Author Report for: Lin XNo contact information in database for Lin X
Pang L, Xiong Y, Feng Z, Li C, Fang B, Huang Q, Lin X Ref: Mediators Inflamm, 2023:6051946, 2023 : PubMed ESTHER: Pang_2023_Mediators.Inflamm_2023_6051946 PubMedSearch: Pang 2023 Mediators.Inflamm 2023 6051946 PubMedID: 36687218 Abstract Based on the multiomics analysis, this study is aimed at investigating the underlying mechanism of didymin against acute liver injury (ALI). The mice were administrated with didymin for 2 weeks, followed by injection with lipopolysaccharide (LPS) plus D-galactosamine (D-Gal) to induce ALI. The pathological examination revealed that didymin significantly ameliorated LPS/D-Gal-induced hepatic damage. Also, it markedly reduced proinflammatory cytokines release by inhibiting the TLR4/NF-kappaB pathway activation, alleviating inflammatory injury. A transcriptome analysis proved 2680 differently expressed genes (DEGs) between the model and didymin groups and suggested that the PI3K/Akt and metabolic pathways might be the most relevant targets. Meanwhile, the metabolome analysis revealed 67 differently expressed metabolites (DEMs) between the didymin and model groups that were mainly clustered into the glycerophospholipid metabolism, which was consistent with the transcriptome study. Importantly, a comprehensive analysis of both the omics indicated a strong correlation between the DEGs and DEMs, and an in-depth study demonstrated that didymin alleviated metabolic disorder and hepatocyte injury likely by inhibiting the glycerophospholipid metabolism pathway through the regulation of PLA2G4B, LPCAT3, and CEPT1 expression. In conclusion, this study demonstrates that didymin can ameliorate LPS/D-Gal-induced ALI by inhibiting the glycerophospholipid metabolism and PI3K/Akt and TLR4/NF-kappaB pathways. Title: Two Extracellular Poly(sigma-caprolactone)-Degrading Enzymes From Pseudomonas hydrolytica sp. DSWY01(T): Purification, Characterization, and Gene Analysis Li L, Lin X, Bao J, Xia H, Li F Ref: Front Bioeng Biotechnol, 10:835847, 2022 : PubMed ESTHER: Li_2022_Front.Bioeng.Biotechnol_10_835847 PubMedSearch: Li 2022 Front.Bioeng.Biotechnol 10 835847 PubMedID: 35372294 Gene_locus related to this paper: psemy-a4xvf4, psemy-a4y035 Abstract Poly(sigma-caprolactone) (PCL) is an artificial polyester with commercially promising application. In this study, two novel PCL-degrading enzymes named PCLase I and PCLase II were purified to homogeneity from the culture supernatant of an effective polyester-degrading bacterium, Pseudomonas hydrolytica sp. DSWY01(T). The molecular masses of PCLase I and PCLase II were determined to be 27.5 and 30.0 kDa, respectively. The optimum temperatures for the enzyme activities were 50 and 40 degreesC, and the optimum pH values were 9.0 and 10.0, respectively. The two enzymes exhibited different physical and chemical properties, but both enzymes could degrade PCL substrates into monomers and oligomers. Weight loss detection and scanning electron microscopy revealed that PCLase I had more effective degradation ability than PCLase II. The genes of the two enzymes were cloned on the basis of the peptide fingerprint analysis results. The sequence analysis and substrate specificity analysis results showed that PCLase I and PCLase II were cutinase and lipase, respectively. Interface activation experiment also confirmed this conclusion. Structural analysis and modeling were further performed to obtain possible insights on the mechanism. Title: Multiple acetylcholinesterases in Pardosa pseudoannulata brain worked collaboratively to provide protection from organophosphorus insecticides Lin X, Zhang Y, Yang B, Zhang L, Chen Y, Liu Z Ref: Ecotoxicology & Environmental Safety, 248:114301, 2022 : PubMed ESTHER: Lin_2022_Ecotoxicol.Environ.Saf_248_114301 PubMedSearch: Lin 2022 Ecotoxicol.Environ.Saf 248 114301 PubMedID: 36410143 Gene_locus related to this paper: 9arac-KU501290, 9arac-KU501289, 9arac-KU501288, 9arac-KU501287, 9arac-v5qqc6, 9arac-v5qqr1 Abstract Acetylcholinesterase (AChE) is an essential neurotransmitter hydrolase in nervous systems of animals and its number varies among species. So far, five AChEs have been identified in the natural enemy Pardosa pseudoannulata. Here we found that Ppace1, Ppace2 and Ppace5 were highly expressed in the spider brain, among which the mRNA level of Ppace5, but not Ppace1 and Ppace2, could be up-regulated by organophosphorus insecticides at their sublethal concentrations. In spider brain, the treatment by organophosphorus insecticides at the sublethal concentrations could increase total AChE activity, although high concentrations inhibited the activity. The activity that increased from the sublethal concentration pretreatment could compensate for the activity inhibition due to subsequent application of organophosphorus insecticides at lethal concentrations, and consequently reduce the mortality of spiders. PpAChE1 and PpAChE2 were highly sensitive to organophosphorus insecticides, and their activities would be strongly inhibited by the insecticides. In contrast, PpAChE5 displayed relative insensitivity towards organophosphorus insecticides, but with the highest catalytic efficiency for ACh. That meant the up-regulation of Ppace5 under insecticide exposure was important for maintaining AChE activity in spider brain, when PpAChE1 and PpAChE2 were inhibited by organophosphorus insecticides. The study demonstrated that multiple AChEs in the spider brain worked collaboratively, with part members for maintaining AChE activity and other members responding to organophosphorus inhibition, to provide protection from organophosphorus insecticides. In fields, high concentration insecticides are often applied when ineffective controls of insect pests occur due to relative-low concentration of insecticides in last round application. This application pattern of organophosphorus insecticides provides more chances for P. pseudoannulata to survive and controlling insect pests as a natural enemy. Title: The effect of neostigmine on postoperative delirium after colon carcinoma surgery: a randomized, double-blind, controlled trial Liu F, Lin X, Lin Y, Deng X, Guo Y, Wang B, Dong R, Bi Y Ref: BMC Anesthesiol, 22:267, 2022 : PubMed ESTHER: Liu_2022_BMC.Anesthesiol_22_267 PubMedSearch: Liu 2022 BMC.Anesthesiol 22 267 PubMedID: 35996073 Abstract BACKGROUND: Postoperative delirium (POD) is a critical complication in patients accepting colon carcinoma surgery. Neostigmine, as a cholinesterase inhibitor, can enhance the transmission of cholinergic transmitters in synaptic space, and play an important role in maintaining the normal level of cognition, attention and consciousness. The objective of this study was to investigate the effect of neostigmine on POD and clinical prognosis. METHODS: A randomized, double-blind controlled trial was implemented in Qingdao Municipal Hospital Affiliated to Qingdao University. A total of 454 patients aged 40 to 90 years old accepted colon carcinoma surgery were enrolled between June 7, 2020, and June 7, 2021, with final follow-up on December 8, 2021. Patients were randomly assigned to two groups: the neostigmine group (group N) and the placebo group (group P), the patients in group N were injected with 0.04 mg/kg neostigmine and 0.02 mg/kg atropine intravenously. The primary endpoint was the incidence of POD, researchers evaluated the occurrence of POD by the Confusion Assessment Method (CAM) twice daily (at 10 a.m. and 2 p.m.) during the first 7 postoperative days, POD severity was assessed by the Memorial Delirium Assessment Scale (MDAS). The secondary endpoints were the extubating time, postanesthesia care unit (PACU) time, the incidence of various postoperative complications, length of hospital stays, and 6 months postoperative mortality. RESULTS: The incidence of POD was 20.20% (81/401), including 19.39% (38/196) in group N and 20.98% (43/205) in group P. There was no significant statistical significance in the incidence of POD between group N and group P (P > 0.05); Compared to group P, the extubating time and PACU time in group N were significantly reduced (P < 0.001), the incidence of postoperative pulmonary complications (POPCs) decreased significantly in group N (P < 0.05), while no significant differences were observed in postoperative hospital stay and mortality in 6 months between the two groups (P > 0.05). CONCLUSION: For patients accepted colon carcinoma surgery, neostigmine did not significantly reduce the incidence of POD, postoperative mortality and postoperative hospital stay, while it indeed reduced the extubating time, PACU time and the incidence of POPCs. TRIAL REGISTRATION: The randomized, double-blind, controlled trial was registered retrospectively at www.chictr.org.cn on 07/06/2020 (ChiCTR2000033639). Title: Asperbenzophenone A and Versicolamide C, New Fungal Metabolites from the Soft Coral Derived Aspergillus sp. SCSIO 41036 Long J, Pang X, Lin X, Liao S, Zhou X, Wang J, Yang B, Liu Y Ref: Chem Biodivers, :e202100925, 2022 : PubMed ESTHER: Long_2022_Chem.Biodivers__e202100925 PubMedSearch: Long 2022 Chem.Biodivers e202100925 PubMedID: 35194907 Abstract Two new compounds, asperbenzophenone A (1) and versicolamide C (5), together with fifteen known compounds were isolated from a soft coral derived fungus Aspergillus sp. SCSIO 41036. Their structures were elucidated by spectroscopic methods, ECD analysis, and by a comparison with data from the literature. In bioassay, compound 8 showed significant inhibitory activity against lipopolysaccharide-inducted nitric oxide (NO) in RAW264.7 cells at the concentration of 10microM. Additionally, the anti-acetylcholinesterase activity assay showed that 14 exhibited weak inhibition with an IC(50) value of 157.8microM. Title: Associations of PNPLA3 rs738409 Polymorphism with Plasma Lipid Levels: A Systematic Review and Meta-Analysis Luo Z, Liu Y, Li H, Zhou Y, Peng Y, Lin X, Fang Y, Wan J, Wei B Ref: Hormone & Metabolic Research, 54:686, 2022 : PubMed ESTHER: Luo_2022_Horm.Metab.Res_54_686 PubMedSearch: Luo 2022 Horm.Metab.Res 54 686 PubMedID: 36206762 Abstract Accumulating evidence has shown that the rs738409 polymorphism of patatin-like phospholipase domain-containing 3 (PNPLA3) is associated with non-alcoholic fatty liver disease (NAFLD). Since NAFLD has been reported to be associated with lipid metabolism, this study is conducted to explore whether the rs738409 polymorphism of PNPLA3 was associated with lipid levels. By searching PubMed and the Cochrane database from May 31, 2020, to June 30, 2021. Sixty-three studies (81 003 subjects) were included for the analysis. The consistent findings for the associations of rs738409 polymorphism with lipid levels were the significantly decreased triglycerides (TG) (SMD=-0.04, 95% CI=-0.07 to -0.01, p=0.02) and total cholesterol (TC) (SMD=-0.03, 95% CI=-0.05 to -0.01, p<0.01) levels. Subgroup analysis indicated that the associations of rs738409 polymorphism with TG and TC levels were stronger in Caucasians, obesity patients, and adult subjects than in Asians, T2DM patients, and children subjects. The rs738409 polymorphism of PNPLA3 was associated with lower TG and TC levels in Caucasians, obese and adult subjects, which may contribute to the reduced coronary artery disease (CAD) risk between PNPLA3 rs738409 polymorphism and CAD. Title: Butenolides from the Coral-Derived Fungus Aspergillius terreus SCSIO41404 Peng Q, Chen W, Lin X, Xiao J, Liu Y, Zhou X Ref: Mar Drugs, 20:, 2022 : PubMed ESTHER: Peng_2022_Mar.Drugs_20_ PubMedSearch: Peng 2022 Mar.Drugs 20 PubMedID: 35323511 Abstract Five undescribed butenolides including two pairs of enantiomers, (+)-asperteretal G (1a), (-)-asperteretal G (1b), (+)-asperteretal H (2a), (-)-asperteretal H (2b), asperteretal I (3), and para-hydroxybenzaldehyde derivative, (S)-3-(2,3-dihydroxy-3-methylbutyl)-4-hydroxybenzaldehyde (14), were isolated together with ten previously reported butenolides 4-13, from the coral-derived fungus Aspergillus terreus SCSIO41404. Enantiomers 1a/1b and 2a/2b were successfully purified by high performance liquid chromatography (HPLC) using a chiral column, and the enantiomers 1a and 1b were new natural products. Structures of the unreported compounds, including the absolute configurations, were elucidated by NMR and MS data, optical rotation, experimental and calculated electronic circular dichroism, induced circular dichroism, and X-ray crystal data. The isolated butenolides were evaluated for antibacterial, cytotoxic, and enzyme inhibitory activities. Compounds 7 and 12 displayed weak antibacterial activity, against Enterococcus faecalis (IC(50) = 25 microg/mL) and Klebsiella pneumoniae (IC(50) = 50 microg/mL), respectively, whereas 6 showed weak inhibitory effect on acetylcholinesterase. Nevertheless, most of the butenolides showed inhibition against pancreatic lipase (PL) with an inhibition rate of 21.2-73.0% at a concentration of 50 microg/mL. Title: Diversified Chaetoglobosins from the Marine-Derived Fungus Emericellopsis sp. SCSIO41202 Shao S, Wang X, She J, Zhang H, Pang X, Lin X, Zhou X, Liu Y, Li Y, Yang B Ref: Molecules, 27:, 2022 : PubMed ESTHER: Shao_2022_Molecules_27_ PubMedSearch: Shao 2022 Molecules 27 PubMedID: 35335187 Abstract Two undescribed cytochalasins, emeriglobosins A (1) and B (2), together with nine previously reported analogues (3-11) and two known tetramic acid derivatives (12, 13) were isolated from the solid culture of Emericellopsis sp. SCSIO41202. Their structures, including the absolute configurations of their stereogenic carbons, were fully elucidated based on spectroscopic analysis and the calculated ECD. Some of the isolated compounds were evaluated for their cytotoxicity and enzyme inhibitory activity against acetylcholinesterase (AChE) in vitro. Among them, 8 showed potent AChE inhibitory activity, with an IC(50) value of 1.31 microM, and 5 showed significant cytotoxicity against PC-3 cells, with an IC(50) value of 2.32 microM. Title: New Carboxamides and a New Polyketide from the Sponge-Derived Fungus Arthrinium sp. SCSIO 41421 She J, Chen Y, Ye Y, Lin X, Yang B, Xiao J, Liu Y, Zhou X Ref: Mar Drugs, 20:, 2022 : PubMed ESTHER: She_2022_Mar.Drugs_20_ PubMedSearch: She 2022 Mar.Drugs 20 PubMedID: 35892943 Abstract New carboxamides, (+/-)-vochysiamide C (1) and (+)-vochysiamide B (2), and a new polyketide, 4S,3aS,9aR-3a,9a-deoxy-3a hydroxy-1-dehydroxyarthrinone (3), were isolated and identified from the sponge-derived fungus Arthrinium sp. SCSIO 41421, together with other fifteen known natural products (4-18). Their structures including absolute configurations were determined by detailed NMR, MS spectroscopic analyses, calculated electronic circular dichroism (ECD), as well as quantum-chemical NMR calculations. Preliminary bioactivity screening and molecular docking analysis revealed that several natural products exhibited obvious enzyme inhibitory activities against acetylcholinesterase (AChE), such as 2,3,6,8-tetrahydroxy-1-methylxanthone (4) with an inhibitory rate 86% at 50 microg/mL. Title: The Role of Insect Symbiotic Bacteria in Metabolizing Phytochemicals and Agrochemicals Zhao M, Lin X, Guo X Ref: Insects, 13:, 2022 : PubMed ESTHER: Zhao_2022_Insects_13_ PubMedSearch: Zhao 2022 Insects 13 PubMedID: 35886759 Abstract The diversity and high adaptability of insects are heavily associated with their symbiotic microbes, which include bacteria, fungi, viruses, protozoa, and archaea. These microbes play important roles in many aspects of the biology and physiology of insects, such as helping the host insects with food digestion, nutrition absorption, strengthening immunity and confronting plant defenses. To maintain normal development and population reproduction, herbivorous insects have developed strategies to detoxify the substances to which they may be exposed in the living habitat, such as the detoxifying enzymes carboxylesterase, glutathione-S-transferases (GSTs), and cytochrome P450 monooxygenases (CYP450s). Additionally, insect symbiotic bacteria can act as an important factor to modulate the adaptability of insects to the exposed detrimental substances. This review summarizes the current research progress on the role of insect symbiotic bacteria in metabolizing phytochemicals and agrochemicals (insecticides and herbicides). Given the importance of insect microbiota, more functional symbiotic bacteria that modulate the adaptability of insects to the detrimental substances to which they are exposed should be identified, and the underlying mechanisms should also be further studied, facilitating the development of microbial-resource-based pest control approaches or protective methods for beneficial insects. Title: Plasma Membrane Calcium ATPase-Neuroplastin Complexes Are Selectively Stabilized in GM1-Containing Lipid Rafts Ilic K, Lin X, Malci A, Stojanovic M, Puljko B, Rozman M, Vukelic z, Heffer M, Montag D and Mlinac-Jerkovic K <3 more author(s)> Ilic K, Lin X, Malci A, Stojanovic M, Puljko B, Rozman M, Vukelic z, Heffer M, Montag D, Schnaar RL, Kalanj-Bognar S, Herrera-Molina R, Mlinac-Jerkovic K (- 3) Ref: Int J Mol Sci, 22:, 2021 : PubMed ESTHER: Ilic_2021_Int.J.Mol.Sci_22_ PubMedSearch: Ilic 2021 Int.J.Mol.Sci 22 PubMedID: 34948386 Abstract The recent identification of plasma membrane (Ca(2+))-ATPase (PMCA)-Neuroplastin (Np) complexes has renewed attention on cell regulation of cytosolic calcium extrusion, which is of particular relevance in neurons. Here, we tested the hypothesis that PMCA-Neuroplastin complexes exist in specific ganglioside-containing rafts, which could affect calcium homeostasis. We analyzed the abundance of all four PMCA paralogs (PMCA1-4) and Neuroplastin isoforms (Np65 and Np55) in lipid rafts and bulk membrane fractions from GM2/GD2 synthase-deficient mouse brains. In these fractions, we found altered distribution of Np65/Np55 and selected PMCA isoforms, namely PMCA1 and 2. Cell surface staining and confocal microscopy identified GM1 as the main complex ganglioside co-localizing with Neuroplastin in cultured hippocampal neurons. Furthermore, blocking GM1 with a specific antibody resulted in delayed calcium restoration of electrically evoked calcium transients in the soma of hippocampal neurons. The content and composition of all ganglioside species were unchanged in Neuroplastin-deficient mouse brains. Therefore, we conclude that altered composition or disorganization of ganglioside-containing rafts results in changed regulation of calcium signals in neurons. We propose that GM1 could be a key sphingolipid for ensuring proper location of the PMCA-Neuroplastin complexes into rafts in order to participate in the regulation of neuronal calcium homeostasis. Title: Novel insights into host receptors and receptor-mediated signaling that regulate arbuscular mycorrhizal symbiosis Nasir F, Bahadur A, Lin X, Gao Y, Tian C Ref: J Exp Bot, 72:1546, 2021 : PubMed ESTHER: Nasir_2021_J.Exp.Bot_72_1546 PubMedSearch: Nasir 2021 J.Exp.Bot 72 1546 PubMedID: 33252650 Abstract More than 80% of land plant species benefit from symbiotic partnerships with arbuscular mycorrhizal (AM) fungi, which assist in nutrient acquisition and enhance the ability of host plants to adapt to environmental constraints. Host-generated plasma membrane-residing receptor-like kinases and the intracellular alpha/beta-hydrolase DWARF14-LIKE, a putative karrikin receptor, detect the presence of AM fungi before physical contact between the host and fungus. Detection induces appropriate symbiotic responses, which subsequently enables a favorable environment for AM symbiosis to occur. To prevent hyper-colonization and maintain a mutually beneficial association, the host plant precisely monitors and controls AM colonization by receptor-like kinases, such as SUPER NUMERIC NODULES. Previous studies have elucidated how host plant receptors and receptor-mediated signaling regulate AM symbiosis, but the underlying molecular mechanisms remain poorly understood. The identification of a rice CHITIN ELICITOR RECEPTOR KINASE 1 interaction partner, MYC FACTOR RECEPTOR 1, and new insights into DWARF14-LIKE receptor- and SUPER NUMERIC NODULES receptor-mediated signaling have expanded our understanding of how host plant receptors and their corresponding signals regulate AM symbiosis. This review summarizes these and other recent relevant findings. The identified receptors and/or their signaling components could be manipulated to engineer crops with improved agronomic traits by conferring the ability to precisely control AM colonization. Title: Substrate Engineering in Lipase-Catalyzed Selective Polymerization of d-/l-Aspartates and Diols to Prepare Helical Chiral Polyester Zhang Y, Xia B, Li Y, Lin X, Wu Q Ref: Biomacromolecules, :, 2021 : PubMed ESTHER: Zhang_2021_Biomacromolecules__ PubMedSearch: Zhang 2021 Biomacromolecules PubMedID: 33427463 Abstract The synthesis of optically pure polymers is one of the most challenging tasks in polymer chemistry. Herein, Novozym 435 (Lipase B from Candida antarctica, immobilized on Lewatit VP OC 1600)-catalyzed polycondensation between d-/l-aspartic acid (Asp) diester and diols for the preparation of helical chiral polyesters was reported. Compared with d-Asp diesters, the fast-reacting l-Asp diesters easily reacted with diols to provide a series of chiral polyesters containing N-substitutional l-Asp repeating units. Besides amino acid configuration, N-substituent side chains and the chain length of diols were also investigated and optimized. It was found that bulky acyl N-substitutional groups like N-Boc and N-Cbz were more favorable for this polymerization than small ones probably due to competitively binding of these small acyl groups into the active site of Novozym 435. The highest molecular weight can reach up to 39.5 x 10(3) g/mol (M(w,) D = 1.64). Moreover, the slow-reacting d-Asp diesters were also successfully polymerized by modifying the substrate structure to create a "nonchiral" condensation environment artificially. These enantiocomplementary chiral polyesters are thermally stable and have specific helical structures, which was confirmed by circular dichroism (CD) spectra, scanning electron microscope (SEM), and molecular calculation. Title: Lipopeptide Epimers and a Phthalide Glycerol Ether with AChE Inhibitory Activities from the Marine-Derived Fungus Cochliobolus Lunatus SCSIO41401 Dai Y, Li K, She J, Zeng Y, Wang H, Liao S, Lin X, Yang B, Wang J and Liu Y <3 more author(s)> Dai Y, Li K, She J, Zeng Y, Wang H, Liao S, Lin X, Yang B, Wang J, Tao H, Dai H, Zhou X, Liu Y (- 3) Ref: Mar Drugs, 18:, 2020 : PubMed ESTHER: Dai_2020_Mar.Drugs_18_ PubMedSearch: Dai 2020 Mar.Drugs 18 PubMedID: 33143384 Abstract A pair of novel lipopeptide epimers, sinulariapeptides A (1) and B (2), and a new phthalide glycerol ether (3) were isolated from the marine algal-associated fungus Cochliobolus lunatus SCSIO41401, together with three known chromanone derivates (4-6). The structures of the new compounds, including the absolute configurations, were determined by comprehensive spectroscopic methods, experimental and calculated electronic circular dichroism (ECD), and Mo(2) (OAc)(4)-induced ECD methods. The new compounds 1-3 showed moderate inhibitory activity against acetylcholinesterase (AChE), with IC(50) values of 1.3-2.5 M, and an in silico molecular docking study was also performed. Title: Cerebrospinal fluid cholinergic biomarkers are associated with postoperative delirium in elderly patients undergoing Total hip/knee replacement: a prospective cohort study Lin X, Tang J, Liu C, Li X, Cao X, Wang B, Dong R, Xu W, Yu X and Bi Y <1 more author(s)> Lin X, Tang J, Liu C, Li X, Cao X, Wang B, Dong R, Xu W, Yu X, Wang M, Bi Y (- 1) Ref: BMC Anesthesiol, 20:246, 2020 : PubMed ESTHER: Lin_2020_BMC.Anesthesiol_20_246 PubMedSearch: Lin 2020 BMC.Anesthesiol 20 246 PubMedID: 32988381 Abstract BACKGROUND: Postoperative delirium (POD) is a frequent complication after surgery and its occurrence is associated with poor outcomes. The neuropathology of this complication is unclear, but it is important to evaluate relevant biomarkers for postoperative status. The purpose of this study is to explore the relationship between expression levels of cholinergic biomarkers in cerebrospinal fluid (CSF) and the occurrence and development of POD in elderly patients. METHODS: Four hundred and ninety-two elderly patients aged 65 years old or older with elective total hip/knee replacement received combined spinal-epidural anesthesia. Preoperative baseline cognitive function was assessed using the Mini-Mental State Examination (MMSE) before surgery. Each patient was interviewed in post-anesthesia care unit (PACU) and on the first, second, third and seventh (or before discharge) postoperative days. POD was diagnosed using the Confusion Assessment Method (CAM), and POD severity was measured using the Memorial Delirium Assessment Scale (MDAS). Preoperative CSF and plasma choline acetyltransferase (ChAT), acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) levels were determined by ELISA. The levels of ChAT, AChE and BuChE activities were determined by spectrophotometry. RESULTS: POD was detected in 11.4% (51/447) of the patients. AChE, BuChE, ChAT, TNF-alpha and IL-6 concentrations in CSF and plasma have higher consistency. In preoperative CSF and preoperative and postoperative plasma, down-regulation of the concentration and activity of AChE and BuChE as well as up-regulation of the concentration and activity of ChAT and the concentrations of IL-6 and TNF-alpha were observed in patients who developed POD, and the decrease in BuChE was the most obvious. Logistic analysis showed the activities of ChAT, AChE and BuChE in CSF were still related to POD after adjusting for related factors such as sex, age, years of education, height, weight, body mass index (BMI), and American Society of Anesthesiologists (ASA) class. Receiver Operating Characteristic (ROC) curve analysis was conducted to determine the Area Under Curve (AUC) of AChE, BuChE and ChAT activity in CSF was 0.679 (P < 0.01), 0.940 (P < 0.01) and 0.819 (P < 0.01) respectively and found that BuChE activity had the most accurate diagnostic value. CONCLUSION: The changes in preoperative activity of AChE, BuChE and ChAT in CSF were associated with the development of POD in elderly patients, and BuChE activity had the greatest diagnostic value, which may be related to central cholinergic degradation. These cholinergic biomarkers might participate in the neuropathology of POD, pending further investigations. TRIAL REGISTRATION: This study was registered at Chictr.org.cn (NO. ChiCTR1900023729 ) June 9th, 2019. (Retrospectively registered). Title: Double-enzymes-mediated fluorescent assay for sensitive determination of organophosphorus pesticides based on the quenching of upconversion nanoparticles by Fe(3) Lin X, Yu Q, Yang W, He C, Zhou Y, Duan N, Wu S Ref: Food Chem, 345:128809, 2020 : PubMed ESTHER: Lin_2020_Food.Chem_345_128809 PubMedSearch: Lin 2020 Food.Chem 345 128809 PubMedID: 33338834 Abstract Herein, a new double-enzymes-modulated fluorescent assay based on the quenching of upconversion nanoparticles (UCNPs) by Fe(3+) was constructed for sensitive determination of OPs. OPs can inhibit the activity of acetylcholinesterase to reduce the production of choline and further lead to the lack of H(2)O(2) in the presence of choline oxidase. Therefore, Fe(2+) cannot be converted into Fe(3+), resulting in "turn-on" fluorescence of UCNPs. Under optimal conditions, an excellent linear correlation between the inhibition efficiency and the logarithm of the chlorpyrifos concentration was achieved with a detection limit (LOD) of 6.7 ng/mL in the range of 20-2000 ng/mL. The recovery for chlorpyrifos in apples and cucumbers was 89.5-97.1%. The results were consistent with those obtained by GC-MS. Overall, the integration of UCNPs into the double-enzymes-mediated Fe(3+)/Fe(2+) conversion endows this method with desirable rapidity, sensitivity, selectivity, stability, operational simplicity, and strong anti-interference capability, holding great potential in the application of food safety. Title: Structurally various sorbicillinoids from the deep-sea sediment derived fungus Penicillium sp. SCSIO06871 Pang X, Zhou X, Lin X, Yang B, Tian X, Wang J, Xu S, Liu Y Ref: Bioorg Chem, 107:104600, 2020 : PubMed ESTHER: Pang_2020_Bioorg.Chem_107_104600 PubMedSearch: Pang 2020 Bioorg.Chem 107 104600 PubMedID: 33453645 Abstract Two new hybrid sorbicillinoids (1 and 5), three new bisorbicillinoids (2-4), and three monomeric sorbicillinoids (6-8), along with eighteen known sorbicillinoids (9-26) were isolated from cultures of the deep-sea sediment derived fungus Penicillium sp. SCSIO06871. Their structures and absolute configurations were elucidated based upon the extensive spectroscopic analysis, X-ray crystallography analysis and the comparison of the experimental and calculated ECD data. Bisorbicillpyrone A (4) is the first example of bisorbicillinoid containing an alpha-pyrone derivative unit. All of the isolated compounds were evaluated for their antibacterial, antifungal and enzyme inhibitory activities against alpha-glycosidase and acetylcholinesterase (AChE) in vitro. Compound 6 displayed more potent inhibitory activity against alpha-glycosidase than acarbose with IC(50) value of 36.0 microM and compounds 4, 12, 18, 22, 23 exhibited moderate inhibitory activity with IC(50) values ranging from 115.8 to 208.5 microM. Compounds 10 and 22 showed weak enzyme inhibitory activities against AChE with 55.1% and 51.1% inhibitions at concentration of 50 microg/mL, respectively. Besides, compounds 11 and 12 exhibited significant antibacterial activities against Staphylococcus aureus with MIC values of 10.0 and 5.0 microg/mL, respectively. The hypothetical biosynthetic pathway of the isolated sorbicillinoids with three different structural types was discussed. Title: Molluscicidal activity and physiological toxicity of quaternary benzo[c]phenanthridine alkaloids (QBAs) from Macleaya cordata fruits on Oncomelania hupensis Ke W, Tu C, Cao D, Lin X, Sun Q, Zhang Q Ref: PLoS Negl Trop Dis, 13:e0007740, 2019 : PubMed ESTHER: Ke_2019_PLoS.Negl.Trop.Dis_13_e0007740 PubMedSearch: Ke 2019 PLoS.Negl.Trop.Dis 13 e0007740 PubMedID: 31603908 Abstract Schistosomiasis is a serious worldwide parasitic disease. One of the best ways to control schistosomiasis is to control the population of Oncomelania hupensis snails. We sought to identify a high-efficiency biogenic molluscicide against Oncomelania with low toxicity, to avoid chemical molluscicide contamination and toxicity in aquatic organisms. We extracted quaternary benzo[c]phenanthridine alkaloids (QBAs) from Macleaya cordata fruits. Molluscicidal activity of the QBAs against Oncomelania was determined using bioassay. Our results showed that the extracted QBAs had a strong molluscicidal effect. In treatment of O. hupensis with QBAs for 48 h and 72 h, the lethal concentration (LC50) was 2.89 mg/L and 1.29 mg/L, respectively. The molluscicidal activity of QBAs was close to that of niclosamide (ethanolamine salt), indicating that QBAs have potential development value as novel biogenic molluscicides. We also analyzed physiological toxicity mechanisms by examining the activity of several important detoxification enzymes. We measured the effect of the extracted QBAs on the activities of glutathione S-transferase (GST), carboxylesterase (CarE), acid phosphatase (ACP), and alkaline phosphatase (AKP) in the liver of O. hupensis. We found that the effects of QBAs on detoxification metabolism in O. hupensis were time and concentration dependent. The activities of GST, CarE, AKP, and ACP in the liver of snails increased significantly in the early stage of treatment (24 h), but decreased sharply in later stages (120 h), compared with these activities in controls. GST, CarE, AKP, and ACP activity in the liver of snails treated with LC50 QBAs for 120 h decreased by 62.3%, 78.1%, 59.2%, and 68.6%, respectively. Our results indicate that these enzymes were seriously inhibited by the extracted QBAs and the detoxification and metabolic functions of the liver gradually weakened, leading to poisoning, which could be the main cause of death in O. hupensis snails. 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: Clinical spectrum and genetic landscape for hereditary spastic paraplegias in China Dong EL, Wang C, Wu S, Lu YQ, Lin XH, Su HZ, Zhao M, He J, Ma LX and Lin X <2 more author(s)> Dong EL, Wang C, Wu S, Lu YQ, Lin XH, Su HZ, Zhao M, He J, Ma LX, Wang N, Chen WJ, Lin X (- 2) Ref: Mol Neurodegener, 13:36, 2018 : PubMed ESTHER: Dong_2018_Mol.Neurodegener_13_36 PubMedSearch: Dong 2018 Mol.Neurodegener 13 36 PubMedID: 29980238 Abstract BACKGROUND: Hereditary spastic paraplegias (HSP) is a heterogeneous group of rare neurodegenerative disorders affecting the corticospinal tracts. To date, more than 78 HSP loci have been mapped to cause HSP. However, both the clinical and mutational spectrum of Chinese patients with HSP remained unclear. In this study, we aim to perform a comprehensive analysis of clinical phenotypes and genetic distributions in a large cohort of Chinese HSP patients, and to elucidate the primary pathogenesis in this population. METHODS: We firstly performed next-generation sequencing targeting 149 genes correlated with HSP in 99 index cases of our cohort. Multiplex ligation-dependent probe amplification testing was further carried out among those patients without known disease-causing gene mutations. We simultaneously performed a retrospective study on the reported patients exhibiting HSP in other Chinese cohorts. All clinical and molecular characterization from above two groups of Chinese HSP patients were analyzed and summarized. Eventually, we further validated the cellular changes in fibroblasts of two major spastic paraplegia (SPG) patients (SPG4 and SPG11) in vitro. RESULTS: Most patients of ADHSP (94%) are pure forms, whereas most patients of ARHSP (78%) tend to be complicated forms. In ADHSP, we found that SPG4 (79%) was the most prevalent, followed by SPG3A (11%), SPG6 (4%) and SPG33 (2%). Subtle mutations were the common genetic cause for SPG4 patients and most of them located in AAA cassette domain of spastin protein. In ARHSP, the most common subtype was SPG11 (53%), followed by SPG5 (32%), SPG35 (6%) and SPG46 (3%). Moreover, haplotype analysis showed a unique haplotype was shared in 14 families carrying c.334C > T (p.R112(*)) mutation in CYP7B1 gene, suggesting the founder effect. Functionally, we observed significantly different patterns of mitochondrial dynamics and network, decreased mitochondrial membrane potential (deltam), increased reactive oxygen species and reduced ATP content in SPG4 fibroblasts. Moreover, we also found the enlargement of LAMP1-positive organelles and abnormal accumulation of autolysosomes in SPG11 fibroblasts. CONCLUSIONS: Our study present a comprehensive clinical spectrum and genetic landscape for HSP in China. We have also provided additional evidences for mitochondrial and autolysosomal-mediated pathways in the pathogenesis of HSP. Title: Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity Turcot V, Lu Y, Highland HM, Schurmann C, Justice AE, Fine RS, Bradfield JP, Esko T, Giri A and Loos RJF <390 more author(s)> Turcot V, Lu Y, Highland HM, Schurmann C, Justice AE, Fine RS, Bradfield JP, Esko T, Giri A, Graff M, Guo X, Hendricks AE, Karaderi T, Lempradl A, Locke AE, Mahajan A, Marouli E, Sivapalaratnam S, Young KL, Alfred T, Feitosa MF, Masca NGD, Manning AK, Medina-Gomez C, Mudgal P, Ng MCY, Reiner AP, Vedantam S, Willems SM, Winkler TW, Abecasis G, Aben KK, Alam DS, Alharthi SE, Allison M, Amouyel P, Asselbergs FW, Auer PL, Balkau B, Bang LE, Barroso I, Bastarache L, Benn M, Bergmann S, Bielak LF, Bluher M, Boehnke M, Boeing H, Boerwinkle E, Boger CA, Bork-Jensen J, Bots ML, Bottinger EP, Bowden DW, Brandslund I, Breen G, Brilliant MH, Broer L, Brumat M, Burt AA, Butterworth AS, Campbell PT, Cappellani S, Carey DJ, Catamo E, Caulfield MJ, Chambers JC, Chasman DI, Chen YI, Chowdhury R, Christensen C, Chu AY, Cocca M, Collins FS, Cook JP, Corley J, Corominas Galbany J, Cox AJ, Crosslin DS, Cuellar-Partida G, D'Eustacchio A, Danesh J, Davies G, Bakker PIW, Groot MCH, Mutsert R, Deary IJ, Dedoussis G, Demerath EW, Heijer M, Hollander AI, Ruijter HM, Dennis JG, Denny JC, Angelantonio E, Drenos F, Du M, Dube MP, Dunning AM, Easton DF, Edwards TL, Ellinghaus D, Ellinor PT, Elliott P, Evangelou E, Farmaki AE, Farooqi IS, Faul JD, Fauser S, Feng S, Ferrannini E, Ferrieres J, Florez JC, Ford I, Fornage M, Franco OH, Franke A, Franks PW, Friedrich N, Frikke-Schmidt R, Galesloot TE, Gan W, Gandin I, Gasparini P, Gibson J, Giedraitis V, Gjesing AP, Gordon-Larsen P, Gorski M, Grabe HJ, Grant SFA, Grarup N, Griffiths HL, Grove ML, Gudnason V, Gustafsson S, Haessler J, Hakonarson H, Hammerschlag AR, Hansen T, Harris KM, Harris TB, Hattersley AT, Have CT, Hayward C, He L, Heard-Costa NL, Heath AC, Heid IM, Helgeland O, Hernesniemi J, Hewitt AW, Holmen OL, Hovingh GK, Howson JMM, Hu Y, Huang PL, Huffman JE, Ikram MA, Ingelsson E, Jackson AU, Jansson JH, Jarvik GP, Jensen GB, Jia Y, Johansson S, Jorgensen ME, Jorgensen T, Jukema JW, Kahali B, Kahn RS, Kahonen M, Kamstrup PR, Kanoni S, Kaprio J, Karaleftheri M, Kardia SLR, Karpe F, Kathiresan S, Kee F, Kiemeney LA, Kim E, Kitajima H, Komulainen P, Kooner JS, Kooperberg C, Korhonen T, Kovacs P, Kuivaniemi H, Kutalik Z, Kuulasmaa K, Kuusisto J, Laakso M, Lakka TA, Lamparter D, Lange EM, Lange LA, Langenberg C, Larson EB, Lee NR, Lehtimaki T, Lewis CE, Li H, Li J, Li-Gao R, Lin H, Lin KH, Lin LA, Lin X, Lind L, Lindstrom J, Linneberg A, Liu CT, Liu DJ, Liu Y, Lo KS, Lophatananon A, Lotery AJ, Loukola A, Luan J, Lubitz SA, Lyytikainen LP, Mannisto S, Marenne G, Mazul AL, McCarthy MI, McKean-Cowdin R, Medland SE, Meidtner K, Milani L, Mistry V, Mitchell P, Mohlke KL, Moilanen L, Moitry M, Montgomery GW, Mook-Kanamori DO, Moore C, Mori TA, Morris AD, Morris AP, Muller-Nurasyid M, Munroe PB, Nalls MA, Narisu N, Nelson CP, Neville M, Nielsen SF, Nikus K, Njolstad PR, Nordestgaard BG, Nyholt DR, O'Connel JR, O'Donoghue ML, Olde Loohuis LM, Ophoff RA, Owen KR, Packard CJ, Padmanabhan S, Palmer CNA, Palmer ND, Pasterkamp G, Patel AP, Pattie A, Pedersen O, Peissig PL, Peloso GM, Pennell CE, Perola M, Perry JA, Perry JRB, Pers TH, Person TN, Peters A, Petersen ERB, Peyser PA, Pirie A, Polasek O, Polderman TJ, Puolijoki H, Raitakari OT, Rasheed A, Rauramaa R, Reilly DF, Renstrom F, Rheinberger M, Ridker PM, Rioux JD, Rivas MA, Roberts DJ, Robertson NR, Robino A, Rolandsson O, Rudan I, Ruth KS, Saleheen D, Salomaa V, Samani NJ, Sapkota Y, Sattar N, Schoen RE, Schreiner PJ, Schulze MB, Scott RA, Segura-Lepe MP, Shah SH, Sheu WH, Sim X, Slater AJ, Small KS, Smith AV, Southam L, Spector TD, Speliotes EK, Starr JM, Stefansson K, Steinthorsdottir V, Stirrups KE, Strauch K, Stringham HM, Stumvoll M, Sun L, Surendran P, Swift AJ, Tada H, Tansey KE, Tardif JC, Taylor KD, Teumer A, Thompson DJ, Thorleifsson G, Thorsteinsdottir U, Thuesen BH, Tonjes A, Tromp G, Trompet S, Tsafantakis E, Tuomilehto J, Tybjaerg-Hansen A, Tyrer JP, Uher R, Uitterlinden AG, Uusitupa M, Laan SW, Duijn CM, Leeuwen N, van Setten J, Vanhala M, Varbo A, Varga TV, Varma R, Velez Edwards DR, Vermeulen SH, Veronesi G, Vestergaard H, Vitart V, Vogt TF, Volker U, Vuckovic D, Wagenknecht LE, Walker M, Wallentin L, Wang F, Wang CA, Wang S, Wang Y, Ware EB, Wareham NJ, Warren HR, Waterworth DM, Wessel J, White HD, Willer CJ, Wilson JG, Witte DR, Wood AR, Wu Y, Yaghootkar H, Yao J, Yao P, Yerges-Armstrong LM, Young R, Zeggini E, Zhan X, Zhang W, Zhao JH, Zhao W, Zhou W, Zondervan KT, Rotter JI, Pospisilik JA, Rivadeneira F, Borecki IB, Deloukas P, Frayling TM, Lettre G, North KE, Lindgren CM, Hirschhorn JN, Loos RJF (- 390) Ref: Nat Genet, 50:26, 2018 : PubMed ESTHER: Turcot_2018_Nat.Genet_50_26 PubMedSearch: Turcot 2018 Nat.Genet 50 26 PubMedID: 29273807 Abstract Genome-wide association studies (GWAS) have identified >250 loci for body mass index (BMI), implicating pathways related to neuronal biology. Most GWAS loci represent clusters of common, noncoding variants from which pinpointing causal genes remains challenging. Here we combined data from 718,734 individuals to discover rare and low-frequency (minor allele frequency (MAF) < 5%) coding variants associated with BMI. We identified 14 coding variants in 13 genes, of which 8 variants were in genes (ZBTB7B, ACHE, RAPGEF3, RAB21, ZFHX3, ENTPD6, ZFR2 and ZNF169) newly implicated in human obesity, 2 variants were in genes (MC4R and KSR2) previously observed to be mutated in extreme obesity and 2 variants were in GIPR. The effect sizes of rare variants are ~10 times larger than those of common variants, with the largest effect observed in carriers of an MC4R mutation introducing a stop codon (p.Tyr35Ter, MAF = 0.01%), who weighed ~7 kg more than non-carriers. Pathway analyses based on the variants associated with BMI confirm enrichment of neuronal genes and provide new evidence for adipocyte and energy expenditure biology, widening the potential of genetically supported therapeutic targets in obesity. 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: Clinicians' prescription preferences for treating patients with Alzheimer's disease in Shanghai Ban CX, Xiao SF, Lin X, Wang T, Qiu Q, Zhu MJ, Li X Ref: Transl Neurodegener, 5:8, 2016 : PubMed ESTHER: Ban_2016_Transl.Neurodegener_5_8 PubMedSearch: Ban 2016 Transl.Neurodegener 5 8 PubMedID: 27114822 Abstract BACKGROUND: China has more cases of Alzheimer's disease (AD) than any other country in the world. As training to recognize and manage dementia is in its early stage, it is important to study clinicians' current prescription preferences for treating patients with AD. Title: Toxicological Differences Between NMDA Receptor Antagonists and Cholinesterase Inhibitors Shi X, Lin X, Hu R, Sun N, Hao J, Gao C Ref: Am J Alzheimers Dis Other Demen, 31:405, 2016 : PubMed ESTHER: Shi_2016_Am.J.Alzheimers.Dis.Other.Demen_31_405 PubMedSearch: Shi 2016 Am.J.Alzheimers.Dis.Other.Demen 31 405 PubMedID: 26769920 Abstract Cholinesterase inhibitors (ChEIs), represented by donepezil, rivastigmine, and galantamine, used to be the only approved class of drugs for the treatment of Alzheimer's disease. After the approval of memantine by the Food and Drug Administration (FDA), N-methyl-d-aspartic acid (NMDA) receptor antagonists have been recognized by authorities and broadly used in the treatment of Alzheimer's disease. Along with complementary mechanisms of action, NMDA antagonists and ChEIs differ not only in therapeutic effects but also in adverse reactions, which is an important consideration in clinical drug use. And the number of patients using NMDA antagonists and ChEIs concomitantly has increased, making the matter more complicated. Here we used the FDA Adverse Event Reporting System for statistical analysis , in order to compare the adverse events of memantine and ChEIs. In general, the clinical evidence confirmed the safety advantages of memantine over ChEIs, reiterating the precautions of clinical drug use and the future direction of antidementia drug development. Title: Subcellular Compartmentalization and Trafficking of the Biosynthetic Machinery for Fungal Melanin Upadhyay S, Xu X, Lowry D, Jackson JC, Roberson RW, Lin X Ref: Cell Rep, 14:2511, 2016 : PubMed ESTHER: Upadhyay_2016_Cell.Rep_14_2511 PubMedSearch: Upadhyay 2016 Cell.Rep 14 2511 PubMedID: 26972005 Gene_locus related to this paper: aspfu-AYG1 Abstract Protection by melanin depends on its subcellular location. Although most filamentous fungi synthesize melanin via a polyketide synthase pathway, where and how melanin biosynthesis occurs and how it is deposited as extracellular granules remain elusive. Using a forward genetic screen in the pathogen Aspergillus fumigatus, we find that mutations in an endosomal sorting nexin abolish melanin cell-wall deposition. We find that all enzymes involved in the early steps of melanin biosynthesis are recruited to endosomes through a non-conventional secretory pathway. In contrast, late melanin enzymes accumulate in the cell wall. Such subcellular compartmentalization of the melanin biosynthetic machinery occurs in both A. fumigatus and A. nidulans. Thus, fungal melanin biosynthesis appears to be initiated in endosomes with exocytosis leading to melanin extracellular deposition, much like the synthesis and trafficking of mammalian melanin in endosomally derived melanosomes. Title: A novel cold-adapted and highly salt-tolerant esterase from Alkalibacterium sp. SL3 from the sediment of a soda lake Wang G, Wang Q, Lin X, Ng TB, Yan R, Lin J, Ye X Ref: Sci Rep, 6:19494, 2016 : PubMed ESTHER: Wang_2016_Sci.Rep_6_19494 PubMedSearch: Wang 2016 Sci.Rep 6 19494 PubMedID: 26915906 Abstract A novel esterase gene (estSL3) was cloned from the Alkalibacterium sp. SL3, which was isolated from the sediment of soda lake Dabusu. The 636-bp full-length gene encodes a polypeptide of 211 amino acid residues that is closely related with putative GDSL family lipases from Alkalibacterium and Enterococcus. The gene was successfully expressed in E. coli, and the recombinant protein (rEstSL3) was purified to electrophoretic homogeneity and characterized. rEstSL3 exhibited the highest activity towards pNP-acetate and had no activity towards pNP-esters with acyl chains longer than C8. The enzyme was highly cold-adapted, showing an apparent temperature optimum of 30 degrees C and remaining approximately 70% of the activity at 0 degrees C. It was active and stable over the pH range from 7 to 10, and highly salt-tolerant up to 5 M NaCl. Moreover, rEstSL3 was strongly resistant to most tested metal ions, chemical reagents, detergents and organic solvents. Amino acid composition analysis indicated that EstSL3 had fewer proline residues, hydrogen bonds and salt bridges than mesophilic and thermophilic counterparts, but more acidic amino acids and less hydrophobic amino acids when compared with other salt-tolerant esterases. The cold active, salt-tolerant and chemical-resistant properties make it a promising enzyme for basic research and industrial applications. Title: Overexpression of miR-155 in the Liver of Transgenic Mice Alters the Expression Profiling of Hepatic Genes Associated with Lipid Metabolism Lin X, Jia J, Du T, Li W, Wang X, Wei J, Zeng H, Yao L, Chen X and Xiao D <8 more author(s)> Lin X, Jia J, Du T, Li W, Wang X, Wei J, Zeng H, Yao L, Chen X, Zhuang J, Weng J, Liu Y, Lin J, Wu Q, Wang W, Yao K, Xu K, Xiao D (- 8) Ref: PLoS ONE, 10:e0118417, 2015 : PubMed ESTHER: Lin_2015_PLoS.One_10_e0118417 PubMedSearch: Lin 2015 PLoS.One 10 e0118417 PubMedID: 25799309 Abstract Hepatic expression profiling has revealed miRNA changes in liver diseases, while hepatic miR-155 expression was increased in murine non-alcoholic fatty liver disease, suggesting that miR-155 might regulate the biological process of lipid metabolism. To illustrate the effects of miR-155 gain of function in transgenic mouse liver on lipid metabolism, transgenic mice (i.e., Rm155LG mice) for the conditional overexpression of mouse miR-155 transgene mediated by Cre/lox P system were firstly generated around the world in this study. Rm155LG mice were further crossed to Alb-Cre mice to realize the liver-specific overexpression of miR-155 transgene in Rm155LG/Alb-Cre double transgenic mice which showed the unaltered body weight, liver weight, epididymal fat pad weight and gross morphology and appearance of liver. Furthermore, liver-specific overexpression of miR-155 transgene resulted in significantly reduced levels of serum total cholesterol, triglycerides (TG) and high-density lipoprotein (HDL), as well as remarkably decreased contents of hepatic lipid, TG, HDL and free fatty acid in Rm155LG/Alb-Cre transgenic mice. More importantly, microarray data revealed a general downward trend in the expression profile of hepatic genes with functions typically associated with fatty acid, cholesterol and triglyceride metabolism, which is likely at least partially responsible for serum cholesterol and triglyceride lowering observed in Rm155LG/Alb-Cre mice. In this study, we demonstrated that hepatic overexpression of miR-155 alleviated nonalcoholic fatty liver induced by a high-fat diet. Additionally, carboxylesterase 3/triacylglycerol hydrolase (Ces3/TGH) was identified as a direct miR-155 target gene that is potentially responsible for the partial liver phenotypes observed in Rm155LG/Alb-Cre mice. Taken together, these data from miR-155 gain of function study suggest, for what we believe is the first time, the altered lipid metabolism and provide new insights into the metabolic state of the liver in Rm155LG/Alb-Cre mice. Title: Pratensein attenuates Abeta-induced cognitive deficits in rats: Enhancement of synaptic plasticity and cholinergic function Wei L, Lv S, Huang Q, Wei J, Zhang S, Huang R, Lu Z, Lin X Ref: Fitoterapia, 101C:208, 2015 : PubMed ESTHER: Wei_2015_Fitoterapia_101C_208 PubMedSearch: Wei 2015 Fitoterapia 101C 208 PubMedID: 25665942 Abstract An isoflavone was isolated from Trifolium pratense using bioassay-guided screening. The structure of this natural compound was elucidated based on its spectral data, and it was identified as pratensein. The protective effect of pratensein was evaluated using a cognitive impairment model induced by injecting amyloid beta (1-42) (Abeta1-42) into the bilateral hippocampus of rats. The results showed that pratensein treatment significantly protected against Abeta1-42-induced cognitive impairments, as evidenced by the improvement in learning and memory and the attenuation of neuronal degeneration and apoptosis in hippocampus. Analysis of the potential mechanisms of action showed that pratensein significantly decreased inflammatory indicators such as MDA, NO, nNOS, IL-1beta and TNF-alpha. Pratensein markedly decreased the content and deposition of beta-amyloid peptide through regulating the expressions of Abeta-related genes including APP, BACE1, CatB, NEP and IDE. Moreover, pratensein significantly increased the expressions of synapse plasticity-related proteins, i.e., PSD-95, p-NMDAR1, p-CaMKII, p-PKACbeta, PKCgamma, p-CREB and BDNF. In addition, pratensein significantly decreased the activity of cholinesterase, then subsequently elevated the level of acetylcholine. In summary, our study indicated that pratensein may have a likely protective effect against Alzheimer's disease (AD) via improving synaptic plasticity and increasing cholinesterase activity. Title: Protective effect of Millettia pulchra polysaccharide on cognitive impairment induced by d-galactose in mice Lin X, Huang Z, Chen X, Rong Y, Zhang S, Jiao Y, Huang Q, Huang R Ref: Carbohydr Polym, 101:533, 2014 : PubMed ESTHER: Lin_2014_Carbohydr.Polym_101_533 PubMedSearch: Lin 2014 Carbohydr.Polym 101 533 PubMedID: 24299809 Abstract A polysaccharide (PMP) was isolated from Millettia pulchra and purified by DEAE-cellulose and Sephadex G-75 chromatography. The results showed that PMP was composed of d-glucose and d-arabinose in a molar ratio of 90.79% and 9.21%, with an average molecular weight of about 14,301Da. Furthermore, the effect of PMP on cognitive impairment induced by d-galactose in mice was evaluated. Treatment with PMP significantly reversed d-galactose-induced learning and memory impairments, as measured by behavioral tests. One of the potential mechanisms of this action was to reduce oxidative stress and suppress inflammatory responses. Furthermore, our results also showed that PMP markedly reduced the content and deposition of beta-amyloid peptide, improved the dysfunction of synaptic plasticity, increased the levels of acetylcholine, but decreased cholinesterase activity. These results suggest that PMP exerts an effective protection against d-galactose-induced cognitive impairment, and PMP may be a major bioactive ingredient in M. pulchra. Title: Increased expression of long noncoding RNA ABHD11-AS1 in gastric cancer and its clinical significance Lin X, Yang M, Xia T, Guo J Ref: Med Oncol, 31:42, 2014 : PubMed ESTHER: Lin_2014_Med.Oncol_31_42 PubMedSearch: Lin 2014 Med.Oncol 31 42 PubMedID: 24984296 Gene_locus related to this paper: human-ABHD11 Abstract Long noncoding RNAs (lncRNAs) play an important role in basic physiological processes, also affect tumor occurrence and development. However, there are still many unknown relationships between the lncRNA expression levels and gastric tumor process. In our study, we selected ABHD11 Antisense RNA 1 (ABHD11-AS1) as a representative lncRNAs to study the different expression levels between gastric tumor and adjacent non-tumor tissues. At the same time, we analyzed the relationship between the expression levels of ABHD11-AS1 in gastric cancer tissues and the clinicopathological features of patients with gastric cancer and evaluated the diagnostic value through the receiver operation characteristic (ROC) curve. Results show that compared with adjacent non-tumor tissues the expression level of ABHD11-AS1 in gastric cancer tissues was significantly increased (P = 0.027). The expression level was also significantly related with the differentiation (P = 0.022), Lauren histologic classification (P = 0.004) and carbohydrate antigen 19-9 (CA19-9) (P = 0.007), and the area under ROC curve was up to 0.613. Thus, ABHD11-AS1 might be a potential biomarker for diagnosis of gastric cancer. Title: Two Enzyme Cooperatively Catalyzed Tandem Polymerization for the Synthesis of Polyester Containing Chiral (R)- or (S)-Ibuprofen Pendants Qian X, Wang J, Li Y, Lin X, Wu Q Ref: Macromol Rapid Commun, 35:1788, 2014 : PubMed ESTHER: Qian_2014_Macromol.Rapid.Commun_35_1788 PubMedSearch: Qian 2014 Macromol.Rapid.Commun 35 1788 PubMedID: 25200738 Abstract An interesting cooperation between Candida antarctica Lipase B (CAL-B) and alkaline protease from Bacillus subtilis (BSP) in the copolymerization of bulky ibuprofen-containing hydroxyacid methyl ester (HAEP) and sigma-caprolactone (sigma-CL) is observed. This cooperation improved the Mn of the polymers from 3130 (CAL-B) to 9200 g mol(-1) (CAL-B/BSP). Experimental results clearly indicate that CAL-B mainly catalyzes the ring-opening polymerization (ROP) of sigma-CL under the initiation of HAEP to form the homopolymer of sigma-CL, while BSP catalyzes the subsequent polycondensation of the ROP product to yield the copolymer with increased molecular weight. Furthermore, using suitable chemo-enzymatic methods, valuable polyesters with chiral (R)- or (S)-ibuprofen pendants can be tailor-made. Title: Signature gene expression reveals novel clues to the molecular mechanisms of dimorphic transition in Penicillium marneffei Yang E, Chow WN, Wang G, Woo PC, Lau SK, Yuen KY, Lin X, Cai JJ Ref: PLoS Genet, 10:e1004662, 2014 : PubMed ESTHER: Yang_2014_PLoS.Genet_10_e1004662 PubMedSearch: Yang 2014 PLoS.Genet 10 e1004662 PubMedID: 25330172 Gene_locus related to this paper: penma-b6qmb1, penmq-b6qrx8, talma-a0a093xi19, talmq-b6qpy9, talmq-b6qez0, talma-a0a093v409 Abstract Systemic dimorphic fungi cause more than one million new infections each year, ranking them among the significant public health challenges currently encountered. Penicillium marneffei is a systemic dimorphic fungus endemic to Southeast Asia. The temperature-dependent dimorphic phase transition between mycelium and yeast is considered crucial for the pathogenicity and transmission of P. marneffei, but the underlying mechanisms are still poorly understood. Here, we re-sequenced P. marneffei strain PM1 using multiple sequencing platforms and assembled the genome using hybrid genome assembly. We determined gene expression levels using RNA sequencing at the mycelial and yeast phases of P. marneffei, as well as during phase transition. We classified 2,718 genes with variable expression across conditions into 14 distinct groups, each marked by a signature expression pattern implicated at a certain stage in the dimorphic life cycle. Genes with the same expression patterns tend to be clustered together on the genome, suggesting orchestrated regulations of the transcriptional activities of neighboring genes. Using qRT-PCR, we validated expression levels of all genes in one of clusters highly expressed during the yeast-to-mycelium transition. These included madsA, a gene encoding MADS-box transcription factor whose gene family is exclusively expanded in P. marneffei. Over-expression of madsA drove P. marneffei to undergo mycelial growth at 37 degrees C, a condition that restricts the wild-type in the yeast phase. Furthermore, analyses of signature expression patterns suggested diverse roles of secreted proteins at different developmental stages and the potential importance of non-coding RNAs in mycelium-to-yeast transition. We also showed that RNA structural transition in response to temperature changes may be related to the control of thermal dimorphism. Together, our findings have revealed multiple molecular mechanisms that may underlie the dimorphic transition in P. marneffei, providing a powerful foundation for identifying molecular targets for mechanism-based interventions. Title: Complete Genome Sequence of Antarctic Bacterium Psychrobacter sp. Strain G Che S, Song L, Song W, Yang M, Liu G, Lin X Ref: Genome Announc, 1:, 2013 : PubMed ESTHER: Che_2013_Genome.Announc_1_e00725 PubMedSearch: Che 2013 Genome.Announc 1 e00725 PubMedID: 24051316 Gene_locus related to this paper: psyck-q1q7w8, psyck-q1qbb9, 9gamm-s4yuz8 Abstract Here, we report the complete genome sequence of Psychrobacter sp. strain G, isolated from King George Island, Antarctica, which can produce lipolytic enzymes at low temperatures. The genomics information of this strain will facilitate the study of the physiology, cold adaptation properties, and evolution of this genus. Title: Insight into substituent effects in Cal-B catalyzed transesterification by combining experimental and theoretical approaches Ni Z, Lin X Ref: J Mol Model, 19:349, 2013 : PubMed ESTHER: Ni_2013_J.Mol.Model_19_349 PubMedSearch: Ni 2013 J.Mol.Model 19 349 PubMedID: 22923134 Abstract Candida antarctica lipase B (Cal-B) is one of the most recognized biocatalysts because of its high degree of selectivity in a broad range of synthetic applications of industrial importance. Herein, the substituent effects involved in transesterification catalyzed by Cal-B are explored in detail using a combination of experimental analysis and theoretical modeling. The transesterification ability of Cal-B was experimentally determined with 22 vinyl ester analogs and ribavirin as substrates and, on this basis, a series of quantitative structure-activity relationship (QSAR) models are developed using various structural parameters characterizing the variation in substituent groups of the substrate molecules. The resulting models exhibit a good stability and predictive power, from which five most important properties are highlighted and engaged to ascertain the structural basis and reaction mechanism underlying the transesterification. From the modeling analysis it is seen that the size, geometry, and charge distributions of substrate exert a significant effect on reaction yield, where, the size of the substituent group was the most significant impact factor on the reaction yield, the charge distribution was the second, and then the topological structure of the substrate. Title: Biocatalysts for cascade reaction: porcine pancreas lipase (PPL)-catalyzed synthesis of bis(indolyl)alkanes Xiang Z, Liu Z, Chen X, Wu Q, Lin X Ref: Amino Acids, 45:937, 2013 : PubMed ESTHER: Xiang_2013_Amino.Acids_45_937 PubMedSearch: Xiang 2013 Amino.Acids 45 937 PubMedID: 23860845 Abstract A cascade reaction between aldehydes and indole catalyzed by lipase from porcine pancreas Type II (PPL) in solvent mixture at 50 degrees C was reported for the first time. Some control experiments had been designed to demonstrate that the PPL was responsible for the cascade reaction. After the optimization of the stepwise process, a series of bis(indolyl)alkanes were prepared in moderate to excellent yields under the catalysis of PPL. Title: A multi-omic map of the lipid-producing yeast Rhodosporidium toruloides Zhu Z, Zhang S, Liu H, Shen H, Lin X, Yang F, Zhou YJ, Jin G, Ye M and Zhao ZK <1 more author(s)> Zhu Z, Zhang S, Liu H, Shen H, Lin X, Yang F, Zhou YJ, Jin G, Ye M, Zou H, Zhao ZK (- 1) Ref: Nat Commun, 3:1112, 2012 : PubMed ESTHER: Zhu_2012_Nat.Commun_3_1112 PubMedSearch: Zhu 2012 Nat.Commun 3 1112 PubMedID: 23047670 Gene_locus related to this paper: rhot1-m7wd80, rhot1-m7x154, rhot1-m7xfd0, rhot1-m7wh41, rhot1-m7x3p3, rhot1-m7x835, rhoto-a0a061bfj5 Abstract Triacylglycerols are among the most attractive alternative raw materials for biofuel development. Current oil plant-based technologies are limited in terms of triacylglycerol production capacity and rate. These limitations may be circumvented by biotransformation of carbohydrates into lipids; however, our understanding of microbial oleaginicity remains limited. Here we present the results of a multi-omic analysis of Rhodosporidium toruloides, a robust triacylglycerol-producing fungus. The assembly of genome and transcriptome sequencing data reveals a genome of 20.2 Mb containing 8,171 protein-coding genes, the majority of which have multiple introns. Genes including a novel fatty acid synthase are predicted to participate in metabolic pathways absent in non-oleaginous yeasts. Transcriptomic and proteomic data suggest that lipid accumulation under nitrogen-limited conditions correlates with the induction of lipogenesis, nitrogenous compound recycling, macromolecule metabolism and autophagy. The multi-omic map of R. toruloides therefore provides a valuable resource for efforts to rationally engineer lipid-production pathways. Title: Sulfated is a negative feedback regulator of wingless in Drosophila You J, Belenkaya T, Lin X Ref: Developmental Dynamics, 240:640, 2011 : PubMed ESTHER: You_2011_Dev.Dyn_240_640 PubMedSearch: You 2011 Dev.Dyn 240 640 PubMedID: 21305649 Gene_locus related to this paper: drome-q9vux3 Abstract Drosophila Wingless (Wg) acts as a morphogen to control pattern formation in a concentration dependent manner. Previous studies demonstrated important roles of heparan sulfate proteoglycans (HSPGs) in controlling Wg signaling and distribution. Here, we examined the role of Sulfated (Sulf1), a Drosophila homolog of vertebrate heparan sulfate 6-O endosulfatase, in Wg signaling and distribution. We show that sulf1 is specifically up-regulated by Wg signaling in the wing disc. We found that expression of Wg target gene senseless (sens) was elevated in the sulf1 mutant wing discs. Sulf1 also negatively regulate extracellular levels of Wg. Genetic interaction experiments indicate that Wg antagonist Notum may work synergistically with Sulf1 to restrict Wg signaling, and Dally, a member of Drosophila HSPGs, is a potential target of Sulf1. Our results demonstrate that sulf1 is a novel Wg target gene and by a feedback mechanism, it negatively regulated Wg signaling and distribution in vivo. Title: Brominated aliphatic hydrocarbons and sterols from the sponge Xestospongia testudinaria with their bioactivities Zhou X, Lu Y, Lin X, Yang B, Yang X, Liu Y Ref: Chemistry & Physic of Lipids, 164:703, 2011 : PubMed ESTHER: Zhou_2011_Chem.Phys.Lipids_164_703 PubMedSearch: Zhou 2011 Chem.Phys.Lipids 164 703 PubMedID: 21864515 Abstract Four brominated aliphatic hydrocarbons (1-4), including a novel brominated ene-tetrahydrofuran named as mutafuran H (1), and five sterols (5-9) were isolated from the South China Sea sponge Xestospongia testudinaria. The structure of 1 was determined on the basis of NMR ((1)H, (13)C NMR, HSQC, HMBC, (1)H-(1)H COSY, and NOESY), MS, and optical rotation analysis. Known compounds were identified by comparison of their NMR data with those reported in the literature. Compounds 1-4, and 6-9 were evaluated for their toxicity against Artemia salina larvae, and anti-acetylcholinesterase activity. Title: Cloning and heterologous expression of two cold-active lipases from the Antarctic bacterium Psychrobacter sp. G. Lin X, Cui S, Xu G, Wang S, Du N Ref: Polar Research, 29:421, 2010 : PubMed ESTHER: Lin_2010_Polar.Res_29_421 PubMedSearch: Lin 2010 Polar.Res 29 421 Gene_locus related to this paper: psyck-q1q7w8 Abstract Antarctic bacteria producing extracellular lipolytic enzymes with activity at low temperature were isolated, and the most promising strain, named G, was identified as a Psychrobacter species based on 16S rDNA sequence alignment. The genomic DNA of this bacterium was used to construct its plasmid genomic library into pUC118 plasmid vectors, and to screen the cold-active lipolytic enzyme genes. Two genes encoding for cold-active lipolytic enzymes, Lip-1452 (with an open reading frame of 1452 bp in length) and Lip-948 (with an open reading frame of 948 bp in length), were screened. The primary structure of the two lipases deduced from the nucleotide sequence showed a consensus pentapeptide containing the active serine (Lip-1452, GDSAG, and Lip-948, GNSMG) and a conserved His-Gly dipeptide in the N-terminal part of the enzyme. Protein sequence alignment and conserved regions analysis indicated that the two lipases probably belonged to family IV and family V of the bacterial lipolytic enzymes, respectively. The upstream and downstream sequences of the two lipolytic lipases were also obtained. The two lipase genes were cloned into the expression vector pCold III and integrated into Escherichia coli BL21 (DE3). The functional expression of both lipase genes by E. coli BL21 (DE3) cells was observed as the formation of clear haloes around colonies on a 1% (vol/vol) tributyrin plate upon induction with isopropyl-b-Dthiogalactopyranoside at 5C. A lipase activity assay showed that the specific activity of the pCold III+Lip-948 expression system was up to 3.7 U ml-1, whereas that of pCold III+Lip-1452 was very low. Title: Conidiation color mutants of Aspergillus fumigatus are highly pathogenic to the heterologous insect host Galleria mellonella Jackson JC, Higgins LA, Lin X Ref: PLoS ONE, 4:e4224, 2009 : PubMed ESTHER: Jackson_2009_PLoS.One_4_e4224 PubMedSearch: Jackson 2009 PLoS.One 4 e4224 PubMedID: 19156203 Gene_locus related to this paper: aspfu-AYG1 Abstract The greater wax moth Galleria mellonella has been widely used as a heterologous host for a number of fungal pathogens including Candida albicans and Cryptococcus neoformans. A positive correlation in pathogenicity of these yeasts in this insect model and animal models has been observed. However, very few studies have evaluated the possibility of applying this heterologous insect model to investigate virulence traits of the filamentous fungal pathogen Aspergillus fumigatus, the leading cause of invasive aspergillosis. Here, we have examined the impact of mutations in genes involved in melanin biosynthesis on the pathogenicity of A. fumigatus in the G. mellonella model. Melanization in A. fumigatus confers bluish-grey color to conidia and is a known virulence factor in mammal models. Surprisingly, conidial color mutants in B5233 background that have deletions in the defined six-gene cluster required for DHN-melanin biosynthesis caused enhanced insect mortality compared to the parent strain. To further examine and confirm the relationship between melanization defects and enhanced virulence in the wax moth model, we performed random insertional mutagenesis in the Af293 genetic background to isolate mutants producing altered conidia colors. Strains producing conidia of previously identified colors and of novel colors were isolated. Interestingly, these color mutants displayed a higher level of pathogenicity in the insect model compared to the wild type. Although some of the more virulent color mutants showed increased resistance to hydrogen peroxide, overall phenotypic characterizations including secondary metabolite production, metalloproteinase activity, and germination rate did not reveal a general mechanism accountable for the enhanced virulence of these color mutants observed in the insect model. Our observations indicate instead, that exacerbated immune response of the wax moth induced by increased exposure of PAMPs (pathogen-associated molecular patterns) may cause self-damage that results in increased mortality of larvae infected with the color mutants. The current study underscores the limitations of using this insect model for inferring the pathogenic potential of A. fumigatus strains in mammals, but also points to the importance of understanding the innate immunity of the insect host in providing insights into the pathogenicity level of different fungal strains in this model. Additionally, our observations that melanization defective color mutants demonstrate increased virulence in the insect wax moth, suggest the potential of using melanization defective mutants of native insect fungal pathogens in the biological control of insect populations. Title: Modulation of TNF release by choline requires alpha7 subunit nicotinic acetylcholine receptor-mediated signaling Parrish WR, Rosas-Ballina M, Gallowitsch-Puerta M, Ochani M, Ochani K, Yang LH, Hudson L, Lin X, Patel N and Pavlov VA <7 more author(s)> Parrish WR, Rosas-Ballina M, Gallowitsch-Puerta M, Ochani M, Ochani K, Yang LH, Hudson L, Lin X, Patel N, Johnson SM, Chavan S, Goldstein RS, Czura CJ, Miller EJ, Al-Abed Y, Tracey KJ, Pavlov VA (- 7) Ref: Mol Med, 14:567, 2008 : PubMed ESTHER: Parrish_2008_Mol.Med_14_567 PubMedSearch: Parrish 2008 Mol.Med 14 567 PubMedID: 18584048 Abstract The alpha7 subunit-containing nicotinic acetylcholine receptor (alpha7nAChR) is an essential component in the vagus nerve-based cholinergic anti-inflammatory pathway that regulates the levels of TNF, high mobility group box 1 (HMGB1), and other cytokines during inflammation. Choline is an essential nutrient, a cell membrane constituent, a precursor in the biosynthesis of acetylcholine, and a selective natural alpha7nAChR agonist. Here, we studied the anti-inflammatory potential of choline in murine endotoxemia and sepsis, and the role of the alpha7nAChR in mediating the suppressive effect of choline on TNF release. Choline (0.1-50 mM) dose-dependently suppressed TNF release from endotoxin-activated RAW macrophage-like cells, and this effect was associated with significant inhibition of NF-kappaB activation. Choline (50 mg/kg, intraperitoneally [i.p.]) treatment prior to endotoxin administration in mice significantly reduced systemic TNF levels. In contrast to its TNF suppressive effect in wild type mice, choline (50 mg/kg, i.p.) failed to inhibit systemic TNF levels in alpha7nAChR knockout mice during endotoxemia. Choline also failed to suppress TNF release from endotoxin-activated peritoneal macrophages isolated from alpha7nAChR knockout mice. Choline treatment prior to endotoxin resulted in a significantly improved survival rate as compared with saline-treated endotoxemic controls. Choline also suppressed HMGB1 release in vitro and in vivo, and choline treatment initiated 24 h after cecal ligation and puncture (CLP)-induced polymicrobial sepsis significantly improved survival in mice. In addition, choline suppressed TNF release from endotoxin-activated human whole blood and macrophages. Collectively, these data characterize the anti-inflammatory efficacy of choline and demonstrate that the modulation of TNF release by choline requires alpha7nAChR-mediated signaling. Title: Cloning and expression of lipP, a gene encoding a cold-adapted lipase from Moritella sp.2-5-10-1 Yang X, Lin X, Fan T, Bian J, Huang X Ref: Curr Microbiol, 56:194, 2008 : PubMed ESTHER: Yang_2008_Curr.Microbiol_56_194 PubMedSearch: Yang 2008 Curr.Microbiol 56 194 PubMedID: 17973159 Abstract A gene (lipP, 837 bp in length) coding for a cold-adapted lipase of psychrophilic bacterium Moritella sp. 2-5-10-1 isolated from Antarctic region was cloned and sequenced in this study. The deduced amino acid sequence revealed a protein of 278 amino acid residues with a molecular mass of 30,521. The primary structure of the lipase deduced from the nucleotide sequence showed consensus pentapeptide containing the active serine [Gly-Trp-Ser-Leu-Gly] and a conserved His-Gly dipeptide in the N-terminal part of the enzyme. These sequences were involved in the lipase active site conformation. Structure factors that would allow proper enzyme flexibility at low temperatures were discussed. It was suggested that the changes in the primary structure of the psychrophilic lipases compared to the thermophilic ones could account for their ability to catalyze lipolysis at temperatures close to 0 degrees C. For expression, the sequence corresponding to the cold-adapted lipase of strain 2-5-10-1 was subcloned into the pET-28a expression vector to construct a recombinant lipase protein. Expression of the lipase by Escherichia coli BL21 (DE3) cells was observed as clear halos on 1% (vol/vol) tributyrin upon induction with IPTG at 25 degrees C. Title: Selective alpha7-nicotinic acetylcholine receptor agonist GTS-21 improves survival in murine endotoxemia and severe sepsis Pavlov VA, Ochani M, Yang LH, Gallowitsch-Puerta M, Ochani K, Lin X, Levi J, Parrish WR, Rosas-Ballina M and Al-Abed Y <4 more author(s)> Pavlov VA, Ochani M, Yang LH, Gallowitsch-Puerta M, Ochani K, Lin X, Levi J, Parrish WR, Rosas-Ballina M, Czura CJ, Larosa GJ, Miller EJ, Tracey KJ, Al-Abed Y (- 4) Ref: Critical Care Medicine, 35:1139, 2007 : PubMed ESTHER: Pavlov_2007_Crit.Care.Med_35_1139 PubMedSearch: Pavlov 2007 Crit.Care.Med 35 1139 PubMedID: 17334244 Abstract OBJECTIVE: Tumor necrosis factor and high mobility group box 1 are critical cytokine mediators of inflammation. The efferent vagus nerve inhibits cytokine release through alpha7-nicotinic acetylcholine receptor-mediated cholinergic signaling. Here we studied whether GTS-21, a selective alpha7-nicotinic acetylcholine receptor agonist, inhibits proinflammatory cytokines in vitro and in vivo and improves survival in murine endotoxemia and severe sepsis. DESIGN: Randomized and controlled in vitro and in vivo study. SETTINGS: Research laboratory and animal facility rooms. SUBJECTS: RAW 264.7 cells and BALB/c mice treated with endotoxin or subjected to cecal ligation and puncture (CLP). INTERVENTIONS: RAW 264.7 cells were exposed to endotoxin (4 ng/mL or 10 ng/mL) in the presence or absence of GTS-21 (1-100 muM), and tumor necrosis factor and high mobility group box 1 release and nuclear factor-kappaB activation were analyzed. Mice were treated with GTS-21 (0.4 mg/kg or 4 mg/kg, intraperitoneally) or saline 30 mins before endotoxin (6 mg/kg, intraperitoneally), and serum tumor necrosis factor was analyzed 1.5 hrs after the onset of endotoxemia. In survival experiments, mice were treated with GTS-21 (0.4 or 4.0 mg/kg, intraperitoneally) or saline 30 mins before and 6 hrs after endotoxin and then twice daily for 3 days. Severe sepsis was induced by CLP. Mice were treated with GTS-21 (4 mg/kg) or saline immediately and 6 hrs and 24 hrs after CLP, and serum high mobility group box 1 was analyzed 30 hrs after CLP. In survival experiments, GTS-21 (0.4 or 4 mg/kg) treatment was initiated 24 hrs after CLP and continued twice daily for 3 days. MEASUREMENTS AND MAIN Title: Ontogeny and chain-length specificity of gastrointestinal lipases affect medium-chain triacylglycerol utilization by newborn pigs Dicklin ME, Robinson JL, Lin X, Odle J Ref: J Anim Sci, 84:818, 2006 : PubMed ESTHER: Dicklin_2006_J.Anim.Sci_84_818 PubMedSearch: Dicklin 2006 J.Anim.Sci 84 818 PubMedID: 16543558 Abstract Ontogeny and fatty acid chain-length specificity of gastrointestinal lipases in neonatal piglets were examined to explore the basis for variations in postnatal use of medium-chain triacylglycerols (MCT). Twenty-four newborn pigs were studied at 4 ages: 0, 6, 18, and 48 h postpartum (n = 6 pigs/age). Piglets were gastrically intubated and given 3.0 mmol/kg of BW(0.75) each of emulsified tri-C6:0 and tri-C8:0. One hour after intubation, the plasma concentration of C6:0 was 7.5-fold greater than that of C8:0 (P < 0.001), with total plasma medium-chain fatty acid concentrations 3.7-fold greater at 48 h than at 6 h of age (P < 0.05). Pancreatic, gastric, and lingual tissues were analyzed for lipase activity using an equimolar mixture of tri-C6:0 and tri-C8:0 as substrate. Pancreatic lipase activity averaged 7.0 +/- 0.8 micromol of fatty acid released/min per mg of protein for the medium-chain fatty acid substrates. Hexanoate (C6:0) release was greater at 0 h than at 6, 18, or 48 h (P < 0.05); however, age did not affect C8:0 release (P > 0.05). The lowest lipase activity was observed at 18 h for both tri-C6:0 and tri-C8:0. Chain-length specificity of pancreatic lipase was measured with tri-C4:0, tri-C6:0, tri-C8:0, and tri-C10:0 as combined or separate substrates. As separate substrates, the lipase activity decreased progressively as chain length increased from tri-C4:0 to tri-C10:0. As combined substrates, tri-C6:0 was hydrolyzed fastest (P < 0.05), followed by C4:0, C8:0, and C10:0. Gastric and lingual lipase activities averaged 2.7 nmol/min per mg of protein for the medium-chain fatty acid substrates, with hydrolysis of C6:0 being 7-fold greater than that of C8:0. In conclusion, pancreatic lipase dominates the preduodenal lipases in the neonatal pig, and greater activity of the gastrointestinal lipases toward tri-C6:0 underlies its increased rate of use. Title: Design, synthesis, and evaluation of 2-phenoxy-indan-1-one derivatives as acetylcholinesterase inhibitors Sheng R, Lin X, Li J, Jiang Y, Shang Z, Hu Y Ref: Bioorganic & Medicinal Chemistry Lett, 15:3834, 2005 : PubMed ESTHER: Sheng_2005_Bioorg.Med.Chem.Lett_15_3834 PubMedSearch: Sheng 2005 Bioorg.Med.Chem.Lett 15 3834 PubMedID: 15993600 Inhibitor(s) related to this paper: BYYT-25 Abstract A series of 2-phenoxy-indan-1-one derivatives have been designed, synthesized, and tested as acetylcholinesterase inhibitors. The most potent compound exhibited high AChE inhibitory activity (IC50 = 50 nM), and the molecular docking study indicated that it was nicely accommodated by AChE. Title: Neuroprotection by D-securinine against neurotoxicity induced by beta-amyloid (25-35) Lin X, Jun-Tian Z Ref: Neurol Res, 26:792, 2004 : PubMed ESTHER: Lin_2004_Neurol.Res_26_792 PubMedSearch: Lin 2004 Neurol.Res 26 792 PubMedID: 15494124 Abstract The effects of (+) securinine on behavior and morphological changes after intracerebral ventricle injection of beta-amyloid (25-35) (Abeta(25-35)) in rats were investigated. A single high dose of Abeta(25-35) could impair the spatial cognitive function. The latency of locating the platform was longer in the model group than in the sham-operated group. While chronic administration of D-securinine (40 mg kg(-1)) could significantly shorten the latency. After Morris water maze, the activity of choline acetyltransferase (ChAT) and acetylcholinesterase (AchE) were detected. The results showed that D-securinine could decrease the AchE activity significantly and have no effect on ChAT. Meanwhile, immunohistochemistry analysis revealed that D-securinine could reduce the glial inflammatory responses induced by beta-amyloid protein. These results suggest that the effect of D-securinine in improving the cognitive deficits and neurodegeneration in betaAP(25-35)-treated rats may involve direct and indirect actions on targets. The GABA receptor plays a key role in these therapeutic effects and may be helpful in the treatment of Alzheimer's disease. Title: Cholinergic agonists inhibit HMGB1 release and improve survival in experimental sepsis Wang H, Liao H, Ochani M, Justiniani M, Lin X, Yang L, Al-Abed Y, Metz C, Miller EJ and Ulloa L <1 more author(s)> Wang H, Liao H, Ochani M, Justiniani M, Lin X, Yang L, Al-Abed Y, Metz C, Miller EJ, Tracey KJ, Ulloa L (- 1) Ref: Nat Med, 10:1216, 2004 : PubMed ESTHER: Wang_2004_Nat.Med_10_1216 PubMedSearch: Wang 2004 Nat.Med 10 1216 PubMedID: 15502843 Abstract Physiological anti-inflammatory mechanisms can potentially be exploited for the treatment of inflammatory disorders. Here we report that the neurotransmitter acetylcholine inhibits HMGB1 release from human macrophages by signaling through a nicotinic acetylcholine receptor. Nicotine, a selective cholinergic agonist, is more efficient than acetylcholine and inhibits HMGB1 release induced by either endotoxin or tumor necrosis factor-alpha (TNF-alpha). Nicotinic stimulation prevents activation of the NF-kappaB pathway and inhibits HMGB1 secretion through a specific 'nicotinic anti-inflammatory pathway' that requires the alpha7 nicotinic acetylcholine receptor (alpha7nAChR). In vivo, treatment with nicotine attenuates serum HMGB1 levels and improves survival in experimental models of sepsis, even when treatment is started after the onset of the disease. These results reveal acetylcholine as the first known physiological inhibitor of HMGB1 release from human macrophages and suggest that selective nicotinic agonists for the alpha7nAChR might have therapeutic potential for the treatment of sepsis. Title: The sequence of the human genome Venter JC, Adams MD, Myers EW, Li PW, Mural RJ, Sutton GG, Smith HO, Yandell M, Evans CA and Zhu X <264 more author(s)> Venter JC, Adams MD, Myers EW, Li PW, Mural RJ, Sutton GG, Smith HO, Yandell M, Evans CA, Holt RA, Gocayne JD, Amanatides P, Ballew RM, Huson DH, Wortman JR, Zhang Q, Kodira CD, Zheng XH, Chen L, Skupski M, Subramanian G, Thomas PD, Zhang J, Gabor Miklos GL, Nelson C, Broder S, Clark AG, Nadeau J, McKusick VA, Zinder N, Levine AJ, Roberts RJ, Simon M, Slayman C, Hunkapiller M, Bolanos R, Delcher A, Dew I, Fasulo D, Flanigan M, Florea L, Halpern A, Hannenhalli S, Kravitz S, Levy S, Mobarry C, Reinert K, Remington K, Abu-Threideh J, Beasley E, Biddick K, Bonazzi V, Brandon R, Cargill M, Chandramouliswaran I, Charlab R, Chaturvedi K, Deng Z, Di Francesco V, Dunn P, Eilbeck K, Evangelista C, Gabrielian AE, Gan W, Ge W, Gong F, Gu Z, Guan P, Heiman TJ, Higgins ME, Ji RR, Ke Z, Ketchum KA, Lai Z, Lei Y, Li Z, Li J, Liang Y, Lin X, Lu F, Merkulov GV, Milshina N, Moore HM, Naik AK, Narayan VA, Neelam B, Nusskern D, Rusch DB, Salzberg S, Shao W, Shue B, Sun J, Wang Z, Wang A, Wang X, Wang J, Wei M, Wides R, Xiao C, Yan C, Yao A, Ye J, Zhan M, Zhang W, Zhang H, Zhao Q, Zheng L, Zhong F, Zhong W, Zhu S, Zhao S, Gilbert D, Baumhueter S, Spier G, Carter C, Cravchik A, Woodage T, Ali F, An H, Awe A, Baldwin D, Baden H, Barnstead M, Barrow I, Beeson K, Busam D, Carver A, Center A, Cheng ML, Curry L, Danaher S, Davenport L, Desilets R, Dietz S, Dodson K, Doup L, Ferriera S, Garg N, Gluecksmann A, Hart B, Haynes J, Haynes C, Heiner C, Hladun S, Hostin D, Houck J, Howland T, Ibegwam C, Johnson J, Kalush F, Kline L, Koduru S, Love A, Mann F, May D, McCawley S, McIntosh T, McMullen I, Moy M, Moy L, Murphy B, Nelson K, Pfannkoch C, Pratts E, Puri V, Qureshi H, Reardon M, Rodriguez R, Rogers YH, Romblad D, Ruhfel B, Scott R, Sitter C, Smallwood M, Stewart E, Strong R, Suh E, Thomas R, Tint NN, Tse S, Vech C, Wang G, Wetter J, Williams S, Williams M, Windsor S, Winn-Deen E, Wolfe K, Zaveri J, Zaveri K, Abril JF, Guigo R, Campbell MJ, Sjolander KV, Karlak B, Kejariwal A, Mi H, Lazareva B, Hatton T, Narechania A, Diemer K, Muruganujan A, Guo N, Sato S, Bafna V, Istrail S, Lippert R, Schwartz R, Walenz B, Yooseph S, Allen D, Basu A, Baxendale J, Blick L, Caminha M, Carnes-Stine J, Caulk P, Chiang YH, Coyne M, Dahlke C, Mays A, Dombroski M, Donnelly M, Ely D, Esparham S, Fosler C, Gire H, Glanowski S, Glasser K, Glodek A, Gorokhov M, Graham K, Gropman B, Harris M, Heil J, Henderson S, Hoover J, Jennings D, Jordan C, Jordan J, Kasha J, Kagan L, Kraft C, Levitsky A, Lewis M, Liu X, Lopez J, Ma D, Majoros W, McDaniel J, Murphy S, Newman M, Nguyen T, Nguyen N, Nodell M, Pan S, Peck J, Peterson M, Rowe W, Sanders R, Scott J, Simpson M, Smith T, Sprague A, Stockwell T, Turner R, Venter E, Wang M, Wen M, Wu D, Wu M, Xia A, Zandieh A, Zhu X (- 264) Ref: Science, 291:1304, 2001 : PubMed ESTHER: Venter_2001_Science_291_1304 PubMedSearch: Venter 2001 Science 291 1304 PubMedID: 11181995 Gene_locus related to this paper: human-AADAC, human-ABHD1, human-ABHD10, human-ABHD11, human-ACHE, human-BCHE, human-LDAH, human-ABHD18, human-CMBL, human-ABHD17A, human-KANSL3, human-LIPA, human-LYPLAL1, human-NDRG2, human-NLGN3, human-NLGN4X, human-NLGN4Y, human-PAFAH2, human-PREPL, human-RBBP9, human-SPG21 Abstract A 2.91-billion base pair (bp) consensus sequence of the euchromatic portion of the human genome was generated by the whole-genome shotgun sequencing method. The 14.8-billion bp DNA sequence was generated over 9 months from 27,271,853 high-quality sequence reads (5.11-fold coverage of the genome) from both ends of plasmid clones made from the DNA of five individuals. Two assembly strategies-a whole-genome assembly and a regional chromosome assembly-were used, each combining sequence data from Celera and the publicly funded genome effort. The public data were shredded into 550-bp segments to create a 2.9-fold coverage of those genome regions that had been sequenced, without including biases inherent in the cloning and assembly procedure used by the publicly funded group. This brought the effective coverage in the assemblies to eightfold, reducing the number and size of gaps in the final assembly over what would be obtained with 5.11-fold coverage. The two assembly strategies yielded very similar results that largely agree with independent mapping data. The assemblies effectively cover the euchromatic regions of the human chromosomes. More than 90% of the genome is in scaffold assemblies of 100,000 bp or more, and 25% of the genome is in scaffolds of 10 million bp or larger. Analysis of the genome sequence revealed 26,588 protein-encoding transcripts for which there was strong corroborating evidence and an additional approximately 12,000 computationally derived genes with mouse matches or other weak supporting evidence. Although gene-dense clusters are obvious, almost half the genes are dispersed in low G+C sequence separated by large tracts of apparently noncoding sequence. Only 1.1% of the genome is spanned by exons, whereas 24% is in introns, with 75% of the genome being intergenic DNA. Duplications of segmental blocks, ranging in size up to chromosomal lengths, are abundant throughout the genome and reveal a complex evolutionary history. Comparative genomic analysis indicates vertebrate expansions of genes associated with neuronal function, with tissue-specific developmental regulation, and with the hemostasis and immune systems. DNA sequence comparisons between the consensus sequence and publicly funded genome data provided locations of 2.1 million single-nucleotide polymorphisms (SNPs). A random pair of human haploid genomes differed at a rate of 1 bp per 1250 on average, but there was marked heterogeneity in the level of polymorphism across the genome. Less than 1% of all SNPs resulted in variation in proteins, but the task of determining which SNPs have functional consequences remains an open challenge. Title: The genome sequence of Drosophila melanogaster Adams MD, Celniker SE, Holt RA, Evans CA, Gocayne JD, Amanatides PG, Scherer SE, Li PW, Hoskins RA and Venter JC <185 more author(s)> Adams MD, Celniker SE, Holt RA, Evans CA, Gocayne JD, Amanatides PG, Scherer SE, Li PW, Hoskins RA, Galle RF, George RA, Lewis SE, Richards S, Ashburner M, Henderson SN, Sutton GG, Wortman JR, Yandell MD, Zhang Q, Chen LX, Brandon RC, Rogers YH, Blazej RG, Champe M, Pfeiffer BD, Wan KH, Doyle C, Baxter EG, Helt G, Nelson CR, Gabor GL, Abril JF, Agbayani A, An HJ, Andrews-Pfannkoch C, Baldwin D, Ballew RM, Basu A, Baxendale J, Bayraktaroglu L, Beasley EM, Beeson KY, Benos PV, Berman BP, Bhandari D, Bolshakov S, Borkova D, Botchan MR, Bouck J, Brokstein P, Brottier P, Burtis KC, Busam DA, Butler H, Cadieu E, Center A, Chandra I, Cherry JM, Cawley S, Dahlke C, Davenport LB, Davies P, de Pablos B, Delcher A, Deng Z, Mays AD, Dew I, Dietz SM, Dodson K, Doup LE, Downes M, Dugan-Rocha S, Dunkov BC, Dunn P, Durbin KJ, Evangelista CC, Ferraz C, Ferriera S, Fleischmann W, Fosler C, Gabrielian AE, Garg NS, Gelbart WM, Glasser K, Glodek A, Gong F, Gorrell JH, Gu Z, Guan P, Harris M, Harris NL, Harvey D, Heiman TJ, Hernandez JR, Houck J, Hostin D, Houston KA, Howland TJ, Wei MH, Ibegwam C, Jalali M, Kalush F, Karpen GH, Ke Z, Kennison JA, Ketchum KA, Kimmel BE, Kodira CD, Kraft C, Kravitz S, Kulp D, Lai Z, Lasko P, Lei Y, Levitsky AA, Li J, Li Z, Liang Y, Lin X, Liu X, Mattei B, McIntosh TC, McLeod MP, McPherson D, Merkulov G, Milshina NV, Mobarry C, Morris J, Moshrefi A, Mount SM, Moy M, Murphy B, Murphy L, Muzny DM, Nelson DL, Nelson DR, Nelson KA, Nixon K, Nusskern DR, Pacleb JM, Palazzolo M, Pittman GS, Pan S, Pollard J, Puri V, Reese MG, Reinert K, Remington K, Saunders RD, Scheeler F, Shen H, Shue BC, Siden-Kiamos I, Simpson M, Skupski MP, Smith T, Spier E, Spradling AC, Stapleton M, Strong R, Sun E, Svirskas R, Tector C, Turner R, Venter E, Wang AH, Wang X, Wang ZY, Wassarman DA, Weinstock GM, Weissenbach J, Williams SM, WoodageT, Worley KC, Wu D, Yang S, Yao QA, Ye J, Yeh RF, Zaveri JS, Zhan M, Zhang G, Zhao Q, Zheng L, Zheng XH, Zhong FN, Zhong W, Zhou X, Zhu S, Zhu X, Smith HO, Gibbs RA, Myers EW, Rubin GM, Venter JC (- 185) Ref: Science, 287:2185, 2000 : PubMed ESTHER: Adams_2000_Science_287_2185 PubMedSearch: Adams 2000 Science 287 2185 PubMedID: 10731132 Gene_locus related to this paper: drome-1vite, drome-2vite, drome-3vite, drome-a1z6g9, drome-abhd2, drome-ACHE, drome-b6idz4, drome-BEM46, drome-CG5707, drome-CG5704, drome-CG1309, drome-CG1882, drome-CG1986, drome-CG2059, drome-CG2493, drome-CG2528, drome-CG2772, drome-CG3160, drome-CG3344, drome-CG3523, drome-CG3524, drome-CG3734, drome-CG3739, drome-CG3744, drome-CG3841, drome-CG4267, drome-CG4382, drome-CG4390, drome-CG4572, drome-CG4582, drome-CG4851, drome-CG4979, drome-CG5068, drome-CG5162, drome-CG5355, drome-CG5377, drome-CG5397, drome-CG5412, drome-CG5665, drome-CG5932, drome-CG5966, drome-CG6018, drome-CG6113, drome-CG6271, drome-CG6283, drome-CG6295, drome-CG6296, drome-CG6414, drome-CG6431, drome-CG6472, drome-CG6567, drome-CG6675, drome-CG6753, drome-CG6847, drome-CG7329, drome-CG7367, drome-CG7529, drome-CG7632, drome-CG8058, drome-CG8093, drome-CG8233, drome-CG8424, drome-CG8425, drome-CG9059, drome-CG9186, drome-CG9287, drome-CG9289, drome-CG9542, drome-CG9858, drome-CG9953, drome-CG9966, drome-CG10116, drome-CG10163, drome-CG10175, drome-CG10339, drome-CG10357, drome-CG10982, drome-CG11034, drome-CG11055, drome-CG11309, drome-CG11319, drome-CG11406, drome-CG11598, drome-CG11600, drome-CG11608, drome-CG11626, drome-CG11935, drome-CG12108, drome-CG12869, drome-CG13282, drome-CG13562, drome-CG13772, drome-CG14034, drome-nlg3, drome-CG14717, drome-CG15101, drome-CG15102, drome-CG15106, drome-CG15111, drome-CG15820, drome-CG15821, drome-CG15879, drome-CG17097, drome-CG17099, drome-CG17101, drome-CG17191, drome-CG17192, drome-CG17292, drome-CG18258, drome-CG18284, drome-CG18301, drome-CG18302, drome-CG18493, drome-CG18530, drome-CG18641, drome-CG18815, drome-CG31089, drome-CG31091, drome-CG32333, drome-CG32483, drome-CG33174, drome-dnlg1, drome-este4, drome-este6, drome-GH02384, drome-GH02439, drome-glita, drome-KRAKEN, drome-lip1, drome-LIP2, drome-lip3, drome-MESK2, drome-nrtac, drome-OME, drome-q7k274, drome-Q9VJN0, drome-Q8IP31, drome-q9vux3 Abstract The fly Drosophila melanogaster is one of the most intensively studied organisms in biology and serves as a model system for the investigation of many developmental and cellular processes common to higher eukaryotes, including humans. We have determined the nucleotide sequence of nearly all of the approximately 120-megabase euchromatic portion of the Drosophila genome using a whole-genome shotgun sequencing strategy supported by extensive clone-based sequence and a high-quality bacterial artificial chromosome physical map. Efforts are under way to close the remaining gaps; however, the sequence is of sufficient accuracy and contiguity to be declared substantially complete and to support an initial analysis of genome structure and preliminary gene annotation and interpretation. The genome encodes approximately 13,600 genes, somewhat fewer than the smaller Caenorhabditis elegans genome, but with comparable functional diversity. Title: Sequence and analysis of chromosome 3 of the plant Arabidopsis thaliana Salanoubat M, Lemcke K, Rieger M, Ansorge W, Unseld M, Fartmann B, Valle G, Blocker H, Perez-Alonso M and Tabata S <127 more author(s)> Salanoubat M, Lemcke K, Rieger M, Ansorge W, Unseld M, Fartmann B, Valle G, Blocker H, Perez-Alonso M, Obermaier B, Delseny M, Boutry M, Grivell LA, Mache R, Puigdomenech P, de Simone V, Choisne N, Artiguenave F, Robert C, Brottier P, Wincker P, Cattolico L, Weissenbach J, Saurin W, Quetier F, Schafer M, Muller-Auer S, Gabel C, Fuchs M, Benes V, Wurmbach E, Drzonek H, Erfle H, Jordan N, Bangert S, Wiedelmann R, Kranz H, Voss H, Holland R, Brandt P, Nyakatura G, Vezzi A, D'Angelo M, Pallavicini A, Toppo S, Simionati B, Conrad A, Hornischer K, Kauer G, Lohnert TH, Nordsiek G, Reichelt J, Scharfe M, Schon O, Bargues M, Terol J, Climent J, Navarro P, Collado C, Perez-Perez A, Ottenwalder B, Duchemin D, Cooke R, Laudie M, Berger-Llauro C, Purnelle B, Masuy D, de Haan M, Maarse AC, Alcaraz JP, Cottet A, Casacuberta E, Monfort A, Argiriou A, Flores M, Liguori R, Vitale D, Mannhaupt G, Haase D, Schoof H, Rudd S, Zaccaria P, Mewes HW, Mayer KF, Kaul S, Town CD, Koo HL, Tallon LJ, Jenkins J, Rooney T, Rizzo M, Walts A, Utterback T, Fujii CY, Shea TP, Creasy TH, Haas B, Maiti R, Wu D, Peterson J, Van Aken S, Pai G, Militscher J, Sellers P, Gill JE, Feldblyum TV, Preuss D, Lin X, Nierman WC, Salzberg SL, White O, Venter JC, Fraser CM, Kaneko T, Nakamura Y, Sato S, Kato T, Asamizu E, Sasamoto S, Kimura T, Idesawa K, Kawashima K, Kishida Y, Kiyokawa C, Kohara M, Matsumoto M, Matsuno A, Muraki A, Nakayama S, Nakazaki N, Shinpo S, Takeuchi C, Wada T, Watanabe A, Yamada M, Yasuda M, Tabata S (- 127) Ref: Nature, 408:820, 2000 : PubMed ESTHER: Salanoubat_2000_Nature_408_820 PubMedSearch: Salanoubat 2000 Nature 408 820 PubMedID: 11130713 Gene_locus related to this paper: arath-MES17, arath-AT3G12150, arath-At3g61680, arath-AT3g62590, arath-CXE12, arath-eds1, arath-SCP25, arath-F1P2.110, arath-F1P2.140, arath-F11F8.28, arath-F14D17.80, arath-F16B3.4, arath-SCP27, arath-At3g50790, arath-At3g05600, arath-PAD4, arath-At3g51000, arath-SCP16, arath-gid1, arath-GID1B, arath-Q9LUG8, arath-Q84JS1, arath-Q9SFF6, arath-q9m236, arath-q9sr22, arath-q9sr23, arath-SCP7, arath-SCP14, arath-SCP15, arath-SCP17, arath-SCP36, arath-SCP37, arath-SCP39, arath-SCP40, arath-SCP49, arath-T19F11.2 Abstract Arabidopsis thaliana is an important model system for plant biologists. In 1996 an international collaboration (the Arabidopsis Genome Initiative) was formed to sequence the whole genome of Arabidopsis and in 1999 the sequence of the first two chromosomes was reported. The sequence of the last three chromosomes and an analysis of the whole genome are reported in this issue. Here we present the sequence of chromosome 3, organized into four sequence segments (contigs). The two largest (13.5 and 9.2 Mb) correspond to the top (long) and the bottom (short) arms of chromosome 3, and the two small contigs are located in the genetically defined centromere. This chromosome encodes 5,220 of the roughly 25,500 predicted protein-coding genes in the genome. About 20% of the predicted proteins have significant homology to proteins in eukaryotic genomes for which the complete sequence is available, pointing to important conserved cellular functions among eukaryotes. Title: Sequence and analysis of chromosome 1 of the plant Arabidopsis thaliana Theologis A, Ecker JR, Palm CJ, Federspiel NA, Kaul S, White O, Alonso J, Altafi H, Araujo R and Davis RW <79 more author(s)> Theologis A, Ecker JR, Palm CJ, Federspiel NA, Kaul S, White O, Alonso J, Altafi H, Araujo R, Bowman CL, Brooks SY, Buehler E, Chan A, Chao Q, Chen H, Cheuk RF, Chin CW, Chung MK, Conn L, Conway AB, Conway AR, Creasy TH, Dewar K, Dunn P, Etgu P, Feldblyum TV, Feng J, Fong B, Fujii CY, Gill JE, Goldsmith AD, Haas B, Hansen NF, Hughes B, Huizar L, Hunter JL, Jenkins J, Johnson-Hopson C, Khan S, Khaykin E, Kim CJ, Koo HL, Kremenetskaia I, Kurtz DB, Kwan A, Lam B, Langin-Hooper S, Lee A, Lee JM, Lenz CA, Li JH, Li Y, Lin X, Liu SX, Liu ZA, Luros JS, Maiti R, Marziali A, Militscher J, Miranda M, Nguyen M, Nierman WC, Osborne BI, Pai G, Peterson J, Pham PK, Rizzo M, Rooney T, Rowley D, Sakano H, Salzberg SL, Schwartz JR, Shinn P, Southwick AM, Sun H, Tallon LJ, Tambunga G, Toriumi MJ, Town CD, Utterback T, Van Aken S, Vaysberg M, Vysotskaia VS, Walker M, Wu D, Yu G, Fraser CM, Venter JC, Davis RW (- 79) Ref: Nature, 408:816, 2000 : PubMed ESTHER: Theologis_2000_Nature_408_816 PubMedSearch: Theologis 2000 Nature 408 816 PubMedID: 11130712 Gene_locus related to this paper: arath-At1g05790, arath-At1g09280, arath-At1g09980, arath-AT1G29120, arath-AT1G52695, arath-AT1G66900, arath-At1g73750, arath-AT1G73920, arath-AT1G74640, arath-AT1G76140, arath-AT1G78210, arath-clh1, arath-F1O17.3, arath-F1O17.4, arath-F1O17.5, arath-F5I6.3, arath-At1g52700, arath-F6D8.27, arath-F6D8.32, arath-F9L1.44, arath-F9P14.11, arath-F12A4.4, arath-MES11, arath-F14G24.2, arath-F14G24.3, arath-F14I3.4, arath-F14O10.2, arath-F16N3.25, arath-LCAT2, arath-At1g34340, arath-MES15, arath-CXE6, arath-ICML1, arath-At1g72620, arath-LCAT1, arath-PLA12, arath-PLA15, arath-PLA17, arath-Q8L7S1, arath-At1g15070, arath-SCP2, arath-SCP4, arath-SCP5, arath-SCP18, arath-SCP32, arath-SCP44, arath-SCP45, arath-SCPL6, arath-F4IE65, arath-At1g30370, arath-T6L1.8, arath-T6L1.20, arath-T14P4.6, arath-MES14, arath-SCP3, arath-AXR4, arath-At1g10040, arath-ZW18, arath-pae2, arath-pae1, arath-a0a1p8awg3 Abstract The genome of the flowering plant Arabidopsis thaliana has five chromosomes. Here we report the sequence of the largest, chromosome 1, in two contigs of around 14.2 and 14.6 megabases. The contigs extend from the telomeres to the centromeric borders, regions rich in transposons, retrotransposons and repetitive elements such as the 180-base-pair repeat. The chromosome represents 25% of the genome and contains about 6,850 open reading frames, 236 transfer RNAs (tRNAs) and 12 small nuclear RNAs. There are two clusters of tRNA genes at different places on the chromosome. One consists of 27 tRNA(Pro) genes and the other contains 27 tandem repeats of tRNA(Tyr)-tRNA(Tyr)-tRNA(Ser) genes. Chromosome 1 contains about 300 gene families with clustered duplications. There are also many repeat elements, representing 8% of the sequence. Title: Sequence and analysis of chromosome 2 of the plant Arabidopsis thaliana Lin X, Kaul S, Rounsley S, Shea TP, Benito MI, Town CD, Fujii CY, Mason T, Bowman CL and Venter JC <27 more author(s)> Lin X, Kaul S, Rounsley S, Shea TP, Benito MI, Town CD, Fujii CY, Mason T, Bowman CL, Barnstead M, Feldblyum TV, Buell CR, Ketchum KA, Lee J, Ronning CM, Koo HL, Moffat KS, Cronin LA, Shen M, Pai G, Van Aken S, Umayam L, Tallon LJ, Gill JE, Adams MD, Carrera AJ, Creasy TH, Goodman HM, Somerville CR, Copenhaver GP, Preuss D, Nierman WC, White O, Eisen JA, Salzberg SL, Fraser CM, Venter JC (- 27) Ref: Nature, 402:761, 1999 : PubMed ESTHER: Lin_1999_Nature_402_761 PubMedSearch: Lin 1999 Nature 402 761 PubMedID: 10617197 Gene_locus related to this paper: arath-At2g45610, arath-AT2G03550, arath-AT2G05260, arath-AT2G12480, arath-At2g15230, arath-At2g18360, arath-At2g19550, arath-At2g19620, arath-At2g24280, arath-AT2G24320, arath-At2g26740, arath-At2g26750, arath-SCP51, arath-AT2G36290, arath-At2g42450, arath-AT2G42690, arath-AT2G44970, arath-At2g47630, arath-AT3g62590, arath-CGEP, arath-F12L6.6, arath-F12L6.7, arath-F12L6.8, arath-At3g50790, arath-MES6, arath-MES7, arath-MES4, arath-MES8, arath-MES2, arath-MES3, arath-MES1, arath-o80731, arath-pip, arath-PLA11, arath-PLA13, arath-PLA16, arath-PLA19, arath-q84w08, arath-SCP8, arath-SCP9, arath-SCP10, arath-SCP11, arath-SCP12, arath-SCP13, arath-SCP23, arath-SCP26, arath-SCP28, arath-SCP46, arath-T26B15.8, arath-SCP22, arath-SFGH, arath-MES19 Abstract Arabidopsis thaliana (Arabidopsis) is unique among plant model organisms in having a small genome (130-140 Mb), excellent physical and genetic maps, and little repetitive DNA. Here we report the sequence of chromosome 2 from the Columbia ecotype in two gap-free assemblies (contigs) of 3.6 and 16 megabases (Mb). The latter represents the longest published stretch of uninterrupted DNA sequence assembled from any organism to date. Chromosome 2 represents 15% of the genome and encodes 4,037 genes, 49% of which have no predicted function. Roughly 250 tandem gene duplications were found in addition to large-scale duplications of about 0.5 and 4.5 Mb between chromosomes 2 and 1 and between chromosomes 2 and 4, respectively. Sequencing of nearly 2 Mb within the genetically defined centromere revealed a low density of recognizable genes, and a high density and diverse range of vestigial and presumably inactive mobile elements. More unexpected is what appears to be a recent insertion of a continuous stretch of 75% of the mitochondrial genome into chromosome 2. | |||||||
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