-aging and anti-oxidation is widely known as well. In this study, three kinds of PC were chose to demonstrate the role of different fatty acids composition on glycerol backbone in improving the brain function of mice induced by scopolamine which was used to impair cholinergic system and cause oxidative stress. Title: Discovering New Acetylcholinesterase Inhibitors by Mining the Buzhongyiqi Decoction Recipe Data Cui L, Wang Y, Liu Z, Chen H, Wang H, Zhou X, Xu J Ref: J Chem Inf Model, 55:2455, 2015 : PubMed ESTHER: Cui_2015_J.Chem.Inf.Model_55_2455 PubMedSearch: Cui 2015 J.Chem.Inf.Model 55 2455 PubMedID: 26509353 Abstract Myasthenia gravis (MG) is a neuromuscular disease that is conventionally treated with acetylcholinesterase (AChE) inhibitors, which may not fully remove the symptom for many reasons. When AChE inhibitors do not work, Chinese patients turn to Chinese medicine, such as the Buzhongyiqi decoction (BD), to treat MG. By elucidating the relations between the herbs of the Buzhongyiqi decoction recipe and AChE inhibitors with structure-based and ligand-based drug design methods and chemoinformatics approaches, we have found the key active components of BD. Using these key active components as templates, we have discovered five new AChE inhibitors through virtual screening of a commercial compound library. The new AChE inhibitors have been confirmed with Ellman assays. This study demonstrates that lead identification can be inspired by elucidating Chinese medicine. Since BD is a mixture, further studies against other drug targets are needed. Title: Silibinin inhibits acetylcholinesterase activity and amyloid beta peptide aggregation: a dual-target drug for the treatment of Alzheimer's disease Duan S, Guan X, Lin R, Liu X, Yan Y, Zhang T, Chen X, Huang J, Sun X and Gu H <4 more author(s)> Duan S, Guan X, Lin R, Liu X, Yan Y, Zhang T, Chen X, Huang J, Sun X, Li Q, Fang S, Xu J, Yao Z, Gu H (- 4) Ref: Neurobiology of Aging, 36:1792, 2015 : PubMed ESTHER: Duan_2015_Neurobiol.Aging_36_1792 PubMedSearch: Duan 2015 Neurobiol.Aging 36 1792 PubMedID: 25771396 Abstract Alzheimer's disease (AD) is characterized by amyloid beta (Abeta) peptide aggregation and cholinergic neurodegeneration. Therefore, in this paper, we examined silibinin, a flavonoid extracted from Silybum marianum, to determine its potential as a dual inhibitor of acetylcholinesterase (AChE) and Abeta peptide aggregation for AD treatment. To achieve this, we used molecular docking and molecular dynamics simulations to examine the affinity of silibinin with Abeta and AChE in silico. Next, we used circular dichroism and transmission electron microscopy to study the anti-Abeta aggregation capability of silibinin in vitro. Moreover, a Morris Water Maze test, enzyme-linked immunosorbent assay, immunohistochemistry, 5-bromo-2-deoxyuridine double labeling, and a gene gun experiment were performed on silibinin-treated APP/PS1 transgenic mice. In molecular dynamics simulations, silibinin interacted with Abeta and AChE to form different stable complexes. After the administration of silibinin, AChE activity and Abeta aggregations were down-regulated, and the quantity of AChE also decreased. In addition, silibinin-treated APP/PS1 transgenic mice had greater scores in the Morris Water Maze. Moreover, silibinin could increase the number of newly generated microglia, astrocytes, neurons, and neuronal precursor cells. Taken together, these data suggest that silibinin could act as a dual inhibitor of AChE and Abeta peptide aggregation, therefore suggesting a therapeutic strategy for AD treatment. Title: Structure of product-bound SMG1 lipase: active site gating implications Guo S, Xu J, Pavlidis IV, Lan D, Bornscheuer UT, Liu J, Wang Y Ref: Febs J, 282:4538, 2015 : PubMed ESTHER: Guo_2015_FEBS.J_282_4538 PubMedSearch: Guo 2015 FEBS.J 282 4538 PubMedID: 26365206 Gene_locus related to this paper: malgo-a8puy1 Abstract Monoacylglycerol and diacylglycerol lipases are industrially interesting enzymes, due to the health benefits that arise from the consumption of diglycerides compared to the traditional triglyceride oils. Most lipases possess an alpha-helix (lid) directly over the catalytic pocket which regulates the activity of the enzyme. Generally, lipases exist in active and inactive conformations, depending on the positioning of this lid subdomain. However, lipase SMG1, a monoacylglycerol and diacylglycerol specific lipase, has an atypical activation mechanism. In the present study we were able to prove by crystallography, in silico analysis and activity tests that only two positions, residues 102 and 278, are responsible for a gating mechanism that regulates the active and inactive states of the lipase, and that no significant structural changes take place during activation except for oxyanion hole formation. The elucidation of the gating effect provided data enabling the rational design of improved lipases with 6-fold increase in the hydrolytic activity toward diacylglycerols, just by providing additional substrate stabilization with a single mutation (F278N or F278T). Due to the conservation of F278 among the monoacylglycerol and diacylglycerol lipases in the Rhizomucor miehei lipase-like family, the gating mechanism described herein might represent a general mechanism applicable to other monoacylglycerol and diacylglycerol lipases as well. DATABASE: Structural data are available in the Protein Data Bank under the accession numbers 4ZRE (F278D mutant) and 4ZRD (F278N mutant). Title: [Effect of Bacillus thuringiensis var. israelensis (Bti) on detoxification en- zyme activity of larvae of Culex pipiens pallens and Aedes aegypti] Han GJ, Li CM, Sun J, Liu Q, Zhao S, Qi JH, Xu J Ref: Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi, 27:385, 2015 : PubMed ESTHER: Han_2015_Zhongguo.Xue.Xi.Chong.Bing.Fang.Zhi.Za.Zhi_27_385 PubMedSearch: Han 2015 Zhongguo.Xue.Xi.Chong.Bing.Fang.Zhi.Za.Zhi 27 385 PubMedID: 26767261 Abstract OBJECTIVE: To investigate the effect of Bacillus thuringiensis var. israelensis (Bti) on the activities of three detoxification enzymes of Culex pipiens pallens and Aedes aegypti larvae. Title: The Interplay between Synaptic Activity and Neuroligin Function in the CNS Hu X, Luo JH, Xu J Ref: Biomed Res Int, 2015:498957, 2015 : PubMed ESTHER: Hu_2015_Biomed.Res.Int_2015_498957 PubMedSearch: Hu 2015 Biomed.Res.Int 2015 498957 PubMedID: 25839034 Abstract Neuroligins (NLs) are postsynaptic transmembrane cell-adhesion proteins that play a key role in the regulation of excitatory and inhibitory synapses. Previous in vitro and in vivo studies have suggested that NLs contribute to synapse formation and synaptic transmission. Consistent with their localization, NL1 and NL3 selectively affect excitatory synapses, whereas NL2 specifically affects inhibitory synapses. Deletions or mutations in NL genes have been found in patients with autism spectrum disorders or mental retardations, and mice harboring the reported NL deletions or mutations exhibit autism-related behaviors and synapse dysfunction. Conversely, synaptic activity can regulate the phosphorylation, expression, and cleavage of NLs, which, in turn, can influence synaptic activity. Thus, in clinical research, identifying the relationship between NLs and synapse function is critical. In this review, we primarily discuss how NLs and synaptic activity influence each other. Title: Residue Asn277 Affects the Stability and Substrate Specificity of the SMG1 Lipase from Malassezia globosa Lan D, Wang Q, Xu J, Zhou P, Yang B, Wang Y Ref: Int J Mol Sci, 16:7273, 2015 : PubMed ESTHER: Lan_2015_Int.J.Mol.Sci_16_7273 PubMedSearch: Lan 2015 Int.J.Mol.Sci 16 7273 PubMedID: 25837472 Gene_locus related to this paper: malgo-a8puy1 Abstract Thermostability and substrate specificity are important characteristics of enzymes for industrial application, which can be improved by protein engineering. SMG1 lipase from Malassezia globosa is a mono- and diacylglycerol lipase (MDL) that shows activity toward mono- and diacylglycerols, but no activity toward triacylglycerols. SMG1 lipase is considered a potential biocatalyst applied in oil/fat modification and its crystal structure revealed that an interesting residue-Asn277 may contribute to stabilize loop 273-278 and the 3104 helix which are important to enzyme characterization. In this study, to explore its role in affecting the stability and catalytic activity, mutagenesis of N277 with Asp (D), Val (V), Leu (L) and Phe (F) was conducted. Circular dichroism (CD) spectral analysis and half-life measurement showed that the N277D mutant has better thermostability. The melting temperature and half-life of the N277D mutant were 56.6 degrees C and 187 min, respectively, while that was 54.6 degrees C and 121 min for SMG1 wild type (WT). Biochemical characterization of SMG1 mutants were carried out to test whether catalytic properties were affected by mutagenesis. N277D had similar enzymatic properties as SMG1 WT, but N277F showed a different substrate selectivity profile as compared to other SMG1 mutants. Analysis of the SMG1 3D model suggested that N277D formed a salt bridge via its negative charged carboxyl group with a positively charged guanidino group of R227, which might contribute to confer N277D higher temperature stability. These findings not only provide some clues to understand the molecular basis of the lipase structure/function relationship but also lay the framework for engineering suitable MDL lipases for industrial applications. Title: Design, synthesis, biological evaluation and docking study of 4-isochromanone hybrids bearing N-benzyl pyridinium moiety as dual binding site acetylcholinesterase inhibitors Wang C, Wu Z, Cai H, Xu S, Liu J, Jiang J, Yao H, Wu X, Xu J Ref: Bioorganic & Medicinal Chemistry Lett, 25:5212, 2015 : PubMed ESTHER: Wang_2015_Bioorg.Med.Chem.Lett_25_5212 PubMedSearch: Wang 2015 Bioorg.Med.Chem.Lett 25 5212 PubMedID: 26454504 Abstract A series of novel 4-isochromanone hybrids bearing N-benzyl pyridinium moiety as dual binding site acetylcholinesterase inhibitors have been designed and synthesized. The screening results showed that most of the compounds exhibited potent anti-AChE activity in the range of nM concentrations. The 1-(4-fluorobenzyl) substituted derivative 9d exhibited the most potent anti-AChE activity with IC50 value of 8.9nM and high AChE/BuChE selectivity (SI>230). Kinetic and molecular modeling studies suggested that compound 9d was mixed-type inhibitor, binding simultaneously to CAS and PAS of AChE. Besides, the preliminary structure-activity relationships were discussed. Title: Epoxide hydrolase activities and epoxy fatty acids in the mosquito Culex quinquefasciatus Xu J, Morisseau C, Yang J, Mamatha DM, Hammock BD Ref: Insect Biochemistry & Molecular Biology, 59:41, 2015 : PubMed ESTHER: Xu_2015_Insect.Biochem.Mol.Biol_59_41 PubMedSearch: Xu 2015 Insect.Biochem.Mol.Biol 59 41 PubMedID: 25686802 Abstract Culex mosquitoes have emerged as important model organisms for mosquito biology, and are disease vectors for multiple mosquito-borne pathogens, including West Nile virus. We characterized epoxide hydrolase activities in the mosquito Culex quinquefasciatus, which suggested multiple forms of epoxide hydrolases were present. We found EH activities on epoxy eicosatrienoic acids (EETs). EETs and other eicosanoids are well-established lipid signaling molecules in vertebrates. We showed EETs can be synthesized in vitro from arachidonic acids by mosquito lysate, and EETs were also detected in vivo both in larvae and adult mosquitoes by LC-MS/MS. The EH activities on EETs can be induced by blood feeding, and the highest activity was observed in the midgut of female mosquitoes. The enzyme activities on EETs can be inhibited by urea-based inhibitors designed for mammalian soluble epoxide hydrolases (sEH). The sEH inhibitors have been shown to play diverse biological roles in mammalian systems, and they can be useful tools to study the function of EETs in mosquitoes. Besides juvenile hormone metabolism and detoxification, insect epoxide hydrolases may also play a role in regulating lipid signaling molecules, such as EETs and other epoxy fatty acids, synthesized in vivo or obtained from blood feeding by female mosquitoes. Title: A New Motif in the N-Terminal of Acetylcholinesterase Triggers Amyloid-beta Aggregation and Deposition Hou LN, Xu JR, Zhao QN, Gao XL, Cui YY, Xu J, Wang H, Chen HZ Ref: CNS Neurosci Ther, 20:59, 2014 : PubMed ESTHER: Hou_2014_CNS.Neurosci.Ther_20_59 PubMedSearch: Hou 2014 CNS.Neurosci.Ther 20 59 PubMedID: 23981668 Abstract BACKGROUND AND PURPOSE: As a molecular chaperone, acetylcholinesterase (AChE; EC 3.1.1.7) plays a critical role in the pathogenesis of Alzheimer's disease (AD). The peripheral anionic site (PAS) of AChE has been indicated as the amyloid-beta (Abeta) binding domain. The goal of this study was to determine other motifs in AChE involved in Abeta aggregation and deposition. METHODS AND Title: Structure of the type VI secretion phospholipase effector Tle1 provides insight into its hydrolysis and membrane targeting Hu H, Zhang H, Gao Z, Wang D, Liu G, Xu J, Lan K, Dong Y Ref: Acta Crystallographica D Biol Crystallogr, 70:2175, 2014 : PubMed ESTHER: Hu_2014_Acta.Crystallogr.D.Biol.Crystallogr_70_2175 PubMedSearch: Hu 2014 Acta.Crystallogr.D.Biol.Crystallogr 70 2175 PubMedID: 25084336 Gene_locus related to this paper: pseae-q9hyv3 Abstract A diverse superfamily of phospholipases consisting of the type VI lipase effectors Tle1-Tle5 secreted by the bacterial type VI secretion system (T6SS) have recently been identified as antibacterial effectors that hydrolyze membrane phospholipids. These effectors show no significant homology to known lipases, and their mechanism of membrane targeting and hydrolysis of phospholipids remains unknown. Here, the crystal structure of Tle1 ( approximately 96.5 kDa) from Pseudomonas aeruginosa refined to 2.0 A resolution is reported, representing the first structure of this superfamily. Its overall structure can be divided into two distinct parts, the phospholipase catalytic module and the putative membrane-anchoring module; this arrangement has not previously been observed in known lipase structures. The phospholipase catalytic module has a canonical alpha/beta-hydrolase fold and mutation of any residue in the Ser-Asp-His catalytic triad abolishes its toxicity. The putative membrane-anchoring module adopts an open conformation composed of three amphipathic domains, and its partial folds are similar to those of several periplasmic or membrane proteins. A cell-toxicity assay revealed that the putative membrane-anchoring module is critical to Tle1 antibacterial activity. A molecular-dynamics (MD) simulation system in which the putative membrane-anchoring module embedded into a bilayer was stable over 50 ns. These structure-function studies provide insight into the hydrolysis and membrane-targeting process of the unique phospholipase Tle1. Title: Synthesis and characterization of 1H-phenanthro[9,10-d]imidazole derivatives as multifunctional agents for treatment of Alzheimer's disease Liu J, Qiu J, Wang M, Wang L, Su L, Gao J, Gu Q, Xu J, Huang SL and Li D <2 more author(s)> Liu J, Qiu J, Wang M, Wang L, Su L, Gao J, Gu Q, Xu J, Huang SL, Gu LQ, Huang ZS, Li D (- 2) Ref: Biochimica & Biophysica Acta, 1840:2886, 2014 : PubMed ESTHER: Liu_2014_Biochim.Biophys.Acta_1840_2886 PubMedSearch: Liu 2014 Biochim.Biophys.Acta 1840 2886 PubMedID: 24821011 Abstract BACKGROUND: Alzheimer's disease (AD) is a progressive neurodegenerative brain disorder that is characterized by dementia, cognitive impairment, and memory loss. Diverse factors are related to the development of AD, such as increased level of beta-amyloid (Abeta), acetylcholine, metal ion deregulation, hyperphosphorylated tau protein, and oxidative stress. Title: Draft Genome Sequence of a Methicillin-Resistant Staphylococcus aureus ST1413 Strain for Studying Genetic Mechanisms of Antibiotic Resistance Marasa BS, Revollo J, Iram S, Sung K, Xu J, Khan S Ref: Genome Announc, 2:, 2014 : PubMed ESTHER: Marasa_2014_Genome.Announc_2_e00162 PubMedSearch: Marasa 2014 Genome.Announc 2 e00162 PubMedID: 24604656 Abstract Here we report the whole draft genome sequence of a methicillin-resistant Staphylococcus aureus ST1413 strain. Determining the distribution and arrangement of various genes associated with drug resistance, toxicity, and diseases will enhance our understanding about its adaptability to thrive in different ecological niches and help in the development of effective treatments for enterotoxigenic staphylococcal infections. Title: Whole-genome sequencing of cultivated and wild peppers provides insights into Capsicum domestication and specialization Qin C, Yu C, Shen Y, Fang X, Chen L, Min J, Cheng J, Zhao S, Xu M and Zhang Z <58 more author(s)> Qin C, Yu C, Shen Y, Fang X, Chen L, Min J, Cheng J, Zhao S, Xu M, Luo Y, Yang Y, Wu Z, Mao L, Wu H, Ling-Hu C, Zhou H, Lin H, Gonzalez-Morales S, Trejo-Saavedra DL, Tian H, Tang X, Zhao M, Huang Z, Zhou A, Yao X, Cui J, Li W, Chen Z, Feng Y, Niu Y, Bi S, Yang X, Cai H, Luo X, Montes-Hernandez S, Leyva-Gonzalez MA, Xiong Z, He X, Bai L, Tan S, Liu D, Liu J, Zhang S, Chen M, Zhang L, Zhang Y, Liao W, Wang M, Lv X, Wen B, Liu H, Luan H, Yang S, Wang X, Xu J, Li X, Li S, Wang J, Palloix A, Bosland PW, Li Y, Krogh A, Rivera-Bustamante RF, Herrera-Estrella L, Yin Y, Yu J, Hu K, Zhang Z (- 58) Ref: Proc Natl Acad Sci U S A, 111:5135, 2014 : PubMed ESTHER: Qin_2014_Proc.Natl.Acad.Sci.U.S.A_111_5135 PubMedSearch: Qin 2014 Proc.Natl.Acad.Sci.U.S.A 111 5135 PubMedID: 24591624 Gene_locus related to this paper: capch-q75qh4, capan-a0a1u8fuf5, capan-a0a1u8gmz3, capan-a0a1u8f879, capan-a0a1u8ftr2, capan-a0a1u8g8s6 Abstract As an economic crop, pepper satisfies people's spicy taste and has medicinal uses worldwide. To gain a better understanding of Capsicum evolution, domestication, and specialization, we present here the genome sequence of the cultivated pepper Zunla-1 (C. annuum L.) and its wild progenitor Chiltepin (C. annuum var. glabriusculum). We estimate that the pepper genome expanded approximately 0.3 Mya (with respect to the genome of other Solanaceae) by a rapid amplification of retrotransposons elements, resulting in a genome comprised of approximately 81% repetitive sequences. Approximately 79% of 3.48-Gb scaffolds containing 34,476 protein-coding genes were anchored to chromosomes by a high-density genetic map. Comparison of cultivated and wild pepper genomes with 20 resequencing accessions revealed molecular footprints of artificial selection, providing us with a list of candidate domestication genes. We also found that dosage compensation effect of tandem duplication genes probably contributed to the pungent diversification in pepper. The Capsicum reference genome provides crucial information for the study of not only the evolution of the pepper genome but also, the Solanaceae family, and it will facilitate the establishment of more effective pepper breeding programs. Title: Complete Genome Sequence of Magnetospirillum gryphiswaldense MSR-1 Wang X, Wang Q, Zhang W, Wang Y, Li L, Wen T, Zhang T, Zhang Y, Xu J and Li J <9 more author(s)> Wang X, Wang Q, Zhang W, Wang Y, Li L, Wen T, Zhang T, Zhang Y, Xu J, Hu J, Li S, Liu L, Liu J, Jiang W, Tian J, Li Y, Schuler D, Wang L, Li J (- 9) Ref: Genome Announc, 2:, 2014 : PubMed ESTHER: Wang_2014_Genome.Announc_2_e00171 PubMedSearch: Wang 2014 Genome.Announc 2 e00171 PubMedID: 24625872 Gene_locus related to this paper: maggm-v6ezc0 Abstract We report the complete genomic sequence of Magnetospirillum gryphiswaldense MSR-1 (DSM 6361), a type strain of the genus Magnetospirillum belonging to the Alphaproteobacteria. Compared to the reported draft sequence, extensive rearrangements and differences were found, indicating high genomic flexibility and "domestication" by accelerated evolution of the strain upon repeated passaging. Title: Hepatic carboxylesterase 1 is induced by glucose and regulates postprandial glucose levels Xu J, Yin L, Xu Y, Li Y, Zalzala M, Cheng G, Zhang Y Ref: PLoS ONE, 9:e109663, 2014 : PubMed ESTHER: Xu_2014_PLoS.One_9_e109663 PubMedSearch: Xu 2014 PLoS.One 9 e109663 PubMedID: 25285996 Abstract Metabolic syndrome, characterized by obesity, hyperglycemia, dyslipidemia and hypertension, increases the risks for cardiovascular disease, diabetes and stroke. Carboxylesterase 1 (CES1) is an enzyme that hydrolyzes triglycerides and cholesterol esters, and is important for lipid metabolism. Our previous data show that over-expression of mouse hepatic CES1 lowers plasma glucose levels and improves insulin sensitivity in diabetic ob/ob mice. In the present study, we determined the physiological role of hepatic CES1 in glucose homeostasis. Hepatic CES1 expression was reduced by fasting but increased in diabetic mice. Treatment of mice with glucose induced hepatic CES1 expression. Consistent with the in vivo study, glucose stimulated CES1 promoter activity and increased acetylation of histone 3 and histone 4 in the CES1 chromatin. Knockdown of ATP-citrate lyase (ACL), an enzyme that regulates histone acetylation, abolished glucose-mediated histone acetylation in the CES1 chromatin and glucose-induced hepatic CES1 expression. Finally, knockdown of hepatic CES1 significantly increased postprandial blood glucose levels. In conclusion, the present study uncovers a novel glucose-CES1-glucose pathway which may play an important role in regulating postprandial blood glucose levels. Title: Expression and characterization of an epoxide hydrolase from Anopheles gambiae with high activity on epoxy fatty acids Xu J, Morisseau C, Hammock BD Ref: Insect Biochemistry & Molecular Biology, 54C:42, 2014 : PubMed ESTHER: Xu_2014_Insect.Biochem.Mol.Biol_54C_42 PubMedSearch: Xu 2014 Insect.Biochem.Mol.Biol 54C 42 PubMedID: 25173592 Abstract In insects, epoxide hydrolases (EHs) play critical roles in the metabolism of xenobiotic epoxides from the food resources and in the regulation of endogenous chemical mediators, such as juvenile hormones. Using the baculovirus expression system, we expressed and characterized an epoxide hydrolase from Anopheles gambiae (AgEH) that is distinct in evolutionary history from insect juvenile hormone epoxide hydrolases (JHEHs). We partially purified the enzyme by ion exchange chromatography and isoelectric focusing. The experimentally determined molecular weight and pI were estimated to be 35 kD and 6.3 respectively, different than the theoretical ones. The AgEH had the greatest activity on long chain epoxy fatty acids such as 14,15-epoxyeicosatrienoic acids (14,15-EET) and 9,10-epoxy-12Z-octadecenoic acids (9,10-EpOME or leukotoxin) among the substrates evaluated. Juvenile hormone III, a terpenoid insect growth regulator, was the next best substrate tested. The AgEH showed kinetics comparable to the mammalian soluble epoxide hydrolases, and the activity could be inhibited by AUDA [12-(3-adamantan-1-yl-ureido) dodecanoic acid], a urea-based inhibitor designed to inhibit the mammalian soluble epoxide hydrolases. The rabbit serum generated against the soluble epoxide hydrolase of Mus musculus can both cross-react with natural and denatured forms of the AgEH, suggesting immunologically they are similar. The study suggests there are mammalian sEH homologs in insects, and epoxy fatty acids may be important chemical mediators in insects. Title: PICK1 Mediates Synaptic Recruitment of AMPA Receptors at Neurexin-Induced Postsynaptic Sites Xu J, Kam C, Luo JH, Xia J Ref: Journal of Neuroscience, 34:15415, 2014 : PubMed ESTHER: Xu_2014_J.Neurosci_34_15415 PubMedSearch: Xu 2014 J.Neurosci 34 15415 PubMedID: 25392508 Abstract In the CNS, synapse formation and maturation play crucial roles in the construction and consolidation of neuronal circuits. Neurexin and neuroligin localize on the opposite sides of synaptic membrane and interact with each other to promote the assembly and specialization of synapses. However, the excitatory synapses induced by the neurexin-neuroligin complex are initially immature synapses that lack AMPA receptors. Previously, PICK1 (protein interacting with C kinase 1) was shown to cluster and regulate the synaptic localization of AMPA receptors. Here, we report that during synaptogenesis induced by neurexin in cultured neurons from rat hippocampus, PICK1 recruited AMPA receptors to immature postsynaptic sites. This synaptic recruitment of AMPA receptors depended on the interaction between GluA2 and PICK1, and on the lipid-binding ability of PICK1, but not the interaction between PICK1 and neuroligin. Last, our results demonstrated that the recruitment of GluA2 to synapses could be prevented by ICA69 (islet cell autoantigen 69 kDa), a key binding partner of PICK1. Our study showed that PICK1, being negatively regulated by ICA69, could facilitate synapse maturation. Title: Determination of Meserine, a new candidate for Alzheimer's disease in mice brain by liquid chromatography-tandem mass spectrometry and its application to a pharmacokinetic and tissue distribution study Zheng Z, Tang Y, Lv H, Xu J, Zhao H, Xie Q, Qiu Z, Chen H, Wang H Ref: Anal Bioanal Chem, 406:3451, 2014 : PubMed ESTHER: Zheng_2014_Anal.Bioanal.Chem_406_3451 PubMedSearch: Zheng 2014 Anal.Bioanal.Chem 406 3451 PubMedID: 24756818 Abstract A rapid and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for determination of Meserine ((-)-meptazinol phenylcarbamate), a novel potent inhibitor of acetylcholinesterase (AChE), was developed, validated, and applied to a pharmacokinetic study in mice brain. The lower limit of quantification (LLOQ) was 1 ng mL(-1) and the linear range was 1-1,000 ng mL(-1). The analyte was eluted on a Zorbax SB-Aq column (2.1 x 100 mm, 3.5 mum) with the mobile phase composed of methanol and water (70:30, v/v, aqueous phase contained 10 mM ammonium formate and 0.3% formic acid) using isocratic elution, and monitored by positive electrospray ionization in multiple reaction monitoring (MRM) mode. The flow rate was 0.25 mL min(-1). The injection volume was 5 muL and total run time was 4 min. The relative standard deviation (RSD) of intraday and interday variation was 2.49-7.81 and 3.01-7.67%, respectively. All analytes were stable after 4 h at room temperature and 6 h in autosampler. The extraction recoveries of Meserine in brain homogenate were over 90%. The main brain pharmacokinetic parameters obtained after intranasal administration were T max = 0.05 h, C max = 462.0 +/- 39.7 ng g(-1), T 1/2 = 0.4 h, and AUC(0-infinity) = 283.1 +/- 9.1 ng h g(-1). Moreover, Meserine was distributed rapidly and widely into brain, heart, liver, spleen, lung, and kidney tissue. The method is validated and could be applied to the pharmacokinetic and tissue distribution study of Meserine in mice. Title: Genomic insights into the atopic eczema-associated skin commensal yeast Malassezia sympodialis Gioti A, Nystedt B, Li W, Xu J, Andersson A, Averette AF, Munch K, Wang X, Kappauf C and Scheynius A <19 more author(s)> Gioti A, Nystedt B, Li W, Xu J, Andersson A, Averette AF, Munch K, Wang X, Kappauf C, Kingsbury JM, Kraak B, Walker LA, Johansson HJ, Holm T, Lehtio J, Stajich JE, Mieczkowski P, Kahmann R, Kennell JC, Cardenas ME, Lundeberg J, Saunders CW, Boekhout T, Dawson TL, Munro CA, de Groot PW, Butler G, Heitman J, Scheynius A (- 19) Ref: MBio, 4:e00572, 2013 : PubMed ESTHER: Gioti_2013_MBio_4_e00572 PubMedSearch: Gioti 2013 MBio 4 e00572 PubMedID: 23341551 Gene_locus related to this paper: mals4-m5ean5 Abstract Malassezia commensal yeasts are associated with a number of skin disorders, such as atopic eczema/dermatitis and dandruff, and they also can cause systemic infections. Here we describe the 7.67-Mbp genome of Malassezia sympodialis, a species associated with atopic eczema, and contrast its genome repertoire with that of Malassezia globosa, associated with dandruff, as well as those of other closely related fungi. Ninety percent of the predicted M. sympodialis protein coding genes were experimentally verified by mass spectrometry at the protein level. We identified a relatively limited number of genes related to lipid biosynthesis, and both species lack the fatty acid synthase gene, in line with the known requirement of these yeasts to assimilate lipids from the host. Malassezia species do not appear to have many cell wall-localized glycosylphosphatidylinositol (GPI) proteins and lack other cell wall proteins previously identified in other fungi. This is surprising given that in other fungi these proteins have been shown to mediate interactions (e.g., adhesion and biofilm formation) with the host. The genome revealed a complex evolutionary history for an allergen of unknown function, Mala s 7, shown to be encoded by a member of an amplified gene family of secreted proteins. Based on genetic and biochemical studies with the basidiomycete human fungal pathogen Cryptococcus neoformans, we characterized the allergen Mala s 6 as the cytoplasmic cyclophilin A. We further present evidence that M. sympodialis may have the capacity to undergo sexual reproduction and present a model for a pseudobipolar mating system that allows limited recombination between two linked MAT loci. IMPORTANCE: Malassezia commensal yeasts are associated with a number of skin disorders. The previously published genome of M. globosa provided some of the first insights into Malassezia biology and its involvement in dandruff. Here, we present the genome of M. sympodialis, frequently isolated from patients with atopic eczema and healthy individuals. We combined comparative genomics with sequencing and functional characterization of specific genes in a population of clinical isolates and in closely related model systems. Our analyses provide insights into the evolution of allergens related to atopic eczema and the evolutionary trajectory of the machinery for sexual reproduction and meiosis. We hypothesize that M. sympodialis may undergo sexual reproduction, which has important implications for the understanding of the life cycle and virulence potential of this medically important yeast. Our findings provide a foundation for the development of genetic and genomic tools to elucidate host-microbe interactions that occur on the skin and to identify potential therapeutic targets. Title: Alignment of synaptic vesicle macromolecules with the macromolecules in active zone material that direct vesicle docking Harlow ML, Szule JA, Xu J, Jung JH, Marshall RM, McMahan UJ Ref: PLoS ONE, 8:e69410, 2013 : PubMed ESTHER: Harlow_2013_PLoS.One_8_e69410 PubMedSearch: Harlow 2013 PLoS.One 8 e69410 PubMedID: 23894473 Abstract Synaptic vesicles dock at active zones on the presynaptic plasma membrane of a neuron's axon terminals as a precondition for fusing with the membrane and releasing their neurotransmitter to mediate synaptic impulse transmission. Typically, docked vesicles are next to aggregates of plasma membrane-bound macromolecules called active zone material (AZM). Electron tomography on tissue sections from fixed and stained axon terminals of active and resting frog neuromuscular junctions has led to the conclusion that undocked vesicles are directed to and held at the docking sites by the successive formation of stable connections between vesicle membrane proteins and proteins in different classes of AZM macromolecules. Using the same nanometer scale 3D imaging technology on appropriately stained frog neuromuscular junctions, we found that approximately 10% of a vesicle's luminal volume is occupied by a radial assembly of elongate macromolecules attached by narrow projections, nubs, to the vesicle membrane at approximately 25 sites. The assembly's chiral, bilateral shape is nearly the same vesicle to vesicle, and nubs, at their sites of connection to the vesicle membrane, are linked to macromolecules that span the membrane. For docked vesicles, the orientation of the assembly's shape relative to the AZM and the presynaptic membrane is the same vesicle to vesicle, whereas for undocked vesicles it is not. The connection sites of most nubs on the membrane of docked vesicles are paired with the connection sites of the different classes of AZM macromolecules that regulate docking, and the membrane spanning macromolecules linked to these nubs are also attached to the AZM macromolecules. We conclude that the luminal assembly of macromolecules anchors in a particular arrangement vesicle membrane macromolecules, which contain the proteins that connect the vesicles to AZM macromolecules during docking. Undocked vesicles must move in a way that aligns this arrangement with the AZM macromolecules for docking to proceed. Title: Dynamics of fecal microbial communities in children with diarrhea of unknown etiology and genomic analysis of associated Streptococcus lutetiensis Jin D, Chen C, Li L, Lu S, Li Z, Zhou Z, Jing H, Xu Y, Du P and Xu J <8 more author(s)> Jin D, Chen C, Li L, Lu S, Li Z, Zhou Z, Jing H, Xu Y, Du P, Wang H, Xiong Y, Zheng H, Bai X, Sun H, Wang L, Ye C, Gottschalk M, Xu J (- 8) Ref: BMC Microbiol, 13:141, 2013 : PubMed ESTHER: Jin_2013_BMC.Microbiol_13_141 PubMedSearch: Jin 2013 BMC.Microbiol 13 141 PubMedID: 23782707 Abstract BACKGROUND: The sequences of the 16S rRNA genes extracted from fecal samples provide insights into the dynamics of fecal microflora. This potentially gives valuable etiological information for patients whose conditions have been ascribed to unknown pathogens, which cannot be accomplished using routine culture methods. We studied 33 children with diarrhea who were admitted to the Children's Hospital in Shanxi Province during 2006. Title: Draft Genome Sequences of Elizabethkingia anophelis Strains R26T and Ag1 from the Midgut of the Malaria Mosquito Anopheles gambiae Kukutla P, Lindberg BG, Pei D, Rayl M, Yu W, Steritz M, Faye I, Xu J Ref: Genome Announc, 1:, 2013 : PubMed ESTHER: Kukutla_2013_Genome.Announc_1_e01030 PubMedSearch: Kukutla 2013 Genome.Announc 1 e01030 PubMedID: 24309745 Gene_locus related to this paper: 9flao-h0kx79 Abstract Elizabethkingia anophelis is a species in the family Flavobacteriaceae. It is a dominant resident in the mosquito gut and also a human pathogen. We present the draft genome sequences of two strains of E. anophelis, R26(T) and Ag1, which were isolated from the midgut of the malaria mosquito Anopheles gambiae. Title: Bis(9)-(-)-nor-meptazinol as a novel dual-binding AChEI potently ameliorates scopolamine-induced cognitive deficits in mice Liu T, Xia Z, Zhang WW, Xu JR, Ge XX, Li J, Cui Y, Qiu ZB, Xu J and Chen HZ <2 more author(s)> Liu T, Xia Z, Zhang WW, Xu JR, Ge XX, Li J, Cui Y, Qiu ZB, Xu J, Xie Q, Wang H, Chen HZ (- 2) Ref: Pharmacol Biochem Behav, 104:138, 2013 : PubMed ESTHER: Liu_2013_Pharmacol.Biochem.Behav_104_138 PubMedSearch: Liu 2013 Pharmacol.Biochem.Behav 104 138 PubMedID: 23262302 Inhibitor(s) related to this paper: bis9-(-)-nor-meptazinol Abstract Alzheimer's disease (AD) is a multifaceted neurodegenerative disorder which is characterized by the progressive deterioration of cognition and the emergence of behavioral and psychological symptoms in aging patients. Given that the clinical effectiveness of acetylcholinesterase inhibitors (AChEIs) has still been questioned due to dubious disease-modifying effects, the multi-target directed ligand (MTDL) design has become an emerging strategy for developing new drugs for AD treatment. Bis(9)-(-)-nor-meptazinol (Bis-Mep) was firstly reported by us as a novel MTDL for both potent cholinesterase and amyloid-beta aggregation inhibition. In this study, we further explored its AChE inhibition kinetic features and cognitive amelioration. Bis-Mep was found to be a mixed-type inhibitor on electric eel AChE by enzyme kinetic study. Molecular docking revealed that two "water bridges" located at the two wings of Bis-Mep stabilized its interaction with both catalytic and peripheral anionic sites of AChE. Furthermore, subcutaneous administration of Bis-Mep (10, 100 or 1000ng/kg) significantly reversed the scopolamine-induced memory deficits in a typical bell-shaped dose-response manner. The maximal cognitive amelioration of Bis-Mep was achieved at 100ng/kg, comparable with the effect of a reference drug Huperzine A at 1mg/kg and also the relevant AChE inhibition in brain. These findings suggested that Bis-Mep might be a promising dual-binding AChE inhibitor for potential AD therapeutics. Title: Hepatic carboxylesterase 1 is essential for both normal and farnesoid X receptor-controlled lipid homeostasis Xu J, Li Y, Chen WD, Xu Y, Yin L, Ge X, Jadhav K, Adorini L, Zhang Y Ref: Hepatology, :1, 2013 : PubMed ESTHER: Xu_2013_Hepatology__1 PubMedSearch: Xu 2013 Hepatology 1 PubMedID: 24038130 Gene_locus related to this paper: mouse-Ces1g Abstract Nonalcoholic fatty liver disease (NAFLD) is one of the major health concerns worldwide. Farnesoid X receptor (FXR) is considered a therapeutic target for treatment of NAFLD. However, the mechanism by which activation of FXR lowers hepatic triglyceride (TG) levels remains unknown. Here we investigated the role of hepatic carboxylesterase 1 (CES1) in regulating both normal and FXR-controlled lipid homeostasis. Overexpression of hepatic CES1 lowered hepatic TG and plasma glucose levels in both wild-type and diabetic mice. In contrast, knockdown of hepatic CES1 increased hepatic TG and plasma cholesterol levels. These effects likely resulted from the TG hydrolase activity of CES1, with subsequent changes in fatty acid oxidation and/or de novo lipogenesis. Activation of FXR induced hepatic CES1, and reduced the levels of hepatic and plasma TG as well as plasma cholesterol in a CES1-dependent manner. Conclusion: Hepatic CES1 plays a critical role in regulating both lipid and carbohydrate metabolism and FXR-controlled lipid homeostasis. (Hepatology 2014). Title: Draft genome sequence of Pseudomonas sp. strain Ag1, isolated from the midgut of the malaria mosquito Anopheles gambiae Alvarez C, Kukutla P, Jiang J, Yu W, Xu J Ref: Journal of Bacteriology, 194:5449, 2012 : PubMed ESTHER: Alvarez_2012_J.Bacteriol_194_5449 PubMedSearch: Alvarez 2012 J.Bacteriol 194 5449 PubMedID: 22965079 Gene_locus related to this paper: 9psed-j0y549, psefl-v7ecg4, psefl-v7dwb3, psefl-v7e7h8, psefl-v7ec59, psefl-v7e2d2 Abstract A Pseudomonas sp. bacterium was isolated from the midguts of Anopheles gambiae mosquitoes. Here we present the annotated Pseudomonas sp. draft genome sequence as a contribution to the efforts of characterization of the mosquito gut microbiome. Title: Bone marrow-derived mesenchymal stem cells up-regulate acetylcholine receptor delta subunit through NRG/ErbB3-mediated mitogen-activated protein kinase pathway Chen L, Jiang J, Xu J, Gu Y, Xu L Ref: Clin Transl Sci, 5:27, 2012 : PubMed ESTHER: Chen_2012_Clin.Transl.Sci_5_27 PubMedSearch: Chen 2012 Clin.Transl.Sci 5 27 PubMedID: 22376253 Abstract To investigate the effect of bone marrow-derived mesenchymal stem cells (BMSCs) on the expression of acetylcholine receptor delta subunit (AChRd), the murine skeletal muscle cell line Sol8 were grown in DMEM with 20% fetal bovine serum added with (conditional medium group) or without (control group) conditional medium of BMSC cells for 48 hours. RT-PCR and Western blot were performed to access the mRNA and protein levels of AChRd in Sol8 cells, respectively. Western blot was used to detect total and phosphorylated protein levels of Ras, Raf-1, Mek1/2, and Erk1/2, respectively. NRG-1 antibody added in conditional medium of BMSCs, si-ErbB3, and four Ras/Raf/MEK/ERK pathway inhibitors (FTS, Sulindac, U0126, and PD98059) were using to investigate the effect of AChRd levels. Our studies indicated that expression of AChRd was significantly enhanced in the conditional medium group when compared with those in control group and phosphorylation of Ras, Raf, Erk1/2 in Sol8 cells was also increased. Although gene silencing for ErbB3 gene, adding of NRG-1 antibody in conditional medium of BMSCs or treatment of Ras/Raf/MEK/ERK pathway inhibitors can down-regulate expression of AChRd and phosphorylation, which suggesting that the Ras/Raf/MEK/ERK pathway may be involved in BMSCs-induced expression of AChRd. Title: Draft genome sequences of Enterobacter sp. isolate Ag1 from the midgut of the malaria mosquito Anopheles gambiae Jiang J, Alvarez C, Kukutla P, Yu W, Xu J Ref: Journal of Bacteriology, 194:5481, 2012 : PubMed ESTHER: Jiang_2012_J.Bacteriol_194_5481 PubMedSearch: Jiang 2012 J.Bacteriol 194 5481 PubMedID: 22965099 Gene_locus related to this paper: 9entr-j0w4q1, 9entr-j0w699, 9entr-j1g9f9, 9entr-j1gk40 Abstract An isolate of Enterobacter sp. was obtained from the microbial community within the gut of the Anopheles gambiae mosquito, a major malaria vector in Africa. This genome was sequenced and annotated. The genome sequences will facilitate subsequent efforts to characterize the mosquito gut microbiome. Title: Comparative genome analysis of Trichophyton rubrum and related dermatophytes reveals candidate genes involved in infection Martinez DA, Oliver BG, Graser Y, Goldberg JM, Li W, Martinez-Rossi NM, Monod M, Shelest E, Barton RC and White TC <18 more author(s)> Martinez DA, Oliver BG, Graser Y, Goldberg JM, Li W, Martinez-Rossi NM, Monod M, Shelest E, Barton RC, Birch E, Brakhage AA, Chen Z, Gurr SJ, Heiman D, Heitman J, Kosti I, Rossi A, Saif S, Samalova M, Saunders CW, Shea T, Summerbell RC, Xu J, Young S, Zeng Q, Birren BW, Cuomo CA, White TC (- 18) Ref: MBio, 3:e00259, 2012 : PubMed ESTHER: Martinez_2012_MBio_3_e00259 PubMedSearch: Martinez 2012 MBio 3 e00259 PubMedID: 22951933 Gene_locus related to this paper: artgp-e4uup9, artgp-e4v450, artgp-e5qzf5, artgp-e5r1t8, artoc-c5fc55, artoc-c5fds1, artoc-c5fig8, artoc-c5fj58, artoc-c5fme4, artoc-c5fva9, triec-f2ph15, triec-f2plk8, triec-f2pwm2, trirc-f2sf42, trirc-f2sn39, trirc-f2srv5, trirc-f2sy06, triru-q5j6j0, triru-SCPB, triru-SPCA, trit1-f2rna8, trit1-f2s2t8, trivh-d4dbr9, artbc-d4avu9, artoc-c5fsf7, artgp-e4unv7, artoc-c5g0v3, triec-f2pub4, triec-f2pi43, artgp-e4v6t4, trit1-f2s3n3, artoc-c5fnl7, artgp-e4upq1, artgp-e4uzl7, triec-f2pp24, triru-a0a022u299, 9euro-a0a059jk56, artoc-c5fu24, artoc-c5fic4, artgp-e4uza8, triec-f2pqf3, artgp-e4uv28, artoc-c5fiv8, triru-a0a022w2d0, artgp-e4uvk8, triru-a0a178f289, artoc-c5fyj1, artoc-cbpya, artoc-kex1 Abstract The major cause of athlete's foot is Trichophyton rubrum, a dermatophyte or fungal pathogen of human skin. To facilitate molecular analyses of the dermatophytes, we sequenced T. rubrum and four related species, Trichophyton tonsurans, Trichophyton equinum, Microsporum canis, and Microsporum gypseum. These species differ in host range, mating, and disease progression. The dermatophyte genomes are highly colinear yet contain gene family expansions not found in other human-associated fungi. Dermatophyte genomes are enriched for gene families containing the LysM domain, which binds chitin and potentially related carbohydrates. These LysM domains differ in sequence from those in other species in regions of the peptide that could affect substrate binding. The dermatophytes also encode novel sets of fungus-specific kinases with unknown specificity, including nonfunctional pseudokinases, which may inhibit phosphorylation by competing for kinase sites within substrates, acting as allosteric effectors, or acting as scaffolds for signaling. The dermatophytes are also enriched for a large number of enzymes that synthesize secondary metabolites, including dermatophyte-specific genes that could synthesize novel compounds. Finally, dermatophytes are enriched in several classes of proteases that are necessary for fungal growth and nutrient acquisition on keratinized tissues. Despite differences in mating ability, genes involved in mating and meiosis are conserved across species, suggesting the possibility of cryptic mating in species where it has not been previously detected. These genome analyses identify gene families that are important to our understanding of how dermatophytes cause chronic infections, how they interact with epithelial cells, and how they respond to the host immune response. Title: Genome sequence of the button mushroom Agaricus bisporus reveals mechanisms governing adaptation to a humic-rich ecological niche Morin E, Kohler A, Baker AR, Foulongne-Oriol M, Lombard V, Nagy LG, Ohm RA, Patyshakuliyeva A, Brun A and Martin F <33 more author(s)> Morin E, Kohler A, Baker AR, Foulongne-Oriol M, Lombard V, Nagy LG, Ohm RA, Patyshakuliyeva A, Brun A, Aerts AL, Bailey AM, Billette C, Coutinho PM, Deakin G, Doddapaneni H, Floudas D, Grimwood J, Hilden K, Kues U, LaButti KM, Lapidus A, Lindquist EA, Lucas SM, Murat C, Riley RW, Salamov AA, Schmutz J, Subramanian V, Wosten HA, Xu J, Eastwood DC, Foster GD, Sonnenberg AS, Cullen D, de Vries RP, Lundell T, Hibbett DS, Henrissat B, Burton KS, Kerrigan RW, Challen MP, Grigoriev IV, Martin F (- 33) Ref: Proc Natl Acad Sci U S A, 109:17501, 2012 : PubMed ESTHER: Morin_2012_Proc.Natl.Acad.Sci.U.S.A_109_17501 PubMedSearch: Morin 2012 Proc.Natl.Acad.Sci.U.S.A 109 17501 PubMedID: 23045686 Gene_locus related to this paper: agabu-k5x1b4, agabu-k5x521, agabu-k5w389, agabu-k5wbk9, agabu-k5wrh0, agabu-k5ws85, agabu-k5wsf9, agabu-k5wxv1, agabu-k5x0d9, agabu-k5x588, agabu-k5x5x2, agabu-k5xd51, agabu-k5xh54, agabu-k5xsm1, agabu-k5xsp8, agabu-k5xtc1, agabu-k5y2v2, agabb-k9i3g9, agabb-k9hnv7, agabb-k9hr46, agabu-k5wys0 Abstract Agaricus bisporus is the model fungus for the adaptation, persistence, and growth in the humic-rich leaf-litter environment. Aside from its ecological role, A. bisporus has been an important component of the human diet for over 200 y and worldwide cultivation of the "button mushroom" forms a multibillion dollar industry. We present two A. bisporus genomes, their gene repertoires and transcript profiles on compost and during mushroom formation. The genomes encode a full repertoire of polysaccharide-degrading enzymes similar to that of wood-decayers. Comparative transcriptomics of mycelium grown on defined medium, casing-soil, and compost revealed genes encoding enzymes involved in xylan, cellulose, pectin, and protein degradation are more highly expressed in compost. The striking expansion of heme-thiolate peroxidases and beta-etherases is distinctive from Agaricomycotina wood-decayers and suggests a broad attack on decaying lignin and related metabolites found in humic acid-rich environment. Similarly, up-regulation of these genes together with a lignolytic manganese peroxidase, multiple copper radical oxidases, and cytochrome P450s is consistent with challenges posed by complex humic-rich substrates. The gene repertoire and expression of hydrolytic enzymes in A. bisporus is substantially different from the taxonomically related ectomycorrhizal symbiont Laccaria bicolor. A common promoter motif was also identified in genes very highly expressed in humic-rich substrates. These observations reveal genetic and enzymatic mechanisms governing adaptation to the humic-rich ecological niche formed during plant degradation, further defining the critical role such fungi contribute to soil structure and carbon sequestration in terrestrial ecosystems. Genome sequence will expedite mushroom breeding for improved agronomic characteristics. Title: Synthesis and evaluation of in vitro bioactivity for vesicular acetylcholine transporter inhibitors containing two carbonyl groups Tu Z, Wang W, Cui J, Zhang X, Lu X, Xu J, Parsons SM Ref: Bioorganic & Medicinal Chemistry, 20:4422, 2012 : PubMed ESTHER: Tu_2012_Bioorg.Med.Chem_20_4422 PubMedSearch: Tu 2012 Bioorg.Med.Chem 20 4422 PubMedID: 22739089 Abstract To identify selective high-affinity ligands for the vesicular acetylcholine transporter (VAChT), we have incorporated a carbonyl group into the structures of trozamicol and prezamicol scaffolds, and also converted the secondary amines of the piperidines of trozamicols and prezamicols into amides. Of 18 new racemic compounds, 4 compounds displayed high affinity for VAChT (K(i)=10-20 nM) and greater than 300-fold selectivity for VAChT over sigma(1) and sigma(2) receptors, namely (4-(4-fluorobenzoyl)-4'-hydroxy-[1,3'-bipiperidin]-1'-yl)(3-methylthiophen-2-yl)m ethanone oxalate (9g) (K(i-VAChT)=11.4 nM, VAChT/sigma(1)=1063, VAChT/sigma(2)=370), (1'-benzoyl-4'-hydroxy-[1,3'-bipiperidin]-4-yl)(4-methoxyphenyl)methanone oxalate (10c) (K(i-VAChT)=15.4 nM, VAChT/sigma(1)=374, VAChT/sigma(2)=315), (4'-hydroxy-1'-(thiophene-2-carbonyl)-[1,3'-bipiperidin]-4-yl)(4-methoxyphenyl)me thanone oxalate (10e) (K(i-VAChT)=19.0 nM, VAChT/sigma(1)=1787, VAChT/sigma(2)=335), and (4'-hydroxy-1'-(3-methylthiophene-2-carbonyl)-[1,3'-bipiperidin]-4-yl)(4-methoxyp henyl)methanone oxalate (10g) (K(i-VAChT)=10.2 nM, VAChT/sigma(1)=1500, VAChT/sigma(2)=2030). These four compounds can be radiosynthesized with C-11 or F-18 to validate their possibilities of serving as PET probes for quantifying the levels of VAChT in vivo. Title: Draft genome sequence of Alicyclobacillus hesperidum strain URH17-3-68 Wang P, Li L, Chen X, Jiang N, Liu G, Chen L, Xu J, Song H, Chen Z, Ma Y Ref: Journal of Bacteriology, 194:6348, 2012 : PubMed ESTHER: Wang_2012_J.Bacteriol_194_6348 PubMedSearch: Wang 2012 J.Bacteriol 194 6348 PubMedID: 23105079 Gene_locus related to this paper: 9bacl-h2esd6, 9bacl-j9e7t9 Abstract Alicyclobacillus hesperidum is a thermoacidophilic bacterium. We isolated strain URH17-3-68 from hot spring sludge in Tengchong, Yunnan province, China. Its extracellular products include heat- and acid-stable enzymes which are important for industrial applications. Here we report the draft genome of this strain. Title: A novel Escherichia coli O157:H7 clone causing a major hemolytic uremic syndrome outbreak in China Xiong Y, Wang P, Lan R, Ye C, Wang H, Ren J, Jing H, Wang Y, Zhou Z and Xu J <7 more author(s)> Xiong Y, Wang P, Lan R, Ye C, Wang H, Ren J, Jing H, Wang Y, Zhou Z, Bai X, Cui Z, Luo X, Zhao A, Zhang S, Sun H, Wang L, Xu J (- 7) Ref: PLoS ONE, 7:e36144, 2012 : PubMed ESTHER: Xiong_2012_PLoS.ONE_7_E36144 PubMedSearch: Xiong 2012 PLoS.ONE 7 E36144 PubMedID: 22558360 Gene_locus related to this paper: ecoli-ycfp, ecoli-YFBB, ecoli-yqia, ecoli-Z1341 Abstract An Escherichia coli O157:H7 outbreak in China in 1999 caused 177 deaths due to hemolytic uremic syndrome. Sixteen outbreak associated isolates were found to belong to a new clone, sequence type 96 (ST96), based on multilocus sequence typing of 15 housekeeping genes. Whole genome sequencing of an outbreak isolate, Xuzhou21, showed that the isolate is phylogenetically closely related to the Japan 1996 outbreak isolate Sakai, both of which share the most recent common ancestor with the US outbreak isolate EDL933. The levels of IL-6 and IL-8 of peripheral blood mononuclear cells induced by Xuzhou21 and Sakai were significantly higher than that induced by EDL933. Xuzhou21 also induced a significantly higher level of IL-8 than Sakai while both induced similar levels of IL-6. The expression level of Shiga toxin 2 in Xuzhou21 induced by mitomycin C was 68.6 times of that under non-inducing conditions, twice of that induced in Sakai (32.7 times) and 15 times higher than that induced in EDL933 (4.5 times). Our study shows that ST96 is a novel clone and provided significant new insights into the evolution of virulence of E. coli O157:H7. Title: Crystal structure of a mono- and diacylglycerol lipase from Malassezia globosa reveals a novel lid conformation and insights into the substrate specificity Xu T, Liu L, Hou S, Xu J, Yang B, Wang Y, Liu J Ref: J Struct Biol, 178:363, 2012 : PubMed ESTHER: Xu_2012_J.Struct.Biol_178_363 PubMedSearch: Xu 2012 J.Struct.Biol 178 363 PubMedID: 22484238 Gene_locus related to this paper: malgo-a8puy1 Abstract Most lipases contain a lid domain to shield the hydrophobic binding site from the water environment. The lid, mostly in helical form, can undergo a conformational change to expose the active cleft during the interfacial activation. Here we report the crystal structures of Malassezia globosa LIP1 (SMG1) at 1.45 and 2.60 resolution in two crystal forms. The structures present SMG1 in its closed form, with a novel lid in loop conformation. SMG1 is one of the few members in the fungal lipase family that has been found to be strictly specific for mono- and diacylglycerol. To date, the mechanism for this substrate specificity remains largely unknown. To investigate the substrate binding properties, we built a model of SMG1 in open conformation. Based on this model, we found that the two bulky hydrophobic residues adjacent to the catalytic site and the N-terminal hinge region of the lid both may act as steric hindrances for triacylglycerols binding. These unique structural features of SMG1 will provide a better understanding on the substrate specificity of mono- and diacylglycerol lipases and a platform for further functional study of this enzyme. Title: Construction of the yeast whole-cell Rhizopus oryzae lipase biocatalyst with high activity Chen ML, Guo Q, Wang RZ, Xu J, Zhou CW, Ruan H, He GQ Ref: J Zhejiang Univ Sci B, 12:545, 2011 : PubMed ESTHER: Chen_2011_J.Zhejiang.Univ.Sci.B_12_545 PubMedSearch: Chen 2011 J.Zhejiang.Univ.Sci.B 12 545 PubMedID: 21726061 Abstract Surface display is effectively utilized to construct a whole-cell biocatalyst. Codon optimization has been proven to be effective in maximizing production of heterologous proteins in yeast. Here, the cDNA sequence of Rhizopus oryzae lipase (ROL) was optimized and synthesized according to the codon bias of Saccharomyces cerevisiae, and based on the Saccharomyces cerevisiae cell surface display system with alpha-agglutinin as an anchor, recombinant yeast displaying fully codon-optimized ROL with high activity was successfully constructed. Compared with the wild-type ROL-displaying yeast, the activity of the codon-optimized ROL yeast whole-cell biocatalyst (25 U/g dried cells) was 12.8-fold higher in a hydrolysis reaction using p-nitrophenyl palmitate (pNPP) as the substrate. To our knowledge, this was the fi rst attempt to combine the techniques of yeast surface display and codon optimization for whole-cell biocatalyst construction. Consequently, the yeast whole-cell ROL biocatalyst was constructed with high activity. The optimum pH and temperature for the yeast whole-cell ROL biocatalyst were pH 7.0 and 40 degrees C. Furthermore, this whole-cell biocatalyst was applied to the hydrolysis of tributyrin and the resulted conversion of butyric acid reached 96.91% after 144 h. Title: N-butyryl-homoserine lactone, a bacterial quorum-sensing signaling molecule, induces intracellular calcium elevation in Arabidopsis root cells Song S, Jia Z, Xu J, Zhang Z, Bian Z Ref: Biochemical & Biophysical Research Communications, 414:355, 2011 : PubMed ESTHER: Song_2011_Biochem.Biophys.Res.Commun_414_355 PubMedSearch: Song 2011 Biochem.Biophys.Res.Commun 414 355 PubMedID: 21964296 Abstract N-acyl-L-homoserine lactones (AHLs) are quorum sensing (QS) signal molecules that are commonly used in gram-negative bacteria. Recently, it has become evident that AHLs can influence the behavior of plant cells. However, little is known about the mechanism of the plants' response to these bacterial signals. Calcium ions (Ca(2+)), ubiquitous intracellular second messengers, play an essential role in numerous signal transduction pathways in plants. In this study, the cytosolic free Ca(2+) concentration ([Ca(2+)](cyt)) was measured by a luminometric method in the excised root cells of Arabidopsis plants that were treated with N-butyryl-homoserine lactone (C4-HSL). There was a transient and immediate increase in [Ca(2+)](cyt) levels, and the highest level (0.4 muM), approximately 2-fold higher than the basal level, was observed at the 6th second after the addition of 10 muM C4-HSL. Pretreatments with La(3+), verapamil or ethylene glycol tetraacetic acid (EGTA) inhibited the increase in [Ca(2+)](cyt) caused by C4-HSL, whereas it remained unaffected by pretreatment with Li(+), indicating that the Ca(2+) contributing to the increase in [Ca(2+)](cyt) was mobilized from the extracellular medium via the plasma membrane Ca(2+) channels but not from the intracellular Ca(2+) stores. Furthermore, electrophysiological approaches showed that the transmembrane Ca(2+) current was significantly increased with the addition of C4-HSL. Taken together, our observations suggest that C4-HSL may act as an elicitor from bacteria to plants and that Ca(2+) signaling participates in the ability of plant cells to sense the bacterial QS signals. Title: Synthesis and in vitro biological evaluation of carbonyl group-containing analogues for sigma1 receptors Wang W, Cui J, Lu X, Padakanti PK, Xu J, Parsons SM, Luedtke RR, Rath NP, Tu Z Ref: Journal of Medicinal Chemistry, 54:5362, 2011 : PubMed ESTHER: Wang_2011_J.Med.Chem_54_5362 PubMedSearch: Wang 2011 J.Med.Chem 54 5362 PubMedID: 21732626 Abstract To identify the ligands for sigma(1) receptors that are potent and selective, analogues of prezamicol and trozamicol scaffolds of carbonyl-containing vesicular acetylcholine transporter (VAChT) inhibitors were explored. Of the 23 analogues synthesized and tested, 5 displayed very high affinity for sigma(1) (K(i) = 0.48-4.05 nM) and high selectivity for sigma(1) relative to sigma(2) receptors (sigma(1)/sigma(2) selectivity of >749-fold). Four of the five compounds (14a, 14b, 14c, and 14e) showed very low affinity for VAChT (K(i) > 290 nM), and the fifth compound (14g) showed moderate affinity for VAChT (K(i) = 44.2 nM). The compound [1'-(4-fluorobenzyl)-3'-hydroxy[1,4']bipiperidinyl-4-yl]-(4-fluorophenyl)methanon e (14a) displayed very high affinity and selectivity for sigma(1) receptor (K(i) = 0.48 nM, sigma(1)/sigma(2) > 3600). All four of these most promising compounds (14a, 14b, 14c, and 14e) can be radiosynthesized with fluorine-18 or carbon-11, which will allow further evaluation of their properties as PET probes for imaging sigma(1) receptor in vivo. Title: Complete genome sequence of a Yersinia enterocolitica Old World (3/O:9) strain and comparison with the New World (1B/O:8) strain Wang X, Li Y, Jing H, Ren Y, Zhou Z, Wang S, Kan B, Xu J, Wang L Ref: J Clin Microbiol, 49:1251, 2011 : PubMed ESTHER: Wang_2011_J.Clin.Microbiol_49_1251 PubMedSearch: Wang 2011 J.Clin.Microbiol 49 1251 PubMedID: 21325549 Gene_locus related to this paper: yere8-menh, yere8-y3204, yeren-YqiA, yeren-k1bwy7 Abstract Yersinia enterocolitica is a heterogeneous bacterial species with a wide range of animal reservoirs through which human intestinal illness can be facilitated. In contrast to the epidemiological pattern observed in the United States, infections in China present a pattern similar to those in European countries and Japan, wherein "Old World" strains (biotypes 2 to 5) are prevalent. To gain insights into the evolution of Y. enterocolitica and pathogenic properties toward human hosts, we sequenced the genome of a biotype 3 strain, 105.5R(r) (O:9), obtained from a Chinese patient. Comparative genome sequence analysis with strain 8081 (1B/O:8) revealed new insights into Y. enterocolitica. Both strains have more than 14% specific genes. In strain 105.5R(r), putative virulence factors were found in strain-specific genomic pathogenicity islands that comprised a novel type III secretion system and rtx-like genes. Many of the loci representing ancestral clusters, which are believed to contribute to enteric survival and pathogenesis, are present in strain 105.5R(r) but lost in strain 8081. Insertion elements in 105.5R(r) have a pattern distinct from those in strain 8081 and were exclusively located in a strain-specific region. In summary, our comparative genome analysis indicates that these two strains may have attained their pathogenicity by completely separate evolutionary events, and the 105.5R(r) strain, a representative of the Old World biogroup, lies in a branch of Y. enterocolitica that is distinct from the "New World" 8081 strain. Title: The genome of the mesopolyploid crop species Brassica rapa Wang X, Wang H, Wang J, Sun R, Wu J, Liu S, Bai Y, Mun JH, Bancroft I and Zhang Z <88 more author(s)> Wang X, Wang H, Wang J, Sun R, Wu J, Liu S, Bai Y, Mun JH, Bancroft I, Cheng F, Huang S, Li X, Hua W, Freeling M, Pires JC, Paterson AH, Chalhoub B, Wang B, Hayward A, Sharpe AG, Park BS, Weisshaar B, Liu B, Li B, Tong C, Song C, Duran C, Peng C, Geng C, Koh C, Lin C, Edwards D, Mu D, Shen D, Soumpourou E, Li F, Fraser F, Conant G, Lassalle G, King GJ, Bonnema G, Tang H, Belcram H, Zhou H, Hirakawa H, Abe H, Guo H, Jin H, Parkin IA, Batley J, Kim JS, Just J, Li J, Xu J, Deng J, Kim JA, Yu J, Meng J, Min J, Poulain J, Hatakeyama K, Wu K, Wang L, Fang L, Trick M, Links MG, Zhao M, Jin M, Ramchiary N, Drou N, Berkman PJ, Cai Q, Huang Q, Li R, Tabata S, Cheng S, Zhang S, Sato S, Sun S, Kwon SJ, Choi SR, Lee TH, Fan W, Zhao X, Tan X, Xu X, Wang Y, Qiu Y, Yin Y, Li Y, Du Y, Liao Y, Lim Y, Narusaka Y, Wang Z, Li Z, Xiong Z, Zhang Z (- 88) Ref: Nat Genet, 43:1035, 2011 : PubMed ESTHER: Wang_2011_Nat.Genet_43_1035 PubMedSearch: Wang 2011 Nat.Genet 43 1035 PubMedID: 21873998 Gene_locus related to this paper: braol-Q8GTM3, braol-Q8GTM4, brarp-m4ei94, brarp-m4c988, brana-a0a078j4a9, brana-a0a078e1m0, brana-a0a078cd75, brarp-m4dwa6, brana-a0a078j4f0, brana-a0a078cus4, brana-a0a078f8c2, brana-a0a078jql1, brana-a0a078dgj3, brana-a0a078hw50, brana-a0a078cuu0, brana-a0a078dfa9, brana-a0a078ic91, brarp-m4ctw3, brana-a0a078ca65, brana-a0a078ctc8, brana-a0a078h021, brana-a0a078jx23, brarp-m4da84, brarp-m4dwr7, brana-a0a078dh94, brana-a0a078h612, brana-a0a078j2t3, braol-a0a0d3dpb2, braol-a0a0d3dx76, brana-a0a078jxa8, brana-a0a078i2k3, brarp-m4cwq4, brarp-m4dcj8, brarp-m4eh17, brarp-m4eey4, brarp-m4dnj8, brarp-m4ey83, brarp-m4ey84 Abstract We report the annotation and analysis of the draft genome sequence of Brassica rapa accession Chiifu-401-42, a Chinese cabbage. We modeled 41,174 protein coding genes in the B. rapa genome, which has undergone genome triplication. We used Arabidopsis thaliana as an outgroup for investigating the consequences of genome triplication, such as structural and functional evolution. The extent of gene loss (fractionation) among triplicated genome segments varies, with one of the three copies consistently retaining a disproportionately large fraction of the genes expected to have been present in its ancestor. Variation in the number of members of gene families present in the genome may contribute to the remarkable morphological plasticity of Brassica species. The B. rapa genome sequence provides an important resource for studying the evolution of polyploid genomes and underpins the genetic improvement of Brassica oil and vegetable crops. Title: Genome sequence and analysis of the tuber crop potato Xu X, Pan S, Cheng S, Zhang B, Mu D, Ni P, Zhang G, Yang S, Li R and Visser RG <87 more author(s)> Xu X, Pan S, Cheng S, Zhang B, Mu D, Ni P, Zhang G, Yang S, Li R, Wang J, Orjeda G, Guzman F, Torres M, Lozano R, Ponce O, Martinez D, De la Cruz G, Chakrabarti SK, Patil VU, Skryabin KG, Kuznetsov BB, Ravin NV, Kolganova TV, Beletsky AV, Mardanov AV, Di Genova A, Bolser DM, Martin DM, Li G, Yang Y, Kuang H, Hu Q, Xiong X, Bishop GJ, Sagredo B, Mejia N, Zagorski W, Gromadka R, Gawor J, Szczesny P, Huang S, Zhang Z, Liang C, He J, Li Y, He Y, Xu J, Zhang Y, Xie B, Du Y, Qu D, Bonierbale M, Ghislain M, Herrera Mdel R, Giuliano G, Pietrella M, Perrotta G, Facella P, O'Brien K, Feingold SE, Barreiro LE, Massa GA, Diambra L, Whitty BR, Vaillancourt B, Lin H, Massa AN, Geoffroy M, Lundback S, DellaPenna D, Buell CR, Sharma SK, Marshall DF, Waugh R, Bryan GJ, Destefanis M, Nagy I, Milbourne D, Thomson SJ, Fiers M, Jacobs JM, Nielsen KL, Sonderkaer M, Iovene M, Torres GA, Jiang J, Veilleux RE, Bachem CW, De Boer J, Borm T, Kloosterman B, van Eck H, Datema E, Hekkert B, Goverse A, van Ham RC, Visser RG (- 87) Ref: Nature, 475:189, 2011 : PubMed ESTHER: Xu_2011_Nature_475_189 PubMedSearch: Xu 2011 Nature 475 189 PubMedID: 21743474 Gene_locus related to this paper: soltu-q2tqv0, soltu-q4h433, soltu-m0zl00, soltu-m1aw23, soltu-m0zxh5, soltu-m1d3q4, soltu-m1bz14, soltu-m1d3q6, sollc-k4b1g3, soltu-m0zzn8, soltu-m1ba60, sollc-k4bf33, soltu-m1c8d8, soltu-m1ced9, soltu-m1a385, soltu-m1bz15, soltu-m1a7s9, soltu-m1bc84, soltu-m1bpd1, sollc-k4bm34, soltu-m1a487, soltu-m1a5u0, soltu-m1cjx7, soltu-m1bvq8, soltu-m1baq1, soltu-m1cfh4, soltu-m1azl4, soltu-m0ztj0, soltu-m1d6d0 Abstract Potato (Solanum tuberosum L.) is the world's most important non-grain food crop and is central to global food security. It is clonally propagated, highly heterozygous, autotetraploid, and suffers acute inbreeding depression. Here we use a homozygous doubled-monoploid potato clone to sequence and assemble 86% of the 844-megabase genome. We predict 39,031 protein-coding genes and present evidence for at least two genome duplication events indicative of a palaeopolyploid origin. As the first genome sequence of an asterid, the potato genome reveals 2,642 genes specific to this large angiosperm clade. We also sequenced a heterozygous diploid clone and show that gene presence/absence variants and other potentially deleterious mutations occur frequently and are a likely cause of inbreeding depression. Gene family expansion, tissue-specific expression and recruitment of genes to new pathways contributed to the evolution of tuber development. The potato genome sequence provides a platform for genetic improvement of this vital crop. Title: Altered activity-rest patterns in mice with a human autosomal-dominant nocturnal frontal lobe epilepsy mutation in the beta2 nicotinic receptor Xu J, Cohen BN, Zhu Y, Dziewczapolski G, Panda S, Lester HA, Heinemann SF, Contractor A Ref: Mol Psychiatry, 16:1048, 2011 : PubMed ESTHER: Xu_2011_Mol.Psychiatry_16_1048 PubMedSearch: Xu 2011 Mol.Psychiatry 16 1048 PubMedID: 20603624 Abstract High-affinity nicotinic receptors containing beta2 subunits (beta2*) are widely expressed in the brain, modulating many neuronal processes and contributing to neuropathologies such as Alzheimer's disease, Parkinson's disease and epilepsy. Mutations in both the alpha4 and beta2 subunits are associated with a rare partial epilepsy, autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE). In this study, we introduced one such human missense mutation into the mouse genome to generate a knock-in strain carrying a valine-to-leucine mutation beta2V287L. beta2(V287L) mice were viable and born at an expected Mendelian ratio. Surprisingly, mice did not show an overt seizure phenotype; however, homozygous mice did show significant alterations in their activity-rest patterns. This was manifest as an increase in activity during the light cycle suggestive of disturbances in the normal sleep patterns of mice; a parallel phenotype to that found in human ADNFLE patients. Consistent with the role of nicotinic receptors in reward pathways, we found that beta2(V287L) mice did not develop a normal proclivity to voluntary wheel running, a model for natural reward. Anxiety-related behaviors were also affected by the V287L mutation. Mutant mice spent more time in the open arms on the elevated plus maze suggesting that they had reduced levels of anxiety. Together, these findings emphasize several important roles of beta2* nicotinic receptors in complex biological processes including the activity-rest cycle, natural reward and anxiety. Title: Complete genome sequence of the plant pathogen Ralstonia solanacearum strain Po82 Xu J, Zheng HJ, Liu L, Pan ZC, Prior P, Tang B, Xu JS, Zhang H, Tian Q and Feng J <1 more author(s)> Xu J, Zheng HJ, Liu L, Pan ZC, Prior P, Tang B, Xu JS, Zhang H, Tian Q, Zhang LQ, Feng J (- 1) Ref: Journal of Bacteriology, 193:4261, 2011 : PubMed ESTHER: Xu_2011_J.Bacteriol_193_4261 PubMedSearch: Xu 2011 J.Bacteriol 193 4261 PubMedID: 21685279 Gene_locus related to this paper: ralso-PCAD, ralso-RSP1108, ralsl-y0kx85 Abstract Ralstonia solanacearum strain Po82, a phylotype IIB/sequevar 4 strain, was found to be pathogenic to both solanaceous plants and banana. Here, we report the complete genome sequence of Po82 and its comparison with seven published R. solanacearum genomes. Title: Genomic and proteomic analyses of the fungus Arthrobotrys oligospora provide insights into nematode-trap formation Yang J, Wang L, Ji X, Feng Y, Li X, Zou C, Xu J, Ren Y, Mi Q and Zhang KQ <16 more author(s)> Yang J, Wang L, Ji X, Feng Y, Li X, Zou C, Xu J, Ren Y, Mi Q, Wu J, Liu S, Liu Y, Huang X, Wang H, Niu X, Li J, Liang L, Luo Y, Ji K, Zhou W, Yu Z, Li G, Li L, Qiao M, Feng L, Zhang KQ (- 16) Ref: PLoS Pathog, 7:e1002179, 2011 : PubMed ESTHER: Yang_2011_PLoS.Pathog_7_E1002179 PubMedSearch: Yang 2011 PLoS.Pathog 7 E1002179 PubMedID: 21909256 Gene_locus related to this paper: artoa-g1wyr4, artoa-g1x1a7, artoa-g1x3f4, artoa-g1x3h6, artoa-g1x9s5, artoa-g1x9z4, artoa-g1xcb5, artoa-g1xhl6, artoa-g1xjb3, artoa-g1xjy0, artoa-g1xkw3, artoa-g1xnf2, artoa-g1xnf8, artoa-g1xqd4, artoa-g1xqt1, artoa-g1xte8, artoa-g1xu91, artoa-g1xv59, artoa-g1x382, artoa-g1x3q3, artoa-g1wxl5, artoa-g1xj75, artoa-g1xd25, artoa-g1wzu7, artoa-g1xt42, artoa-g1xhm8, artoa-g1wy43 Abstract Nematode-trapping fungi are "carnivorous" and attack their hosts using specialized trapping devices. The morphological development of these traps is the key indicator of their switch from saprophytic to predacious lifestyles. Here, the genome of the nematode-trapping fungus Arthrobotrys oligospora Fres. (ATCC24927) was reported. The genome contains 40.07 Mb assembled sequence with 11,479 predicted genes. Comparative analysis showed that A. oligospora shared many more genes with pathogenic fungi than with non-pathogenic fungi. Specifically, compared to several sequenced ascomycete fungi, the A. oligospora genome has a larger number of pathogenicity-related genes in the subtilisin, cellulase, cellobiohydrolase, and pectinesterase gene families. Searching against the pathogen-host interaction gene database identified 398 homologous genes involved in pathogenicity in other fungi. The analysis of repetitive sequences provided evidence for repeat-induced point mutations in A. oligospora. Proteomic and quantitative PCR (qPCR) analyses revealed that 90 genes were significantly up-regulated at the early stage of trap-formation by nematode extracts and most of these genes were involved in translation, amino acid metabolism, carbohydrate metabolism, cell wall and membrane biogenesis. Based on the combined genomic, proteomic and qPCR data, a model for the formation of nematode trapping device in this fungus was proposed. In this model, multiple fungal signal transduction pathways are activated by its nematode prey to further regulate downstream genes associated with diverse cellular processes such as energy metabolism, biosynthesis of the cell wall and adhesive proteins, cell division, glycerol accumulation and peroxisome biogenesis. This study will facilitate the identification of pathogenicity-related genes and provide a broad foundation for understanding the molecular and evolutionary mechanisms underlying fungi-nematodes interactions. Title: Enhanced production of longer side-chain polyhydroxyalkanoic acid with omega-aromatic group substitution in phaZ-disrupted Pseudomonas fluorescens BM07 mutant through unrelated carbon source cometabolism and salicylic acid beta-oxidation inhibition Choi MH, Xu J, Rho JK, Zhao XP, Yoon SC Ref: Bioresour Technol, 101:4540, 2010 : PubMed ESTHER: Choi_2010_Bioresour.Technol_101_4540 PubMedSearch: Choi 2010 Bioresour.Technol 101 4540 PubMedID: 20153638 Abstract The deletion of the intracellular polyhydroxyalkanoate (PHA) depolymerase gene (phaZ) in Pseudomonas fluorescens BM07 was found to increase more efficiently the levels of longer medium-chain-length (MCL) omega-aromatic monomer-units than in the wild-type strain when the cells were grown with a mixture of fructose and MCL omega-aromatic fatty acid in the presence of salicylic acid that is known as a beta-oxidation inhibitor in BM07 strain. When 11-phenoxyundecanoic acid was used as co-carbon source, the longest monomer-unit 3-hydroxy-11-phenoxyundecanoate, not reported in literature yet, was incorporated into the polymer chain up to approximately 10 mol%. An advantage of salicylic acid inhibition technique is that salicylic acid is not metabolized in BM07 strain, thus, the effective concentration of the inhibitor remaining constant throughout the cultivation. In conclusion, this new technique could be exploited for the enhanced production of side-chain modulated functional MCL-PHA with improved physicochemical properties in P. fluorescens BM07. Title: Genetic study of capsular switching between Neisseria meningitidis sequence type 7 serogroup A and C strains Wang Q, Shao Z, Wang X, Gao Y, Li M, Xu L, Xu J, Wang L Ref: Infect Immun, 78:3883, 2010 : PubMed ESTHER: Wang_2010_Infect.Immun_78_3883 PubMedSearch: Wang 2010 Infect.Immun 78 3883 PubMedID: 20624905 Gene_locus related to this paper: neime-r0tza2 Abstract Neisseria meningitidis is a leading cause of septicemia and meningitis worldwide. N. meningitidis capsular polysaccharides have been classified into 13 distinct serogroups which are defined by antibody reactivity and structural analysis, and the capsule plays an important role in virulence. Serogroups A, B, C, W135, and Y have been reported to be clinically important. Several newly identified serogroup C isolates belonging to the unique sequence type 7 (ST-7) were identified in China. Since most ST-7 isolates from China belonged to serogroup A, the newly identified ST-7 serogroup C strains were proposed to have arisen from those belonging to ST-7 serogroup A. In this study, six ST-7 serogroup C and three ST-7 serogroup A isolates were analyzed by pulsed-field gel electrophoresis to confirm their sequence type. In order to clarify the genetic basis of capsular switching between ST-7 serogroup A and C strains, the whole capsular gene clusters and surrounding genes of the two representative ST-7 strains belonging to serogroups A and C, respectively, were sequenced and compared. Potential recombination sites were analyzed using the RDP3 beta software, and recombination-related regions in two other ST-7 serogroup A and five ST-7 serogroup C strains were also sequenced and compared to the representative ST-7 serogroup A and C strain sequences. Title: Thrombospondin 1 accelerates synaptogenesis in hippocampal neurons through neuroligin 1 Xu J, Xiao N, Xia J Ref: Nat Neurosci, 13:22, 2010 : PubMed ESTHER: Xu_2010_Nat.Neurosci_13_22 PubMedSearch: Xu 2010 Nat.Neurosci 13 22 PubMedID: 19915562 Abstract In cultured rat hippocampal neurons, we found that thrombospondin 1 (TSP1) increased the speed of synapse formation in young neurons, but not the final density of synapses in mature neurons. TSP1 interacted with neuroligin 1 (NL1) and application of the NL1 extracellular domain blocked TSP1-induced synaptogenesis. Furthermore, knocking down endogenous NL1 inhibited TSP1's effect. Our results indicate that TSP1 accelerates the speed of synaptogenesis through NL1 in hippocampal neurons. Title: Emergence of a new multidrug-resistant serotype X variant in an epidemic clone of Shigella flexneri Ye C, Lan R, Xia S, Zhang J, Sun Q, Zhang S, Jing H, Wang L, Li Z and Xu J <11 more author(s)> Ye C, Lan R, Xia S, Zhang J, Sun Q, Zhang S, Jing H, Wang L, Li Z, Zhou Z, Zhao A, Cui Z, Cao J, Jin D, Huang L, Wang Y, Luo X, Bai X, Wang P, Xu Q, Xu J (- 11) Ref: J Clin Microbiol, 48:419, 2010 : PubMed ESTHER: Ye_2010_J.Clin.Microbiol_48_419 PubMedSearch: Ye 2010 J.Clin.Microbiol 48 419 PubMedID: 19955273 Gene_locus related to this paper: shifl-AES, shifl-BIOH, shifl-entf, shifl-FES, shifl-PLDB, shifl-PTRB, shifl-S2753, shifl-SF1808, shifl-SF3046, shifl-SF3908, shifl-yafa, shifl-YBFF, shifl-YCDJ, shifl-ycfp, shifl-YFBB, shifl-YHET, shifl-YJFP, shifl-YPFH, shiss-yqia Abstract Shigella spp. are the causative agent of shigellosis with Shigella flexneri serotype 2a being the most prevalent in developing countries. Epidemiological surveillance in China found that a new serotype of S. flexneri appeared in 2001 and replaced serotype 2a in 2003 as the most prevalent serotype in Henan Province. The new serotype also became the dominant serotype in 7 of the 10 other provinces under surveillance in China by 2007. The serotype was identified as a variant of serotype X. It differs from serotype X by agglutination to the monovalent anti-IV type antiserum and the group antigen-specific monoclonal antibody MASF IV-I. Genome sequencing of a serotype X variant isolate, 2002017, showed that it acquired a Shigella serotype conversion island, also as an SfX bacteriophage, containing gtr genes for type X-specific glucosylation. Multilocus sequence typing of 15 genes from 37 serotype X variant isolates and 69 isolates of eight other serotypes, 1a, 2a, 2b, 3a, 4a, 5b, X, and Y, found that all belong to a new sequence type (ST), ST91. Pulsed-field gel electrophoresis revealed 154 pulse types with 655 S. flexneri isolates analyzed and identified 57 serotype switching events. The data suggest that S. flexneri epidemics in China have been caused by a single epidemic clone, ST91, with frequent serotype switching to evade infection-induced immunity to serotypes to which the population was exposed previously. The clone has also acquired resistance to multiple antibiotics. These findings underscore the challenges to the current vaccine development and control strategies for shigellosis. Title: Derivation of Escherichia coli O157:H7 from its O55:H7 precursor Zhou Z, Li X, Liu B, Beutin L, Xu J, Ren Y, Feng L, Lan R, Reeves PR, Wang L Ref: PLoS ONE, 5:e8700, 2010 : PubMed ESTHER: Zhou_2010_PLoS.ONE_5_E8700 PubMedSearch: Zhou 2010 PLoS.ONE 5 E8700 PubMedID: 20090843 Gene_locus related to this paper: ecoli-Aes, ecoli-rutD, ecoli-bioh, ecoli-C0410, ecoli-dlhh, ecoli-entf, ecoli-fes, ecoli-mhpc, ecoli-pldb, ecoli-ptrb, ecoli-yafa, ecoli-yaim, ecoli-ybff, ecoli-ycfp, ecoli-ycjy, ecoli-yeiG, ecoli-YFBB, ecoli-yghX, ecoli-yhet, ecoli-yjfp, ecoli-YNBC, ecoli-ypfh, ecoli-yqia, ecoli-Z0347, ecoli-Z1930, ecoli-Z2445, ecoli-YfhR Abstract There are 29 E. coli genome sequences available, mostly related to studies of species diversity or mode of pathogenicity, including two genomes of the well-known O157:H7 clone. However, there have been no genome studies of closely related clones aimed at exposing the details of evolutionary change. Here we sequenced the genome of an O55:H7 strain, closely related to the major pathogenic O157:H7 clone, with published genome sequences, and undertook comparative genomic and proteomic analysis. We were able to allocate most differences between the genomes to individual mutations, recombination events, or lateral gene transfer events, in specific lineages. Major differences include a type II secretion system present only in the O55:H7 chromosome, fewer type III secretion system effectors in O55:H7, and 19 phage genomes or phagelike elements in O55:H7 compared to 23 in O157:H7, with only three common to both. Many other changes were found in both O55:H7 and O157:H7 lineages, but in general there has been more change in the O157:H7 lineages. For example, we found 50% more synonymous mutational substitutions in O157:H7 compared to O55:H7. The two strains also diverged at the proteomic level. Mutational synonymous SNPs were used to estimate a divergence time of 400 years using a new clock rate, in contrast to 14,000 to 70,000 years using the traditional clock rates. The same approaches were applied to three closely related extraintestinal pathogenic E. coli genomes, and similar levels of mutation and recombination were found. This study revealed for the first time the full range of events involved in the evolution of the O157:H7 clone from its O55:H7 ancestor, and suggested that O157:H7 arose quite recently. Our findings also suggest that E. coli has a much lower frequency of recombination relative to mutation than was observed in a comparable study of a Vibrio cholerae lineage. Title: Rapid evolution of virulence and drug resistance in the emerging zoonotic pathogen Streptococcus suis Holden MT, Hauser H, Sanders M, Ngo TH, Cherevach I, Cronin A, Goodhead I, Mungall K, Quail MA and Parkhill J <25 more author(s)> Holden MT, Hauser H, Sanders M, Ngo TH, Cherevach I, Cronin A, Goodhead I, Mungall K, Quail MA, Price C, Rabbinowitsch E, Sharp S, Croucher NJ, Chieu TB, Mai NT, Diep TS, Chinh NT, Kehoe M, Leigh JA, Ward PN, Dowson CG, Whatmore AM, Chanter N, Iversen P, Gottschalk M, Slater JD, Smith HE, Spratt BG, Xu J, Ye C, Bentley S, Barrell BG, Schultsz C, Maskell DJ, Parkhill J (- 25) Ref: PLoS ONE, 4:e6072, 2009 : PubMed ESTHER: Holden_2009_PLoS.ONE_4_E6072 PubMedSearch: Holden 2009 PLoS.ONE 4 E6072 PubMedID: 19603075 Gene_locus related to this paper: strsu-q302y4, strsy-a4vus4, strsy-a4vwf6 Abstract BACKGROUND: Streptococcus suis is a zoonotic pathogen that infects pigs and can occasionally cause serious infections in humans. S. suis infections occur sporadically in human Europe and North America, but a recent major outbreak has been described in China with high levels of mortality. The mechanisms of S. suis pathogenesis in humans and pigs are poorly understood. METHODOLOGY/PRINCIPAL FINDINGS: The sequencing of whole genomes of S. suis isolates provides opportunities to investigate the genetic basis of infection. Here we describe whole genome sequences of three S. suis strains from the same lineage: one from European pigs, and two from human cases from China and Vietnam. Comparative genomic analysis was used to investigate the variability of these strains. S. suis is phylogenetically distinct from other Streptococcus species for which genome sequences are currently available. Accordingly, approximately 40% of the approximately 2 Mb genome is unique in comparison to other Streptococcus species. Finer genomic comparisons within the species showed a high level of sequence conservation; virtually all of the genome is common to the S. suis strains. The only exceptions are three approximately 90 kb regions, present in the two isolates from humans, composed of integrative conjugative elements and transposons. Carried in these regions are coding sequences associated with drug resistance. In addition, small-scale sequence variation has generated pseudogenes in putative virulence and colonization factors. CONCLUSIONS/SIGNIFICANCE: The genomic inventories of genetically related S. suis strains, isolated from distinct hosts and diseases, exhibit high levels of conservation. However, the genomes provide evidence that horizontal gene transfer has contributed to the evolution of drug resistance. Title: Genetic and epigenetic inactivation of LPL gene in human prostate cancer Kim JW, Cheng Y, Liu W, Li T, Yegnasubramanian S, Zheng SL, Xu J, Isaacs WB, Chang BL Ref: International Journal of Cancer, 124:734, 2009 : PubMed ESTHER: Kim_2009_Int.J.Cancer_124_734 PubMedSearch: Kim 2009 Int.J.Cancer 124 734 PubMedID: 19004026 Abstract Lipoprotein lipase (LPL) is in chromosome 8p22, site of one of the most common somatic deletions in prostate tumors. Additionally, a CpG island (CGI) was identified in the LPL promoter region. To test the hypothesis that LPL is a tumor suppressor gene, which is inactivated by somatic deletion and hypermethylation in prostate cancer, we evaluated somatic DNA deletion and methylation status at LPL in 56 pairs of DNA samples isolated from prostate cancer tissues and matching normal controls and 11 prostate cell lines. We found that the DNA in 21 of 56 primary cancers (38%) was methylated in the LPL promoter CGI, whereas no methylation was detected in any normal samples. In addition, we found a hemizygous deletion at LPL in 38 of the 56 tumors (68%). When the results of deletion and methylation were considered together, we found LPL promoter CGI methylation occurred in 45% of LPL deleted tumors and in 22% of LPL retained tumors. Within several clinical characteristics tested, the preoperative PSA levels were found to be significantly higher in subjects with LPL promoter CGI methylation compared with subjects without LPL promoter methylation (p=0.0012). Additionally, demethylation of the LPL promoter CGI was accompanied by transcriptional reactivation of LPL in the prostate cancer cell lines DU145 and PC3. In summary, we report a novel finding that the LPL gene is commonly methylated in prostate tumors, and our results suggest that biallelic inactivation of LPL by chromosomal deletion and promoter hypermethylation may play a role in human prostate cancer. Title: An unannotated alpha/beta hydrolase superfamily member, ABHD6 differentially expressed among cancer cell lines Li F, Fei X, Xu J, Ji C Ref: Mol Biol Rep, 36:691, 2009 : PubMed ESTHER: Li_2009_Mol.Biol.Rep_36_691 PubMedSearch: Li 2009 Mol.Biol.Rep 36 691 PubMedID: 18360779 Gene_locus related to this paper: human-ABHD6 Abstract Abhydrolase domain containing (Abhd) gene was a small group belongs to alpha/beta hydrolase superfamily. Known members of this group are all found to be involved in important biochemical processes and related to various diseases. In this paper, we report the tissue distribution, subcellular location and differential distribution among cancer cell lines of Abhd6, one unannotated member of this group. Title: Novel features of the polysaccharide-digesting gliding bacterium Flavobacterium johnsoniae as revealed by genome sequence analysis McBride MJ, Xie G, Martens EC, Lapidus A, Henrissat B, Rhodes RG, Goltsman E, Wang W, Xu J and Stein JL <4 more author(s)> McBride MJ, Xie G, Martens EC, Lapidus A, Henrissat B, Rhodes RG, Goltsman E, Wang W, Xu J, Hunnicutt DW, Staroscik AM, Hoover TR, Cheng YQ, Stein JL (- 4) Ref: Applied Environmental Microbiology, 75:6864, 2009 : PubMed ESTHER: McBride_2009_Appl.Environ.Microbiol_75_6864 PubMedSearch: McBride 2009 Appl.Environ.Microbiol 75 6864 PubMedID: 19717629 Gene_locus related to this paper: flaj1-a5fb12, flaj1-a5fmd7, flaj1-a5fns3 Abstract The 6.10-Mb genome sequence of the aerobic chitin-digesting gliding bacterium Flavobacterium johnsoniae (phylum Bacteroidetes) is presented. F. johnsoniae is a model organism for studies of bacteroidete gliding motility, gene regulation, and biochemistry. The mechanism of F. johnsoniae gliding is novel, and genome analysis confirms that it does not involve well-studied motility organelles, such as flagella or type IV pili. The motility machinery is composed of Gld proteins in the cell envelope that are thought to comprise the "motor" and SprB, which is thought to function as a cell surface adhesin that is propelled by the motor. Analysis of the genome identified genes related to sprB that may encode alternative adhesins used for movement over different surfaces. Comparative genome analysis revealed that some of the gld and spr genes are found in nongliding bacteroidetes and may encode components of a novel protein secretion system. F. johnsoniae digests proteins, and 125 predicted peptidases were identified. F. johnsoniae also digests numerous polysaccharides, and 138 glycoside hydrolases, 9 polysaccharide lyases, and 17 carbohydrate esterases were predicted. The unexpected ability of F. johnsoniae to digest hemicelluloses, such as xylans, mannans, and xyloglucans, was predicted based on the genome analysis and confirmed experimentally. Numerous predicted cell surface proteins related to Bacteroides thetaiotaomicron SusC and SusD, which are likely involved in binding of oligosaccharides and transport across the outer membrane, were also identified. Genes required for synthesis of the novel outer membrane flexirubin pigments were identified by a combination of genome analysis and genetic experiments. Genes predicted to encode components of a multienzyme nonribosomal peptide synthetase were identified, as were novel aspects of gene regulation. The availability of techniques for genetic manipulation allows rapid exploration of the features identified for the polysaccharide-digesting gliding bacteroidete F. johnsoniae. Title: Synthesis and in vitro and in vivo evaluation of 18F-labeled positron emission tomography (PET) ligands for imaging the vesicular acetylcholine transporter Tu Z, Efange SM, Xu J, Li S, Jones LA, Parsons SM, Mach RH Ref: Journal of Medicinal Chemistry, 52:1358, 2009 : PubMed ESTHER: Tu_2009_J.Med.Chem_52_1358 PubMedSearch: Tu 2009 J.Med.Chem 52 1358 PubMedID: 19203271 Abstract A new class of vesicular acetylcholine transporter inhibitor that incorporates a carbonyl group into the benzovesamicol structure was synthesized, and analogues were evaluated in vitro. (+/-)-trans-2-Hydroxy-3-(4-(4-[(18)F]fluorobenzoyl)piperidino)tetralin (9e) has K(i) values of 2.70 nM for VAChT, 191 nM for sigma(1), and 251 nM for sigma(2). The racemic precursor (9d) was resolved via chiral HPLC, and (+/-)-[(18)F]9e, (-)-[(18)F]9e, and (+)-[(18)F]9e were respectively radiolabeled via microwave irradiation of the appropriate precursors with [(18)F]/F(-) and Kryptofix/K(2)CO(3) in DMSO with radiochemical yields of approximately 50-60% and specific activities of >2000 mCi/micromol. (-)-[(18)F]9e uptake in rat brain was consistent with in vivo selectivity for the VAChT with an initial uptake of 0.911 %ID/g in rat striatum and a striatum/cerebellum ratio of 1.88 at 30 min postinjection (p.i.). MicroPET imaging of macaques demonstrated a 2.1 ratio of (-)-[(18)F]9e in putamen versus cerebellum at 2 h p.i. (-)-[(18)F]9e has potential to be a PET tracer for clinical imaging of the VAChT. Title: Procyanidins extracted from the lotus seedpod ameliorate scopolamine-induced memory impairment in mice Xu J, Rong S, Xie B, Sun Z, Zhang L, Wu H, Yao P, Zhang Y, Liu L Ref: Phytother Res, 23:1742, 2009 : PubMed ESTHER: Xu_2009_Phytother.Res_23_1742 PubMedSearch: Xu 2009 Phytother.Res 23 1742 PubMedID: 19367674 Abstract The major purpose of this study was to determine the effect of procyanidins extracted from the lotus seedpod (LSPC) on the learning and memory impairments induced by scopolamine (1 mg/kg, i.p.) in mice. The capacities of memory and learning were evaluated by the Morris water maze and the step-down avoidance test. LSPC (50, 100, 150 mg/kg BW, p.o.) significantly reversed scopolamine-induced learning and memory impairments in the Morris water maze test, as evaluated by shortened escape latency and swimming distance. In the step-down avoidance test, LSPC (50, 100, 150 mg/kg BW, p.o.) treatment significantly reduced the number of errors and shortened latency compared with that of scopolamine. In addition, LSPC was also found to inhibit acetyl cholinesterase (AChE) activity. These results of this study suggest that LSPC may play a useful role in the treatment of cognitive impairment caused by AD and aging. Title: Rejuvenation of antioxidant and cholinergic systems contributes to the effect of procyanidins extracted from the lotus seedpod ameliorating memory impairment in cognitively impaired aged rats Xu J, Rong S, Xie B, Sun Z, Zhang L, Wu H, Yao P, Zhang X, Zhang Y, Liu L Ref: European Neuropsychopharmacology, 19:851, 2009 : PubMed ESTHER: Xu_2009_Eur.Neuropsychopharmacol_19_851 PubMedSearch: Xu 2009 Eur.Neuropsychopharmacol 19 851 PubMedID: 19716273 Abstract The major purpose of this study was to determine the effect of procyanidins extracted from the lotus seedpod (LSPC) on the learning and memory impairments in cognitively impaired aged rats. Based on Morris water maze performance compared with young female rats, aged unimpaired (AU) and aged impaired (AI) rats were chosen from aged female rats. LSPC supplementation (50, 100 mg/kg BW, p.o.) for 7 weeks significantly improved learning and memory impairments in AI animals in the Morris water maze test, as evaluated by shortened escape latency and swimming distance. Aged rats had significantly declined antioxidant defense capacities and significantly increased lipid peroxidation and protein oxidation levels in hippocampus and cerebral cortex than young rats. Further, AI group had higher protein oxidation level compared with AU group. LSPC (50, 100 mg/kg BW, p.o.) significantly reversed the decline of antioxidant defense capacities and significantly reduced lipid peroxidation and protein oxidation levels in hippocampus and cerebral cortex of AI rats. In addition, LSPC significantly restored acetylcholine (ACh) contents and acetylcholinesterase (AChE) activities in hippocampus and cerebral cortex of AI animals. The results of this study suggest that LSPC may play a useful role in the treatment of cognitive impairment caused by Alzheimer's disease and aging. Title: Clinical, experimental, and genomic differences between intermediately pathogenic, highly pathogenic, and epidemic Streptococcus suis Ye C, Zheng H, Zhang J, Jing H, Wang L, Xiong Y, Wang W, Zhou Z, Sun Q and Xu J <3 more author(s)> Ye C, Zheng H, Zhang J, Jing H, Wang L, Xiong Y, Wang W, Zhou Z, Sun Q, Luo X, Du H, Gottschalk M, Xu J (- 3) Ref: J Infect Dis, 199:97, 2009 : PubMed ESTHER: Ye_2009_J.Infect.Dis_199_97 PubMedSearch: Ye 2009 J.Infect.Dis 199 97 PubMedID: 19016627 Gene_locus related to this paper: strsu-a4vws4, strsu-q673u2, strsy-a4vus4 Abstract BACKGROUND: Streptococcus suis emerged to cause an unusual outbreak of streptococcal toxic-shock-like syndrome (STSLS) in 2005. The mechanisms involved are unknown. METHODS: Clinical, laboratory, and epidemiologic data on patients infected with culture-confirmed S. suis were analyzed. The strain involved in the outbreak, "epidemic" strain ST7, was compared with both a classical highly pathogenic strain, ST1, and an intermediately pathogenic strain, ST25, to determine both its capacity to induce cytokines in experimentally infected mice and its genomic difference. RESULTS: Of 38 patients infected with culture-confirmed S. suis, 14 presented with STSLS. During the early phase of the disease, serum levels of interleukin (IL)-1beta, IL-6, IL-8, IL-12p70, interferon-gamma, and tumor necrosis factor-alpha were more elevated in patients with STSLS than in those with meningitis only. Serum levels of proinflammatory cytokines were significantly higher in mice infected with ST7 than in those infected with either ST1 or ST25. Genomic comparisons with ST25 showed that ST1 had acquired 132 genomic islands, including 5 pathogenicity islands, and that ST7, the epidemic strain, had acquired an additional 5 genomic islands. CONCLUSION: Intermediately pathogenic strain ST25 has evolved to become highly pathogenic strain ST1, which, in turn, has more recently evolved to become epidemic strain ST7. ST7 has the ability to stimulate the production of massive amounts of proinflammatory cytokines, leading to STSLS. Title: Spatial variation of Yersinia pestis from Yunnan Province of China Zhang Z, Hai R, Song Z, Xia L, Liang Y, Cai H, Shen X, Zhang E, Xu J and Yu XJ <1 more author(s)> Zhang Z, Hai R, Song Z, Xia L, Liang Y, Cai H, Shen X, Zhang E, Xu J, Yu D, Yu XJ (- 1) Ref: American Journal of Tropical Medicine & Hygiene, 81:714, 2009 : PubMed ESTHER: Zhang_2009_Am.J.Trop.Med.Hyg_81_714 PubMedSearch: Zhang 2009 Am.J.Trop.Med.Hyg 81 714 PubMedID: 19815893 Gene_locus related to this paper: yerpe-BIOH, yerpe-dlhh, yerpe-PIP, yerpe-PLDB, yerpe-PTRB, yerpe-Y0507, yerpe-y1616, yerpe-y3224, yerpe-YPLA, yerpe-YPO0180, yerpe-YPO0667, yerpe-YPO0773, yerpe-YPO0986, yerpe-YPO1501, yerpe-YPO2526, yerpe-YPO2814 Abstract Yunnan Province of China is considered the site of origin for modern plague. We analyzed the genotypes of eight Yersinia pestis strains isolated from three counties in Yunnan Province by pulse field gel electrophoresis (PFGE). PFGE showed that strains isolated from the same site were identical regardless of hosts or year of isolation. However, Y. pestis strains isolated from geographically distinct loci were genetically divergent. Whole genome sequences of two strains from two foci in Yunnan showed that the genetic variation of Y. pestis strains was caused by genome rearrangement. We concluded that Y. pestis strains in each epidemic focus in Yunnan were a clonal population and selected by host environments. The genomic variability of the Y. pestis strains from different foci were caused by genome rearrangement, which may provide a positive selective advantage for Y. pestis to adapt to its host environments. Title: Fluoroolefins as amide bond mimics in dipeptidyl peptidase IV inhibitors Edmondson SD, Wei L, Xu J, Shang J, Xu S, Pang J, Chaudhary A, Dean DC, He H and Weber AE <8 more author(s)> Edmondson SD, Wei L, Xu J, Shang J, Xu S, Pang J, Chaudhary A, Dean DC, He H, Leiting B, Lyons KA, Patel RA, Patel SB, Scapin G, Wu JK, Beconi MG, Thornberry NA, Weber AE (- 8) Ref: Bioorganic & Medicinal Chemistry Lett, 18:2409, 2008 : PubMed ESTHER: Edmondson_2008_Bioorg.Med.Chem.Lett_18_2409 PubMedSearch: Edmondson 2008 Bioorg.Med.Chem.Lett 18 2409 PubMedID: 18331795 Gene_locus related to this paper: human-DPP4 Inhibitor(s) related to this paper: Flouroolefin-1, Flouroolefin-2 Abstract The synthesis, selectivity, rat pharmacokinetic profile, and drug metabolism profiles of a series of potent fluoroolefin-derived DPP-4 inhibitors (4) are reported. A radiolabeled fluoroolefin 33 was shown to possess a high propensity to form reactive metabolites, thus revealing a potential liability for this class of DPP-4 inhibitors. Title: Characterization of ST-4821 complex, a unique Neisseria meningitidis clone Peng J, Yang L, Yang F, Yang J, Yan Y, Nie H, Zhang X, Xiong Z, Jiang Y and Jin Q <9 more author(s)> Peng J, Yang L, Yang F, Yang J, Yan Y, Nie H, Zhang X, Xiong Z, Jiang Y, Cheng F, Xu X, Chen S, Sun L, Li W, Shen Y, Shao Z, Liang X, Xu J, Jin Q (- 9) Ref: Genomics, 91:78, 2008 : PubMed ESTHER: Peng_2008_Genomics_91_78 PubMedSearch: Peng 2008 Genomics 91 78 PubMedID: 18031983 Gene_locus related to this paper: neigo-pip, neima-metx, neimb-q9k0t9, neime-ESD, neime-NMA2216, neime-NMB0276, neime-NMB1877 Abstract Ten outbreaks of a new serogroup C meningococcal disease emerged during 2003-2005 in China. The multilocus sequence typing results indicated that unique sequence type 4821 clone meningococci were responsible for these outbreaks. Herein, we determined the entire genomic DNA sequence of serogroup C isolate 053442, which belongs to ST-4821. Comparison of 053442 gene contents with other meningococcal genomes shows that they have similar characteristics, including thousands of repetitive elements and simple sequence repeats, numerous phase-variable genes, and similar virulence-related factors. However, many strain-specific regions were found in each genome. We also present the results of a genomic comparison of 28 ST-4821 complex isolates that were isolated from different serogroups using comparative genomic hybridization analysis. Genome comparison between the newly emerged hyperinvasive isolates belonging to different serogroups will further our understanding of their respective pathogenetic mechanisms. Title: Isolation and expression of a Malassezia globosa lipase gene, LIP1 Deangelis YM, Saunders CW, Johnstone KR, Reeder NL, Coleman CG, Kaczvinsky JR, Jr., Gale C, Walter R, Mekel M and Dawson TL, Jr. <9 more author(s)> Deangelis YM, Saunders CW, Johnstone KR, Reeder NL, Coleman CG, Kaczvinsky JR, Jr., Gale C, Walter R, Mekel M, Lacey MP, Keough TW, Fieno A, Grant RA, Begley B, Sun Y, Fuentes G, Youngquist RS, Xu J, Dawson TL, Jr. (- 9) Ref: Journal of Investigative Dermatology, 127:2138, 2007 : PubMed ESTHER: DeAngelis_2007_J.Invest.Dermatol_127_2138 PubMedSearch: DeAngelis 2007 J.Invest.Dermatol 127 2138 PubMedID: 17460728 Gene_locus related to this paper: malgo-a8puy1 Abstract Dandruff and seborrheic dermatitis (D/SD) are common hyperproliferative scalp disorders with a similar etiology. Both result, in part, from metabolic activity of Malassezia globosa and Malassezia restricta, commensal basidiomycete yeasts commonly found on human scalps. Current hypotheses about the mechanism of D/SD include Malassezia-induced fatty acid metabolism, particularly lipase-mediated breakdown of sebaceous lipids and release of irritating free fatty acids. We report that lipase activity was detected in four species of Malassezia, including M. globosa. We isolated lipase activity by washing M. globosa cells. The isolated lipase was active against diolein, but not triolein. In contrast, intact cells showed lipase activity against both substrates, suggesting the presence of at least another lipase. The diglyceride-hydrolyzing lipase was purified from the extract, and much of its sequence was determined by peptide sequencing. The corresponding lipase gene (LIP1) was cloned and sequenced. Confirmation that LIP1 encoded a functional lipase was obtained using a covalent lipase inhibitor. LIP1 was differentially expressed in vitro. Expression was detected on three out of five human scalps, as indicated by reverse transcription-PCR. This is the first step in a molecular description of lipid metabolism on the scalp, ultimately leading toward a test of its role in D/SD etiology. Title: Triazolopiperazine-amides as dipeptidyl peptidase IV inhibitors: close analogs of JANUVIA (sitagliptin phosphate) Kim D, Kowalchick JE, Edmondson SD, Mastracchio A, Xu J, Eiermann GJ, Leiting B, Wu JK, Pryor KD and Weber AE <4 more author(s)> Kim D, Kowalchick JE, Edmondson SD, Mastracchio A, Xu J, Eiermann GJ, Leiting B, Wu JK, Pryor KD, Patel RA, He H, Lyons KA, Thornberry NA, Weber AE (- 4) Ref: Bioorganic & Medicinal Chemistry Lett, 17:3373, 2007 : PubMed ESTHER: Kim_2007_Bioorg.Med.Chem.Lett_17_3373 PubMedSearch: Kim 2007 Bioorg.Med.Chem.Lett 17 3373 PubMedID: 17434732 Abstract A series of beta-aminoamides bearing triazolopiperazines has been prepared and evaluated as potent, selective, orally active dipeptidyl peptidase IV (DPP-4) inhibitors. Efforts at optimization of the beta-aminoamide series, which ultimately led to the discovery of JANUVIA (sitagliptin phosphate, compound 1), are described. Title: Dandruff-associated Malassezia genomes reveal convergent and divergent virulence traits shared with plant and human fungal pathogens Xu J, Saunders CW, Hu P, Grant RA, Boekhout T, Kuramae EE, Kronstad JW, Deangelis YM, Reeder NL and Dawson TL, Jr. <11 more author(s)> Xu J, Saunders CW, Hu P, Grant RA, Boekhout T, Kuramae EE, Kronstad JW, Deangelis YM, Reeder NL, Johnstone KR, Leland M, Fieno AM, Begley WM, Sun Y, Lacey MP, Chaudhary T, Keough T, Chu L, Sears R, Yuan B, Dawson TL, Jr. (- 11) Ref: Proc Natl Acad Sci U S A, 104:18730, 2007 : PubMed ESTHER: Xu_2007_Proc.Natl.Acad.Sci.U.S.A_104_18730 PubMedSearch: Xu 2007 Proc.Natl.Acad.Sci.U.S.A 104 18730 PubMedID: 18000048 Gene_locus related to this paper: malgo-a8puy5, malgo-a8puy1, malgo-a8pvh8, malgo-a8pwh6, malgo-a8pwm2, malgo-a8pwr6, malgo-a8px35, malgo-a8pzh3, malgo-a8q1i5, malgo-a8q4e6, malgo-a8q7d0, malgo-a8q8v5, malgo-a8q9m3, malgo-a8q9n0, malgo-a8q902, malgo-a8qcr1, malgo-a8qcv4, malgo-a8qcv7, malgo-a8qcw4, malgo-a8qdf0 Abstract Fungi in the genus Malassezia are ubiquitous skin residents of humans and other warm-blooded animals. Malassezia are involved in disorders including dandruff and seborrheic dermatitis, which together affect >50% of humans. Despite the importance of Malassezia in common skin diseases, remarkably little is known at the molecular level. We describe the genome, secretory proteome, and expression of selected genes of Malassezia globosa. Further, we report a comparative survey of the genome and secretory proteome of Malassezia restricta, a close relative implicated in similar skin disorders. Adaptation to the skin environment and associated pathogenicity may be due to unique metabolic limitations and capabilities. For example, the lipid dependence of M. globosa can be explained by the apparent absence of a fatty acid synthase gene. The inability to synthesize fatty acids may be complemented by the presence of multiple secreted lipases to aid in harvesting host lipids. In addition, an abundance of genes encoding secreted hydrolases (e.g., lipases, phospholipases, aspartyl proteases, and acid sphingomyelinases) was found in the M. globosa genome. In contrast, the phylogenetically closely related plant pathogen Ustilago maydis encodes a different arsenal of extracellular hydrolases with more copies of glycosyl hydrolase genes. M. globosa shares a similar arsenal of extracellular hydrolases with the phylogenetically distant human pathogen, Candida albicans, which occupies a similar niche, indicating the importance of host-specific adaptation. The M. globosa genome sequence also revealed the presence of mating-type genes, providing an indication that Malassezia may be capable of sex. Title: Evolution of symbiotic bacteria in the distal human intestine Xu J, Mahowald MA, Ley RE, Lozupone CA, Hamady M, Martens EC, Henrissat B, Coutinho PM, Minx P and Gordon JI <9 more author(s)> Xu J, Mahowald MA, Ley RE, Lozupone CA, Hamady M, Martens EC, Henrissat B, Coutinho PM, Minx P, Latreille P, Cordum H, Van Brunt A, Kim K, Fulton RS, Fulton LA, Clifton SW, Wilson RK, Knight RD, Gordon JI (- 9) Ref: PLoS Biol, 5:e156, 2007 : PubMed ESTHER: Xu_2007_PLoS.Biol_5_e156 PubMedSearch: Xu 2007 PLoS.Biol 5 e156 PubMedID: 17579514 Gene_locus related to this paper: 9bace-b6w170, 9bace-c6z6f2, 9bace-e1z049, 9porp-c7xbp3, 9porp-c7xci2, 9porp-c7xdx2, bacv8-a6kwf6, bacv8-a6kzc1, bacv8-a6kze8, bacv8-a6l0d9, bacv8-a6l1d0, bacv8-a6l1u9, bacv8-a6l7p9, bacv8-a6l7w1, bacv8-a6l018, bacv8-a6l378, bacv8-a6l415, bacv8-a6l715, pard8-a6lc23, pard8-a6lca7, pard8-a6ld87, pard8-a6le10, pard8-a6le63, pard8-a6lfj2, pard8-a6lgh2, pard8-a6lgi6, pard8-a6lgn7, pard8-a6lhe1, pard8-a6li91, bacv8-a6l3w9 Abstract The adult human intestine contains trillions of bacteria, representing hundreds of species and thousands of subspecies. Little is known about the selective pressures that have shaped and are shaping this community's component species, which are dominated by members of the Bacteroidetes and Firmicutes divisions. To examine how the intestinal environment affects microbial genome evolution, we have sequenced the genomes of two members of the normal distal human gut microbiota, Bacteroides vulgatus and Bacteroides distasonis, and by comparison with the few other sequenced gut and non-gut Bacteroidetes, analyzed their niche and habitat adaptations. The results show that lateral gene transfer, mobile elements, and gene amplification have played important roles in affecting the ability of gut-dwelling Bacteroidetes to vary their cell surface, sense their environment, and harvest nutrient resources present in the distal intestine. Our findings show that these processes have been a driving force in the adaptation of Bacteroidetes to the distal gut environment, and emphasize the importance of considering the evolution of humans from an additional perspective, namely the evolution of our microbiomes. Title: Identification of genes subject to positive selection in uropathogenic strains of Escherichia coli: a comparative genomics approach Chen SL, Hung CS, Xu J, Reigstad CS, Magrini V, Sabo A, Blasiar D, Bieri T, Meyer RR and Gordon JI <8 more author(s)> Chen SL, Hung CS, Xu J, Reigstad CS, Magrini V, Sabo A, Blasiar D, Bieri T, Meyer RR, Ozersky P, Armstrong JR, Fulton RS, Latreille JP, Spieth J, Hooton TM, Mardis ER, Hultgren SJ, Gordon JI (- 8) Ref: Proc Natl Acad Sci U S A, 103:5977, 2006 : PubMed ESTHER: Chen_2006_Proc.Natl.Acad.Sci.U.S.A_103_5977 PubMedSearch: Chen 2006 Proc.Natl.Acad.Sci.U.S.A 103 5977 PubMedID: 16585510 Gene_locus related to this paper: ecoli-Aes, ecoli-rutD, ecoli-bioh, ecoli-C0410, ecoli-C2429, ecoli-C2451, ecoli-C4836, ecoli-dlhh, ecoli-entf, ecoli-fes, ecoli-IROD, ecoli-IROE, ecoli-pldb, ecoli-ptrb, ecoli-yafa, ecoli-yaim, ecoli-ybff, ecoli-ycfp, ecoli-ycjy, ecoli-yeiG, ecoli-YFBB, ecoli-yghX, ecoli-yhet, ecoli-yiel, ecoli-yjfp, ecoli-YNBC, ecoli-ypfh, ecoli-ypt1, ecoli-yqia, ecoli-YfhR, ecout-q1r7l6, yerpe-YBTT Abstract Escherichia coli is a model laboratory bacterium, a species that is widely distributed in the environment, as well as a mutualist and pathogen in its human hosts. As such, E. coli represents an attractive organism to study how environment impacts microbial genome structure and function. Uropathogenic E. coli (UPEC) must adapt to life in several microbial communities in the human body, and has a complex life cycle in the bladder when it causes acute or recurrent urinary tract infection (UTI). Several studies designed to identify virulence factors have focused on genes that are uniquely represented in UPEC strains, whereas the role of genes that are common to all E. coli has received much less attention. Here we describe the complete 5,065,741-bp genome sequence of a UPEC strain recovered from a patient with an acute bladder infection and compare it with six other finished E. coli genome sequences. We searched 3,470 ortholog sets for genes that are under positive selection only in UPEC strains. Our maximum likelihood-based analysis yielded 29 genes involved in various aspects of cell surface structure, DNA metabolism, nutrient acquisition, and UTI. These results were validated by resequencing a subset of the 29 genes in a panel of 50 urinary, periurethral, and rectal E. coli isolates from patients with UTI. These studies outline a computational approach that may be broadly applicable for studying strain-specific adaptation and pathogenesis in other bacteria. Title: The complete genome sequence of a chronic atrophic gastritis Helicobacter pylori strain: evolution during disease progression Oh JD, Kling-Backhed H, Giannakis M, Xu J, Fulton RS, Fulton LA, Cordum HS, Wang C, Elliott G and Gordon JI <3 more author(s)> Oh JD, Kling-Backhed H, Giannakis M, Xu J, Fulton RS, Fulton LA, Cordum HS, Wang C, Elliott G, Edwards J, Mardis ER, Engstrand LG, Gordon JI (- 3) Ref: Proc Natl Acad Sci U S A, 103:9999, 2006 : PubMed ESTHER: Oh_2006_Proc.Natl.Acad.Sci.U.S.A_103_9999 PubMedSearch: Oh 2006 Proc.Natl.Acad.Sci.U.S.A 103 9999 PubMedID: 16788065 Gene_locus related to this paper: helpy-o25061 Abstract Helicobacter pylori produces acute superficial gastritis in nearly all of its human hosts. However, a subset of individuals develops chronic atrophic gastritis (ChAG), a condition characterized in part by diminished numbers of acid-producing parietal cells and increased risk for development of gastric adenocarcinoma. Previously, we used a gnotobiotic transgenic mouse model with an engineered ablation of parietal cells to show that loss of parietal cells provides an opportunity for a H. pylori isolate from a patient with ChAG (HPAG1) to bind to, enter, and persist within gastric stem cells. This finding raises the question of how ChAG influences H. pylori genome evolution, physiology, and tumorigenesis. Here we describe the 1,596,366-bp HPAG1 genome. Custom HPAG1 Affymetrix GeneChips, representing 99.6% of its predicted ORFs, were used for whole-genome genotyping of additional H. pylori ChAG isolates obtained from Swedish patients enrolled in a case-control study of gastric cancer, as well as ChAG- and cancer-associated isolates from an individual who progressed from ChAG to gastric adenocarcinoma. The results reveal a shared gene signature among ChAG strains, as well as genes that may have been lost or gained during progression to adenocarcinoma. Whole-genome transcriptional profiling of HPAG1's response to acid during in vitro growth indicates that genes encoding components of metal uptake and utilization pathways, outer membrane proteins, and virulence factors are among those associated with H. pylori's adaptation to ChAG. Title: A mediator-free screen-printed amperometric biosensor for screening of organophosphorus pesticides with flow-injection analysis (FIA) system Shi M, Xu J, Zhang S, Liu B, Kong J Ref: Talanta, 68:1089, 2006 : PubMed ESTHER: Shi_2006_Talanta_68_1089 PubMedSearch: Shi 2006 Talanta 68 1089 PubMedID: 18970436 Abstract A mediator-free amperometric biosensor for screening organophosphorus pesticides (OPs) in flow-injection analysis (FIA) system based on anticholinesterase activity of OPs to immobilized acetylcholinesterase enzyme (AChE) has been developed. The enzyme biosensor is prepared by entrapping AChE in Al(2)O(3) sol-gel matrix screen-printed on an integrated 3-electrode plastic chip. This strategy is found not only increase the stability of the embedded AChE, but also effectively catalyze the oxidative reaction of thiocholine, making the Al(2)O(3)-AChE biosensor detects the substrate at 0.25V (versus Ag/AgCl), hundreds mini-volt lower than other reported mediator-free ones. The Al(2)O(3)-AChE biosensor is thus coupled to FIA system to build up a simple and low-cost FIA-EC system for screening OPs in real samples. A wide linear inhibition response for dichlorvos, typical OP, is observed in the range of 0.1-80muM, corresponding to 7.91-84.94% inhibition for AChE. The detection limit for dichlorvos is achieved at 10nM in the simulated seawater for 15min inhibiting time, which allows the biosensor quantitatively detects the ecotoxicological effect of the real samples from the seaports in eastern China, where the OPs pollution is confirmed by GC-MS. Title: Peptidolipid as binding site of acetylcholinesterase: molecular recognition of paraoxon in Langmuir films Wang C, Li C, Ji X, Orbulescu J, Xu J, Leblanc RM Ref: Langmuir, 22:2200, 2006 : PubMed ESTHER: Wang_2006_Langmuir_22_2200 PubMedSearch: Wang 2006 Langmuir 22 2200 PubMedID: 16489807 Abstract Peptidolipid C18H35O (stearoyl)-Phe-Trp-Ser-His-Glu (peptidolipid A) was synthesized and spread at the air-water interface to study the interaction with an organophosphorus compound. Paraoxon, sodium dihydrogen phosphate, or 4-nitrophenyl phosphate disodium was added to the subphase, but only paraoxon changed the surface pressure-area (pi-A) isotherm of peptidolipid A. This indicated a specific interaction between paraoxon and peptidolipid A. To clarify which amino acid residue of peptidolipid A was responsible for the interaction, peptidolipid B, namely, C18H35O-Gly-His-Ser-Glu-Glu, was synthesized and studied as a Langmuir film. The difference between the pi-A isotherms of peptidolipid B in the absence and presence of paraoxon in the subphase was minimal; consequently, the presence of amino acids phenylalanine (Phe) and tryptophan (Trp) in peptidolipid A may explain the interaction between peptidolipid A and paraoxon. The compression-decompression cycles and kinetic studies of peptidolipid A showed that the Langmuir film was stable. The in situ optical properties of the peptidolipid A Langmuir film such as UV-vis and fluorescence spectroscopies were examined to elucidate the interaction between peptidolipid A and paraoxon. UV-vis absorption of peptidolipid A was investigated in the presence and absence of paraoxon in the subphase. The emission maximum of fluorescence of Trp in peptidolipid A was observed at 351 nm on pure water, and the band intensity decreased when the concentration of paraoxon increased in the subphase. This suggested that the Trp was involved in the molecular recognition process. Epifluorescence micrographs showed domains of peptidolipid A on the pure water subphase. In the presence of paraoxon in the subphase, the Langmuir film of peptidolipid A showed a homogeneity, which was another indication of the recognition between paraoxon and peptidolipid A. Title: Identification of sequence motifs that target neuronal nicotinic receptors to dendrites and axons Xu J, Zhu Y, Heinemann SF Ref: Journal of Neuroscience, 26:9780, 2006 : PubMed ESTHER: Xu_2006_J.Neurosci_26_9780 PubMedSearch: Xu 2006 J.Neurosci 26 9780 PubMedID: 16988049 Abstract Neuronal nicotinic acetylcholine receptors (nAChRs) belong to a family of ligand-gated ion channels that play important roles in central and peripheral nervous systems. The subcellular distribution of neuronal nAChRs has important implications for function and is not well understood. Here, we analyzed the targeting of two major types of neuronal nAChRs by expressing epitope-tagged subunits in cultured hippocampal neurons. Surprisingly, the alpha7 nAChR (alpha7) and alpha4/beta2 nAChR (alpha4beta2) displayed distinct patterns of expression, with alpha7 targeted preferentially to the somatodendritic compartments, whereas alpha4beta2 was localized to both axonal and dendritic domains. When fused to CD4 or IL2RA (interleukin 2 receptor alpha subunit) proteins, which are normally distributed ubiquitously, the M3-M4 intracellular loop from the alpha7 subunit promoted dendritic expression, whereas the homologous M3-M4 loop from the alpha4 subunit led to surface axonal expression. Systemic screening and alanine substitution further identified a 25-residue leucine motif ([DE]XXXL[LI]) containing an axonal targeting sequence within the alpha4 loop and a 48-residue dileucine and tyrosine motif (YXXO) containing a dendritic targeting sequence from the alpha7 loop. These results provide valuable information in understanding diverse roles of neuronal nAChRs in mediating and modulating synaptic transmission, synaptic plasticity, and nicotine addiction. Title: Discovery of potent, selective, and orally bioavailable pyridone-based dipeptidyl peptidase-4 inhibitors Xu J, Wei L, Mathvink R, Edmondson SD, Mastracchio A, Eiermann GJ, He H, Leone JF, Leiting B and Weber AE <6 more author(s)> Xu J, Wei L, Mathvink R, Edmondson SD, Mastracchio A, Eiermann GJ, He H, Leone JF, Leiting B, Lyons KA, Marsilio F, Patel RA, Petrov A, Wu JK, Thornberry NA, Weber AE (- 6) Ref: Bioorganic & Medicinal Chemistry Lett, 16:1346, 2006 : PubMed ESTHER: Xu_2006_Bioorg.Med.Chem.Lett_16_1346 PubMedSearch: Xu 2006 Bioorg.Med.Chem.Lett 16 1346 PubMedID: 16332437 Abstract anti-Substituted beta-methylphenylalanine derived amides have been shown to be potent DPP-IV inhibitors exhibiting excellent selectivity over both DPP8 and DPP9. The optimized compound exhibited good pharmacokinetic profiles in three preclinical species. Title: Discovery of potent, selective, and orally bioavailable oxadiazole-based dipeptidyl peptidase IV inhibitors Xu J, Wei L, Mathvink RJ, Edmondson SD, Eiermann GJ, He H, Leone JF, Leiting B, Lyons KA and Weber AE <7 more author(s)> Xu J, Wei L, Mathvink RJ, Edmondson SD, Eiermann GJ, He H, Leone JF, Leiting B, Lyons KA, Marsilio F, Patel RA, Patel SB, Petrov A, Scapin G, Wu JK, Thornberry NA, Weber AE (- 7) Ref: Bioorganic & Medicinal Chemistry Lett, 16:5373, 2006 : PubMed ESTHER: Xu_2006_Bioorg.Med.Chem.Lett_16_5373 PubMedSearch: Xu 2006 Bioorg.Med.Chem.Lett 16 5373 PubMedID: 16919457 Gene_locus related to this paper: human-DPP4 Inhibitor(s) related to this paper: 3TP Abstract A novel series of oxadiazole based amides have been shown to be potent DPP-4 inhibitors. The optimized compound 43 exhibited excellent selectivity over a variety of DPP-4 homologs. Title: Brain activity in cigarette smokers performing a working memory task: effect of smoking abstinence Xu J, Mendrek A, Cohen MS, Monterosso J, Rodriguez P, Simon SL, Brody A, Jarvik M, Domier CP and London ED <2 more author(s)> Xu J, Mendrek A, Cohen MS, Monterosso J, Rodriguez P, Simon SL, Brody A, Jarvik M, Domier CP, Olmstead R, Ernst M, London ED (- 2) Ref: Biological Psychiatry, 58:143, 2005 : PubMed ESTHER: Xu_2005_Biol.Psychiatry_58_143 PubMedSearch: Xu 2005 Biol.Psychiatry 58 143 PubMedID: 16038685 Abstract BACKGROUND: When nicotine-dependent human subjects abstain from cigarette smoking, they exhibit deficits in working memory. An understanding of the neural substrates of such impairments may help to understand how nicotine affects cognition. Our aim, therefore, was to identify abnormalities in the circuitry that mediates working memory in nicotine-dependent subjects after they initiate abstinence from smoking. Title: Discovery of potent and selective phenylalanine based dipeptidyl peptidase IV inhibitors Xu J, Wei L, Mathvink R, He J, Park YJ, He H, Leiting B, Lyons KA, Marsilio F and Weber AE <3 more author(s)> Xu J, Wei L, Mathvink R, He J, Park YJ, He H, Leiting B, Lyons KA, Marsilio F, Patel RA, Wu JK, Thornberry NA, Weber AE (- 3) Ref: Bioorganic & Medicinal Chemistry Lett, 15:2533, 2005 : PubMed ESTHER: Xu_2005_Bioorg.Med.Chem.Lett_15_2533 PubMedSearch: Xu 2005 Bioorg.Med.Chem.Lett 15 2533 PubMedID: 15863311 Abstract anti-Substituted beta-methylphenylalanine derived amides have been shown to be potent DPP-IV inhibitors exhibiting excellent selectivity over both DPP8 and DPP9. These are among the most potent compounds reported to date lacking an electrophilic trap. The most potent compound among these is 5-oxo-1,2,4-oxadiazole 44, which is a 3 nM DPP-IV inhibitor. Title: Genome dynamics and diversity of Shigella species, the etiologic agents of bacillary dysentery Yang F, Yang J, Zhang X, Chen L, Jiang Y, Yan Y, Tang X, Wang J, Xiong Z and Jin Q <17 more author(s)> Yang F, Yang J, Zhang X, Chen L, Jiang Y, Yan Y, Tang X, Wang J, Xiong Z, Dong J, Xue Y, Zhu Y, Xu X, Sun L, Chen S, Nie H, Peng J, Xu J, Wang Y, Yuan Z, Wen Y, Yao Z, Shen Y, Qiang B, Hou Y, Yu J, Jin Q (- 17) Ref: Nucleic Acids Research, 33:6445, 2005 : PubMed ESTHER: Yang_2005_Nucleic.Acids.Res_33_6445 PubMedSearch: Yang 2005 Nucleic.Acids.Res 33 6445 PubMedID: 16275786 Gene_locus related to this paper: ecoli-yeiG, shidy-IROD, shidy-q67dv1, shifl-AES, shifl-BIOH, shifl-entf, shifl-FES, shifl-PLDB, shifl-PTRB, shifl-S2753, shifl-SF1334, shifl-SF1808, shifl-SF3046, shifl-SF3908, shifl-yafa, shifl-YBFF, shifl-YCDJ, shifl-ycfp, shifl-YCJY, shifl-YFBB, shifl-YHET, shifl-YJFP, shifl-YPFH, shiss-yaim, shiss-yeiG, shiss-yqia Abstract The Shigella bacteria cause bacillary dysentery, which remains a significant threat to public health. The genus status and species classification appear no longer valid, as compelling evidence indicates that Shigella, as well as enteroinvasive Escherichia coli, are derived from multiple origins of E.coli and form a single pathovar. Nevertheless, Shigella dysenteriae serotype 1 causes deadly epidemics but Shigella boydii is restricted to the Indian subcontinent, while Shigella flexneri and Shigella sonnei are prevalent in developing and developed countries respectively. To begin to explain these distinctive epidemiological and pathological features at the genome level, we have carried out comparative genomics on four representative strains. Each of the Shigella genomes includes a virulence plasmid that encodes conserved primary virulence determinants. The Shigella chromosomes share most of their genes with that of E.coli K12 strain MG1655, but each has over 200 pseudogenes, 300 approximately 700 copies of insertion sequence (IS) elements, and numerous deletions, insertions, translocations and inversions. There is extensive diversity of putative virulence genes, mostly acquired via bacteriophage-mediated lateral gene transfer. Hence, via convergent evolution involving gain and loss of functions, through bacteriophage-mediated gene acquisition, IS-mediated DNA rearrangements and formation of pseudogenes, the Shigella spp. became highly specific human pathogens with variable epidemiological and pathological features. Title: The Genomes of Oryza sativa: a history of duplications Yu J, Wang J, Lin W, Li S, Li H, Zhou J, Ni P, Dong W, Hu S and Yang H <88 more author(s)> Yu J, Wang J, Lin W, Li S, Li H, Zhou J, Ni P, Dong W, Hu S, Zeng C, Zhang J, Zhang Y, Li R, Xu Z, Li X, Zheng H, Cong L, Lin L, Yin J, Geng J, Li G, Shi J, Liu J, Lv H, Li J, Deng Y, Ran L, Shi X, Wang X, Wu Q, Li C, Ren X, Li D, Liu D, Zhang X, Ji Z, Zhao W, Sun Y, Zhang Z, Bao J, Han Y, Dong L, Ji J, Chen P, Wu S, Xiao Y, Bu D, Tan J, Yang L, Ye C, Xu J, Zhou Y, Yu Y, Zhang B, Zhuang S, Wei H, Liu B, Lei M, Yu H, Li Y, Xu H, Wei S, He X, Fang L, Huang X, Su Z, Tong W, Tong Z, Ye J, Wang L, Lei T, Chen C, Chen H, Huang H, Zhang F, Li N, Zhao C, Huang Y, Li L, Xi Y, Qi Q, Li W, Hu W, Tian X, Jiao Y, Liang X, Jin J, Gao L, Zheng W, Hao B, Liu S, Wang W, Yuan L, Cao M, McDermott J, Samudrala R, Wong GK, Yang H (- 88) Ref: PLoS Biol, 3:e38, 2005 : PubMed ESTHER: Yu_2005_PLoS.Biol_3_e38 PubMedSearch: Yu 2005 PLoS.Biol 3 e38 PubMedID: 15685292 Gene_locus related to this paper: orysa-Q7XTC5, orysa-Q852M6, orysa-Q8GSE8, orysa-Q9S7P1, orysa-Q9FYP7, orysa-Q5ZBH3, orysa-Q5ZA26, orysa-Q5JLP6, orysa-Q8H5P9, orysa-Q8H5P5, orysa-Q7F1Y5, orysa-Q949C9, orysa-cbp1, orysa-cbp3, orysa-cbpx, orysa-Q33B71, orysa-Q8GSJ3, orysa-LPL1, orysa-Q6YSZ8, orysa-Q8S5X5, orysa-Q8LIG3, orysa-Q6K7F5, orysa-Q7F1B1, orysa-Q8H4S9, orysa-Q69UB1, orysa-Q9FW17, orysa-Q337C3, orysa-Q7F959, orysa-Q84QZ6, orysa-Q84QY7, orysa-Q851E3, orysa-Q6YTH5, orysa-Q0JK71, orysa-Q8S1D9, orysa-Q5N8V4, orysa-Q0JCY4, orysa-Q8GTK2, orysa-B9EWJ8, orysa-Q8H3K6, orysa-Q6ZDG8, orysa-Q6ZDG6, orysa-Q6ZDG5, orysa-Q6ZDG4, orysa-Q5NAI4, orysa-Q658B2, orysa-Q5JMQ8, orysa-Q5QMD9, orysa-Q5N7L1, orysa-Q8RYV9, orysa-Q8H3R3, orysa-Q5SNH3, orysa-Q8W0F0, orysa-pir7a, orysa-pir7b, orysa-q2qlm4, orysa-q2qm78, orysa-q2qm82, orysa-q2qn31, orysa-q2qnj4, orysa-q2qnt9, orysa-q2qur1, orysa-q2qx94, orysa-q2qyi1, orysa-q2qyj1, orysa-q2r051, orysa-q2r077, orysa-q2ram0, orysa-q2rat1, orysa-q2rbb3, orysa-Q4VWY7, orysa-q5na00, orysa-q5nbu1, orysa-Q5QLC0, orysa-q5smv5, orysa-Q5VP27, orysa-q5vrt2, orysa-q5w6c5, orysa-q5z5a3, orysa-q5z9i2, orysa-q5z417, orysa-q5z901, orysa-Q5ZAM8, orysa-Q5ZBI5, orysa-Q5ZCR3, orysa-q6atz0, orysa-q6ave2, orysa-q6f358, orysa-q6h6s1, orysa-q6h7i6, orysa-q6i5q3, orysa-q6i5u7, orysa-q6j657, orysa-q6k3d9, orysa-q6k4q2, orysa-q6k880, orysa-q6l5b6, orysa-Q6L5F5, orysa-q6l556, orysj-q6yse8, orysa-q6yy42, orysa-q6yzk1, orysa-q6z8b1, orysa-q6z995, orysa-q6zc62, orysa-q6zia4, orysa-q6zjq6, orysa-q7x7y5, orysa-Q7XC50, orysa-q7xej4, orysa-q7xem8, orysa-q7xkj9, orysa-q7xr62, orysa-q7xr63, orysa-q7xr64, orysa-q7xsg1, orysa-q7xsq2, orysa-q7xts6, orysa-q7xv53, orysa-Q7XVB5, orysa-Q8L562, orysa-Q8LQS5, orysa-Q8RZ40, orysa-Q8RZ79, orysa-Q8S0U8, orysa-Q8S0V0, orysa-Q8S125, orysa-Q8SAY7, orysa-Q8SAY9, orysa-Q8W3C6, orysa-Q8W3F2, orysa-Q8W3F4, orysa-Q8W3F6, orysa-Q9LHX5, orysa-q33aq0, orysa-q53lh1, orysa-q53m20, orysa-q53nd8, orysa-q60e79, orysa-q60ew8, orysa-q67iz2, orysa-q67iz3, orysa-q67iz7, orysa-q67iz8, orysa-q67j02, orysa-q67j05, orysa-q67j07, orysa-q67j09, orysa-q67j10, orysa-q67tr6, orysa-q67tv0, orysa-q67uz1, orysa-q67v34, orysa-q67wz5, orysa-q69j38, orysa-q69k08, orysa-q69md7, orysa-q69me0, orysa-q69pf3, orysa-q69ti3, orysa-q69xr2, orysa-q69y12, orysa-q69y21, orysa-q75hy2, orysa-q75i01, orysa-Q94JD7, orysa-Q0J0A4, orysa-q651a8, orysa-q651z3, orysa-q652g4, orysa-q688m0, orysa-q688m8, orysa-q688m9, orysa-Q6H8G1, orysi-a2wn01, orysi-a2xc83, orysi-a2yh83, orysi-a2z179, orysi-a2zef2, orysi-b8a7e6, orysi-b8a7e7, orysi-b8bfe5, orysi-b8bhp9, orysj-a3b9l8, orysj-b9eub8, orysj-b9eya5, orysj-b9fi05, orysj-b9fkb0, orysj-b9fn42, orysj-b9gbb7, orysj-cgep, orysj-PLA7, orysj-q0d4u5, orysj-q0djj0, orysj-q0jaf0, orysj-q5jl22, orysj-q5jlw7, orysj-q5z419, orysj-q6h7q9, orysj-q6yvk6, orysj-q6z6i1, orysj-q7f8x1, orysj-q7xcx3, orysj-q9fwm6, orysj-q10j20, orysj-q10ss2, orysj-q69uw6, orysj-q94d71, orysj-q338c0, orysi-b8bly4, orysj-b9gbs4, orysi-a2zb88, orysj-b9gbs1, orysi-b8b698, orysj-pla4, orysj-pla1 Abstract We report improved whole-genome shotgun sequences for the genomes of indica and japonica rice, both with multimegabase contiguity, or almost 1,000-fold improvement over the drafts of 2002. Tested against a nonredundant collection of 19,079 full-length cDNAs, 97.7% of the genes are aligned, without fragmentation, to the mapped super-scaffolds of one or the other genome. We introduce a gene identification procedure for plants that does not rely on similarity to known genes to remove erroneous predictions resulting from transposable elements. Using the available EST data to adjust for residual errors in the predictions, the estimated gene count is at least 38,000-40,000. Only 2%-3% of the genes are unique to any one subspecies, comparable to the amount of sequence that might still be missing. Despite this lack of variation in gene content, there is enormous variation in the intergenic regions. At least a quarter of the two sequences could not be aligned, and where they could be aligned, single nucleotide polymorphism (SNP) rates varied from as little as 3.0 SNP/kb in the coding regions to 27.6 SNP/kb in the transposable elements. A more inclusive new approach for analyzing duplication history is introduced here. It reveals an ancient whole-genome duplication, a recent segmental duplication on Chromosomes 11 and 12, and massive ongoing individual gene duplications. We find 18 distinct pairs of duplicated segments that cover 65.7% of the genome; 17 of these pairs date back to a common time before the divergence of the grasses. More important, ongoing individual gene duplications provide a never-ending source of raw material for gene genesis and are major contributors to the differences between members of the grass family. Title: Brain-specific deletion of neuropathy target esterase/swisscheese results in neurodegeneration Akassoglou K, Malester B, Xu J, Tessarollo L, Rosenbluth J, Chao MV Ref: Proc Natl Acad Sci U S A, 101:5075, 2004 : PubMed ESTHER: Akassoglou_2004_Proc.Natl.Acad.Sci.U.S.A_101_5075 PubMedSearch: Akassoglou 2004 Proc.Natl.Acad.Sci.U.S.A 101 5075 PubMedID: 15051870 Abstract Neuropathy target esterase (NTE) is a neuronal membrane protein originally identified for its property to be modified by organo-phosphates (OPs), which in humans cause neuropathy characterized by axonal degeneration. Drosophila mutants for the homolog gene of NTE, swisscheese (sws), indicated a possible involvement of sws in the regulation of axon-glial cell interaction during glial wrapping. However, the role of NTE/sws in mammalian brain pathophysiology remains unknown. To investigate NTE function in vivo, we used the cre/loxP site-specific recombination strategy to generate mice with a specific deletion of NTE in neuronal tissues. Here we show that loss of NTE leads to prominent neuronal pathology in the hippocampus and thalamus and also defects in the cerebellum. Absence of NTE resulted in disruption of the endoplasmic reticulum, vacuolation of nerve cell bodies, and abnormal reticular aggregates. Thus, these results identify a physiological role for NTE in the nervous system and indicate that a loss-of-function mechanism may contribute to neurodegenerative diseases characterized by vacuolation and neuronal loss. Title: Cryopreservation of organotypic brain spheroid cultures Purcell WM, Atterwill CK, Xu J Ref: Altern Lab Anim, 31:563, 2003 : PubMed ESTHER: Purcell_2003_Altern.Lab.Anim_31_563 PubMedSearch: Purcell 2003 Altern.Lab.Anim 31 563 PubMedID: 15560746 Abstract The cryopreservation of hen and rat brain spheroids was investigated. Brain spheroid cultures were prepared from 7-day-old hen embryos or 16-day-old rat embryos, by using a rotation-mediated culture system. The spheroids were cryopreserved in medium containing 5-15% dimethyl sulphoxide (DMSO) and stored in liquid nitrogen, by using a two-stage cooling procedure. The results show that the viability, as indicated by the total protein content of hen embryo brain spheroids at 24 hours, and at 3, 7 and 28 days after thawing, ranged from 45.5% to 64.2% of control values. It took 3 days for the post-thaw brain spheroids to stabilise, as indicated by their morphology and selected neural markers of functionality. These functions were maintained over a 28-day observation period. Spheroids cultured for 12-15 days in vitro before cryopreservation survived better than those that were cryopreserved after 5-7 days in vitro. The viability and biochemical functionality of spheroids after long-term (up to 6 months) storage were similar to those following short-term storage. The viability of rat brain spheroids cryopreserved in 15% DMSO, as indicated by total protein content, at 24 hours, and at 3 or 7 days after thawing, ranged from 23.1% to 32.1% of control values. This study shows for the first time that brain spheroids prepared from primary tissue can be successfully cryopreserved. Title: A genomic view of the human-Bacteroides thetaiotaomicron symbiosis Xu J, Bjursell MK, Himrod J, Deng S, Carmichael LK, Chiang HC, Hooper LV, Gordon JI Ref: Science, 299:2074, 2003 : PubMed ESTHER: Xu_2003_Science_299_2074 PubMedSearch: Xu 2003 Science 299 2074 PubMedID: 12663928 Gene_locus related to this paper: bacth-BT1008, bacth-BT1087, bacth-BT1121, bacth-BT1192, bacth-BT1400, bacth-BT1838, bacth-BT2436, bacth-BT3100, bacth-BT4214, bactn-BT0152, bactn-BT0587, bactn-BT1114, bactn-BT1261, bactn-BT2379, bactn-BT2525, bactn-BT3084, bactn-BT3112, bactn-BT3254, bactn-BT3286, bactn-BT3608, bactn-BT4077, bactn-BT4193, bactn-q8a7t0 Abstract The human gut is colonized with a vast community of indigenous microorganisms that help shape our biology. Here, we present the complete genome sequence of the Gram-negative anaerobe Bacteroides thetaiotaomicron, a dominant member of our normal distal intestinal microbiota. Its 4779-member proteome includes an elaborate apparatus for acquiring and hydrolyzing otherwise indigestible dietary polysaccharides and an associated environment-sensing system consisting of a large repertoire of extracytoplasmic function sigma factors and one- and two-component signal transduction systems. These and other expanded paralogous groups shed light on the molecular mechanisms underlying symbiotic host-bacterial relationships in our intestine. Title: Genome sequence of Shigella flexneri 2a: insights into pathogenicity through comparison with genomes of Escherichia coli K12 and O157 Jin Q, Yuan Z, Xu J, Wang Y, Shen Y, Lu W, Wang J, Liu H, Yang J and Yu J <23 more author(s)> Jin Q, Yuan Z, Xu J, Wang Y, Shen Y, Lu W, Wang J, Liu H, Yang J, Yang F, Zhang X, Zhang J, Yang G, Wu H, Qu D, Dong J, Sun L, Xue Y, Zhao A, Gao Y, Zhu J, Kan B, Ding K, Chen S, Cheng H, Yao Z, He B, Chen R, Ma D, Qiang B, Wen Y, Hou Y, Yu J (- 23) Ref: Nucleic Acids Research, 30:4432, 2002 : PubMed ESTHER: Jin_2002_Nucleic.Acids.Res_30_4432 PubMedSearch: Jin 2002 Nucleic.Acids.Res 30 4432 PubMedID: 12384590 Gene_locus related to this paper: ecoli-Aes, ecoli-yafa, ecoli-ycfp, ecoli-yqia, ecoli-YfhR, shifl-AES, shifl-BIOH, shifl-entf, shifl-FES, shifl-PLDB, shifl-PTRB, shifl-SF1334, shifl-SF1808, shifl-SF3046, shifl-SF3908, shifl-yafa, shifl-YBFF, shifl-YCDJ, shifl-YCJY, shifl-YFBB, shifl-YHET, shifl-YIEL, shifl-YJFP, shifl-YPFH Abstract We have sequenced the genome of Shigella flexneri serotype 2a, the most prevalent species and serotype that causes bacillary dysentery or shigellosis in man. The whole genome is composed of a 4 607 203 bp chromosome and a 221 618 bp virulence plasmid, designated pCP301. While the plasmid shows minor divergence from that sequenced in serotype 5a, striking characteristics of the chromosome have been revealed. The S.flexneri chromosome has, astonishingly, 314 IS elements, more than 7-fold over those possessed by its close relatives, the non-pathogenic K12 strain and enterohemorrhagic O157:H7 strain of Escherichia coli. There are 13 translocations and inversions compared with the E.coli sequences, all involve a segment larger than 5 kb, and most are associated with deletions or acquired DNA sequences, of which several are likely to be bacteriophage-transmitted pathogenicity islands. Furthermore, S.flexneri, resembling another human-restricted enteric pathogen, Salmonella typhi, also has hundreds of pseudogenes compared with the E.coli strains. All of these could be subjected to investigations towards novel preventative and treatment strategies against shigellosis. Title: Multistep expression and assembly of neuronal nicotinic receptors is both host-cell- and receptor-subtype-dependent Sweileh W, Wenberg K, Xu J, Forsayeth J, Hardy S, Loring RH Ref: Brain Research Mol Brain Res, 75:293, 2000 : PubMed ESTHER: Sweileh_2000_Brain.Res.Mol.Brain.Res_75_293 PubMedSearch: Sweileh 2000 Brain.Res.Mol.Brain.Res 75 293 PubMedID: 10686351 Abstract We tested the hypothesis that the folding, assembly and insertion of neuronal nicotinic receptors are critically dependent on the host cell line. We used recombinant adenoviruses encoding either the rat alpha7, alpha4 or beta2 subunits in which expression of the subunit is controlled by a tetracycline-dependent promoter to screen five cell lines (GH4C1, SH-EP1, CV1, SN-56, and CHO-CAR). All five lines do not express detectable nicotinic receptor but do express receptor for human adenovirus, and all expressed mRNA for alpha7, alpha4 and beta2 subunits when infected with viruses. Each cell line expressed varying levels of alpha4beta2 receptors that bound [3H]cytisine, but only the GH4C1 and SH-EP1 cell lines expressed either surface or internal alpha7 receptors that bound [125I]alpha-bungarotoxin ([125I]alpha-BGT). All five cell lines expressed a 60 kDa protein immunoblotted by anti-alpha7 antibodies when infected with the alpha7 virus, presumably representing unassembled alpha7 subunits. In addition, GH4C1 cells expressed over 10-fold more surface alpha7 receptor than SH-EP1 cells, even though the total alpha7 receptor in the two cell lines was similar. Sedimentation experiments indicate that SH-EP1 cells only partially assemble alpha7 receptors compared with GH4C1 cells and control alpha7 from rat brain. These data suggest that not only is surface alpha7 receptor expression a multistep process, but that each step may involve cell-specific assembly factors. Title: [Effect of 13 cholinergic antagonists on M-cholinergic receptors in rat hearts] Shen SY, Xu J, Jin GZ Ref: Acta Pharmacol Sin, 6:158, 1985 : PubMed ESTHER: Shen_1985_Zhongguo.Yao.Li.Xue.Bao_6_158 PubMedSearch: Shen 1985 Zhongguo.Yao.Li.Xue.Bao 6 158 PubMedID: 2943116 Title: [Comparison of effects of M-cholinergic compounds on M-acetylcholine receptors in the rat cortex, parotid gland and longitudinal muscle from the small intestine of the guinea pig] Yu AY, Jin GZ, Xu J, Yu LP, Li JH Ref: Sheng Li Xue Bao, 37:282, 1985 : PubMed ESTHER: Yu_1985_Sheng.Li.Xue.Bao_37_282 PubMedSearch: Yu 1985 Sheng.Li.Xue.Bao 37 282 PubMedID: 3834603 Title: [Central antimuscarinic cholinergic effects of scopolamine and other cholinergic antagonists] Xu J, Jin GZ, Yu LP, Li JH, Yu AY Ref: Acta Pharmacol Sin, 4:156, 1983 : PubMed ESTHER: Xu_1983_Zhongguo.Yao.Li.Xue.Bao_4_156 PubMedSearch: Xu 1983 Zhongguo.Yao.Li.Xue.Bao 4 156 PubMedID: 6228112 | |||||||
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