Author Report for: Wang MNo contact information in database for Wang M
Lei K, Liang R, Tan B, Li L, Lyu Y, Wang K, Wang W, Hu X, Wu D and Wang M <1 more author(s)> Lei K, Liang R, Tan B, Li L, Lyu Y, Wang K, Wang W, Hu X, Wu D, Lin H, Wang M (- 1) Ref: Oxid Med Cell Longev, 2023:6811625, 2023 : PubMed ESTHER: Lei_2023_Oxid.Med.Cell.Longev_2023_6811625 PubMedSearch: Lei 2023 Oxid.Med.Cell.Longev 2023 6811625 PubMedID: 36703911 Abstract BACKGROUND: Lipid metabolism reprogramming played an important role in cancer occurrence, development, and immune regulation. The aim of this study was to identify and validate lipid metabolism-related genes (LMRGs) associated with the phenotype, prognosis, and immunological characteristics of lung squamous cell carcinoma (LUSC). METHODS: In the TCGA cohort, bioinformatics and survival analysis were used to identify lipid metabolism-related differentially expressed genes (DEGs) associated with the prognosis of LUSC. PTGIS/HRASLS knockdown and overexpression effects on the LUSC phenotype were analyzed in vitro experiments. Based on the expression distribution of PTGIS/HRASLS, LUSC patients were divided into two clusters by consensus clustering. Clinical information, prognosis, immune infiltration, expression of immune checkpoints, and tumor mutation burden (TMB) level were compared between the TCGA and GSE4573 cohorts. The genes related to clustering and tumor immunity were screened by weighted gene coexpression network analysis (WGCNA), and the target module genes were analyzed by functional enrichment analysis, protein-protein interaction (PPI) analysis, and immune correlation analysis. RESULTS: 191 lipid metabolism-related DEGs were identified, of which 5 genes were independent prognostic genes of LUSC. PTGIS/HRASLS were most closely related to LUSC prognosis and immunity. RT-qPCR, western blot (WB) analysis, and immunohistochemistry (IHC) showed that the expression of PTGIS was low in LUSC, while HRASLS was high. Functionally, PTGIS promoted LUSC proliferation, migration, and invasion, while HRASLS inhibited LUSC proliferation, migration, and invasion. The two clusters' expression and distribution of PTGIS/HRASLS had the opposite trend. Cluster 1 was associated with lower pathological staging (pT, pN, and pTNM stages), better prognosis, stronger immune infiltration, higher expression of immune checkpoints, and higher TMB level than cluster 2. WGCNA found that 28 genes including CD4 and IL10RA were related to the expression of PTGIS/HRASLS and tumor immune infiltration. PTGIS/HRASLS in the GSE4573 cohort had the same effect on LUSC prognosis and tumor immunity as the TCGA cohort. CONCLUSIONS: PTGIS and HRASLS can be used as new therapeutic targets for LUSC as well as biomarkers for prognosis and tumor immunity, which has positive significance for guiding the immunotherapy of LUSC. Title: Changes in the VOC of Fruits at Different Refrigeration Stages of 'Ruixue' and the Participation of Carboxylesterase MdCXE20 in the Catabolism of Volatile Esters Li L, Ding L, Shao Y, Sun S, Wang M, Xiang J, Zhou J, Wu G, Song Z and Gao H <9 more author(s)> Li L, Ding L, Shao Y, Sun S, Wang M, Xiang J, Zhou J, Wu G, Song Z, Xin Z, Li D, Guo J, Ma H, Pei L, Liu X, Wang H, Chen R, Zhao Z, Gao H (- 9) Ref: Foods, 12:, 2023 : PubMed ESTHER: Li_2023_Foods_12_ PubMedSearch: Li 2023 Foods 12 PubMedID: 36981096 37238795 Abstract Aroma is a crucial quality attribute of apple fruit, which significantly impacts its commercial value and consumer choice. Despite its importance the volatile aroma substances produced by the new variety 'Ruixue' after harvest remain unclear. In this study, we utilized headspace solid phase microextraction-gas chromatography-mass spectrometry (HS-SPME-GC-MS) to investigate the changes in volatile substances, fruit hardness, crispness, and related aroma synthase activity of commercially mature 'Ruixue' apples during cold storage. Our findings revealed a gradual decline in fruit firmness and brittleness of 'Ruixue' apples during cold storage, with hexyl acetate, hexyl caproate, and hexyl thiocyanate being the main hexyl esters detected. To gain a better understanding of the metabolic pathway of esters, we identified 42 MdCXE gene members that are associated with ester degradation. Through RT-qPCR analysis, we discovered that carboxylesterase MdCXE20 exhibited higher expression levels compared to other MdCXE genes during cold storage. To confirm the role of MdCXE20, we conducted a transient injection of apple fruits and observed that overexpression of MdCXE20 led to the degradation of esters such as hexyl hexanoate, butyl hexanoate, butyl 2-methylbutyrate, hexyl butyrate, and hexyl 2-methylbutyrate. The results of the study showed that the virus-induced gene silencing of MdCXE20 found the opposite results. Additionally, the esters of OE-MdCXE20 callus showed a lower content of ester VOC than the control callus, according to the homologous stable transformation of 'Wanglin' callus. Overall, these findings suggest that the MdCXE20 gene plays a crucial role in the decrease of esters in 'Ruixue' apples, which ultimately affects their flavor. Title: Development of a Nomogram for Predicting Mortality Risk in Sepsis Patients During Hospitalization: A Retrospective Study Lu B, Pan X, Wang B, Jin C, Liu C, Wang M, Shi Y Ref: Infect Drug Resist, 16:2311, 2023 : PubMed ESTHER: Lu_2023_Infect.Drug.Resist_16_2311 PubMedSearch: Lu 2023 Infect.Drug.Resist 16 2311 PubMedID: 37155474 Abstract PURPOSE: We attempted to establish a model for predicting the mortality risk of sepsis patients during hospitalization. PATIENTS AND METHODS: Data on patients with sepsis were collected from a clinical record mining database, who were hospitalized at the Affiliated Dongyang Hospital of Wenzhou Medical University between January 2013 and August 2022. These included patients were divided into modeling and validation groups. In the modeling group, the independent risk factors of death during hospitalization were determined using univariate and multi-variate regression analyses. After stepwise regression analysis (both directions), a nomogram was drawn. The discrimination ability of the model was evaluated using the area under the curve (AUC) of the receiver operating characteristic (ROC) curve, and the GiViTI calibration chart assessed the model calibration. The Decline Curve Analysis (DCA) was performed to evaluate the clinical effectiveness of the prediction model. Among the validation group, the logistic regression model was compared to the models established by the SOFA scoring system, random forest method, and stacking method. RESULTS: A total of 1740 subjects were included in this study, 1218 in the modeling population and 522 in the validation population. The results revealed that serum cholinesterase, total bilirubin, respiratory failure, lactic acid, creatinine, and pro-brain natriuretic peptide were the independent risk factors of death. The AUC values in the modeling group and validation group were 0.847 and 0.826. The P values of calibration charts in the two population sets were 0.838 and 0.771. The DCA curves were above the two extreme curves. Moreover, the AUC values of the models established by the SOFA scoring system, random forest method, and stacking method in the validation group were 0.777, 0.827, and 0.832, respectively. CONCLUSION: The nomogram model established by combining multiple risk factors could effectively predict the mortality risk of sepsis patients during hospitalization. Title: Ultra-small magnetic Candida antarctica lipase B nanoreactors for enzyme synthesis of bixin-maltitol ester Lv D, Wang M, He W, Wu J, Liu X, Guan Y Ref: Food Chem, 421:136132, 2023 : PubMed ESTHER: Lv_2023_Food.Chem_421_136132 PubMedSearch: Lv 2023 Food.Chem 421 136132 PubMedID: 37094396 Abstract Bixin has desirable bioactivities but poor water solubility, which limits its practical applications. Enzymatic transesterification of methyl to alditol groups in bixin by Candida antarctica lipase B (CALB) improves bixin water solubility. Herein, magnetic CALB nanoreactors with diameter of 11.7 nm and CALB layer thickness of 3.5 nm were developed by covalently linking CALB onto silicon covered Fe(3)O(4) nanoparticles. The CALB loading capacity in nanoreactors achieved 30%. The Michaelis constant (Km) and maximum reaction rate of magnetic CALB nanoreactors were 56.1 mmol/L and 0.2 mmol/(L.min). Magnetic CALB nanoreactors could circularly catalyze bixin-maltitol ester synthesis and keep catalytic efficiency of 62.6% after eight repetitive enzymatic reactions. Additionally, the optimal bixin-maltitol ester synthesis procedure was heating bixin-maltitol mixture at molar ratio of 1:7 in anhydrous 2-methyl-2-butanol-dimethylsulfoxide (8:2, v/v) at 50 degreesC for 24 h. Bixin-maltitol ester showed improved water solubility at pH 5.5 and 7.0. Title: A covalent crosslinking strategy to construct a robust peptide-based artificial esterase Tian Y, Yang L, Peng X, Qi W, Wang M Ref: Soft Matter, :, 2023 : PubMed ESTHER: Tian_2023_Soft.Matter__ PubMedSearch: Tian 2023 Soft.Matter PubMedID: 37129250 Abstract Peptide-based artificial enzymes derived from the supramolecular assembly of short peptides have attracted growing attention in recent years. However, the stability of these artificial enzymes is still a problem since their noncovalent supramolecular structure is quite sensitive and frail under environmental conditions. In this study, we reported a covalent crosslinking strategy for the fabrication of a robust peptide-based artificial esterase. Inspired by the di-tyrosine bonds in many natural structural proteins, multi-tyrosines were designed into a peptide sequence with histidine as the catalytic residue for the ester hydrolysis reaction. Upon the photo-induced oxidation reaction, the short peptide YYHYY rapidly transferred into nanoparticle-shaped aggregates (CL-YYHYY) and displayed improved esterase-like catalytic activity than some previously reported noncovalent-based artificial esterases. Impressively, CL-YYHYY showed outstanding reusability and superior stability under high temperature, strong acid and alkaline and organic solvent conditions. This study provides a promising approach to improving the catalytic activity and stability of peptide-based artificial enzymes. Title: The Cell-Cell Communication Signal Indole Controls the Physiology and Interspecies Communication of Acinetobacter baumannii Cui B, Chen X, Guo Q, Song S, Wang M, Liu J, Deng Y Ref: Microbiol Spectr, :e0102722, 2022 : PubMed ESTHER: Cui_2022_Microbiol.Spectr__e0102722 PubMedSearch: Cui 2022 Microbiol.Spectr e0102722 PubMedID: 35862954 Gene_locus related to this paper: acicp-AbiS Abstract Many bacteria utilize quorum sensing (QS) to control group behavior in a cell density-dependent manner. Previous studies have demonstrated that Acinetobacter baumannii employs an N-acyl-L-homoserine lactone (AHL)-based QS system to control biological functions and virulence. Here, we report that indole controls biological functions, virulence and AHL signal production in A. baumannii. The biosynthesis of indole is performed by A1S_3160 (AbiS, Acinetobacter baumannii indole synthase), which is a novel indole synthase annotated as an alpha/beta hydrolase in A. baumannii. Heterologous expression of AbiS in an Escherichia coli indole-deficient mutant also rescued the production of indole by using a distinct biosynthetic pathway from the tryptophanase TnaA, which produces indole directly from tryptophan in E. coli. Moreover, we revealed that indole from A. baumannii reduced the competitive fitness of Pseudomonas aeruginosa by inhibiting its QS systems and type III secretion system (T3SS). As A. baumannii and P. aeruginosa usually coexist in human lungs, our results suggest the crucial roles of indole in both the bacterial physiology and interspecies communication. IMPORTANCE Acinetobacter baumannii is an important human opportunistic pathogen that usually causes high morbidity and mortality. It employs the N-acyl-L-homoserine lactone (AHL)-type quorum sensing (QS) system, AbaI/AbaR, to regulate biological functions and virulence. In this study, we found that A. baumannii utilizes another QS signal, indole, to modulate biological functions and virulence. It was further revealed that indole positively controls the production of AHL signals by regulating abaI expression at the transcriptional levels. Furthermore, indole represses the QS systems and type III secretion system (T3SS) of P. aeruginosa and enhances the competitive ability of A. baumannii. Together, our work describes a QS signaling network where a pathogen uses to control the bacterial physiology and pathogenesis, and the competitive ability in microbial community. Title: Comprehensive Enantioselectivity Evaluation of Insecticidal Activity and Mammalian Toxicity of Fenobucarb He Z, Li C, Xia W, Wang Z, Li R, Zhang Y, Wang M Ref: Journal of Agricultural and Food Chemistry, :, 2022 : PubMed ESTHER: He_2022_J.Agric.Food.Chem__ PubMedSearch: He 2022 J.Agric.Food.Chem PubMedID: 35451821 Abstract To comprehensively evaluate the efficiency and risk of the chiral pesticide fenobucarb, the bioactivity, toxicity, and environmental behavior of fenobucarb (FNC) enantiomers were investigated. The results showed that R-FNC possesses 1.8-2.7 times more bioactivity than S-FNC but 1.3-3.0 times lower toxicity than S-FNC against four nontarget organisms: Chlorella pyrenoidosa, HepG2, and Danio rerio and its embryos. The corresponding enzyme inhibitory activity showed consistent results; the acetylcholinesterase inhibitory activity of target organisms was ordered as R-FNC > rac-FNC > S-FNC, while the reduction in catalase activity after exposure to R-FNC was 2.5 times that after exposure to S-FNC in zebrafish. The enantioselective bioactivity mechanism of FNC enantiomers was further explored in silico. No significant enantioselective degradation was found in soils or rat liver microsomes. In sum, R-FNC possesses higher insecticidal activity and lower toxicity. The development of R-FNC as a commercial agrochemical is beneficial for reducing pesticide inputs. Title: Interleukin-6 and YKL-40 predicted recurrent stroke after ischemic stroke or TIA: analysis of 6 inflammation biomarkers in a prospective cohort study Li J, Lin J, Pan Y, Wang M, Meng X, Li H, Wang Y, Zhao X, Qin H, Liu L Ref: J Neuroinflammation, 19:131, 2022 : PubMed ESTHER: Li_2022_J.Neuroinflammation_19_131 PubMedSearch: Li 2022 J.Neuroinflammation 19 131 PubMedID: 35761288 Abstract OBJECTIVE: Contribution of individual and combined inflammatory markers in prognosis after stroke was still undefined. We aimed to investigate the association of systemic and local vascular inflammatory markers and recurrent stroke as well as impact on poor functional outcome. METHODS: In this pre-specified substudy of the Third China National Stroke Registry (CNSR-III), 10,472 consecutive acute ischemic stroke or TIA patients with available centralized-measured levels of Interleukin-6 (IL-6), high sensitive C-reactive protein (hsCRP), IL-1 receptor antagonist (IL-1Ra), lipoprotein-associated phospholipase A(2) mass (Lp-PLA(2)) and activity (Lp-PLA(2)-A), and YKL-40 from 171 sites were enrolled. The primary outcomes consisted of stroke recurrence and poor functional outcome defined as modified Rankin Scale (mRS) score of 2-6 within 1 year. RESULTS: There were 1026 (9.8%) and 2395 (23.4%) patients with recurrent stroke and poor functional outcome within 1 year. The highest quartiles of IL-6 (adjusted HR, 1.36; 95% CI 1.13-1.64; P = 0.001), hsCRP (adjusted HR, 1.41; 95% CI 1.17-1.69; P = 0.0003) and YKL-40 (adjusted HR, 1.28; 95% CI 1.06-1.56; P = 0.01) were associated with increased risk of recurrent stroke; and the highest quartiles of IL-6 (adjusted OR 1.93; 95% CI 1.64-2.27; P < 0.0001), IL-1Ra (adjusted OR 1.60; 95% CI 1.37-1.87; P < 0.0001), hsCRP (adjusted OR 1.60; 95% CI 1.37-1.86; P < 0.0001) and YKL-40 (adjusted OR 1.21; 95% CI 1.03-1.42; P = 0.02) were correlated with increased risk of poor functional outcome. In the multivariate stepwise regression analysis including all markers with backward selection, elevated levels of IL-6 or YKL-40 were associated with recurrent stroke (IL6: OR, 1.34; 95% CI 1.19-1.52; P < 0.0001; YKL-40: OR, 1.01; 95% CI 1.01-1.03; P = 0.004) and poor functional outcome (IL6: OR, 1.68; 95% CI 1.46-1.93; P < 0.0001; YKL-40: OR, 1.02; 95% CI 1.01-1.03; P = 0.0001). Adding IL-6 and YKL-40 significantly increased the area under the receiver operating characteristic curves for the prediction models of Essen Stroke Risk Score (0.03, P < 0.0001) and Totaled Health Risks in Vascular Events Score (0.07, P < 0.0001), and yielded continuous net reclassification improvement (19.0%, P < 0.0001; 33.0, P < 0.0001). CONCLUSIONS: In the patients with ischemic stroke or TIA, IL-6 and YKL-40 were independently associated with recurrent stroke and poor functional outcome, and improved risk classification of clinical risk algorithms. Title: Fosthiazate exposure induces oxidative stress, nerve damage, and reproductive disorders in nontarget nematodes Liu BD, Dong HT, Rong HW, Zhang RJ, Liu S, Wu Q, Zhong Y, He Z, Wang Z and Wang M <1 more author(s)> Liu BD, Dong HT, Rong HW, Zhang RJ, Liu S, Wu Q, Zhong Y, He Z, Wang Z, Li R, Wang M (- 1) Ref: Environ Sci Pollut Res Int, :, 2022 : PubMed ESTHER: Liu_2022_Environ.Sci.Pollut.Res.Int__ PubMedSearch: Liu 2022 Environ.Sci.Pollut.Res.Int PubMedID: 35796928 36112285 Abstract As a forceful nematicide, fosthiazate has been largely applied in the management of root-knot nematodes and other herbivorous nematodes. However, the toxicity of fosthiazate to nontarget nematodes is unclear. To explore the toxicity and the mechanisms of fosthiazate in nontarget nematodes, Caenorhabditis elegans was exposed to 0.01-10 mg/L fosthiazate. The results implied that treatment with fosthiazate at doses above 0.01 mg/L could cause injury to the growth, locomotion behavior, and reproduction of the nematodes. Moreover, L1 larvae were more vulnerable to fosthiazate exposure than L4 larvae. Reactive oxygen species (ROS) production and lipofuscin accumulation were fairly increased in 1 mg/L fosthiazate-exposed nematodes. Treatment with 0.1 mg/L fosthiazate significantly inhibited the activity of acetylcholinesterase (p < 0.01). Furthermore, subacute exposure to 10 mg/L fosthiazate strongly influenced the expression of genes related to oxidative stress, reproduction, and nerve function (e.g., gst-1, sod-1, puf-8, wee-1.3, and ace-1 genes). These findings suggested that oxidative stress, reproduction and nerve disorders could serve as key endpoints of toxicity induced by fosthiazate. The cyp-35a family gene was the main metabolic fosthiazate in C. elegans, and the cyp-35a5 subtype was the most sensitive, with a change in expression level of 2.11-fold compared with the control. These results indicate that oxidative stress and neurological and reproductive disorders played fundamental roles in the toxicity of fosthiazate in C. elegans and may affect the abundance and function of soil nematodes. Title: An esterase-activatable curcumin prodrug for tumor-targeting therapy Liu L, Zhang L, Tao M, Wang M, Dong L, Hai Z Ref: Chem Commun (Camb), :, 2022 : PubMed ESTHER: Liu_2022_Chem.Commun.(Camb)__ PubMedSearch: Liu 2022 Chem.Commun.(Camb) PubMedID: 36373630 Abstract A tumor-targeting therapy strategy is urgently needed to increase the accumulation of drugs in tumors and reduce the side effects in normal tissues. Herein, we developed an esterase-activatable curcumin prodrug Cur-RGD for tumor-targeting therapy. Armed with the tumor-targeting RGD peptide and in situ esterase-triggered drug release, this prodrug Cur-RGD can efficiently improve the therapeutic effect of curcumin in tumors. Title: Pesticide Residues in Commonly Consumed Vegetables in Henan Province of China in 2020 Ma C, Wei D, Liu P, Fan K, Nie L, Song Y, Wang M, Wang L, Xu Q and Zeng X <10 more author(s)> Ma C, Wei D, Liu P, Fan K, Nie L, Song Y, Wang M, Wang L, Xu Q, Wang J, Shi J, Geng J, Zhao M, Jia Z, Huan C, Huo W, Wang C, Mao Z, Huang S, Zeng X (- 10) Ref: Front Public Health, 10:901485, 2022 : PubMed ESTHER: Ma_2022_Front.Public.Health_10_901485 PubMedSearch: Ma 2022 Front.Public.Health 10 901485 PubMedID: 35757605 Abstract BACKGROUND: Pesticides are widely used in agricultural production to control insect pests and regulate plant growth in China, which may result in the presence of some pesticide residues in the vegetables. However, few studies of monitoring pesticides have been conducted in Henan Province. The aim of this study was to evaluate the level of pesticide residues in commonly consumed vegetables in the regions of Henan Province. METHODS: In this study, we collected 5,576 samples of 15 different vegetables in 17 areas from Henan Province during 2020. Eight kinds of pesticides were analyzed by gas chromatography-mass spectrometry (GC-MS), including procymidone, lambda-cyhalothrin, cypermethrin, pendimethalin, isocarbophos, isazophos, fenthion and deltamethrin. The chi-square test was used to compare the detection rates of pesticide residues in different regions. RESULTS: Of all the pesticides above, procymidone, lambda-cyhalothrin, cypermethrin, pendimethalin and isocarbophos were detected in vegetables, the detection rates were 27.0%, 16.2%, 11.4%, 3.5%, and 1.9%, respectively. However, isazophos, fenthion, and deltamethrin were not detected. In addition, procymidone, lambda-cyhalothrin, and cypermethrin were detected in urban areas, while pendimethalin was detected in rural areas. The detection rates of cypermethrin and pendimethalin in rural were 19.8% and 5.4%, respectively, which in urban were at relatively lower levels (13.7% and 1.9%, respectively) (P < 0.05). Compared the differences of pesticide detection rates among five areas of Henan province, we found that there were statistical differences in the detection rates of procymidone, cypermethrin and lambda-cyhalothrin in different regions (all P < 0.05). CONCLUSION: The results have revealed that the pesticide residues are present. Higher detection rates and more types of pesticides were found in rural areas than urban areas. In addition, there were higher detection rates in Eastern Henan. The findings provided valuable information on the current pesticide residues status, which can be a reference of pesticide supervision and management. Title: Development of indole-2-carbonyl piperazine urea derivatives as selective FAAH inhibitors for efficient treatment of depression and pain Shang Y, Wang M, Hao Q, Meng T, Li L, Shi J, Yang G, Zhang Z, Yang K, Wang J Ref: Bioorg Chem, 128:106031, 2022 : PubMed ESTHER: Shang_2022_Bioorg.Chem_128_106031 PubMedSearch: Shang 2022 Bioorg.Chem 128 106031 PubMedID: 36037600 Abstract Fatty acid amide hydrolase (FAAH), aserinehydrolase with significant role in thehydrolysis of endocannabinoids, is a promising therapeutic target for peripheral and central nervous system related disorders, including pain, neuroinflammation and depression. Employing a structure-based approach, a novel series of indole-2-carbonyl piperazine urea derivatives were designed and synthesized as FAAH inhibitors for the treatment of pain-depression comorbidity. Among them, compound 4i emerged as the most potent inhibitor (IC(50) = 0.12 microM) with fine selectivity versus CES2, ABHD6, MAGL and the cannabinoid receptor, which also displayed superior metabolic stability in human liver microsome and an adequate pharmacokinetic profile in rodents. Treatment of depressed rats with 4i demonstrated favorable antidepressant-like effects not only by increasing the level of BDNF in the hippocampus but also by restraining the apoptosis of hippocampal neurons. Also, 4i effectively suppressed the LPS-induced neuroinflammation in vitro. Moreover, 4i exhibited potent analgesic activity, which indicated its promising therapeutical application for pain and depression. These meaningful results shed light on FAAH inhibitors as promising pain-depression comorbidity therapeutics. Title: Discovery of pyrrole derivatives as acetylcholinesterase-sparing butyrylcholinesterase inhibitor Sun S, Shi T, Peng Y, Zhang H, Zhuo L, Peng X, Li Q, Wang M, Wang S, Wang Z Ref: Front Pharmacol, 13:1043397, 2022 : PubMed ESTHER: Sun_2022_Front.Pharmacol_13_1043397 PubMedSearch: Sun 2022 Front.Pharmacol 13 1043397 PubMedID: 36561337 Abstract Inspired by the crucial roles of (hetero)aryl rings in cholinesterase inhibitors and the pyrrole ring in new drug discovery, we synthesized 19 pyrrole derivatives and investigated their cholinesterase inhibitory activity. As a result, compounds 3o, 3p, and 3s with a 1,3-diaryl-pyrrole skeleton showed high selectivity toward BChE over AChE with a best IC(50) value of 1.71 +/- 0.087smicroM, which were comparable to donepezil. The pharmaceutical potential of these structures was further predicted and compounds 3o and 3p were proved to meet well with the Lipinsky's five rules. In combination of the inhibition kinetic studies with the results of molecular docking, we concluded that compound 3p inhibited BChE in a mixed competitive mode. This research has proved the potential of the 1,3-diaryl-pyrrole skeleton as a kind of selective BChE inhibitor. Title: Novel Bisamide Alkaloids Enantiomers from Pepper Roots (Piper nigrum L.) with Acetylcholinesterase Inhibitory and Anti-Neuroinflammatory Effects Wang Z, Li R, Wu Q, Duan J, Tan Y, Sun X, Chen R, Shi H, Wang M and Song SJ <7 more author(s)> Wang Z, Li R, Wu Q, Duan J, Tan Y, Sun X, Chen R, Shi H, Wang M, Wang YX, Xu ZY, Qin SY, Du NN, Yao GD, Lin B, Huang XX, Song SJ (- 7) Ref: Journal of Agricultural and Food Chemistry, :, 2022 : PubMed ESTHER: Wang_2022_J.Agric.Food.Chem__ PubMedSearch: Wang 2022 J.Agric.Food.Chem PubMedID: 35184556 36450093 Abstract The roots of Piper nigrum L., a seasoning for cooking various types of broths, are renowned for their high nutritional content and potential medicinal benefits. In this study, nine pairs of novel cyclohexene-type bisamide alkaloids (1a/1b-9a/9b) were isolated from the pepper roots using molecular network analysis strategies. Their structures were determined by extensive spectroscopic data, electronic circular dichroism (ECD) calculations, and X-ray diffraction analyses. Using an intermolecular Diels-Alder reaction, a strategy for the synthesis of bisamide alkaloids from different monomeric amide alkaloids was developed. Furthermore, these compounds were chirally separated for the first time, and compounds 3a and 5a/5b showed significant anti-neuroinflammation effects in the models of lipopolysaccharide(LPS)-induced BV2 microglial cells. Meanwhile, compounds 6b and 7a displayed concentration-dependent inhibitory activities against acetylcholinesterase with IC(50) values of 6.05 +/- 1.10 and 3.81 +/- 0.10 microM, respectively. These findings confirmed that these bisamide alkaloids could be applied in functional food formulations and pharmaceutical products as well as facilitate the further development and usage of pepper roots. Title: Penicipurate A, a new polyketide derivative from the endophytic fungus Penicillium purpurogenum Wang LY, Xia GY, Wang M, Wu YZ, Wang YN, Chai LM, Lin S Ref: J Asian Nat Prod Res, :1, 2022 : PubMed ESTHER: Wang_2022_J.Asian.Nat.Prod.Res__1 PubMedSearch: Wang 2022 J.Asian.Nat.Prod.Res 1 PubMedID: 35852111 Abstract A new polyketide derivative containing a 3-hydroxydecanoic acid ester moiety, penicipurate A (1), was purified from the solid cultures of the fungus Penicillium purpurogenum, a fungal strain endophytic in the leaves of Edgeworthia chrysantha. The structure of 1 was established by spectroscopic methods, including UV, IR, HRESIMS, 1D, and 2D NMR and (13)C NMR chemical shifts calculations coupled with DP4+ analysis, as well as the chemical degradation method. Compound 1 showed moderate inhibitory activity against pancreatic lipase (PL) with an IC(50) value of 9.61 +/- 1.42 microM. Title: Novel Ce-based coordination polymer nanoparticles with excellent oxidase mimic activity applied for colorimetric assay to organophosphorus pesticides Wang J, Wang X, Wang M, Bian Q, Zhong J Ref: Food Chem, 397:133810, 2022 : PubMed ESTHER: Wang_2022_Food.Chem_397_133810 PubMedSearch: Wang 2022 Food.Chem 397 133810 PubMedID: 35917788 Abstract Cerium, as a lanthanide, has attracted considerable interest because of its excellent catalytic activity. Here, we propose a novel cerium-based coordination polymer nanoparticles named DPA-Ce-GMP, which have excellent oxidase-mimicking properties. Furthermore, a colorimetric probe that can act as an inhibitor to suppress the activity of acetylcholinesterase (AChE) was developed for detecting organophosphorus pesticides (OPs). DPA-Ce-GMP catalyzes colorless 3,3',5,5'-tetramethylbenzidine (TMB) to produce a blue color, and AChE catalyzes acetylthiocholine to produce thiocholine (TCh), which can weaken DPA-Ce-GMP-catalyzed TMB. After the addition of OPs, the enzymatic activity of AChE was inhibited to produce less amount of TCh, resulting in more DPA-Ce-GMP-catalyst oxidized TMB to show an increasing blue color. Dichlorvos, as the samples, with the limit of 0.024 microg/L. Overall, we believe that the colorimetric probe can be used for the rapid, low-cost, and large-scale field detection of OPs in food samples. Title: The role of butyrylcholinesterase in the regulation of cognitive dysfunction in minimal hepatic encephalopathy: A potential blood marker of disease evolution Yang X, Dang P, Liu W, Ma W, Ge X, Zhu K, Wang M, Huang X, Ding X, Wang X Ref: Front Neurol, 13:900997, 2022 : PubMed ESTHER: Yang_2022_Front.Neurol_13_900997 PubMedSearch: Yang 2022 Front.Neurol 13 900997 PubMedID: 36341087 Abstract BACKGROUND AND AIMS: Patients with cirrhosis commonly experience minimal hepatic encephalopathy (MHE), and alterations in neurotransmitters have been thought to be related to cognitive function. However, the relationship between alterations in peripheral and central butyrylcholinesterase (BuChE) with MHE disease progression remains unknown. As such, this study was designed to investigate potential changes in peripheral and central BuChE activity and their effects on cognitive function in the context of MHE. MATERIALS AND METHODS: We enrolled 43 patients with cirrhosis secondary to hepatitis B, 20 without MHE and 23 with MHE, and 25 with healthy controls (HC). All the selected subjects underwent resting-state functional MRI, and the original images were processed to obtain the regional homogeneity (ReHo) brain maps. Thereafter, the correlation of BuChE activity with ReHo, number connection test of type A (NCT-A), and digital symbol test (DST) scores with MHE patients were analyzed using Person correlation analysis. Meanwhile, we purchased 12 Sprague-Dawley (SD) rats and divided them into an experimental group (n = 6) and a control group (n = 6). The rats in the experimental group were intraperitoneally injected with thioacetamide (TAA) to prepare MHE model rats. After modeling, we used the Morris water maze (MWM) and elevated plus maze (EPM) to assess the cognition function and exploratory behavior of all rats. The activity of serum, hippocampus, and frontal lobe tissue BuChE was detected by ELISA. RESULTS: BuChE activity gradually decreased among the HC, patients with cirrhosis, and MHE groups (all P < 0.01). We observed a linear correlation between serum BuChE and NCT-A and DST scores in MHE patients (all P < 0.01). We noted that BuChE activity can negatively correlate with ReHo values in the left middle temporal gyrus and left inferior temporal gyrus, and positively correlate with ReHo values in the right inferior frontal gyrus, and also found that the peripheral BuChE activity of MHE rats was significantly lower than their control counterparts, and the BuChE activity in frontal lobe extracts was significantly higher than the control rats (all P < 0.05). CONCLUSION: The altered activity of BuChE may contribute to cognitive impairment in MHE patients, which may be a potential biomarker of disease evolution in the context of MHE. Title: The Functional Characterization of Carboxylesterases Involved in the Degradation of Volatile Esters Produced in Strawberry Fruits Zhang L, Zhou K, Wang M, Li R, Dai X, Liu Y, Jiang X, Xia T, Gao L Ref: Int J Mol Sci, 24:383, 2022 : PubMed ESTHER: Zhang_2022_Int.J.Mol.Sci_24_383 PubMedSearch: Zhang 2022 Int.J.Mol.Sci 24 383 PubMedID: 36613824 Gene_locus related to this paper: frave-FanCXE17, frave-FanCXE19, frave-FanCXE3, frave-FanCXE2, fraan-FaTA Abstract Volatile ester compounds are important contributors to the flavor of strawberry, which affect consumer preference. Here, the GC-MS results showed that volatile esters are the basic aroma components of strawberry, banana, apple, pear, and peach, and the volatile esters were significantly accumulated with the maturation of strawberry fruits. The main purpose of this study is to discuss the relationship between carboxylesterases (CXEs) and the accumulation of volatile ester components in strawberries. FaCXE2 and FaCXE3 were found to have the activity of hydrolyzing hexyl acetate, Z-3-hexenyl acetate, and E-2-hexenyl acetate to the corresponding alcohols. The enzyme kinetics results showed that FaCXE3 had the higher affinity for hexyl acetate, E-2-hexenyl acetate, and Z-3-hexenyl acetate compared with FaCXE2. The volatile esters were mainly accumulated at the maturity stages in strawberry fruits, less at the early stages, and the least during the following maturation stages. The expression of FaCXE2 gradually increased with fruit ripening and the expression level of FaCXE3 showed a decreasing trend, which suggested the complexity of the true function of CXEs. The transient expression of FaCXE2 and FaCXE3 genes in strawberry fruits resulted in a significantly decreased content of volatile esters, such as Z-3-hexenyl acetate, methyl hexanoate, methyl butyrate, and other volatile esters. Taken together, FaCXE2 and FaCXE3 are indeed involved in the regulation of the synthesis and degradation of strawberry volatile esters. Title: Acer truncatum Bunge: A comprehensive review on ethnobotany, phytochemistry and pharmacology Fan Y, Lin F, Zhang R, Wang M, Gu R, Long C Ref: J Ethnopharmacol, :114572, 2021 : PubMed ESTHER: Fan_2021_J.Ethnopharmacol__114572 PubMedSearch: Fan 2021 J.Ethnopharmacol 114572 PubMedID: 34487848 Abstract ETHNOPHARMACOLOGICAL RELEVANCE: Acer truncatum Bunge is a multifunctional plant in northern China. It has traditionally been used to prevent cardiovascular and cerebrovascular diseases and treat skin trauma by different linguistic groups including Mongolian, Tibetan, and Korean. Although research has verified that A. truncatum contains a variety of active ingredients, especially nervonic acid, an important component in delaying brain aging, to date no review has been made to compile its traditional use, phytochemistry, and pharmacology. AIMS OF THE REVIEW: This review aimed to update the traditional uses, phytochemistry, and pharmacology of A. truncatum, which expect to provide theoretical support for the future utilization as well as highlight the further investigation of this important plant. MATERIALS AND METHODS: The ethnobotanical, phytochemical, and pharmacological information related to A. truncatum from 1949 to March 2021 were collated by surveying the traditional medicinal books and ethnomedicinal publications and searching the online databases including Google Scholar, Sci Finder, Web of Science, Springer Link, PubMed, Wiley, China National Knowledge Infrastructure (CNKI), Baidu Scholar, and Wan Fang Database. RESULTS: A. truncatum has traditionally been used for medicinal, edible and ornamental purposes in northern China for many centuries. Different parts of the plant including leaves, fruits and bark, are mainly used as herbal medicine to treat hyperpiesia, hyperlipidemia, bruises, back pain, etc. A total of 288 compounds in A. truncatum, including polyphenols, organic acids or lipids, and biological volatile organic compounds were isolated or identified by phytochemical studies. Pharmacological research showed that A. truncatum has various bioactivities such as acetylcholinesterase inhibition, antibacterial, antioxidant, antitumor, and fatty acid synthase inhibition effects. CONCLUSION: A. truncatum has been used as a traditional herbal medicine for centuries in northern China. Polyphenols, organic acids, lipids and other compounds were isolated or identified from different parts of the plant. Most of the pharmacological activities of A. truncatum have been reported, which showed its potential in the development of new drugs or nutraceuticals. However, detailed information on the molecular mechanisms, metabolic activity, and toxicology of active components is limited. Further comprehensive research to evaluate the medicinal properties of A. truncatum will be necessary. Title: Strigolactone mimic 2-nitrodebranone is highly active in Arabidopsis growth and development Li S, Li Y, Chen L, Zhang C, Wang F, Li H, Wang M, Wang Y, Nan F and Yan J <1 more author(s)> Li S, Li Y, Chen L, Zhang C, Wang F, Li H, Wang M, Wang Y, Nan F, Xie D, Yan J (- 1) Ref: Plant J, :, 2021 : PubMed ESTHER: Li_2021_Plant.J__ PubMedSearch: Li 2021 Plant.J PubMedID: 33860570 Abstract Strigolactones play crucial roles in regulating plant architecture and development, as endogenous hormones, and orchestrating symbiotic interactions with fungi and parasitic plants, as components of root exudates. rac-GR24 is currently the most widely used strigolactone analog and serves as a reference compound in investigating the action of strigolactones. In this study, we evaluated a suite of debranones and found that 2-nitrodebranone (2NOD) exhibited higher biological activity than rac-GR24 in various aspects of plant growth and development in Arabidopsis, including hypocotyl elongation inhibition, root hair promotion and senescence acceleration. The enhanced activity of 2NOD in promoting AtD14-SMXL7 and AtD14-MAX2 interactions indicates that the molecular structure of 2NOD is a better match for the ligand perception site pocket of D14. Moreover, 2NOD showed lower activity than rac-GR24 in promoting Orobanche cumana seed germination, suggesting its higher ability to control plant architecture than parasitic interactions. In combination with the improved stability of 2NOD, these results demonstrate that 2NOD is a strigolactone analog that can specifically mimic the activity of strigolactones and that 2NOD exhibits strong potential as a tool for studying the strigolactone signaling pathway in plants. Title: Excitatory Impact of Dental Occlusion on Dorsal Motor Nucleus of Vagus Liu X, Shi M, Ren H, Xie M, Zhang C, Wang D, Li J, Wang M Ref: Front Neural Circuits, 15:638000, 2021 : PubMed ESTHER: Liu_2021_Front.Neural.Circuits_15_638000 PubMedSearch: Liu 2021 Front.Neural.Circuits 15 638000 PubMedID: 33776655 Abstract Neurons in the trigeminal mesencephalic nucleus (Vme) have axons that branch peripherally to innervate the orofacial region and project centrally to several motor nuclei in brainstem. The dorsal motor nucleus of vagus nerve (DMV) resides in the brainstem and takes a role in visceral motor function such as pancreatic exocrine secretion. The present study aimed to demonstrate the presence of Vme-DMV circuit, activation of which would elicit a trigeminal neuroendocrine response. A masticatory dysfunctional animal model termed unilateral anterior crossbite (UAC) model created by disturbing the dental occlusion was used. Cholera toxin B subunit (CTb) was injected into the inferior alveolar nerve of rats to help identify the central axon terminals of Vme neurons around the choline acetyltransferase (ChAT) positive motor neurons in the DMV. The level of vesicular glutamate transporter 1 (VGLUT1) expressed in DMV, the level of acetylcholinesterase (AChE) expressed in pancreas, the level of glucagon and insulin expression in islets and serum, and the blood glucose level were detected and compared between UAC and the age matched sham-operation control mice. Data indicated that compared with the controls, there were more CTb/VGLUT1 double labeled axon endings around the ChAT positive neurons in the DMV of UAC groups. Mice in UAC group expressed a higher VGLUT1 protein level in DMV, AChE protein level in pancreas, glucagon and insulin level in islet and serum, and higher postprandial blood glucose level, but lower fasting blood glucose level. All these were reversed at 15-weeks when UAC cessation was performed from 11-weeks (all, P < 0.05). Our findings demonstrated Vme-DMV circuit via which the aberrant occlusion elicited a trigeminal neuroendocrine response such as alteration in the postprandial blood glucose level. Dental occlusion is proposed as a potential therapeutic target for reversing the increased postprandial glucose level. Title: Stability comparison of four lipases and catalytic mechanism during the synthesis of 1,3-di-oleic-2-medium chain triacylglycerols in a trace water-in-oil system: Experimental analyses and computational simulations Peng B, Luo T, Chen F, Wang M, Fu JH, Zheng LF, Li J, Deng ZY Ref: J Food Biochem, :e13667, 2021 : PubMed ESTHER: Peng_2021_J.Food.Biochem__e13667 PubMedSearch: Peng 2021 J.Food.Biochem e13667 PubMedID: 33837552 Abstract In the present study, a kind of structured lipids, namely 1,3-di-oleic-2-medium chain (OMO) triacylglycerols, were synthesized through lipase-catalyzed reactions using coconut oil and rapeseed acid as materials in a trace water-in-oil system. Experimental analysis and computational simulations were undertaken to compare the stability of four lipases including Lipozyme RMIM, Lipozyme TLIM, Novozym 435, and Aspergillus oryzae immobilized lipase (AOIM), and illustrate catalytic mechanism of Novozym 435 during the synthesis of OMO. Fourier transform infrared and molecular dynamics simulation results demonstrated that a decrease in ordered structure (alpha-helix and beta-sheet) led to a reduction in enzyme activity. Compared with Lipozyme RMIM and Novozym 435, Lipozyme TLIM and AOIM exhibited better stability due to a short-chain lid in TLIM, which covers activity sites, and hydrogen bonds formed between activity center of AOIM and water. Among four lipases, AOIM exhibited best catalytic performance: a OMO yield of 30.7% at 3 hr and a good stability of long term (48 hr). Density functional theory results demonstrated that specifically, during the synthesis of OMO triacylglycerol, the addition of Novozym 435 (derived from Candida antarctica lipase B, CALB) substantially lowered reaction barriers (64.4 KJ/mol with CALB vs. 332.7 KJ/mol with no lipase), aiding in the generation of OMO because of the formations of transitional tetrahedral intermediates. A trace water-in-oil system was a green and efficient alternative for lipase-catalyzed production of OMO, and this study provided crucial insights into the stability/instability and catalytic mechanisms of lipase in the synthesis of structured lipids. PRACTICAL APPLICATIONS: We compared the stability of Lipozyme RMIM, Lipozyme 435, Lipozyme TLIM, and AOIM during the synthesis of the OMO triacylglycerols in a trace water-in-oil system, where exhibited a high catalytic activity of lipase in water-oil interface. AOIM had the highest stability and showed the best catalytic performance due to the formation of hydrogen bonds. Besides, for the first time, the transition tetrahedral structure was revealed in the enzymatic synthesis of medium- and long-chain triacylglycerols. This study provides a rational approach to compare lipase stability and a possible hint to choose appropriate enzyme in a specific catalytic condition. Title: The role of N-cadherin/c-Jun/NDRG1 axis in the progression of prostate cancer Quan Y, Zhang X, Butler W, Du Z, Wang M, Liu Y, Ping H Ref: Int J Biol Sci, 17:3288, 2021 : PubMed ESTHER: Quan_2021_Int.J.Biol.Sci_17_3288 PubMedSearch: Quan 2021 Int.J.Biol.Sci 17 3288 PubMedID: 34512147 Abstract The dysregulation of androgen receptor (AR) signaling is a critical event in the progression of prostate cancer (PCa) and hormone therapy consisting of androgen deprivation (ADT) or AR inhibition is therefore used to treat advanced cases. It is known that N-cadherin becomes upregulated following ADT and can directly induce PCa transformation to the castration-resistant stage (CRPC). However, the relationship between AR and N-cadherin is unclear and may promote better understanding of CRPC pathogenesis and progression. Here, we demonstrate a new axis of N-cadherin/c-Jun/N-myc downstream regulated gene 1 (NDRG1) that N-cadherin promotes c-Jun expression and suppresses NDRG1 to promote invasion and migration of PCa cells through epithelial to mesenchymal transition (EMT). Targeting N-cadherin in combination with enzalutamide (ENZ) treatment synergistically suppressed PC3 cell proliferation in vivo and in vitro. Further studies showed that compared to lower Gleason score (GS) (GS < 7) cases, high GS (GS > 7) cases exhibited elevated N-cadherin expression and reduced NDRG1 expression, corroborating our in vitro observations. We further demonstrate that c-Jun, AR, and DNA methyltransferase-1 (DNMT1) form a complex in the 12-O-tetradecanoyl phorbol-13-acetate (TPA) response elements (TREs) region of the NDRG1 promoter, which suppresses NDRG1 transcription through DNA hypermethylation. In conclusion, we demonstrate an underlying mechanism for how N-cadherin collaborates with AR and NDRG1 to promote CRPC progression. Controlling N-cadherin/c-Jun/NDRG1 axis may help to overcome resistance to commonly used hormone therapy to improve long-term patient outcomes. Title: Esterase-activatable and GSH-responsive Triptolide Nano-prodrug for the Eradication of Pancreatic Cancer Sui B, Cheng C, Shi S, Wang M, Xu P Ref: Adv Nanobiomed Res, 1:, 2021 : PubMed ESTHER: Sui_2021_Adv.Nanobiomed.Res_1_ PubMedSearch: Sui 2021 Adv.Nanobiomed.Res 1 PubMedID: 34870282 Abstract Triptolide (TPL) is a small molecule isolated from a traditional Chinese herb Tripterygium wilfordii Hook F and shows excellent anticancer effect for pancreatic cancer cells. However, the poor water solubility and severe liver toxicity of TPL hindered its clinical application. In this study, TPL was covalently conjugated to a polymer and entrapped inside the core of the TPL nanogel (nTPL) to protect it from premature leakage during blood circulation. With the help of lactobionic acid (LBA), nTPL-LBA could selectively target the tumors in an orthotopic pancreatic cancer mouse model. TPL could be subsequently released intracellularly in its original form due to the presence of elevated intracellular esterase and GSH, and eventually kills cancer cells. nTPL-LBA treatment reduced tumor burden by 99% while not introducing TPL associated liver and kidney toxicities. Most importantly, more than half of the nTPL-LBA treated animals were tumor-free, suggesting that nTPL-LBA is an effective approach in eradicating pancreatic cancer. Title: Fabrication of Bioresource-Derived Porous Carbon-Supported Iron as an Efficient Oxidase Mimic for Dual-Channel Biosensing Wang M, Zhou X, Wang S, Xie X, Wang Y, Su X Ref: Analytical Chemistry, :, 2021 : PubMed ESTHER: Wang_2021_Anal.Chem__ PubMedSearch: Wang 2021 Anal.Chem PubMedID: 33535742 Abstract Herein, we designed a new strategy for fabricating a renewable bioresource-derived N-doped hierarchical porous carbon-supported iron (Fe/NPC)-based oxidase mimic. The obtained results suggested that Fe/NPC possessed a large specific surface area (1144 m(2)/g) and pore volume (0.62 cm(3)/g) to afford extensive Fe-Nx active sites. Taking advantages of the remarkable oxidase-mimicking activity, outstanding stability, and reusability of Fe/NPC, a novel dual-channel biosensing system was strategically fabricated for sensitively determining acetylcholinesterase (AChE) through the integration of Fe/NPC and fluorescent silver nanoclusters (AgNCs) for the first time. The limits of detection for AChE can achieve as low as 0.0032 and 0.0073 U/L by the outputting fluorometric and colorimetric dual signals, respectively. Additionally, this dual-signal system was applied to analyze human erythrocyte AChE and its inhibitor with robust analytical performance. This work provides one sustainable and effective avenue to apply a bioresource for fabricating an Fe/NPC-based oxidase mimic with high catalytic performance and also gives new impetuses for developing novel biosensors by applying Fe/NPC-based enzyme mimics as substitutes for the natural enzyme. Title: Dammarane Sapogenins Improving Simulated Weightlessness-Induced Depressive-Like Behaviors and Cognitive Dysfunction in Rats Wang Q, Dong L, Wang M, Chen S, Li S, Chen Y, He W, Zhang H, Zhang Y and Liu X <2 more author(s)> Wang Q, Dong L, Wang M, Chen S, Li S, Chen Y, He W, Zhang H, Zhang Y, Pires Dias AC, Yang S, Liu X (- 2) Ref: Front Psychiatry, 12:638328, 2021 : PubMed ESTHER: Wang_2021_Front.Psychiatry_12_638328 PubMedSearch: Wang 2021 Front.Psychiatry 12 638328 PubMedID: 33841208 Abstract Background: Our studies demonstrated that the space environment has an impact on the brain function of astronauts. Numerous ground-based microgravity and social isolation showed that the space environment can induce brain function damages in humans and animals. Dammarane sapogenins (DS), an active fraction from oriental ginseng, possesses neuropsychic protective effects and has been shown to improve depression and memory. This study aimed to explore the effects and mechanisms of DS in attenuating depressive-like behaviors and cognitive deficiency induced by simulated weightlessness and isolation [hindlimb suspension and isolation (HLSI)] in rats. Methods: Male rats were orally administered with two different doses of DS (37.5, 75 mg/kg) for 14 days, and huperzine-A (1 mg/kg) served as positive control. Rats were subjected to HLSI for 14 days except the control group during drug administration. The depressive-like behaviors were then evaluated by the open-field test, the novel object recognition test, and the forced swimming test. The spatial memory and working memory were evaluated by the Morris water maze (MWM) test, and the related mechanism was further explored by analyzing the activity of choline acetyltransferase (ChAT), acetylcholinesterase (AChE), and superoxide dismutase (SOD) in the hippocampus of rats. Results: The results showed that DS treatment significantly reversed the HLSI-induced depressive-like behaviors in the open-field test, the novel object recognition test, and the forced swimming test and improved the HLSI-induced cognitive impairment in the MWM test. Furthermore, after DS treatment, the ChAT and SOD activities of HLSI rats were increased while AChE activity was significantly suppressed. Conclusions: These findings clearly demonstrated that DS might exert a significant neuropsychic protective effect induced by spaceflight environment, driven in part by the modulation of cholinergic system and anti-oxidation in the hippocampus. Title: Discovery of 7-O-1, 2, 3-triazole hesperetin derivatives as multi-target-directed ligands against Alzheimer's disease Wang M, Fang L, Liu T, Chen X, Zheng Y, Zhang Y, Chen S, Li Z Ref: Chemico-Biological Interactions, :109489, 2021 : PubMed ESTHER: Wang_2021_Chem.Biol.Interact__109489 PubMedSearch: Wang 2021 Chem.Biol.Interact 109489 PubMedID: 33905740 Abstract The development of multi-target-directed ligands (MTDLs) may improve complex central nervous system diseases such as Alzheimer's disease (AD). Here, a series of 7-O-1, 2, 3-triazole hesperetin derivatives was evaluated for their inhibition of cholinesterase, anti-neuroinflammatory, and neuroprotective activity. Among the hesperetin derivatives, compound a8 (7-O-((1-(3-chlorobenzyl)-1H-1,2,3-triazol-4-yl)methyl)hesperetin) possessed excellent anti-butyrylcholinesterase activity (IC(50) = 3.08 +/- 0.29 microM) and exhibited good anti-neuroinflammatory activity (IC(50) = 2.91 +/- 0.47 microM) against NO production through remarkably blocking the NF-kappaB signaling pathway and inhibiting the phosphorylation of P65. In addition, a8 showed a remarkable neuroprotective effect and lacked neurotoxicity up to 50 microM concentration. Furthermore, possessing significant self-mediated Abeta(1-42) aggregation inhibitory activity, chelated biometals and reduced ROS production were found in compound a8. In the bi-directional transport assay, a8 exhibited a blood-brain barrier penetrating ability. In this study, the Morris water maze task showed that compound a8 significantly improved the learning and memory impairment of the scopolamine-induced AD mice model. Results highlighted the potential of compound a8 to be a potential MTDL for the development of anti-AD agents. Title: Conjugation of haloalkane dehalogenase DhaA with arabinogalactan to increase its stability Wang M, Yu W, Shen L, Zheng H, Guo X, Zhong J, Hu T Ref: J Biotechnol, 335:47, 2021 : PubMed ESTHER: Wang_2021_J.Biotechnol_335_47 PubMedSearch: Wang 2021 J.Biotechnol 335 47 PubMedID: 34118331 Abstract Haloalkane dehalogenase DhaA can catalyze the hydrolytic cleavage of carbonhalogen bonds, along with production of the corresponding alcohol, a proton and a halide. However, DhaA suffers from poor environmental tolerance, such as sensitivity to high temperature, low pH and hypersaline. Arabinogalactan (AG) is a hydrophilic polysaccharide with highly branched long chains. DhaA was conjugated with AG to improve the environmental stability of DhaA in the present study. Each DhaA was averagely conjugated with 4-5 AG molecules. Conjugation of AG essentially maintained the enzymatic activity of DhaA (91.4 %) without apparent structural alteration. The hydration layer formed by AG could reduce the solvent accessible area of DhaA and slow the protonation process, thereby improving the pH and high salt stability of DhaA. In particular, the remaining activities of the conjugate (AG-DhaA) were 35.3 % after treatment at pH4.0 for 1 h, and 80.8 % in 1 M NaCl after treatment for 16 h. As compared with DhaA, AG-DhaA showed slightly different kinetic parameters (K M of 1.90 micromol/L and k cat of 2.60 s -1). Title: Two novel Mutations of the LPL Gene in two Chinese family cases with Familial Chylomicronemia Syndrome Wang M, Zhou Y, He X, Deng C, Liu X, Li J, Zhou L, Li Y, Zhang Y and Li L <1 more author(s)> Wang M, Zhou Y, He X, Deng C, Liu X, Li J, Zhou L, Li Y, Zhang Y, Liu H, Li L (- 1) Ref: Clinica Chimica Acta, :, 2021 : PubMed ESTHER: Wang_2021_Clin.Chim.Acta__ PubMedSearch: Wang 2021 Clin.Chim.Acta PubMedID: 34324844 Abstract The aim of this study was to investigate the clinical features and genetic causes of two family cases with familial chylomicronemia syndrome (FCS). Clinical manifestations of proband 1 and her families, and also proband 2 showed severe hypertriglyceridemia, especially the triglycerides levels of two probands were extremely high. Gene sequencing results showed that the LPL genes in each of the two probands had a new mutation site. For the proband 1, a compound heterozygous mutation at c.429 (c.429+1G>T) was detected in the LPL gene, which was splicing mutation and inherited from her mother. Homozygous mutation was detected in the LPL gene of proband 2, the nucleotide mutation at c.802 (c.802C > T) exhibited missense mutation, his parents and brother had a heterozygous mutation at the same site. It was confirmed that the conservative lipoprotein lipase superfamily domain changed an amino acid from histidine to tyrosine at p. 268 (p. His268Tyr). Flow cytometry confirmed the deficient expression of LPL protein in two families. These results indicated that the mutation in LPL gene might be the cause of familial chylomicronemia syndrome. Title: An Evolving Technology That Integrates Classical Methods with Continuous Technological Developments: Thin-Layer Chromatography Bioautography Wang M, Zhang Y, Wang R, Wang Z, Yang B, Kuang H Ref: Molecules, 26:, 2021 : PubMed ESTHER: Wang_2021_Molecules_26_ PubMedSearch: Wang 2021 Molecules 26 PubMedID: 34361800 Abstract Thin-layer chromatography (TLC) bioautography is an evolving technology that integrates the separation and analysis technology of TLC with biological activity detection technology, which has shown a steep rise in popularity over the past few decades. It connects TLC with convenient, economic and intuitive features and bioautography with high levels of sensitivity and specificity. In this study, we discuss the research progress of TLC bioautography and then establish a definite timeline to introduce it. This review summarizes known TLC bioautography types and practical applications for determining antibacterial, antifungal, antitumor and antioxidant compounds and for inhibiting glucosidase, pancreatic lipase, tyrosinase and cholinesterase activity constitutes. Nowadays, especially during the COVID-19 pandemic, it is important to identify original, natural products with anti-COVID potential compounds from Chinese traditional medicine and natural medicinal plants. We also give an account of detection techniques, including in situ and ex situ techniques; even in situ ion sources represent a major reform. Considering the current technical innovations, we propose that the technology will make more progress in TLC plates with higher separation and detection technology with a more portable and extensive scope of application. We believe this technology will be diffusely applied in medicine, biology, agriculture, animal husbandry, garden forestry, environmental management and other fields in the future. Title: The cholinergic system, intelligence, and dental fluorosis in school-aged children with low-to-moderate fluoride exposure Wang S, Zhao Q, Li G, Wang M, Liu H, Yu X, Chen J, Li P, Dong L and Wang A <3 more author(s)> Wang S, Zhao Q, Li G, Wang M, Liu H, Yu X, Chen J, Li P, Dong L, Zhou G, Cui Y, Liu L, Wang A (- 3) Ref: Ecotoxicology & Environmental Safety, 228:112959, 2021 : PubMed ESTHER: Wang_2021_Ecotoxicol.Environ.Saf_228_112959 PubMedSearch: Wang 2021 Ecotoxicol.Environ.Saf 228 112959 PubMedID: 34808511 Abstract Disruption of cholinergic neurotransmission can affect cognition, but little is known about whether low-to-moderate fluoride exposure affects cholinergic system and its effect on the prevalence of dental fluorosis (DF) and intelligence quotient (IQ). A cross-sectional study was conducted to explore the associations of moderate fluoride exposure and cholinergic system in relation to children's DF and IQ. We recruited 709 resident children in Tianjin, China. Ion selective electrode method was used to detect fluoride concentrations in water and urine. Cholinergic system was assessed by the detection of choline acetyltransferase (ChAT), acetylcholinesterase (AChE) and acetylcholine (ACh) levels in serum. Compared with children in the first quartile, those in fourth quartile the risk of either developing DF or IQ < 120 increased by 19% and 20% for water and urinary fluoride. The risk of having both increased by 58% and 62% in third and fourth quartile for water fluoride, 52% and 65% for urinary fluoride. Water fluoride concentrations were positively associated with AChE and negatively associated with ChAT and ACh, trends were same for urinary fluoride except for ACh. The risk of either developing DF or having non-high intelligence rose by 22% (95%CI: 1.07%, 1.38%) for the fourth quartile than those in the first quartile of AChE, for having the both, the risk was 1.27 (95%CI: 1.07, 1.50), 1.37 (95%CI: 1.17, 1.62) and 1.44 (95%CI: 1.23, 1.68) in second, third and fourth quartiles. The mediation proportion by AChE between water fluoride and either developing DF or IQ < 120 was 15.7%. For both to exist, the proportion was 6.7% and 7.2% for water and urinary fluoride. Our findings suggest low-to-moderate fluoride exposure was associated with dysfunction of cholinergic system for children. AChE may partly mediate the prevalence of DF and lower probability of having superior and above intelligence. Title: Influence of seasonal migration on evolution of insecticide resistance in Plutella xylostella Wang M, Zhu B, Zhang L, Xiao Y, Liang P, Wu K Ref: Insect Sci, :, 2021 : PubMed ESTHER: Wang_2021_Insect.Sci__ PubMedSearch: Wang 2021 Insect.Sci PubMedID: 34873833 Abstract The diamondback moth, Plutella xylostella (L.), is one of the most destructive migratory pest species of cruciferous vegetables worldwide and has developed resistance to most of the insecticides used for its control. The migration regularity, migratory behavior, and relationship between flight and reproduction of P. xylostella have been widely reported. However, the effect of migration on insecticide resistance in this pest is still unclear. In this study, the effect of migration on P. xylostella resistance to seven insecticides was investigated using populations across the Bohai Sea that were collected in the early and late seasons during 2017-2019. The bioassay results showed that the early season populations of P. xylostella from South China possessed much higher resistance to insecticides because of intensive insecticide application; alternatively, the late season populations migrated from Northeast China, where the insecticides were only used occasionally, showed much lower insecticide resistance. The genome re-sequencing results revealed that, among the eight mutations involved in insecticide resistance, the frequencies of two acetylcholinesterase mutations (A298S and G324A) responsible for organophosphorus insecticide resistance were significantly decreased in the late season populations. The results indicated that P. xylostella migration between tropical and temperate regions significantly delayed the development of insecticide resistance. These findings illustrated the effect of regional migration on the evolution of insecticide resistance in P. xylostella, and provided foundational information for further research on the relationship between migration and insecticide resistance development in other insects. This article is protected by copyright. All rights reserved. Title: Celastrol Attenuates Learning and Memory Deficits in an Alzheimer's Disease Rat Model Xiao Y, Wang X, Wang S, Li J, Xu X, Wang M, Li G, Shen W Ref: Biomed Res Int, 2021:5574207, 2021 : PubMed ESTHER: Xiao_2021_Biomed.Res.Int_2021_5574207 PubMedSearch: Xiao 2021 Biomed.Res.Int 2021 5574207 PubMedID: 34350293 Abstract Alzheimer's disease (AD) is a chronic progressive neurodegenerative disorder that is associated with learning, memory, and cognitive deficits. Neuroinflammation and synapse loss are involved in the pathology of AD. Diverse measures have been applied to treat AD, but currently, there is no effective treatment. Celastrol (CEL) is a pentacyclic triterpene isolated from Tripterygium wilfordii Hook F that has been shown to enhance cell viability and inhibit amyloid-beta production induced by lipopolysaccharides in vitro. In the present study, the protective effect of CEL on Abeta (25-35)-induced rat model of AD was assessed. Our results showed that CEL administration at a dose of 2 mg/kg/day improved spatial memory in the Morris water maze. Further biochemical analysis showed that CEL treatment of intrahippocampal Abeta (25-35)-microinjected rats attenuated hippocampal NF-kappaB activity; inhibited proinflammatory markers, namely, IL-1beta, IL-6, and TNF-alpha; and upregulated anti-inflammatory factors, such as IL-4 and IL-10. Furthermore, CEL upregulated hippocampal neurexin-1beta, neuroligin-1, CA1, and PSD95 expression levels, which may improve synaptic function. Simultaneously, CEL also increased glucose metabolism in Abeta (25-35)-microinjected rats. In conclusion, CEL could exert protective effects against learning and memory decline induced by intrahippocampal Abeta (25-35) through anti-inflammation, promote synaptic development, and maintain hippocampal energy metabolism. Title: Neuroprotective Potential of Mung Bean (Vigna radiata L.) Polyphenols in Alzheimer's Disease: A Review Xu H, Zhou Q, Liu B, Cheng KW, Chen F, Wang M Ref: Journal of Agricultural and Food Chemistry, 69:11554, 2021 : PubMed ESTHER: Xu_2021_J.Agric.Food.Chem_69_11554 PubMedSearch: Xu 2021 J.Agric.Food.Chem 69 11554 PubMedID: 34551518 Abstract Mung bean contains various neuroprotective polyphenols, so it might be a healthy food for Alzheimer's disease (AD) prevention. Totally, 19 major phenolic compounds were quantified in mung bean, including 10 phenolic acids and 9 flavonoids. After summarizing their contents and effective doses in rodent AD models, it was speculated that vitexin, isovitexin, sinapic acid, and ferulic acid might be the major bioactive compounds for mung bean-mediated neuroprotection. The mechanisms involved inhibition of beta-amyloidogenesis, tau hyperphosphorylation, oxidative stress, and neuroinflammation, and promotion of autophagy and acetylcholinesterase enzyme activity. Notably, the neuroprotective phenolic profile in mung bean changed after germination, with decreased vitexin and isovitexin, and increased rutin, isoquercitrin, isorhamnetin, and caffeic acid detected. However, only studies of individual phenolic compounds in mung bean are published at present. Hence, further studies are needed to elucidate the neuroprotective activities and mechanisms of extractions of mung bean seeds and sprouts, and the synergism between different phenolic compounds. Title: An Overview on the Mechanisms and Applications of Enzyme Inhibition-Based Methods for Determination of Organophosphate and Carbamate Pesticides Cao J, Wang M, Yu H, She Y, Cao Z, Ye J, Abd El-Aty AM, Hacimuftuoglu A, Wang J, Lao S Ref: Journal of Agricultural and Food Chemistry, 68:7298, 2020 : PubMed ESTHER: Cao_2020_J.Agric.Food.Chem_68_7298 PubMedSearch: Cao 2020 J.Agric.Food.Chem 68 7298 PubMedID: 32551623 Abstract Acetylcholinesterase inactivating compounds, such as organophosphate (OP) and carbamate (CM) pesticides, are widely used in agriculture to ensure sustainable production of food and feed. As a consequence of their applications, they would result in neurotoxicity, even death. In this essence, the development of enzyme inhibition methods still shows great significance as rapid detection techniques for on-site large-scale screening of OPs and CMs. Initially, mechanisms and applications of various enzyme-inhibition-based methods and devices, including optical colorimetric assay, fluorometric assays, electrochemical biosensors, rapid test card, and microfluidic device, are highlighted in the present overview. Further, to enhance the enzyme sensitivity for detection; alternative enzyme sources or high yield enrichment methods (such as abzyme, artificial enzyme, and recombinant enzyme), as well as enzyme reactivation and identification, are also addressed in this comprehensive overview. Title: Modulation of the MAPKs pathways affects Abeta-induced cognitive deficits in Alzheimer's disease via activation of alpha7nAChR Chang KW, Zong HF, Yasir Rizvi M, Ma KG, Zhai W, Wang M, Yang WN, Ji SF, Qian YH Ref: Neurobiol Learn Mem, :107154, 2020 : PubMed ESTHER: Chang_2020_Neurobiol.Learn.Mem__107154 PubMedSearch: Chang 2020 Neurobiol.Learn.Mem 107154 PubMedID: 31904546 Abstract Cognitive impairment in Alzheimer's disease (AD) is characterized by being deficient at learning and memory. Abeta1-42 oligomers have been shown to impair rodent cognitive function. We previously demonstrated that activation of alpha7nAChR, inhibition of p38 or JNK could alleviate Abeta-induced memory deficits in Y maze test. In this study, we investigated whether the effects of alpha7nAChR and MAPKs on Y maze test is reproducible with a hippocampus-dependent spatial memory test such as Morris water maze. We also assessed the possible co-existence of hippocampus-independent recognition memory dysfunction using a novel object recognition test and an alternative and stress free hippocampus-dependent recognition memory test such as the novel place recognition. Besides, previous research from our lab has shown that MAPKs pathways regulate Abeta internalization through mediating alpha7nAChR. In our study, whether MAPKs pathways exert their functions in cognition by modulating alpha7nAChR through regulating glutamate receptors and synaptic protein, remain little known. Our results showed that activation of alpha7nAChR restored spatial memory, novel place recognition memory, and short-term and long-term memory in novel object recognition. Inhibition of p38 restored spatial memory and short-term and long-term memory in novel object recognition. Inhibition of ERK restored short-term memory in novel object recognition and novel place recognition memory. Inhibition of JNK restored spatial memory, short-term memory in novel object recognition and novel place recognition memory. Beside this, the activation of alpha7nAChR, inhibition of p38 or JNK restored Abeta-induced levels of NMDAR1, NMDAR2A, NMDAR2B, GluR1, GluR2 and PSD95 in Abeta-injected mice without influencing synapsin 1. In addition, these treatments also recovered the expression of acetylcholinesterase (AChE). Finally, we found that the inhibition of p38 or JNK resulted in the upregulation of alpha7nAChR mRNA levels in the hippocampus. Our results indicated that inhibition of p38 or JNK MAPKs could alleviate Abeta-induced spatial memory deficits through regulating activation of alpha7nAChR via recovering memory-related proteins. Moreover, p38, ERK and JNK MAPKs exert different functions in spatial and recognition memory. Title: 14,15-Epoxyeicosatrienoic Acid Alleviates Pathology in a Mouse Model of Alzheimer's Disease Chen W, Wang M, Zhu M, Xiong W, Qin X, Zhu X Ref: Journal of Neuroscience, 40:8188, 2020 : PubMed ESTHER: Chen_2020_J.Neurosci_40_8188 PubMedSearch: Chen 2020 J.Neurosci 40 8188 PubMedID: 32973044 Abstract Alzheimer's disease (AD) is the leading cause of late-onset dementia, and there exists an unmet medical need for effective treatments for AD. The accumulation of neurotoxic amyloid-beta (Abeta) plaques contributes to the pathophysiology of AD. EPHX2 encoding soluble epoxide hydrolase (sEH)-a key enzyme for epoxyeicosatrienoic acid (EET) signaling that is mainly expressed in lysosomes of astrocytes in the adult brain-is cosited at a locus associated with AD, but it is unclear whether and how it contributes to the pathophysiology of AD. In this report, we show that the pharmacologic inhibition of sEH with 1-trifluoromethoxyphenyl- 3-(1-propionylpiperidin-4-yl) urea (TPPU) or the genetic deletion of Ephx2 reduces Abeta deposition in the brains of both male and female familial Alzheimer's disease (5xFAD) model mice. The inhibition of sEH with TPPU or the genetic deletion of Ephx2 alleviated cognitive deficits and prevented astrocyte reactivation in the brains of 6-month-old male 5xFAD mice. 14,15-EET levels in the brains of these mice were also increased by sEH inhibition. In cultured adult astrocytes treated with TPPU or 14,15-EET, astrocyte Abeta clearance was increased through enhanced lysosomal biogenesis. Infusion of 14,15-EET into the hippocampus of 5xFAD mice prevented the aggregation of Abeta. Notably, a higher concentration of 14,15-EET (200 ng/ml) infusion into the hippocampus reversed Abeta deposition in the brains of 6-month-old male 5xFAD mice. These results indicate that EET signaling, especially 14,15-EET, plays a key role in the pathophysiology of AD, and that targeting this pathway is a potential therapeutic strategy for the treatment of AD.SIGNIFICANCE STATEMENT There are limited treatment options for Alzheimer's disease (AD). EPHX2 encoding soluble epoxide hydrolase (sEH) is located at a locus that is linked to late-onset AD, but its contribution to the pathophysiology of AD is unclear. Here, we demonstrate that sEH inhibition or Ephx2 deletion alleviates pathology in familial Alzheimer's disease (5xFAD) mice. Inhibiting sEH or increasing 14,15-epoxyeicosatrienoic acid (EET) enhanced lysosomal biogenesis and amyloid-beta (Abeta) clearance in cultured adult astrocytes. Moreover, the infusion of 14,15-EET into the hippocampus of 5xFAD mice not only prevented the aggregation of Abeta, but also reversed the deposition of Abeta. Thus, 14,15-EET plays a key role in the pathophysiology of AD and therapeutic strategies that target this pathway may be an effective treatment. Title: The Anti-inflammatory Effect of Soluble Epoxide Hydrolase Inhibitor and 14, 15-EET in Kawasaki Disease Through PPARgamma/STAT1 Signaling Pathway Dai N, Yang C, Fan Q, Wang M, Liu X, Zhao H, Zhao C Ref: Front Pediatr, 8:451, 2020 : PubMed ESTHER: Dai_2020_Front.Pediatr_8_451 PubMedSearch: Dai 2020 Front.Pediatr 8 451 PubMedID: 32903307 Abstract Soluble epoxide hydrolase (sEH) is responsible for rapid degradation of 14, 15-EET, which is one of the isomers of EETs and plays an important role in cardiovascular diseases. In this study, we investigated the mechanism by which sEH inhibitor AUDA played an anti-inflammatory effect in HCAECs. Our results indicated that AUDA treatment promoted PPARgamma expression, while knockdown of PPARgamma blocked the cell growth and STAT1 expression inhibition induced by 100 mumol/L AUDA in HCAECs. AUDA also inhibited the overexpression of TNF-alpha, IL-1 beta, and MMP-9 induced by KD sera in HCAECs. Moreover, 30 blood samples from children with Kawasaki disease (KD) were collected with 30 healthy children as the control group. QPCR and ELISA assays were used to detect the level of 14, 15-EET, TNF-alpha, IL-1beta, and MMP-9. We found that the level of 14, 15-EET was higher in peripheral blood of children with KD compared with healthy controls (P < 0.05). In comparison to KD children with non-coronary artery lesion (nCAL), the level of 14, 15-EET was higher in peripheral blood of KD children with coronary artery lesion (CAL) (P < 0.05). Compared with healthy control group, the expression levels of TNF-alpha, IL-1beta, and MMP-9 in patients with KD were significantly up-regulated. Compared with nCAL KD children, the expression levels of TNF-alpha, IL-1beta, and MMP-9 in CAL children were abnormally high (P < 0.05). Our study indicated that AUDA played an anti-inflammatory effect in HCAECs through PPARgamma/STAT1 signaling pathway, and 14, 15-EET is up-regulated in children with KD, suggesting that 14, 15-EET involved in the progression of KD. Title: Enantioselective disposition and metabolic products of isofenphos-methyl in rats and the hepatotoxic effects Gao B, Zhao S, Shi H, Zhang Z, Li L, He Z, Wen Y, Covaci A, Wang M Ref: Environ Int, 143:105940, 2020 : PubMed ESTHER: Gao_2020_Environ.Int_143_105940 PubMedSearch: Gao 2020 Environ.Int 143 105940 PubMedID: 32663714 Abstract Isofenphos-methyl (IFP), a chiral organophosphorus pesticide, is one of the main chemicals used to control underground insects and nematodes. Recently, the use of IFP on vegetables and fruits has been prohibited due to its high toxicity. In this study, we investigated the enantioselective distribution and metabolism of IFP and its metabolites, namely, isofenphos-methyl oxon (IFPO) and isocarbophos oxon (ICPO), in male Sprague Dawley (SD) rats. Forty eight hours (48 h) after exposure, ICPO was the main detectable compound in blood (up to 75%) and urine (up to 77%), and we found that (S)-ICPO was significantly more stable than (R)-ICPO (p < 0.05). Therefore, (S)-ICPO was proposed as a suitable candidate biomarker for the biomonitoring of IFP in human urine and blood. After 48 h exposure, 21.2-41.0%, 4.1-15.1%, and 8.6-18.7% of dosed IFP was detected in the liver of racemic, R and S enantiomer-exposed rats, respectively, and R-IFP and R-IFPO showed a faster degradation (p < 0.05). Our results showed that after one week of consecutive exposure to IFP, ICPO was accumulated in the liver of rats in both racemic and enantiopure groups (no difference between the groups, p > 0.05). We found that cytochrome P450 (CYP) (i.e. CYP2C11, CYP2D2 and CYP3A2 enzymes and carboxylesterases) is responsible for the enantioselective metabolism of IFP in liver. In addition, rats exposed to (S)-IFP exhibited hepatic lipid peroxidation, liver inflammation and hepatic fibrosis. This study provides useful information and a reference for the biomonitoring and risk assessment of IFP and organophosphorus pesticide exposure. Title: Hyperbaric oxygen therapy may be effective to improve hypoxemia in patients with severe COVID-2019 pneumonia: two case reports Guo D, Pan S, Wang M, Guo Y Ref: Undersea Hyperb Med, 47:181, 2020 : PubMed ESTHER: Guo_2020_Undersea.Hyperb.Med_47_181 PubMedSearch: Guo 2020 Undersea.Hyperb.Med 47 181 PubMedID: 32574433 Abstract Objectives: To determine whether hyperbaric oxygen (HBO2) therapy be effective to improve hypoxemia for severe COVID-19 pneumonia patients. Methods: Two male patients ages 57 and 64 years old were treated. Each met at least one of the following criteria: shortness of breath; respiratory rate (RR) >/=30 breaths/minute; finger pulse oxygen saturation (SpO2) Title: Tunicyclin L, a cyclic peptide from Psammosilene tunicoides: Isolation, characterization, conformational studies and biological activity Hou Y, Wang M, Sun C, Peng C, Zhang Y, Li X Ref: Fitoterapia, :104628, 2020 : PubMed ESTHER: Hou_2020_Fitoterapia__104628 PubMedSearch: Hou 2020 Fitoterapia 104628 PubMedID: 32433930 Abstract Tunicyclin L (1), cyclo (L-Pro(1)-Gly-L-Phe(1)-L-Ile-L-Pro(2)-L-Phe -L-Thr-L-Val), and 11 known compounds, including one cyclic peptide (2), eight carboline alkaloids (3-10), one lignan (11) and one flavone (12) were isolated from the roots of Psammosilene tunicoides. Their structures were elucidated on the basis of extensive UV, IR, MS, NMR spectroscopic data and comparison with literature. Single-crystal X-ray diffraction results revealed the stereochemistry of the 24-membered ring cyclic peptide (1). Among these known compounds, compound 6 was found to be a new natural product, and compounds 3, 4, and 11 were isolated from this plant for the first time. Five compounds (1, 3, 4, 7, and 9) showed moderate anti-acetylcholinesterase (AChE) activity. Title: Inhibition of acetylcholinesterase activity and beta-amyloid oligomer formation by 6-bromotryptamine A, a multi-target anti-Alzheimer's molecule Jin X, Wang M, Shentu J, Huang C, Bai Y, Pan H, Zhang D, Yuan Z, Zhang H and Cui W <5 more author(s)> Jin X, Wang M, Shentu J, Huang C, Bai Y, Pan H, Zhang D, Yuan Z, Zhang H, Xiao X, Wu X, Ding L, Wang Q, He S, Cui W (- 5) Ref: Oncol Lett, 19:1593, 2020 : PubMed ESTHER: Jin_2020_Oncol.Lett_19_1593 PubMedSearch: Jin 2020 Oncol.Lett 19 1593 PubMedID: 31966085 Abstract Alzheimer's disease (AD) is a neurodegenerative disorder characterized by learning and memory impairments. Recent studies have suggested that AD can be induced by multiple factors, such as cholinergic system dysfunction and beta-amyloid (Abeta) neurotoxicity. It was reported that 6-bromo-N-propionyltryptamine could treat neurological diseases, including AD. In the present study, 6-bromotryptamine A, a derivative of 6-bromo-N-propionyltryptamine, was synthesized by the condensation of 2-(6-bromo-1H-indol-3-yl)ethan-1-amine and 2-(4-bromophenyl)acetic acid, and was used as a potential anti-AD molecule. Furthermore, scopolamine can induce impairments of learning and memory, and was widely used to establish AD animal models. The results demonstrated that 6-bromotryptamine A significantly prevented scopolamine-induced short-term cognitive impairments, as revealed by various behavioral tests in mice. Furthermore, an acetylcholinesterase (AChE) activity assay revealed that 6-bromotryptamine A directly inhibited AChE activity. Notably, it was observed that 6-bromotryptamine A blocked the formation of Abeta oligomer, as evaluated by the dot blot assay. All these results suggested that 6-bromotryptamine A may be used to prevent impairments in short-term learning and memory ability possibly via the inhibition of AChE and the blockade of Abeta oligomer formation. Title: Chiral organophosphorous pesticides fosthiazate: absolute configuration, stereoselective bioactivity, toxicity, and degradation in vegetables Li L, Xu JY, Lv B, Kaziem AE, Liu F, Shi HY, Wang M Ref: Journal of Agricultural and Food Chemistry, 68:7609, 2020 : PubMed ESTHER: Li_2020_J.Agric.Food.Chem_68_7609 PubMedSearch: Li 2020 J.Agric.Food.Chem 68 7609 PubMedID: 32598147 Abstract Fosthiazate is a widely used chiral organophosphorous nematicide with four stereoisomers. The present study systemically assessed the stereoselectivity of fosthiazate for the first time, including absolute configuration confirmation, stereoselective bioactivity toward nematode and aphid, toxicity to honeybees, and the stereoselective degradation in cucumber and pepper under field conditions. The absolute configurations of the four stereoisomers that eluted on the Superchiral IG-3 column were confirmed as (1S,3R)-(-)-fosthiazate, (1S,3S)-(-)-fosthiazate, (1R,3S)-(+)-fosthiazate, and (1R,3R)-(+)-fosthiazate. Compared with other two stereoisomers, (1S,3R)-fosthiazate and (1S,3S)-fosthiazate possess more than 100 times bioactive and 10 times toxic toward the target and non-target organisms, respectively. The molecular docking found that (1S,3R)-fosthiazate and (1S,3S)-fosthiazate had shorter binding distances and lower energies with acetylcholinesterase (AChE) which illuminated the mechanism of the experimental results. In addition, both the high-bioactive stereoisomers had faster degradation rates in cucumber and pepper. Based on the results of bioactivity, toxicity, and degradation behavior, the stereoisomer mixture of (1S,3R)-fosthiazate and (1S,3S)-fosthiazate will be a better option than the racemic fosthiazate to increase the bioactivity and reduce application dosage. 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: A Review of the Pharmacological Properties of Psoralen Ren Y, Song X, Tan L, Guo C, Wang M, Liu H, Cao Z, Li Y, Peng C Ref: Front Pharmacol, 11:571535, 2020 : PubMed ESTHER: Ren_2020_Front.Pharmacol_11_571535 PubMedSearch: Ren 2020 Front.Pharmacol 11 571535 PubMedID: 33013413 Abstract Psoralen is the principal bioactive component in the dried fruits of Cullen corylifolium (L.) Medik (syn. Psoralea corylifolia L), termed "Buguzhi" in traditional Chinese medicine (TCM). Recent studies have demonstrated that psoralen displays multiple bioactive properties, beneficial for the treatment of osteoporosis, tumors, viruses, bacteria, and inflammation. The present review focuses on the research evidence relating to the properties of psoralen gathered over recent years. Firstly, multiple studies have demonstrated that psoralen exerts strong anti-osteoporotic effects via regulation of osteoblast/osteoclast/chondrocyte differentiation or activation due to the participation in multiple molecular mechanisms of the wnt/beta-catenin, bone morphogenetic protein (BMP), inositol-requiring enzyme 1 (IRE1)/apoptosis signaling kinase 1 (ASK1)/c-jun N-terminal kinase (JNK) and the Protein Kinase B(AKT)/activator protein-1 (AP-1) axis, and the expression of miR-488, peroxisome proliferators-activated receptor-gamma (PPARgamma), and matrix metalloproteinases (MMPs). In addition, the antitumor properties of psoralen are associated with the induction of ER stress-related cell death via enhancement of PERK: Pancreatic Endoplasmic Reticulum Kinase (PERK)/activating transcription factor (ATF), 78kD glucose-regulated protein (GRP78)/C/EBP homologous protein (CHOP), and 94kD glucose-regulated protein (GRP94)/CHOP signaling, and inhibition of P-glycoprotein (P-gp) or ATPase that overcomes multidrug resistance. Furthermore, multiple articles have shown that the antibacterial, anti-inflammatory and neuroprotective effects of psoralen are a result of its interaction with viral polymerase (Pol), destroying the formation of biofilm, and regulating the activation of tumor necrosis factor alpha (TNF-alpha), transforming growth factor beta (TGF-beta), interleukin 4/5/6/8/12/13 (IL-4/5/6/8/12/13), GATA-3, acetylcholinesterase (AChE), and the hypothalamic-pituitary-adrenal (HPA) axis. Finally, the toxic effects and mechanisms of action of psoralen have also been reviewed. Title: Increased cross-linking micelle retention in the brain of Alzheimer's disease mice by elevated asparagine endopeptidase protease responsive aggregation Ren J, Jiang F, Wang M, Hu H, Zhang B, Chen L, Dai F Ref: Biomater Sci, 8:6533, 2020 : PubMed ESTHER: Ren_2020_Biomater.Sci_8_6533 PubMedSearch: Ren 2020 Biomater.Sci 8 6533 PubMedID: 33111725 Abstract Current forms of medication for Alzheimer's disease (AD) provide a symptomatic benefit limited to those with early onset, but there is no single drug available for later stage patients. Given the recent failures of AD drugs in clinical trials, an intensive treatment strategy based on drug combination that is approved is attractive. At present, the greatest difficulty lies in the low accumulation of drugs in the brain. All hydrophilic drugs are limited by the physical and biochemical barriers within the blood-brain barrier and lipophilic drugs are often transported back into the blood by efflux pumps located in the blood-brain barrier. Here, we select elevated asparagine endopeptidase (AEP) as a target to trigger in situ cross-linking of small sized particles to form large sized drug clusters to block the efflux of the brain. Subsequently, responsive cross-linking micelles (RCMs) loaded with the acetylcholinesterase inhibitor, donepezil (DON), the microtubule therapeutic agent, Paclitaxel (PTX), and the glucose metabolism disorder regulator, insulin (INS) are investigated, with a focus on high levels of drug accumulation in the brain in AD. These smart multi-drug delivery RCMs provide a powerful system for AD treatment and can be adapted for other central nervous system (CNS) disorders. Title: Characterization of a novel halotolerant esterase from Chromohalobacter canadensis isolated from salt well mine Wang M, Ai L, Zhang M, Wang F, Wang C Ref: 3 Biotech, 10:430, 2020 : PubMed ESTHER: Wang_2020_3.Biotech_10_430 PubMedSearch: Wang 2020 3.Biotech 10 430 PubMedID: 32983823 Gene_locus related to this paper: 9gamm-EstSHJ2 Abstract A esterase gene was characterized from a halophilic bacterium Chromohalobacter canadensis which was originally isolated from a salt well mine. Sequence analysis showed that the esterase, named as EstSHJ2, contained active site serine encompassed by a conserved pentapeptide motif (GSSMG). The EstSHJ2 was classified into a new lipase/esterase family by phylogenetic association analysis. Molecular weight of EstSHJ2 was 26 kDa and the preferred substrate was p-NP butyrate. The EstSHJ2 exhibited a maximum activity at 2.5 M NaCl concentration. Intriguingly, the optimum temperature, pH and stability of EstSHJ2 were related to NaCl concentration. At 2.5 M NaCl concentration, the optimum temperature and pH of EstSHJ2 were 65 C and pH 9.0, and enzyme remained 81% active after 80 C treatment for 2 h. Additionally, the EstSHJ2 showed strong tolerance to metal ions and organic solvents. Among these, 10 mM K(+), Ca(2+) , Mg(2+) and 30% hexane, benzene, toluene has significantly improved activity of EstSHJ2. The EstSHJ2 was the first reported esterase from Chromohalobacter canadensis, and may carry considerable potential for industrial applications under extreme conditions. Title: Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro Wang M, Cao R, Zhang L, Yang X, Liu J, Xu M, Shi Z, Hu Z, Zhong W, Xiao G Ref: Cell Res, 30:269, 2020 : PubMed Title: Biological evaluation of 7-O-amide hesperetin derivatives as multitarget-directed ligands for the treatment of Alzheimer's disease Wu M, Zhu X, Zhang Y, Wang M, Liu T, Han J, Li J, Li Z Ref: Chemico-Biological Interactions, 334:109350, 2020 : PubMed ESTHER: Wu_2020_Chem.Biol.Interact_334_109350 PubMedSearch: Wu 2020 Chem.Biol.Interact 334 109350 PubMedID: 33307048 Abstract A series of 7-O-amide hesperetin derivatives were subjected to multi-target biological evaluation of anti-Alzheimer's disease. Most of the compounds showed good in vitro inhibitory activity against cholinesterase, of which compound 7c (7-O-(4-(morpholinoethyl)-acetamide) hesperetin) was the most effective anti-eqBuChE derivative (IC(50) = 0.28 +/- 0.05 M) and exerted neuroprotective effects. Further biological evaluation found that compounds 4d, 4e and 7c showed strong antioxidant, anti-Abeta self-aggregation and anti-neuroinflammatory activities. Compound 7c could inhibit the expression of iNOS and COX-2 proteins and prevent LPS-induced inflammatory response in BV2 cells. In addition, compound 7c could chelate biometal ions such as Cu(2+) and Zn(2+). In the vivo study, the MWM test confirmed that compound 7c could improve the cognitive impairment caused by scopolamine. In summary, the above studies have shown that the optimized compound 7c has great development potential as MTDL for the treatment of AD. Title: GDSL esterase/lipases OsGELP34 and OsGELP110/OsGELP115 are essential for rice pollen development Zhang H, Wang M, Li Y, Yan W, Chang Z, Ni H, Chen Z, Wu J, Xu C and Tang X <1 more author(s)> Zhang H, Wang M, Li Y, Yan W, Chang Z, Ni H, Chen Z, Wu J, Xu C, Deng XW, Tang X (- 1) Ref: J Integr Plant Biol, :, 2020 : PubMed ESTHER: Zhang_2020_J.Integr.Plant.Biol__ PubMedSearch: Zhang 2020 J.Integr.Plant.Biol PubMedID: 32068333 Abstract Pollen exine contains complex biopolymers of aliphatic lipids and phenolics. Abnormal development of pollen exine often leads to plant sterility. Molecular mechanisms regulating exine formation have been studied extensively but remain ambiguous. Here we report the analyses of three GDSL esterase/lipase protein genes, OsGELP34, OsGELP110, and OsGELP115, for rice exine formation. OsGELP34 was identified by cloning of a male sterile mutant gene. OsGELP34 encodes an endoplasmic reticulum protein and was mainly expressed in anthers during pollen exine formation. osgelp34 mutant displayed abnormal exine and altered expression of a number of key genes required for pollen development. OsGELP110 was previously identified as a gene differentially expressed in meiotic anthers. OsGELP110 was most homologous to OsGELP115, and the two genes showed similar gene expression patterns. Both OsGELP110 and OsGELP115 proteins were localized in peroxisomes. Individual knockout of OsGELP110 and OsGELP115 did not affect the plant fertility, but double knockout of both genes altered the exine structure and rendered the plant male sterile. OsGELP34 is distant from OsGELP110 and OsGELP115 in sequence, and osgelp34 and osgelp110/osgelp115 mutants were different in anther morphology despite both were male sterile. These results suggested that OsGELP34 and OsGELP110/OsGELP115 catalyze different compounds for pollen exine development. This article is protected by copyright. All rights reserved. Title: Identifying genes for resistant starch, slowly digestible starch, and rapidly digestible starch in rice using genome-wide association studies Zhang N, Wang M, Fu J, Shen Y, Ding Y, Wu D, Shu X, Song W Ref: Genes Genomics, 42:1227, 2020 : PubMed ESTHER: Zhang_2020_Genes.Genomics_42_1227 PubMedSearch: Zhang 2020 Genes.Genomics 42 1227 PubMedID: 32901332 Abstract BACKGROUND: The digestibility of starch is important for the nutritive value of staple food. Although several genes are responsible for resistant starch (RS) and slowly digestible starch (SDS), gaps persist concerning the molecular basis of RS and SDS formation due to the complex genetic mechanisms of starch digestibility. OBJECTIVES: The objective of this study was to identify new genes for starch digestibility in rice and interprete the genetic mechanisms of RS and SDS by GWAS. METHODS: Genome-wide association studies were conducted by associating the RS and SDS phenotypes of 104 re-sequenced rice lines to an SNP dataset of 2,288,867 sites using a compressed mixed linear model. Candidate genes were identified according to the position of the SNPs based on data from the MSU Rice Genome Annotation Project. RESULTS: Seven quantitative trait loci (QTLs) were detected to be associated with the RS content, among which the SNP 6 m1765761 was located on Waxy. Starch branching enzymes IIa (BEIIa) close to QTL qRS-I4 was detected and further identified as a specific candidate gene for RS in INDICA. Two QTLs were associated with SDS, and the LOC_Os09g09360 encoding lipase was identified as a causal gene for SDS. CONCLUSIONS: GWAS is a valid strategy to genetically dissect the formation of starch digestion properties in rice. RS formation in grains is dependent on the rice type; lipid might also contribute to starch digestibility and should be an alternative factor to improve rice starch digestibility. Title: Rapid colorimetric determination of the pesticides carbofuran and dichlorvos by exploiting their inhibitory effect on the aggregation of peroxidase-mimicking platinum nanoparticles Cao J, Wang M, She Y, El-Aty AMA, Hacimuftuoglu A, Wang J, Yan M, Hong S, Lao S, Wang Y Ref: Mikrochim Acta, 186:390, 2019 : PubMed ESTHER: Cao_2019_Mikrochim.Acta_186_390 PubMedSearch: Cao 2019 Mikrochim.Acta 186 390 PubMedID: 31152243 Abstract A novel and highly sensitive enzyme inhibition assay was developed for the rapid detection of the organophosphate pesticide dichlorvos and the carbamate pesticide carbofuran. It achieves signal amplification by the secondary catalysis of platinum nanoparticles. Acetylcholinesterase (AChE) is capable of catalyzing the hydrolysis of acetylthiocholine to form thiocholine. Thiocholine causes the aggregation of citrate-capped platinum nanoparticles which then lose their peroxidase-mimicking properties. After addition of pesticides, the activity of AChE is inhibited, less thiocholine is produced, less aggregation occurs, and the peroxidase-mimetic properties are increasingly retained. In the presence of tetramethylbenzidine and H2O2, a deep blue coloration with an absorption maximum at 650 nm will be formed. The assay was applied to the determination of dichlorvos and carbofuran, and detection limits of 2.3 mug.L(-1) and 1.4 mug.L(-1) were obtained, respectively. Recovery experiments with spiked tap water and pears gave satisfactory relative standard deviations. Graphical abstract The blue product formed by platinum nanoparticle-catalyzed oxidation of 3,3'5,5'-tetramethylbenzidine (TMB) by H2O2 is reduced if acetylthiocholine (ATCh) is hydrolyzed by acetylcholinesterase (AChE) to form thiocholine. However, if AChE is inhibited by pesticides, color formation will recover. Title: Spectroscopic and molecular modeling investigation on inhibition effect of nitroaromatic compounds on acetylcholinesterase activity Chen Y, Wang M, Fu H, Qu X, Zhang Z, Kang F, Zhu D Ref: Chemosphere, 236:124365, 2019 : PubMed ESTHER: Chen_2019_Chemosphere_236_124365 PubMedSearch: Chen 2019 Chemosphere 236 124365 PubMedID: 31325829 Abstract Nitroaromatic compounds (NACs) are widely distributed in the environment and are considered toxic or carcinogenic. However, little attention has been paid to the binding interactions between NACs and biomacromolecules (e.g., proteins). Here we investigated the effects of three model NACs, nitrobenzene (NB), 1,3-dinitrobenzene (DNB), and 1,3,5-trinitrobenzene (TNB), on the activity of acetylcholinesterase (AChE). The presence of NACs (up to 0.5mM) effectively suppressed the AChE-catalyzed hydrolysis of acetylthiocholine iodide, with the suppression effect increasing with the nitro-group substitution (TNB>DNB>NB). Consistently, the UV absorption of AChE at 206nm arising from the skeleton structure decreased by the addition NACs, and the decrease exhibited the same compound sequence, reflecting the perturbing interactions with the skeleton enzyme structure. However, no changes were made on the secondary structure of AChE, as evidenced by the circular dichroism analysis. The fluorescence quenching analysis of AChE demonstrated that NB and DNB interacted with both tryptophan (Trp) and tyrosine (Tyr) residues, whereas TNB interacted only with Trp. The UV absorption and fluorescence quenching analyses both reflected that the interactions with the non-skeleton aromatic amino acids were weak. (1)H NMR analysis confirmed the strong pi-pi coupling interactions between TNB and model Trp. Molecular simulation indicated that the DNB or TNB molecule was sandwiched between Trp84 and Phe330 at the catalytic site via pi-pi coupling interactions. The findings highlight the importance of specific interactions of NACs with proteins to cause them to malfunction. Title: A potential biomarker of isofenphos-methyl in humans: A chiral view Gao B, Zhao S, Zhang Z, Li L, Hu K, Kaziem AE, He Z, Hua X, Shi H, Wang M Ref: Environ Int, 127:694, 2019 : PubMed ESTHER: Gao_2019_Environ.Int_127_694 PubMedSearch: Gao 2019 Environ.Int 127 694 PubMedID: 30991225 Inhibitor(s) related to this paper: Isocarbophos, Isofenphos-methyl Abstract Isofenphos-methyl (IFP) is a very active and persistent chiral insecticide. However, IFP has lower activity against acetylcholinesterases (AChEs). Previously, it was confirmed that phosphorothioate organophosphorus pesticides with N-alkyl (POPN) require activation by oxidative desulfuration and N-dealkylation. In this work, we demonstrated that IFP could be metabolized in human liver microsomes to isofenphos-methyl oxon (IFPO, 52.7%), isocarbophos (ICP, 14.2%) and isocarbophos oxon (ICPO, 11.2%). It was found that (R)-IFP was preferentially degraded compared to the (S)-enantiomer, and the enantiomeric fraction (EF) value reached 0.61 at 60min. However, (S)-enantiomers of the three metabolites, were degraded preferentially, and the EF values ranged from 0.34 to 0.45. Cytochrome P450 (CYP) isoforms CYP3A4, CYP2E1, and CYP1A2 and carboxylesterase enzyme have an essential role in the enantioselective metabolism of IFP; but, the enzymes that participate in the degradation of IFP metabolites are different. The AChE inhibition bioassay indicated that ICPO is the only effective inhibitor of AChE. The covalent molecular docking has proposed that the metabolites of IFP and its analogs after N-dealkylation and oxidative desulfuration will possess the highest inhibitory activity against AChE. This study is the first to demonstrate that ICPO can be regarded as a potential biomarker for the biomonitoring of IFP and ICP exposure in humans. Title: Single and joint oxidative stress-related toxicity of sediment-associated cadmium and lead on Bellamya aeruginosa Liu X, Chen Q, Ali N, Zhang J, Wang M, Wang Z Ref: Environ Sci Pollut Res Int, 26:24695, 2019 : PubMed ESTHER: Liu_2019_Environ.Sci.Pollut.Res.Int_26_24695 PubMedSearch: Liu 2019 Environ.Sci.Pollut.Res.Int 26 24695 PubMedID: 31240645 Abstract The biotoxicity of heavy metals in sediments toward benthic organisms has evoked great concern for the health of freshwater ecosystems. This study applied a sediment toxicity testing protocol to investigate the single and joint toxicity of cadmium (Cd) and lead (Pb) on Bellamya aeruginosa. B. aeruginosa were exposed to different concentrations of Cd (5, 25, and 100 mg/kg), Pb (20, 100, and 400 mg/kg), and their different concentration combinations. A suite of biomarkers, including superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), metallothionein (MT), malondialdehyde (MDA), and acetylcholinesterase (AChE), were measured after 7, 14, 21, and 28 days of exposure to evaluate their oxidative stress status. Cell apoptosis of soft tissue was also determined after exposure. Results revealed that these endpoints represented sensitive biomarkers for the characterization of the oxidative stress response induced by these metals. Specifically, a decrease of SOD and GPx and an increase of MDA were indicative of the potential failure of the antioxidant defense system in neutralizing the reactive oxygen species (ROS) generated in the exposure of the Pb-treated group. The integrated biomarker response (IBR) index revealed the most significant sub-lethal toxicity for Pb-spiked sediments, leading to the highest rate of cell apoptosis (70.8%). Exposure to Cd resulted in a time- and dose-dependent effect on MT levels, which suggested active detoxification of this metal. Exposure to the mixture resulted in amelioration of Pb toxicity, likely due to the competitive binding of Cd to active enzyme, with the result of an observed antagonistic interaction. This study indicated that B. aeruginosa represents a good biomonitor for assessing Cd and Pb contamination of sediments, and laid the foundation for their potential risk assessments in freshwater ecosystems. Title: Design, synthesis, and biological evaluation of rutacecarpine derivatives as multitarget-directed ligands for the treatment of Alzheimer's disease Wu M, Ma J, Ji L, Wang M, Han J, Li Z Ref: Eur Journal of Medicinal Chemistry, 177:198, 2019 : PubMed ESTHER: Wu_2019_Eur.J.Med.Chem_177_198 PubMedSearch: Wu 2019 Eur.J.Med.Chem 177 198 PubMedID: 31136894 Abstract A series of 3-amino-substituted rutacecarpine derivatives were synthesized to identify novel multitarget-directed ligands (MTDLs) for the treatment of Alzheimer's disease (AD). Biological evaluation showed that most of the synthesized compounds inhibited butyrylcholinesterase (BuChE) and exerted antioxidant effects. Among the synthesized compounds, 6n was subjected to further biological evaluation. Lineweaver-Burk plotting and molecular modeling illustrated that 6n bound simultaneously to the peripheral anionic site (PAS) and catalytic sites (CAS) of BuChE. Furthermore, 6n modulated Abeta aggregation; chelated biometals; presented good absorption, distribution, metabolism, excretion, and toxicity properties; and showed remarkable neuroprotective activity. Previous research has shown that the optimized compound 6n has considerable potential for development as an MTDL for the treatment of AD. Title: Insights into the improvement of the enzymatic hydrolysis of bovine bone protein using lipase pretreatment Yao Y, Wang M, Liu Y, Han L, Liu X Ref: Food Chem, 302:125199, 2019 : PubMed ESTHER: Yao_2019_Food.Chem_302_125199 PubMedSearch: Yao 2019 Food.Chem 302 125199 PubMedID: 31400699 Abstract Animal bones are a high-quality source of protein and comprehensive nutrients and improper handling can cause resource wasting and environmental issues. Pretreatment before enzymatic hydrolysis of bone could significantly improve the enzymolytic efficiency, which is an essential step to achieve high value-added utilization of bones. This study investigated the effect of lipase pretreatment on the enzymatic hydrolysis of bones. The degree of hydrolysis after lipase pretreatment was 12.58%, which was 8.19% higher than that without pretreatment. Lipase pretreatment was optimal at 9% substrate concentration and initial pH 7.5, with 0.08% lipase, followed by 4h incubation at 40 degrees C. Mechanism analysis indicated that lipase pretreatment improved the enzymolytic efficiency by significantly decreasing the lipid content, and changing the surface structure and surface element content of C, N, and O, promoting the attachment of alkaline protease onto the sample. Overall, lipase pretreatment was an effective method to reduce the costs of production. Title: Transfection of neurotrophin-3 into neural stem cells using ultrasound with microbubbles to treat denervated muscle atrophy Gong L, Jiang C, Liu L, Wan S, Tan W, Ma S, Jia X, Wang M, Hu A and Chen Y <4 more author(s)> Gong L, Jiang C, Liu L, Wan S, Tan W, Ma S, Jia X, Wang M, Hu A, Shi Y, Zhang Y, Shen Y, Wang F, Chen Y (- 4) Ref: Exp Ther Med, 15:620, 2018 : PubMed ESTHER: Gong_2018_Exp.Ther.Med_15_620 PubMedSearch: Gong 2018 Exp.Ther.Med 15 620 PubMedID: 29403547 Abstract Neurotrophin-3 (NT-3) has potential as a therapeutic agent for the treatment of patients with denervated muscle atrophy. However, the endogenous secretion of NT-3 is low and exogenous NT-3 lacks sufficient time to accumulate due to its short half-life. The transfection of NT-3 has been demonstrated to have a beneficial effect on denervated muscle and motor endplates. Neural stem cells (NSCs) differentiate into neurons and form motor endplate nerve-muscle connections. It has been previously demonstrated that local and noninvasive transfection can be performed using ultrasound with microbubbles (MBs). In the current study, hematoxylin and eosin, acetylcholinesterase and gold chloride staining, as well as transmission electron microscopy, were performed to verify the effects of this treatment strategy. The results demonstrated that using ultrasound with MBs for the transfection of NT-3 into NSCs, and their subsequent transplantation in vivo, attenuated the atrophy of denervated muscle and reduced motor endplate degeneration. This noninvasive, efficient and targeted treatment strategy may therefore be a potential treatment for patients with denervated muscle atrophy. Title: Dental malocclusion stimulates neuromuscular circuits associated with temporomandibular disorders Liu X, Zhang C, Liu Q, Zhou K, Yin N, Zhang H, Shi M, Wang M Ref: Eur J Oral Sci, 126:466, 2018 : PubMed ESTHER: Liu_2018_Eur.J.Oral.Sci_126_466 PubMedSearch: Liu 2018 Eur.J.Oral.Sci 126 466 PubMedID: 30341927 Abstract Unilateral anterior crossbite (UAC) has been demonstrated to cause masseter hyperactivity via the periodontal trigeminal mesencephalic nucleus (Vme)-trigeminal motor nucleus circuit. Here, we studied activation of motor neurons of the facial nucleus (VII), hypoglossal nucleus (XII), nucleus ambiguus (Amb), and spinal nucleus of the accessory nerve (SNA) in rats with UAC via their similar connections with Vme. An anterograde tracer, biotinylated dextran amine (BDA), was injected into the Vme to identify the central axon terminals around the motor neurons of VII, XII, Amb, and SNA. The expression of vesicular glutamate transporter 1 (VGLUT1) in neurons of VII, XII, Amb, and SNA, and the expression of acetylcholinesterase (AChE) were measured in the stapedius, lingualis, palatopharyngeal, and sternocleidomastoid muscles. In BDA-treated rats, many BDA-labeled cell bodies in the Vme and terminals in VII, XII, Amb, and SNA were identified. Compared with control rats, rats with UAC showed higher expression of VGLUT1 in these nuclei, and statistically significantly higher expression of AChE in the stapedius, lingualis, and sternocleidomastoid muscles, but not in the palatopharyngeal muscle. These findings suggest that UAC activates orofacial, head, and cervical multimotor behaviors via connections between the Vme and the corresponding motor nuclei. Title: Design, Synthesis, and Biological Evaluation of Orally Available First-Generation Dual-Target Selective Inhibitors of Acetylcholinesterase (AChE) and Phosphodiesterase 5 (PDE5) for the Treatment of Alzheimer's Disease Mao F, Wang H, Ni W, Zheng X, Wang M, Bao K, Ling D, Li X, Xu Y and Li J <1 more author(s)> Mao F, Wang H, Ni W, Zheng X, Wang M, Bao K, Ling D, Li X, Xu Y, Zhang H, Li J (- 1) Ref: ACS Chem Neurosci, 9:328, 2018 : PubMed ESTHER: Mao_2018_ACS.Chem.Neurosci_9_328 PubMedSearch: Mao 2018 ACS.Chem.Neurosci 9 328 PubMedID: 29068218 Abstract Through drug discovery strategies of repurposing and redeveloping existing drugs, a series of novel tadalafil derivatives were rationally designed, synthesized, and evaluated to seek dual-target AChE/PDE5 inhibitors as good candidate drugs for Alzheimer's disease (AD). Among these derivatives, 1p and 1w exhibited excellent selective dual-target AChE/PDE5 inhibitory activities and improved blood-brain barrier (BBB) penetrability. Importantly, 1w.Cit (citrate of 1w) could reverse the cognitive dysfunction of scopolamine-induced AD mice and exhibited an excellent effect on enhancing cAMP response element-binding protein (CREB) phosphorylation in vivo, a crucial factor in memory formation and synaptic plasticity. Moreover, the molecular docking simulations of 1w with hAChE and hPDE5A confirmed that our design strategy was rational. In summary, our research provides a potential selective dual-target AChE/PDE5 inhibitor as a good candidate drug for the treatment of AD, and it could also be regarded as a small molecule probe to validate the novel AD therapeutic approach in vivo. Title: Comparative genomics and transcriptomics depict ericoid mycorrhizal fungi as versatile saprotrophs and plant mutualists Martino E, Morin E, Grelet GA, Kuo A, Kohler A, Daghino S, Barry KW, Cichocki N, Clum A and Perotto S <18 more author(s)> Martino E, Morin E, Grelet GA, Kuo A, Kohler A, Daghino S, Barry KW, Cichocki N, Clum A, Dockter RB, Hainaut M, Kuo RC, LaButti K, Lindahl BD, Lindquist EA, Lipzen A, Khouja HR, Magnuson J, Murat C, Ohm RA, Singer SW, Spatafora JW, Wang M, Veneault-Fourrey C, Henrissat B, Grigoriev IV, Martin FM, Perotto S (- 18) Ref: New Phytol, 217:1213, 2018 : PubMed ESTHER: Martino_2018_New.Phytol_217_1213 PubMedSearch: Martino 2018 New.Phytol 217 1213 PubMedID: 29315638 Gene_locus related to this paper: amore-a0a2t3axk4, amore-a0a2t3avs4, amore-a0a2t3ay04, amore-a0a2t3aph0 Abstract Some soil fungi in the Leotiomycetes form ericoid mycorrhizal (ERM) symbioses with Ericaceae. In the harsh habitats in which they occur, ERM plant survival relies on nutrient mobilization from soil organic matter (SOM) by their fungal partners. The characterization of the fungal genetic machinery underpinning both the symbiotic lifestyle and SOM degradation is needed to understand ERM symbiosis functioning and evolution, and its impact on soil carbon (C) turnover. We sequenced the genomes of the ERM fungi Meliniomyces bicolor, M. variabilis, Oidiodendron maius and Rhizoscyphus ericae, and compared their gene repertoires with those of fungi with different lifestyles (ecto- and orchid mycorrhiza, endophytes, saprotrophs, pathogens). We also identified fungal transcripts induced in symbiosis. The ERM fungal gene contents for polysaccharide-degrading enzymes, lipases, proteases and enzymes involved in secondary metabolism are closer to those of saprotrophs and pathogens than to those of ectomycorrhizal symbionts. The fungal genes most highly upregulated in symbiosis are those coding for fungal and plant cell wall-degrading enzymes (CWDEs), lipases, proteases, transporters and mycorrhiza-induced small secreted proteins (MiSSPs). The ERM fungal gene repertoire reveals a capacity for a dual saprotrophic and biotrophic lifestyle. This may reflect an incomplete transition from saprotrophy to the mycorrhizal habit, or a versatile life strategy similar to fungal endophytes. Title: Epidemiology of Dementia in Elderly Chronic Obstructive Pulmonary Disease Patients Living in China's Northwestern High-Elevation Area Mei L, Wu S, Wang D, Li H, Zhang H, Wang M Ref: Med Sci Monit, 24:7742, 2018 : PubMed ESTHER: Mei_2018_Med.Sci.Monit_24_7742 PubMedSearch: Mei 2018 Med.Sci.Monit 24 7742 PubMedID: 30372705 Abstract BACKGROUND The aim of this study was to investigate the effects of oxygen and cholinesterase inhibitor (donepezil) therapy on dementia in patients with age-exacerbated chronic obstructive pulmonary disease (COPD) in China's northwestern high-altitude area. MATERIAL AND METHODS A total of 145 patients with acute exacerbation of COPD admitted to the Gerontology Department of the First People's Hospital of Xining City were initially retrospectively screened. From among these 145 patients, we selected 33 cases with dementia and 33 patients without dementia through use of the Mini-Mental State Examination (MMSE), the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), and Activities of Daily Living (ADL) Scale evaluated before, 7 days after, and at the end of the treatment after 3 months. Both patient groups received oxygen therapy for 7 days, but patients with dementia in the intervention group were medicated additionally with donepezil (5 mg/day for 1 week, followed by 10 mg/day for another 12 weeks). RESULTS Mild dementia was found in 35 of the 145 COPD patients. ADL, MMSE, and ADAS-Cog scores were all significantly lower in the intervention group before treatment, improved after the first 7 days, and continued to improve significantly until week 12 in the intervention group, but were still significantly lower than in the control group. CONCLUSIONS Dementia in elderly COPD patients was mainly manifested as decreased executive function, attention, language, and delayed recall, while oxygen and donepezil therapy had beneficial effects on the symptoms. Title: Integrative visual omics of the white-rot fungus Polyporus brumalis exposes the biotechnological potential of its oxidative enzymes for delignifying raw plant biomass Miyauchi S, Rancon A, Drula E, Hage H, Chaduli D, Favel A, Grisel S, Henrissat B, Herpoel-Gimbert I and Rosso MN <13 more author(s)> Miyauchi S, Rancon A, Drula E, Hage H, Chaduli D, Favel A, Grisel S, Henrissat B, Herpoel-Gimbert I, Ruiz-Duenas FJ, Chevret D, Hainaut M, Lin J, Wang M, Pangilinan J, Lipzen A, Lesage-Meessen L, Navarro D, Riley R, Grigoriev IV, Zhou S, Raouche S, Rosso MN (- 13) Ref: Biotechnol Biofuels, 11:201, 2018 : PubMed ESTHER: Miyauchi_2018_Biotechnol.Biofuels_11_201 PubMedSearch: Miyauchi 2018 Biotechnol.Biofuels 11 201 PubMedID: 30061923 Gene_locus related to this paper: 9aphy-a0a371d1b5, 9aphy-a0a371dju9 Abstract Background: Plant biomass conversion for green chemistry and bio-energy is a current challenge for a modern sustainable bioeconomy. The complex polyaromatic lignin polymers in raw biomass feedstocks (i.e., agriculture and forestry by-products) are major obstacles for biomass conversions. White-rot fungi are wood decayers able to degrade all polymers from lignocellulosic biomass including cellulose, hemicelluloses, and lignin. The white-rot fungus Polyporus brumalis efficiently breaks down lignin and is regarded as having a high potential for the initial treatment of plant biomass in its conversion to bio-energy. Here, we describe the extraordinary ability of P. brumalis for lignin degradation using its enzymatic arsenal to break down wheat straw, a lignocellulosic substrate that is considered as a biomass feedstock worldwide. Results: We performed integrative multi-omics analyses by combining data from the fungal genome, transcriptomes, and secretomes. We found that the fungus possessed an unexpectedly large set of genes coding for Class II peroxidases involved in lignin degradation (19 genes) and GMC oxidoreductases/dehydrogenases involved in generating the hydrogen peroxide required for lignin peroxidase activity and promoting redox cycling of the fungal enzymes involved in oxidative cleavage of lignocellulose polymers (36 genes). The examination of interrelated multi-omics patterns revealed that eleven Class II Peroxidases were secreted by the fungus during fermentation and eight of them where tightly co-regulated with redox cycling enzymatic partners. Conclusion: As a peculiar feature of P. brumalis, we observed gene family extension, up-regulation and secretion of an abundant set of versatile peroxidases and manganese peroxidases, compared with other Polyporales species. The orchestrated secretion of an abundant set of these delignifying enzymes and redox cycling enzymatic partners could contribute to the delignification capabilities of the fungus. Our findings highlight the diversity of wood decay mechanisms present in Polyporales and the potentiality of further exploring this taxonomic order for enzymatic functions of biotechnological interest. Title: Pezizomycetes genomes reveal the molecular basis of ectomycorrhizal truffle lifestyle Murat C, Payen T, Noel B, Kuo A, Morin E, Chen J, Kohler A, Krizsan K, Balestrini R and Martin FM <40 more author(s)> Murat C, Payen T, Noel B, Kuo A, Morin E, Chen J, Kohler A, Krizsan K, Balestrini R, Da Silva C, Montanini B, Hainaut M, Levati E, Barry KW, Belfiori B, Cichocki N, Clum A, Dockter RB, Fauchery L, Guy J, Iotti M, Le Tacon F, Lindquist EA, Lipzen A, Malagnac F, Mello A, Molinier V, Miyauchi S, Poulain J, Riccioni C, Rubini A, Sitrit Y, Splivallo R, Traeger S, Wang M, Zifcakova L, Wipf D, Zambonelli A, Paolocci F, Nowrousian M, Ottonello S, Baldrian P, Spatafora JW, Henrissat B, Nagy LG, Aury JM, Wincker P, Grigoriev IV, Bonfante P, Martin FM (- 40) Ref: Nat Ecol Evol, 2:1956, 2018 : PubMed ESTHER: Murat_2018_Nat.Ecol.Evol_2_1956 PubMedSearch: Murat 2018 Nat.Ecol.Evol 2 1956 PubMedID: 30420746 Gene_locus related to this paper: 9pezi-a0a3n4l4q5, 9pezi-a0a3n4lpg7 Abstract Tuberaceae is one of the most diverse lineages of symbiotic truffle-forming fungi. To understand the molecular underpinning of the ectomycorrhizal truffle lifestyle, we compared the genomes of Piedmont white truffle (Tuber magnatum), Perigord black truffle (Tuber melanosporum), Burgundy truffle (Tuber aestivum), pig truffle (Choiromyces venosus) and desert truffle (Terfezia boudieri) to saprotrophic Pezizomycetes. Reconstructed gene duplication/loss histories along a time-calibrated phylogeny of Ascomycetes revealed that Tuberaceae-specific traits may be related to a higher gene diversification rate. Genomic features in Tuber species appear to be very similar, with high transposon content, few genes coding lignocellulose-degrading enzymes, a substantial set of lineage-specific fruiting-body-upregulated genes and high expression of genes involved in volatile organic compound metabolism. Developmental and metabolic pathways expressed in ectomycorrhizae and fruiting bodies of T. magnatum and T. melanosporum are unexpectedly very similar, owing to the fact that they diverged ~100 Ma. Volatile organic compounds from pungent truffle odours are not the products of Tuber-specific gene innovations, but rely on the differential expression of an existing gene repertoire. These genomic resources will help to address fundamental questions in the evolution of the truffle lifestyle and the ecology of fungi that have been praised as food delicacies for centuries. Title: Novel Tadalafil Derivatives Ameliorates Scopolamine-Induced Cognitive Impairment in Mice via Inhibition of Acetylcholinesterase (AChE) and Phosphodiesterase 5 (PDE5) Ni W, Wang H, Li X, Zheng X, Wang M, Zhang J, Gong Q, Ling D, Mao F and Li J <1 more author(s)> Ni W, Wang H, Li X, Zheng X, Wang M, Zhang J, Gong Q, Ling D, Mao F, Zhang H, Li J (- 1) Ref: ACS Chem Neurosci, 9:1625, 2018 : PubMed ESTHER: Ni_2018_ACS.Chem.Neurosci_9_1625 PubMedSearch: Ni 2018 ACS.Chem.Neurosci 9 1625 PubMedID: 29616790 Abstract On the basis of the drug-repositioning and redeveloping strategy, first-generation dual-target inhibitors of acetylcholinesterase (AChE) and phosphodiesterase 5 (PDE5) have been recently reported as a potentially novel therapeutic method for the treatment of Alzheimer's disease (AD), and the lead compound 2 has proven this method was feasible in AD mouse models. In this study, our work focused on exploring alternative novel tadalafil derivatives (3a-s). Among the 19 analogues, compound 3c exhibited good selective dual-target AChE/PDE5 inhibition and good blood-brain barrier (BBB) permeability. Moreover, its citrate (3c.Cit) possessed improved water solubility and good effects against scopolamine-induced cognitive impairment with inhibition of cortical AChE activities and enhancement of cAMP response element-binding protein (CREB) phosphorylation ex vivo. Title: A manually annotated Actinidia chinensis var. chinensis (kiwifruit) genome highlights the challenges associated with draft genomes and gene prediction in plants Pilkington SM, Crowhurst R, Hilario E, Nardozza S, Fraser L, Peng Y, Gunaseelan K, Simpson R, Tahir J and Schaffer RJ <89 more author(s)> Pilkington SM, Crowhurst R, Hilario E, Nardozza S, Fraser L, Peng Y, Gunaseelan K, Simpson R, Tahir J, Deroles SC, Templeton K, Luo Z, Davy M, Cheng C, McNeilage M, Scaglione D, Liu Y, Zhang Q, Datson P, De Silva N, Gardiner SE, Bassett H, Chagne D, McCallum J, Dzierzon H, Deng C, Wang YY, Barron L, Manako K, Bowen J, Foster TM, Erridge ZA, Tiffin H, Waite CN, Davies KM, Grierson EP, Laing WA, Kirk R, Chen X, Wood M, Montefiori M, Brummell DA, Schwinn KE, Catanach A, Fullerton C, Li D, Meiyalaghan S, Nieuwenhuizen N, Read N, Prakash R, Hunter D, Zhang H, McKenzie M, Knabel M, Harris A, Allan AC, Gleave A, Chen A, Janssen BJ, Plunkett B, Ampomah-Dwamena C, Voogd C, Leif D, Lafferty D, Souleyre EJF, Varkonyi-Gasic E, Gambi F, Hanley J, Yao JL, Cheung J, David KM, Warren B, Marsh K, Snowden KC, Lin-Wang K, Brian L, Martinez-Sanchez M, Wang M, Ileperuma N, Macnee N, Campin R, McAtee P, Drummond RSM, Espley RV, Ireland HS, Wu R, Atkinson RG, Karunairetnam S, Bulley S, Chunkath S, Hanley Z, Storey R, Thrimawithana AH, Thomson S, David C, Testolin R, Huang H, Hellens RP, Schaffer RJ (- 89) Ref: BMC Genomics, 19:257, 2018 : PubMed ESTHER: Pilkington_2018_BMC.Genomics_19_257 PubMedSearch: Pilkington 2018 BMC.Genomics 19 257 PubMedID: 29661190 Gene_locus related to this paper: actde-CXE3, actde-CXE5, actch-a0a2r6p9v4, actch-a0a2r6phk8, actch-a0a2r6pty2, actch-q0zpu6, actcc-a0a2r6q553, actcc-a0a2r6quq2, actcc-a0a2r6q2m9, actcc-a0a2r6q2n7, actcc-a0a2r6ru97, actcc-a0a2r6r3e8, actcc-a0a2r6qy24, actcc-a0a2r6pzy5, actcc-a0a2r6p5n3, actcc-a0a2r6qdp0, actcc-a0a2r6qgs9 Abstract BACKGROUND: Most published genome sequences are drafts, and most are dominated by computational gene prediction. Draft genomes typically incorporate considerable sequence data that are not assigned to chromosomes, and predicted genes without quality confidence measures. The current Actinidia chinensis (kiwifruit) 'Hongyang' draft genome has 164 Mb of sequences unassigned to pseudo-chromosomes, and omissions have been identified in the gene models. RESULTS: A second genome of an A. chinensis (genotype Red5) was fully sequenced. This new sequence resulted in a 554.0 Mb assembly with all but 6 Mb assigned to pseudo-chromosomes. Pseudo-chromosomal comparisons showed a considerable number of translocation events have occurred following a whole genome duplication (WGD) event some consistent with centromeric Robertsonian-like translocations. RNA sequencing data from 12 tissues and ab initio analysis informed a genome-wide manual annotation, using the WebApollo tool. In total, 33,044 gene loci represented by 33,123 isoforms were identified, named and tagged for quality of evidential support. Of these 3114 (9.4%) were identical to a protein within 'Hongyang' The Kiwifruit Information Resource (KIR v2). Some proportion of the differences will be varietal polymorphisms. However, as most computationally predicted Red5 models required manual re-annotation this proportion is expected to be small. The quality of the new gene models was tested by fully sequencing 550 cloned 'Hort16A' cDNAs and comparing with the predicted protein models for Red5 and both the original 'Hongyang' assembly and the revised annotation from KIR v2. Only 48.9% and 63.5% of the cDNAs had a match with 90% identity or better to the original and revised 'Hongyang' annotation, respectively, compared with 90.9% to the Red5 models. CONCLUSIONS: Our study highlights the need to take a cautious approach to draft genomes and computationally predicted genes. Our use of the manual annotation tool WebApollo facilitated manual checking and correction of gene models enabling improvement of computational prediction. This utility was especially relevant for certain types of gene families such as the EXPANSIN like genes. Finally, this high quality gene set will supply the kiwifruit and general plant community with a new tool for genomics and other comparative analysis. Title: Developmental neurotoxicity of triphenyl phosphate in zebrafish larvae Shi Q, Wang M, Shi F, Yang L, Guo Y, Feng C, Liu J, Zhou B Ref: Aquat Toxicol, 203:80, 2018 : PubMed ESTHER: Shi_2018_Aquat.Toxicol_203_80 PubMedSearch: Shi 2018 Aquat.Toxicol 203 80 PubMedID: 30096480 Inhibitor(s) related to this paper: TPHP Abstract Triphenyl phosphate (TPhP), a typical organophosphate ester, is frequently detected in the environment and biota samples. It has been implicated as a neurotoxin as its structure is similar to neurotoxic organophosphate pesticides. The purpose of the present study was to investigate its potential developmental neurotoxicity in fish by using zebrafish larvae as a model. Zebrafish (Danio rerio) embryos were exposed to 0.8, 4, 20 and 100 mug/L of TPhP from 2 until 144 h post-fertilization. TPhP was found to have high bioconcentrations in zebrafish larvae after exposure. Further, it significantly reduced locomotor activity as well as the heart rate at the 100 mug/L concentration. TPhP exposure significantly altered the content of the neurotransmitters gamma-aminobutyric and histamine. Downregulation of the genes related to central nervous system development (e.g., alpha1-tubulin, mbp, syn2a, shha, and elavl3) as well as the corresponding proteins (e.g., alpha1-tubulin, mbp, and syn2a) was observed, but the gap-43 protein was found to upregulated. Finally, marked inhibition of total acetylcholinesterase activity, which is considered as a biomarker of neurotoxicant exposure, was also observed in the larvae. Our results indicate that exposure to environmentally relevant concentrations of TPhP can affect different parameters related to center nervous system development, and thus contribute to developmental neurotoxicity in early developing zebrafish larvae. Title: Synthesis and biological evaluation of new tetramethylpyrazine-based chalcone derivatives as potential anti-Alzheimer agents Wang M, Qin HL, Leng J, Ameeduzzafar, Amjad MW, Raja MAG, Hussain MA, Bukhari SNA Ref: Chemical Biology Drug Des, 92:1859, 2018 : PubMed ESTHER: Wang_2018_Chem.Biol.Drug.Des_92_1859 PubMedSearch: Wang 2018 Chem.Biol.Drug.Des 92 1859 PubMedID: 29923315 Abstract In the current study, a series of new ligustrazine-based chalcones was synthesized. For insertion of tetramethylpyrazine (TMP, also designated as ligustrazine) in chemical backbone of chalcone, a new ligustrazine-based aldehyde was prepared. New ketones were synthesized for inclusion of quinazolin-4-yl amino and pyrazin-2-yl amino moieties. The newly synthesized compounds were screened for acetylcholinesterase, butyrylcholinesterase, and monoamine oxidases (MAO) inhibitory activities and also for in vitro cytotoxicity on PC12 cells. The effect of these compounds against amyloid beta-induced cytotoxicity and aggregation was also investigated. The synthesized compounds effectively inhibited the related enzymes and also exhibited neuroprotective effects. Most of the compounds displayed better inhibitory potencies against Abeta aggregation than reference compounds. Some compounds such as 11e and 16b showed very potent effects on multiple targets exhibiting behavior as multifunctional anti-Alzheimer agents. Title: Expression, functional analysis and mutation of a novel neutral zearalenone-degrading enzyme Wang M, Yin L, Hu H, Selvaraj JN, Zhou Y, Zhang G Ref: Int J Biol Macromol, 118:1284, 2018 : PubMed ESTHER: Wang_2018_Int.J.Biol.Macromol_118_1284 PubMedSearch: Wang 2018 Int.J.Biol.Macromol 118 1284 PubMedID: 29949749 Gene_locus related to this paper: 9euro-a0a0d2ilk1 Abstract The crops and grains were often contaminated by high level of mycotoxin zearalenone (ZEN). In order to remove ZEN and keep food safe, ZEN-degrading or detoxifying enzymes are urgently needed. Here, a newly identified lactonohydrolase responsible for the detoxification of ZEN, annotated as Zhd518, was expressed and characterized. Zhd518 showed 65% amino acid identity with Zhd101, which was widely studied for its ZEN-degrading ability. A detailed activity measurement method of ZEN-degrading enzyme was provided. Biochemical analysis indicated that the purified recombinant Zhd518 from E. coli exhibited a high activity against ZEN (207.0 U/mg), with the optimal temperature and pH of 40 degreeC and 8.0, respectively. The Zhd518 can degrade ZEN derivatives, and the specific activities against alpha-Zearalenol, beta-Zearalenol, alpha-Zearalanol and beta-Zearalanol were 23.0 U/mg, 64.7 U/mg, 119.8 U/mg and 66.5 U/mg, respectively. The active sites of Zhd518 were predicted by structure modeling and determined by mutation analysis. A point mutant N156H exhibited 3.3-fold activity against alpha-Zearalenol comparing to Zhd518. Zhd518 is the first reported neutral and the second characterized ZEN-degrading enzyme, which provides a new and more excellent candidate for ZEN detoxifying in food and feed industry. Title: Csn5 Is Required for the Conidiogenesis and Pathogenesis of the Alternaria alternata Tangerine Pathotype Wang M, Yang X, Ruan R, Fu H, Li H Ref: Front Microbiol, 9:508, 2018 : PubMed ESTHER: Wang_2018_Front.Microbiol_9_508 PubMedSearch: Wang 2018 Front.Microbiol 9 508 PubMedID: 29616013 Gene_locus related to this paper: altal-actt2 Abstract The COP9 signalosome (CSN) is a highly conserved protein complex involved in the ubiquitin-proteasome system. Its metalloisopeptidase activity resides in subunit 5 (CSN5). Functions of csn5 in phytopathogenic fungi are poorly understood. Here, we knocked out the csn5 ortholog (Aacsn5) in the tangerine pathotype of Alternaria alternata. The deltaAacsn5 mutant showed a moderately reduced growth rate compared to the wildtype strain and was unable to produce conidia. The growth of deltaAacsn5 mutant was not affected in response to oxidative and osmotic stresses. Virulence assays revealed that deltaAacsn5 induced no or significantly reduced necrotic lesions on detached citrus leaves. The defects in hyphal growth, conidial sporulation, and pathogenicity of deltaAacsn5 were restored by genetic complementation of the mutant with wildtype Aacsn5. To explore the molecular mechanisms of conidiation and pathogenesis underlying Aacsn5 regulation, we systematically examined the transcriptomes of both deltaAacsn5 and the wildtype. Generally, 881 genes were overexpressed and 777 were underexpressed in the deltaAacsn5 mutant during conidiation while 694 overexpressed and 993 underexpressed during infection. During asexual development, genes related to the transport processes and nitrogen metabolism were significantly downregulated; the expression of csn1-4 and csn7 in deltaAacsn5 was significantly elevated; secondary metabolism gene clusters were broadly affected; especially, the transcript level of the whole of cluster 28 and 30 was strongly induced. During infection, the expression of the host-specific ACT toxin gene cluster which controls the biosynthesis of the citrus specific toxin was significantly repressed; many other SM clusters with unknown products were also regulated; 86 out of 373 carbohydrate-active enzymes responsible for breaking down the plant dead tissues showed uniquely decreased expression. Taken together, our results expand our understanding of the roles of csn5 on conidiation and pathogenicity in plant pathogenic fungi and provide a foundation for future investigations. Title: Muscarinic cholinergic signaling and overactive bladder-like symptoms associated with invasive bladder cancer Wei W, Wang M, Li Y, Meng Q, Tang Y, Lu H, Yu W, Cheng Q, Xu L and Xie K <3 more author(s)> Wei W, Wang M, Li Y, Meng Q, Tang Y, Lu H, Yu W, Cheng Q, Xu L, Jian S, Wu Y, Yi X, Xie K (- 3) Ref: Oncol Lett, 16:775, 2018 : PubMed ESTHER: Wei_2018_Oncol.Lett_16_775 PubMedSearch: Wei 2018 Oncol.Lett 16 775 PubMedID: 29963145 Abstract The objective of the present study was to explore the association between muscarinic cholinergic signaling and urothelial bladder tumors. Possible associations among overactive bladder (OAB) symptoms and bladder tumors were retrospectively investigated using a multicenter Chinese database with prospectively collected data since 2010. Firstly, it was demonstrated that OAB symptoms, such as urgency, were more severe in patients with invasive bladder cancer and were associated with a reduced prognosis. Following this, muscarinic cholinergic receptor 3 (M3R) expression in urothelium was determined to be lower in invasive cancer tissue than in adjacent non-cancerous tissue, yet M3R upregulation was associated with a reduced progression free survival (PFS) time. Additionally, it was also demonstrated that muscarinic cholinergic receptor 2 (M2R) was upregulated in the sub-urothelium, and this was also associated with a reduced PFS time. Furthermore, it was determined that cholinesterase and acetylcholinesterase were lower in invasive cancer than in non-invasive cancer. In conclusion, the results indicated that M3R expression was downregulated in invasive bladder cancer, which may have a role as a protective anti-oncogene, in contrast to its oncogenic role in numerous other cancer types. Therefore, muscarinic cholinergic signaling may be a novel therapeutic target for treating bladder cancer. Title: Production of new human milk fat substitutes by enzymatic acidolysis of microalgae oils from Nannochloropsis oculata and Isochrysis galbana He Y, Qiu C, Guo Z, Huang J, Wang M, Chen B Ref: Bioresour Technol, 238:129, 2017 : PubMed ESTHER: He_2017_Bioresour.Technol_238_129 PubMedSearch: He 2017 Bioresour.Technol 238 129 PubMedID: 28433900 Abstract Human milk fat substitutes (HMFs) with four kinds of n-3 fatty acid for infant formula were firstly synthesized using triacylglycerols (TAGs) from Nannochloropsis oculata rich in PA at the sn-2 position and free fatty acids (FFAs) from Isochrysis galbana rich in n-3 polyunsaturated fatty acids (n-3 PUFAs-ALA/SDA/DHA) via solvent-free acidolysis with Novozym 435, Lipozyme 435, TL-IM and RM-IM as biocatalysts. The results show that the resulting HMFs contain total n-3 PUFA of 13.92-17.12% and PA of 59.38-68.13% at the sn-2 position under the optimal conditions (mole ratio FFAs/TAG 3:1, 60 degC (Novozym 435 and Lipozyme TL-IM) and 50 degC (Lipozyme 435 and RM-IM), lipase loading 10%, reaction time 24h). Moreover, among the tested enzymes, Lipozyme 435, TL-IM, and RM-IM display the fatty acid selectivity towards SDA, LA and ALA, and OA, respectively. Overall, the examined lipases are promising biocatalysts for producing high-value microalgal HMFs in a cost-effective manner. Title: Compound Schisandra-Ginseng-Notoginseng-Lycium Extract Ameliorates Scopolamine-Induced Learning and Memory Disorders in Mice Li N, Liu C, Jing S, Wang M, Wang H, Sun J, Wang C, Chen J, Li H Ref: Evid Based Complement Alternat Med, 2017:8632016, 2017 : PubMed ESTHER: Li_2017_Evid.Based.Complement.Alternat.Med_2017_8632016 PubMedSearch: Li 2017 Evid.Based.Complement.Alternat.Med 2017 8632016 PubMedID: 28814961 Abstract Schisandra, Ginseng, Notoginseng, and Lycium barbarum are traditional Chinese medicinal plants sharing cognitive-enhancing properties. To design a functional food to improve memory, we prepared a compound Schisandra-Ginseng-Notoginseng-Lycium (CSGNL) extract and investigated its effect on scopolamine-induced learning and memory loss in mice. To optimize the dose ratios of the four herbal extracts in CSGNL, orthogonal experiments were performed. Mice were administered CSGNL by gavage once a day for 30 days and then mouse learning and memory were evaluated by Morris water maze and step-through tests. The mechanisms of CSGNL improving learning and memory were investigated by assaying acetylcholine (ACh) levels and choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) activities in the brain tissues of treated mice. The results showed that CSGNL significantly ameliorated scopolamine-induced learning and memory impairment, at least in part, by modulating ACh levels and ChAT and AChE activities in the mouse brain. Our data support the use of CSGNL as a functional food for learning and memory enhancement. Title: Soluble epoxide hydrolase inhibitors might prevent ischemic arrhythmias via microRNA-1 repression in primary neonatal mouse ventricular myocytes Liu Q, Zhao X, Peng R, Wang M, Zhao W, Gui YJ, Liao CX, Xu DY Ref: Mol Biosyst, 13:556, 2017 : PubMed ESTHER: Liu_2017_Mol.Biosyst_13_556 PubMedSearch: Liu 2017 Mol.Biosyst 13 556 PubMedID: 28112313 Abstract Ischemic arrhythmias are the main causes of sudden cardiac death. It has been reported that soluble epoxide hydrolase inhibitors (sEHis) could prevent arrhythmias; however, the underlying molecular mechanisms remain unclear. In recent years, the proarrhythmic role of microRNA-1 (miR-1) has been investigated. This study aimed to elucidate whether sEHis prevented ischemic arrhythmias by suppressing miR-1. The primary neonatal mouse ventricular myocyte model of miR-1 overexpression was established by incubating with agonist microONTM mmu-miR-1a-3p agomir (DAEDstainTM Dye) (agomiR-1). The sEHi, trans-4-[4-(3-adamantan-1-yl-ureido)-cyclohexyloxy]-benzoic acid (t-AUCB), was administered following miR-1 overexpression. Quantitative real-time PCR (qPCR) and western blotting were used to test alterations in the expression of miR-1 and its target mRNAs GJA1 and KCNJ2 and their respective encoded proteins connexin 43 (Cx43) and the K+ channel subunit (Kir2.1). The whole-cell patch-clamp technique was used to record the alterations of the inward rectifying K+ current (IK1). Compared with the control group, miR-1 levels were significantly increased in the agomiR-1 group (p < 0.05), which suggested the successful construction of the miR-1 overexpression model. Compared with the control group, the levels of GJA1 and KCNJ2 mRNAs and Cx43 and Kir2.1 proteins in the agomiR-1 group were significantly decreased, and IK1 was significantly impaired (all p < 0.05). The miR-1 levels were dose-dependently decreased by t-AUCB, whereas t-AUCB dose-dependently increased the levels of GJA1 and KCNJ2 mRNAs and Cx43 and Kir2.1 proteins. Furthermore, t-AUCB restored the impaired IK1 (all p < 0.05). In conclusion, the sEHi t-AUCB has the ability to down-regulate proarrhythmic miR-1 and up-regulate its target genes and proteins, eventually restoring IK1. Title: Proprioceptive mechanisms in occlusion-stimulated masseter hypercontraction Liu X, Zhang C, Wang D, Zhang H, Li J, Wang M Ref: Eur J Oral Sci, 125:127, 2017 : PubMed ESTHER: Liu_2017_Eur.J.Oral.Sci_125_127 PubMedSearch: Liu 2017 Eur.J.Oral.Sci 125 127 PubMedID: 28145597 Abstract Neurons in the trigeminal mesencephalic nucleus (Vme) have an axon that branches peripherally to innervate the orofacial region and projects centrally to the trigeminal motor nucleus (Vmo). They function as the primary neurons conveying proprioceptive messages. The present study aimed to demonstrate the presence of a periodontal-Vme-Vmo circuit and to provide evidence for its involvement in an experimental unilateral anterior crossbite (UAC) model, which can induce osteoarthritis in the temporomandibular joint. Cholera toxin B subunit (CTb) was injected into the inferior alveolar nerve of rats to help identify the central axon terminals of Vme neurons in the Vmo. The levels of vesicular glutamate transporter 1 (VGLUT1) expressed in the periodontal region, Vme, Vmo, and masseter, and the level of acetylcholinesterase (AChE) expressed in the masseter, were assessed in UAC rats and controls. In CTb-treated rats, many CTb-labeled cell bodies and endings were identified in the Vme and in the Vmo, respectively. In UAC rats, VGLUT1 was expressed at a statistically significantly higher level in the periodontal ligament, Vme, Vmo, and masseter than it was in control rats. The level of AChE protein was 1.97 times higher in UAC rat masseter compared with control rat masseter. These findings reveal a trigeminal mechanism underlying masseter hyperactivity induced by an altered occlusion. Title: The metastatic suppressor NDRG1 inhibits EMT, migration and invasion through interaction and promotion of caveolin-1 ubiquitylation in human colorectal cancer cells Mi L, Zhu F, Yang X, Lu J, Zheng Y, Zhao Q, Wen X, Lu A, Wang M and Sun J <2 more author(s)> Mi L, Zhu F, Yang X, Lu J, Zheng Y, Zhao Q, Wen X, Lu A, Wang M, Zheng M, Ji J, Sun J (- 2) Ref: Oncogene, 36:4323, 2017 : PubMed ESTHER: Mi_2017_Oncogene_36_4323 PubMedSearch: Mi 2017 Oncogene 36 4323 PubMedID: 28346422 Gene_locus related to this paper: human-NDRG1 Abstract N-myc downstream-regulated gene 1 (NDRG1) has been reported to act as a key regulatory molecule in tumor progression-related signaling pathways, especially in tumor metastasis. However, the related mechanism has not been fully discovered yet. Herein we demonstrated that the novel molecule of cell migration and invasion, caveolin-1, has direct interaction with NDRG1 in human colorectal cancer (CRC) cells. Moreover, we discovered that NDRG1 reduces caveolin-1 protein expression through promoting its ubiquitylation and subsequent degradation via the proteasome in CRC cells. In addition, caveolin-1 mediates the suppressive function of NDRG1 in epithelial-mesenchymal transition, migration and invasion in vitro and metastasis in vivo. These results help to fulfill the potential mechanisms of NDRG1 in anti-metastatic treatment for human colorectal cancer. Title: ChAT-positive neurons participate in subventricular zone neurogenesis after middle cerebral artery occlusion in mice Wang J, Fu X, Zhang D, Yu L, Li N, Lu Z, Gao Y, Wang M, Liu X and Yan B <2 more author(s)> Wang J, Fu X, Zhang D, Yu L, Li N, Lu Z, Gao Y, Wang M, Liu X, Zhou C, Han W, Yan B (- 2) Ref: Behavioural Brain Research, 316:145, 2017 : PubMed ESTHER: Wang_2017_Behav.Brain.Res_316_145 PubMedSearch: Wang 2017 Behav.Brain.Res 316 145 PubMedID: 27609645 Abstract The mechanisms of post-stroke neurogenesis in the subventricular zone (SVZ) are unclear. However, neural stem cell-intrinsic and neurogenic niche mechanisms, as well as neurotransmitters, have been shown to play important roles in SVZ neurogenesis. Recently, a previously unknown population of choline acetyltransferase (ChAT)+ neurons residing in rodent SVZ were identified to have direct control over neural stem cell proliferation by indirectly activating fibroblast growth factor receptor (FGFR). This finding revealed possible neuronal control over SVZ neurogenesis. In this study, we assessed whether these ChAT+ neurons also participate in stroke-induced neurogenesis. We used a permanent middle cerebral artery occlusion (MCAO) model produced by transcranial electrocoagulation in mice, atropine (muscarinic cholinergic receptor [mAchR] antagonist), and donepezil (acetylcholinesterase inhibitor) to investigate the role of ChAT+ neurons in stroke-induced neurogenesis. We found that mAchRs, phosphorylated protein kinase C (p-PKC), and p-38 levels in the SVZ were upregulated in mice on day 7 after MCAO. MCAO also significantly increased the number of BrdU/doublecortin-positive cells and protein levels of phosphorylated-neural cell adhesion molecule and mammalian achaete scute homolog-1. FGFR was activated in the SVZ, and doublecortin-positive cells increased in the peri-infarction region. These post-stroke neurogenic effects were enhanced by donepezil and partially decreased by atropine. Neither atropine nor donepezil affected peri-infarct microglial activation or serum concentrations of TNF-alpha, IFN-gamma, or TGF-beta on day 7 after MCAO. We conclude that ChAT+ neurons in the SVZ may participate in stroke-induced neurogenesis, suggesting a new mechanism for neurogenesis after stroke. Title: Ameliorating effect of Alpinia oxyphylla-Schisandra chinensis herb pair on cognitive impairment in a mouse model of Alzheimer's disease Wang M, Bi W, Fan K, Li T, Yan T, Xiao F, He B, Bi K, Jia Y Ref: Biomed Pharmacother, 97:128, 2017 : PubMed ESTHER: Wang_2017_Biomed.Pharmacother_97_128 PubMedSearch: Wang 2017 Biomed.Pharmacother 97 128 PubMedID: 29080453 Abstract Alzheimer's disease (AD) is the most common cause of dementia. In our previous study, we found both Alpinia oxyphylla and Schisandra chinensis can improve the cognitive function of AD. To investigate whether the Alpinia oxyphylla - Schisandra chinensis herb pair (ASHP) has ameliorating effect on cognitive impairment, we used scopolamine to induce learning and memory impairments, as a mouse model of AD. Subsequently, we carried out Y-maze test and Morris water maze test to observe the behavior of mice. Finally, the level of Acetylcholine (Ach) and muscarinic receptor (M1) receptors, the activity of choline acetyltransferase (ChAT) and acetyl cholinesterase (AChE) were measured by commercial assay kits and ELISA kit. And we used hematoxylin-eosin (HE) staining to check the changes in cortex and the CA1 region of hippocampus. ASHP significantly protected against learning and memory impairments induced by scopolamine in Y-maze test and Morris water maze test. Besides, ASHP was able to increase the level of ACh and M1 receptors, and decrease the activity of AChE, but did not significantly affect the activity of ChAT. In addition, from the results of histopathological examination, we speculated ASHP may have neuroprotective effects. This study provided an experimental basis for further study of Alpinia oxyphylla - Schisandra chinensis herb pair in AD therapy. Title: Evaluation and application of constitutive promoters for cutinase production by Saccharomyces cerevisiae Zhang J, Cai Y, Du G, Chen J, Wang M, Kang Z Ref: J Microbiol, 55:538, 2017 : PubMed ESTHER: Zhang_2017_J.Microbiol_55_538 PubMedSearch: Zhang 2017 J.Microbiol 55 538 PubMedID: 28664516 Abstract Cutinase as a promising biocatalyst has been intensively studied and applied in processes targeted for industrial scale. In this work, the cutinase gene tfu from Thermobifida fusca was artificially synthesized according to codon usage bias of Saccharomyces cerevisiae and investigated in Saccharomyces cerevisiae. Using the alpha-factor signal peptide, the T. fusca cutinase was successfully overexpressed and secreted with the GAL1 expression system. To increase the cutinase level and overcome some of the drawbacks of induction, four different strong promoters (ADH1, HXT1, TEF1, and TDH3) were comparatively evaluated for cutinase production. By comparison, promoter TEF1 exhibited an outstanding property and significantly increased the expression level. By fed-batch fermentation with a constant feeding approach, the activity of cutinase was increased to 29.7 U/ml. The result will contribute to apply constitutive promoter TEF1 as a tool for targeted cutinase production in S. cerevisiae cell factory. Title: The Apostasia genome and the evolution of orchids Zhang GQ, Liu KW, Li Z, Lohaus R, Hsiao YY, Niu SC, Wang JY, Lin YC, Xu Q and Liu ZJ <25 more author(s)> Zhang GQ, Liu KW, Li Z, Lohaus R, Hsiao YY, Niu SC, Wang JY, Lin YC, Xu Q, Chen LJ, Yoshida K, Fujiwara S, Wang ZW, Zhang YQ, Mitsuda N, Wang M, Liu GH, Pecoraro L, Huang HX, Xiao XJ, Lin M, Wu XY, Wu WL, Chen YY, Chang SB, Sakamoto S, Ohme-Takagi M, Yagi M, Zeng SJ, Shen CY, Yeh CM, Luo YB, Tsai WC, Van de Peer Y, Liu ZJ (- 25) Ref: Nature, 549:379, 2017 : PubMed ESTHER: Zhang_2017_Nature_549_379 PubMedSearch: Zhang 2017 Nature 549 379 PubMedID: 28902843 Gene_locus related to this paper: 9aspa-a0a2i0b2l6, 9aspa-a0a2i0w093, 9aspa-a0a2i0asr1, 9aspa-a0a2i0vyy1, 9aspa-a0a2i0a218, 9aspa-a0a2i0x5j6, 9aspa-a0a2i0aji0, 9aspa-a0a2i0a3k8, 9aspa-a0a2i0win6, 9aspa-a0a2i0vg82, 9aspa-a0a2h9zyy3 Abstract Constituting approximately 10% of flowering plant species, orchids (Orchidaceae) display unique flower morphologies, possess an extraordinary diversity in lifestyle, and have successfully colonized almost every habitat on Earth. Here we report the draft genome sequence of Apostasia shenzhenica, a representative of one of two genera that form a sister lineage to the rest of the Orchidaceae, providing a reference for inferring the genome content and structure of the most recent common ancestor of all extant orchids and improving our understanding of their origins and evolution. In addition, we present transcriptome data for representatives of Vanilloideae, Cypripedioideae and Orchidoideae, and novel third-generation genome data for two species of Epidendroideae, covering all five orchid subfamilies. A. shenzhenica shows clear evidence of a whole-genome duplication, which is shared by all orchids and occurred shortly before their divergence. Comparisons between A. shenzhenica and other orchids and angiosperms also permitted the reconstruction of an ancestral orchid gene toolkit. We identify new gene families, gene family expansions and contractions, and changes within MADS-box gene classes, which control a diverse suite of developmental processes, during orchid evolution. This study sheds new light on the genetic mechanisms underpinning key orchid innovations, including the development of the labellum and gynostemium, pollinia, and seeds without endosperm, as well as the evolution of epiphytism; reveals relationships between the Orchidaceae subfamilies; and helps clarify the evolutionary history of orchids within the angiosperms. Title: Effects and mechanism of cerebroprotein hydrolysate on learning and memory ability in mice An L, Han X, Li H, Ma Y, Shi L, Xu G, Yuan G, Sun J, Zhao N and Du P <2 more author(s)> An L, Han X, Li H, Ma Y, Shi L, Xu G, Yuan G, Sun J, Zhao N, Sheng Y, Wang M, Du P (- 2) Ref: Genet Mol Res, 15:, 2016 : PubMed ESTHER: An_2016_Genet.Mol.Res_15_ PubMedSearch: An 2016 Genet.Mol.Res 15 PubMedID: 27525868 Abstract Cerebroprotein hydrolysate is an extract from porcine brain tissue that acts on the central nervous system in various ways to protect neurons and improve memory, attention, and vigilance. This study examined the effect and mechanism of cerebroprotein hydrolysate on learning and memory in mice with scopolamine-induced impairment. Mice were given an intraperitoneal injection of scopolamine hydrobromide to establish a murine model of learning and memory impairment. After 35 successive days of cerebroprotein hydrolysate treatment, their behaviors were observed in the Morris water maze and step-down test. Superoxide dismutase (SOD), Na+-K+-ATPase, and acetylcholinesterase (AChE) activity, and malondialdehyde (MDA), gamma-aminobutyric acid (GABA), and glutamic acid (Glu) levels in the brain tissue of the mice were determined, and pathological changes in the hippocampus were examined. The results of the water-maze test showed that cerebroprotein hydrolysate shortened the escape latency and increased the number of platform crossings. In the step-down test, cerebroprotein hydrolysate treatment prolonged the step-down latency and reduced the number of errors; cerebroprotein hydrolysate increased the activity of SOD, Na+-K+-ATPase, and AChE, reduced the levels of MDA, decreased the Glu/GABA ratio in brain tissue, and reduced pathological changes in the hippocampus. The results indicate that cerebroprotein hydrolysate can improve learning and memory in mice with scopolamine-induced impairment. This effect may be associated with its ability to reduce injury caused by free radicals, improve acetylcholine function, and modulate the Glu/GABA learning and memory regulation system, reducing excitotoxicity caused by Glu. Title: A sensitive fluorescent sensor for selective determination of dichlorvos based on the recovered fluorescence of carbon dots-Cu(II) system Hou J, Dong G, Tian Z, Lu J, Wang Q, Ai S, Wang M Ref: Food Chem, 202:81, 2016 : PubMed ESTHER: Hou_2016_Food.Chem_202_81 PubMedSearch: Hou 2016 Food.Chem 202 81 PubMedID: 26920268 Abstract In this paper, a simple and sensitive fluorescent sensor for dichlorvos was first constructed based on carbon dots-Cu(II) system. These carbon dots were obtained by simple hydrothermal reaction of feather. The fluorescence of these carbon dots can be selectively quenched by Cu(2+) ion. When acetylcholinesterase and acetylthiocholine were introduced into the system, thiocholine came into being, which can react with Cu(2+) ion and restore the fluorescence of the system. The reaction mechanism between Cu(2+) ion and thiocholine was confirmed by X-ray photoelectron spectroscopy. As one kind of acetylcholinesterase inhibitor, organophosphorus pesticides can be detected based on this sensing system. As an example of organophosphorus pesticides, dichlorvos was detected with a linear range of 6.0x10(-9)-6.0x10(-8)M. This sensing system has been successfully used for the analysis of cabbage and fruit juice samples. Title: Molecular cloning and expression analysis on LPL of Coilia nasus Wang M, Xu D, Liu K, Yang J, Xu P Ref: Gene, 583:147, 2016 : PubMed ESTHER: Wang_2016_Gene_583_147 PubMedSearch: Wang 2016 Gene 583 147 PubMedID: 26877109 Gene_locus related to this paper: 9tele-a0a140b115 Abstract Coilia nasus is one important commercial anadromous species which mainly distributed in the Yangtze River in China. At present, it has been on the "National Key Protective Species List" because of its severe resource damage. Lipid metabolism is very important during its long-distance migration. To make further research on lipid metabolism of C.nasus, we cloned lipoprotein lipase gene with homologous cloning method. A full-length cDNA of LPL of C.nasus was cloned from liver which covered 3537bp with a 1519bp open reading frame encoding 505 deduced amino acids whose molecular mass was 57.5kDa and theoretical isoelectric point was 7.58. The deduced amino acids had high similarity with the reported LPL sequence of other species. It had typical conserved domain of LPL protein containing catalytic triad, N-linked glycosylation sites and conserved heparin-binding site, etc. We adopted quantitative real-time RT-PCR method to detect the mRNA expression of LPL of C.nasus in ten tissues including mesenteric adipose, liver, muscle, stomach, spleen, heart, head kidney, trunk kidney, gill and brain with beta-actin as internal reference. LPL expressed in all the detected tissues. The highest expression was in mesenteric adipose, and followed by liver, muscle, stomach. Lipid expressed lowly in spleen, heart, head kidney, trunk kidney, gill and brain. The research on the cloning and differential expression of LPL of C.nasus will lay foundation for further research on lipid metabolism of C.nasus. Title: The Dendrobium catenatum Lindl. genome sequence provides insights into polysaccharide synthase, floral development and adaptive evolution Zhang GQ, Xu Q, Bian C, Tsai WC, Yeh CM, Liu KW, Yoshida K, Zhang LS, Chang SB and Liu ZJ <26 more author(s)> Zhang GQ, Xu Q, Bian C, Tsai WC, Yeh CM, Liu KW, Yoshida K, Zhang LS, Chang SB, Chen F, Shi Y, Su YY, Zhang YQ, Chen LJ, Yin Y, Lin M, Huang H, Deng H, Wang ZW, Zhu SL, Zhao X, Deng C, Niu SC, Huang J, Wang M, Liu GH, Yang HJ, Xiao XJ, Hsiao YY, Wu WL, Chen YY, Mitsuda N, Ohme-Takagi M, Luo YB, Van de Peer Y, Liu ZJ (- 26) Ref: Sci Rep, 6:19029, 2016 : PubMed ESTHER: Zhang_2016_Sci.Rep_6_19029 PubMedSearch: Zhang 2016 Sci.Rep 6 19029 PubMedID: 26754549 Gene_locus related to this paper: 9aspa-a0a2i0w093, 9aspa-a0a2i0vyy1, 9aspa-a0a2i0x5j6, 9aspa-a0a2i0win6, 9aspa-a0a2i0vg82 Abstract Orchids make up about 10% of all seed plant species, have great economical value, and are of specific scientific interest because of their renowned flowers and ecological adaptations. Here, we report the first draft genome sequence of a lithophytic orchid, Dendrobium catenatum. We predict 28,910 protein-coding genes, and find evidence of a whole genome duplication shared with Phalaenopsis. We observed the expansion of many resistance-related genes, suggesting a powerful immune system responsible for adaptation to a wide range of ecological niches. We also discovered extensive duplication of genes involved in glucomannan synthase activities, likely related to the synthesis of medicinal polysaccharides. Expansion of MADS-box gene clades ANR1, StMADS11, and MIKC(*), involved in the regulation of development and growth, suggests that these expansions are associated with the astonishing diversity of plant architecture in the genus Dendrobium. On the contrary, members of the type I MADS box gene family are missing, which might explain the loss of the endospermous seed. The findings reported here will be important for future studies into polysaccharide synthesis, adaptations to diverse environments and flower architecture of Orchidaceae. Title: TMPyP4, a Stabilizer of Nucleic Acid Secondary Structure, Is a Novel Acetylcholinesterase Inhibitor Fujiwara N, Mazzola M, Cai E, Wang M, Cave JW Ref: PLoS ONE, 10:e0139167, 2015 : PubMed ESTHER: Fujiwara_2015_PLoS.One_10_e0139167 PubMedSearch: Fujiwara 2015 PLoS.One 10 e0139167 PubMedID: 26402367 Abstract The porphyrin compound, TMPyP4 (5,10,15,20-Tetrakis-(N-methyl-4-pyridyl)porphine), is widely used as a photosensitizer and a modulator of nucleic acid secondary structure stability. Our group recently showed in cultured cells and forebrain slice cultures that this compound can also down regulate expression of Tyrosine hydroxylase (Th), which encodes the rate-limiting enzyme in catecholamine biosynthesis, by stabilizing DNA secondary structures in the Th proximal promoter. The current study sought to establish whether treatment with TMPyP4 could modify mouse Th expression levels in vivo. Intraperitoneal administration of low TMPyP4 doses (10mg/kg), similar to those used for photosensitization, did not significantly reduce Th transcript levels in several catecholaminergic regions. Administration of a high dose (40 mg/kg), similar to those used for tumor xenograph reduction, unexpectedly induced flaccid paralysis in an age and sex-dependent manner. In vitro analyses revealed that TMPyP4, but not putative metabolites, inhibited Acetylcholinesterase activity and pre-treatment of TMPyP4 with Hemeoxygenase-2 (HO-2) rescued Acetylcholinesterase function. Age-dependent differences in HO-2 expression levels may account for some of the variable in vivo effects of high TMPyP4 doses. Together, these studies indicate that only low doses of TMPyP4, such as those typically used for photosensitization, are well tolerated in vivo. Thus, despite its widespread use in vitro, TMPyP4 is not ideal for modifying neuronal gene expression in vivo by manipulating nucleic acid secondary structure stability, which highlights the need to identify more clinically suitable compounds that can modulate nucleic acid secondary structure and gene expression. Title: Effects of supplementation of rumen-protected choline on growth performance, meat quality and gene expression in longissimus dorsi muscle of lambs Li H, Wang H, Yu L, Wang M, Liu S, Sun L, Chen Q Ref: Arch Anim Nutr, 69:340, 2015 : PubMed ESTHER: Li_2015_Arch.Anim.Nutr_69_340 PubMedSearch: Li 2015 Arch.Anim.Nutr 69 340 PubMedID: 26305383 Abstract This study determined the effects of rumen-protected choline (RPC) on growth performance, blood lipids, meat quality and expression of genes involved in fatty-acid metabolism in young lambs. A total of 24 Dorper x Hu lambs (about 20 kg body weight) were kept in individual pens and fed diets with 0%, 0.25%, 0.50% and 0.75% RPC for 60 d. Supplementation of 0.25% RPC increased average daily gain of lambs, whereas treatments had no significant effect on feed intake. The pH values of meat were increased at 0.25% RPC and both, dripping loss and shear force of meat, were significantly decreased in RPC-supplemented lambs. No significant changes were observed for dressing percentage and intramuscular fat. RPC supplementations had no significant effect on the concentrations of triglycerides and cholesterols in serum, but the concentration of high-density lipoprotein was decreased at 0.50% RPC and that of low-density lipoprotein was increased at 0.75% RPC. In m. longissimus dorsi, the expressions of cluster of differentiation 36 (CD36), acetyl-CoA carboxylase (ACC) and fatty-acid synthase (FASN) genes were increased at 0.25% RPC. Supplementation of 0.75% RPC increased the expressions of lipoprotein lipase (LPL) and FASN genes, decreased the expression of ACC gene and had no effect on CD36 gene. The results of this study showed that supplementation of 0.25% RPC could promote growth performance of lambs and improve meat quality. This may be mediated by effects on blood lipid profiles and the metabolism of fatty acids in skeleton muscles. However, the beneficial effects of 0.25% RPC supplementation need to be validated with a larger number of animals. Higher doses, particularly 0.75% RPC, showed adverse effects on live weight gain and ACC expression. Title: Prevalence of myasthenia gravis and associated autoantibodies in paraneoplastic pemphigus and their correlations with symptoms and prognosis Wang R, Li J, Wang M, Hao H, Chen X, Li R, Zhu X Ref: Br J Dermatol, 172:968, 2015 : PubMed ESTHER: Wang_2015_Br.J.Dermatol_172_968 PubMedSearch: Wang 2015 Br.J.Dermatol 172 968 PubMedID: 25388377 Abstract BACKGROUND: Paraneoplastic pemphigus (PNP) involves multiple organs, but little is known about its neurological involvement. OBJECTIVES: To investigate the symptoms, prognosis and profiles of associated autoantibodies in myasthenia gravis (MG), and their correlations in patients with PNP. Title: Avertoxins A-D, Prenyl Asteltoxin Derivatives from Aspergillus versicolor Y10, an Endophytic Fungus of Huperzia serrata Wang M, Sun M, Hao H, Lu C Ref: Journal of Natural Products, 78:3067, 2015 : PubMed ESTHER: Wang_2015_J.Nat.Prod_78_3067 PubMedSearch: Wang 2015 J.Nat.Prod 78 3067 PubMedID: 26618211 Abstract Aspergillus versicolor Y10 is an endophytic fungus isolated from Huperzia serrata, which showed inhibitory activity against acetylcholinesterase. An investigation of the chemical constituents of Y10 led to the isolation of four new prenylated asteltoxin derivatives, named avertoxins A-D (2-5), together with the known mycotoxin asteltoxin (1). In the present study, we report structure elucidation for 2-5 and the revised NMR assignments for asteltoxin and demonstrated that avertoxin B (3) is an active inhibitor against human acetylcholinesterase with the IC50 value of 14.9 muM (huperzine A as the positive control had an IC50 of 0.6 muM). In addition, the cytotoxicity of asteltoxin (1) and avertoxins A-D (2-5) against MDA-MB-231, HCT116, and HeLa cell lines was evaluated. Title: Muscle-specific deletion of comparative gene identification-58 (CGI-58) causes muscle steatosis but improves insulin sensitivity in male mice Xie P, Kadegowda AK, Ma Y, Guo F, Han X, Wang M, Groban L, Xue B, Shi H and Yu L <1 more author(s)> Xie P, Kadegowda AK, Ma Y, Guo F, Han X, Wang M, Groban L, Xue B, Shi H, Li H, Yu L (- 1) Ref: Endocrinology, 156:1648, 2015 : PubMed ESTHER: Xie_2015_Endocrinology_156_1648 PubMedSearch: Xie 2015 Endocrinology 156 1648 PubMedID: 25751639 Abstract Intramyocellular accumulation of lipids is often associated with insulin resistance. Deficiency of comparative gene identification-58 (CGI-58) causes cytosolic deposition of triglyceride (TG)-rich lipid droplets in most cell types, including muscle due to defective TG hydrolysis. It was unclear, however, whether CGI-58 deficiency-induced lipid accumulation in muscle influences insulin sensitivity. Here we show that muscle-specific CGI-58 knockout mice relative to their controls have increased glucose tolerance and insulin sensitivity on a Western-type high-fat diet, despite TG accumulation in both heart and oxidative skeletal muscle and cholesterol deposition in heart. Although the intracardiomyocellular lipid deposition results in cardiac ventricular fibrosis and systolic dysfunction, muscle-specific CGI-58 knockout mice show increased glucose uptake in heart and soleus muscle, improved insulin signaling in insulin-sensitive tissues, and reduced plasma concentrations of glucose, insulin, and cholesterol. Hepatic contents of TG and cholesterol are also decreased in these animals. Cardiac steatosis is attributable, at least in part, to decreases in cardiac TG hydrolase activity and peroxisome proliferator-activated receptor-alpha/peroxisome proliferator-activated receptor-gamma coactivator-1-dependent mitochondrial fatty acid oxidation. In conclusion, muscle CGI-58 deficiency causes cardiac dysfunction and fat deposition in oxidative muscles but induces a series of favorable metabolic changes in mice fed a high-fat diet. Title: Structure of Drosophila Oskar reveals a novel RNA binding protein Yang N, Yu Z, Hu M, Wang M, Lehmann R, Xu RM Ref: Proc Natl Acad Sci U S A, 112:11541, 2015 : PubMed ESTHER: Yang_2015_Proc.Natl.Acad.Sci.U.S.A_112_11541 PubMedSearch: Yang 2015 Proc.Natl.Acad.Sci.U.S.A 112 11541 PubMedID: 26324911 Abstract Oskar (Osk) protein plays critical roles during Drosophila germ cell development, yet its functions in germ-line formation and body patterning remain poorly understood. This situation contrasts sharply with the vast knowledge about the function and mechanism of osk mRNA localization. Osk is predicted to have an N-terminal LOTUS domain (Osk-N), which has been suggested to bind RNA, and a C-terminal hydrolase-like domain (Osk-C) of unknown function. Here, we report the crystal structures of Osk-N and Osk-C. Osk-N shows a homodimer of winged-helix-fold modules, but without detectable RNA-binding activity. Osk-C has a lipase-fold structure but lacks critical catalytic residues at the putative active site. Surprisingly, we found that Osk-C binds the 3'UTRs of osk and nanos mRNA in vitro. Mutational studies identified a region of Osk-C important for mRNA binding. These results suggest possible functions of Osk in the regulation of stability, regulation of translation, and localization of relevant mRNAs through direct interaction with their 3'UTRs, and provide structural insights into a novel protein-RNA interaction motif involving a hydrolase-related domain. Title: Genome sequencing of adzuki bean (Vigna angularis) provides insight into high starch and low fat accumulation and domestication Yang K, Tian Z, Chen C, Luo L, Zhao B, Wang Z, Yu L, Li Y, Sun Y and Wan P <17 more author(s)> Yang K, Tian Z, Chen C, Luo L, Zhao B, Wang Z, Yu L, Li Y, Sun Y, Li W, Chen Y, Zhang Y, Ai D, Zhao J, Shang C, Ma Y, Wu B, Wang M, Gao L, Sun D, Zhang P, Guo F, Wang W, Wang J, Varshney RK, Ling HQ, Wan P (- 17) Ref: Proc Natl Acad Sci U S A, 112:13213, 2015 : PubMed ESTHER: Yang_2015_Proc.Natl.Acad.Sci.U.S.A_112_13213 PubMedSearch: Yang 2015 Proc.Natl.Acad.Sci.U.S.A 112 13213 PubMedID: 26460024 Gene_locus related to this paper: phaan-a0a0l9ttq5, phaan-a0a0l9vh69, phaan-a0a0l9vh89, phaan-a0a0s3tc53, vigrr-a0a1s3v914, phaan-a0a0s3s998, phaan-a0a0s3siv8, phaan-a0a0l9uys5, phaan-a0a0s3rp07, phaan-a0a0s3rbq0, vigrr-a0a1s3tul4, phaan-a0a0s3smk7, phaan-a0a0s3slm9, phaan-a0a0l9ujf5, phaan-a0a0l9til9, phaan-a0a0l9uqr2, phaan-a0a0l9v1m8, phaan-a0a0l9uc60, phaan-a0a0l9ucr8 Abstract Adzuki bean (Vigna angularis), an important legume crop, is grown in more than 30 countries of the world. The seed of adzuki bean, as an important source of starch, digestible protein, mineral elements, and vitamins, is widely used foods for at least a billion people. Here, we generated a high-quality draft genome sequence of adzuki bean by whole-genome shotgun sequencing. The assembled contig sequences reached to 450 Mb (83% of the genome) with an N50 of 38 kb, and the total scaffold sequences were 466.7 Mb with an N50 of 1.29 Mb. Of them, 372.9 Mb of scaffold sequences were assigned to the 11 chromosomes of adzuki bean by using a single nucleotide polymorphism genetic map. A total of 34,183 protein-coding genes were predicted. Functional analysis revealed that significant differences in starch and fat content between adzuki bean and soybean were likely due to transcriptional abundance, rather than copy number variations, of the genes related to starch and oil synthesis. We detected strong selection signals in domestication by the population analysis of 50 accessions including 11 wild, 11 semiwild, 17 landraces, and 11 improved varieties. In addition, the semiwild accessions were illuminated to have a closer relationship to the cultigen accessions than the wild type, suggesting that the semiwild adzuki bean might be a preliminary landrace and play some roles in the adzuki bean domestication. The genome sequence of adzuki bean will facilitate the identification of agronomically important genes and accelerate the improvement of adzuki bean. Title: Huperzine A Alleviates Mechanical Allodynia but Not Spontaneous Pain via Muscarinic Acetylcholine Receptors in Mice Zuo ZX, Wang YJ, Liu L, Wang Y, Mei SH, Feng ZH, Wang M, Li XY Ref: Neural Plast, 2015:453170, 2015 : PubMed ESTHER: Zuo_2015_Neural.Plast_2015_453170 PubMedSearch: Zuo 2015 Neural.Plast 2015 453170 PubMedID: 26697233 Abstract Chronic pain is a major health issue and most patients suffer from spontaneous pain. Previous studies suggest that Huperzine A (Hup A), an alkaloid isolated from the Chinese herb Huperzia serrata, is a potent analgesic with few side effects. However, whether it alleviates spontaneous pain is unclear. We evaluated the effects of Hup A on spontaneous pain in mice using the conditioned place preference (CPP) behavioral assay and found that application of Hup A attenuated the mechanical allodynia induced by peripheral nerve injury or inflammation. This effect was blocked by atropine. However, clonidine but not Hup A induced preference for the drug-paired chamber in CPP. The same effects occurred when Hup A was infused into the anterior cingulate cortex. Furthermore, ambenonium chloride, a competitive inhibitor of acetylcholinesterase, also increased the paw-withdrawal threshold but failed to induce place preference in CPP. Therefore, our data suggest that acetylcholinesterase in both the peripheral and central nervous systems is involved in the regulation of mechanical allodynia but not the spontaneous pain. Title: Association between esophageal cancer risk and EPHX1 polymorphisms: a meta-analysis Li QT, Kang W, Wang M, Yang J, Zuo Y, Zhang W, Su DK Ref: World J Gastroenterol, 20:5124, 2014 : PubMed ESTHER: Li_2014_World.J.Gastroenterol_20_5124 PubMedSearch: Li 2014 World.J.Gastroenterol 20 5124 PubMedID: 24803829 Abstract AIM: To summarize the relationship between p.Tyr113His and p.His139Arg polymorphisms in microsomal epoxide hydrolase (EPHX1) and risk for esophageal cancer (EC). Title: A novel acetylcholinesterase biosensor based on carboxylic graphene coated with silver nanoparticles for pesticide detection Liu Y, Wang G, Li C, Zhou Q, Wang M, Yang L Ref: Mater Sci Eng C Mater Biol Appl, 35:253, 2014 : PubMed ESTHER: Liu_2014_Mater.Sci.Eng.C.Mater.Biol.Appl_35_253 PubMedSearch: Liu 2014 Mater.Sci.Eng.C.Mater.Biol.Appl 35 253 PubMedID: 24411376 Abstract A novel acetylcholinesterase (AChE) biosensor based on Ag NPs, carboxylic graphene (CGR) and Nafion (NF) hybrid modified glass carbon electrode (GCE) has been successfully developed. Ag NPs-CGR-NF possessed predominant conductivity, catalysis and biocompatibility and provided a hydrophilic surface for AChE adhesion. Chitosan (CS) was used to immobilize AChE on the surface of Ag NPs-CGR-NF/GCE to keep the AChE activities. The AChE biosensor showed favorable affinity to acetylthiocholine chloride (ATCl) and could catalyze the hydrolysis of ATCl with an apparent Michaelis-Menten constant value of 133muM, which was then oxidized to produce a detectable and fast response. Under optimum conditions, the biosensor detected chlorpyrifos and carbaryl at concentrations ranging from 1.0x10(-13) to 1x10(-8)M and from 1.0x10(-12) to 1x10(-8)M. The detection limits for chlorpyrifos and carbaryl were 5.3x10(-14)M and 5.45x10(-13)M, respectively. The developed biosensor exhibited good sensitivity, stability, reproducibility and low cost, thus providing a promising tool for analysis of enzyme inhibitors. This study could provide a simple and effective immobilization platform for meeting the demand of the effective immobilization enzyme on the electrode surface. Title: Synthesis and characterization of 1H-phenanthro[9,10-d]imidazole derivatives as multifunctional agents for treatment of Alzheimer's disease Liu J, Qiu J, Wang M, Wang L, Su L, Gao J, Gu Q, Xu J, Huang SL and Li D <2 more author(s)> Liu J, Qiu J, Wang M, Wang L, Su L, Gao J, Gu Q, Xu J, Huang SL, Gu LQ, Huang ZS, Li D (- 2) Ref: Biochimica & Biophysica Acta, 1840:2886, 2014 : PubMed ESTHER: Liu_2014_Biochim.Biophys.Acta_1840_2886 PubMedSearch: Liu 2014 Biochim.Biophys.Acta 1840 2886 PubMedID: 24821011 Abstract BACKGROUND: Alzheimer's disease (AD) is a progressive neurodegenerative brain disorder that is characterized by dementia, cognitive impairment, and memory loss. Diverse factors are related to the development of AD, such as increased level of beta-amyloid (Abeta), acetylcholine, metal ion deregulation, hyperphosphorylated tau protein, and oxidative stress. Title: Separation and purification of bioactive botrallin and TMC-264 by a combination of HSCCC and semi-preparative HPLC from endophytic fungus Hyalodendriella sp. Ponipodef12 Mao Z, Luo R, Luo H, Tian J, Liu H, Yue Y, Wang M, Peng Y, Zhou L Ref: World J Microbiol Biotechnol, 30:2533, 2014 : PubMed ESTHER: Mao_2014_World.J.Microbiol.Biotechnol_30_2533 PubMedSearch: Mao 2014 World.J.Microbiol.Biotechnol 30 2533 PubMedID: 24898177 Abstract Two dibenzo-alpha-pyrones, botrallin (1) and TMC-264 (2) were preparatively separated from crude ethyl acetate extract of the endophytic fungus Hyalodendriella sp. Ponipodef12, which was isolated from the hybrid 'Neva' of Populus deltoides Marsh x P. nigra L. using a combination of high-speed counter-current chromatography (HSCCC) and semi-preparative HPLC. Botrallin (1) with 74.73 % of purity and TMC-264 (2) with 82.29 % of purity were obtained through HSCCC by employing a solvent system containing n-hexane-ethyl acetate-methanol-water at a volume ratio of 1.2:1.0:0.9:1.0. It was the first time for TMC-264 (2) to be isolated from this fungus. TMC-264 (2) showed strong antimicrobial and antinematodal activity, and botrallin (1) exhibited moderate inhibitory activity on acetylcholinesterase. Title: Macrophage CGI-58 deficiency activates ROS-inflammasome pathway to promote insulin resistance in mice Miao H, Ou J, Ma Y, Guo F, Yang Z, Wiggins M, Liu C, Song W, Han X and Yu L <8 more author(s)> Miao H, Ou J, Ma Y, Guo F, Yang Z, Wiggins M, Liu C, Song W, Han X, Wang M, Cao Q, Chung BH, Yang D, Liang H, Xue B, Shi H, Gan L, Yu L (- 8) Ref: Cell Rep, 7:223, 2014 : PubMed ESTHER: Miao_2014_Cell.Rep_7_223 PubMedSearch: Miao 2014 Cell.Rep 7 223 PubMedID: 24703845 Abstract Overnutrition activates a proinflammatory program in macrophages to induce insulin resistance (IR), but its molecular mechanisms remain incompletely understood. Here, we show that saturated fatty acid and lipopolysaccharide, two factors implicated in high-fat diet (HFD)-induced IR, suppress macrophage CGI-58 expression. Macrophage-specific CGI-58 knockout (MaKO) in mice aggravates HFD-induced glucose intolerance and IR, which is associated with augmented systemic/tissue inflammation and proinflammatory activation of adipose tissue macrophages. CGI-58-deficient macrophages exhibit mitochondrial dysfunction due to defective peroxisome proliferator-activated receptor (PPAR)gamma signaling. Consequently, they overproduce reactive oxygen species (ROS) to potentiate secretion of proinflammatory cytokines by activating NLRP3 inflammasome. Anti-ROS treatment or NLRP3 silencing prevents CGI-58-deficient macrophages from oversecreting proinflammatory cytokines and from inducing proinflammatory signaling and IR in the cocultured fat slices. Anti-ROS treatment also prevents exacerbation of inflammation and IR in HFD-fed MaKO mice. Our data thus establish CGI-58 as a suppressor of overnutrition-induced NLRP3 inflammasome activation in macrophages. Title: Whole-genome sequencing of cultivated and wild peppers provides insights into Capsicum domestication and specialization Qin C, Yu C, Shen Y, Fang X, Chen L, Min J, Cheng J, Zhao S, Xu M and Zhang Z <58 more author(s)> Qin C, Yu C, Shen Y, Fang X, Chen L, Min J, Cheng J, Zhao S, Xu M, Luo Y, Yang Y, Wu Z, Mao L, Wu H, Ling-Hu C, Zhou H, Lin H, Gonzalez-Morales S, Trejo-Saavedra DL, Tian H, Tang X, Zhao M, Huang Z, Zhou A, Yao X, Cui J, Li W, Chen Z, Feng Y, Niu Y, Bi S, Yang X, Cai H, Luo X, Montes-Hernandez S, Leyva-Gonzalez MA, Xiong Z, He X, Bai L, Tan S, Liu D, Liu J, Zhang S, Chen M, Zhang L, Zhang Y, Liao W, Wang M, Lv X, Wen B, Liu H, Luan H, Yang S, Wang X, Xu J, Li X, Li S, Wang J, Palloix A, Bosland PW, Li Y, Krogh A, Rivera-Bustamante RF, Herrera-Estrella L, Yin Y, Yu J, Hu K, Zhang Z (- 58) Ref: Proc Natl Acad Sci U S A, 111:5135, 2014 : PubMed ESTHER: Qin_2014_Proc.Natl.Acad.Sci.U.S.A_111_5135 PubMedSearch: Qin 2014 Proc.Natl.Acad.Sci.U.S.A 111 5135 PubMedID: 24591624 Gene_locus related to this paper: capch-q75qh4, capan-a0a1u8fuf5, capan-a0a1u8gmz3, capan-a0a1u8f879, capan-a0a1u8ftr2, capan-a0a1u8g8s6 Abstract As an economic crop, pepper satisfies people's spicy taste and has medicinal uses worldwide. To gain a better understanding of Capsicum evolution, domestication, and specialization, we present here the genome sequence of the cultivated pepper Zunla-1 (C. annuum L.) and its wild progenitor Chiltepin (C. annuum var. glabriusculum). We estimate that the pepper genome expanded approximately 0.3 Mya (with respect to the genome of other Solanaceae) by a rapid amplification of retrotransposons elements, resulting in a genome comprised of approximately 81% repetitive sequences. Approximately 79% of 3.48-Gb scaffolds containing 34,476 protein-coding genes were anchored to chromosomes by a high-density genetic map. Comparison of cultivated and wild pepper genomes with 20 resequencing accessions revealed molecular footprints of artificial selection, providing us with a list of candidate domestication genes. We also found that dosage compensation effect of tandem duplication genes probably contributed to the pungent diversification in pepper. The Capsicum reference genome provides crucial information for the study of not only the evolution of the pepper genome but also, the Solanaceae family, and it will facilitate the establishment of more effective pepper breeding programs. Title: A reference genome for common bean and genome-wide analysis of dual domestications Schmutz J, McClean PE, Mamidi S, Wu GA, Cannon SB, Grimwood J, Jenkins J, Shu S, Song Q and Jackson SA <31 more author(s)> Schmutz J, McClean PE, Mamidi S, Wu GA, Cannon SB, Grimwood J, Jenkins J, Shu S, Song Q, Chavarro C, Torres-Torres M, Geffroy V, Moghaddam SM, Gao D, Abernathy B, Barry K, Blair M, Brick MA, Chovatia M, Gepts P, Goodstein DM, Gonzales M, Hellsten U, Hyten DL, Jia G, Kelly JD, Kudrna D, Lee R, Richard MM, Miklas PN, Osorno JM, Rodrigues J, Thareau V, Urrea CA, Wang M, Yu Y, Zhang M, Wing RA, Cregan PB, Rokhsar DS, Jackson SA (- 31) Ref: Nat Genet, 46:707, 2014 : PubMed ESTHER: Schmutz_2014_Nat.Genet_46_707 PubMedSearch: Schmutz 2014 Nat.Genet 46 707 PubMedID: 24908249 Gene_locus related to this paper: phavu-v7azs2, phavu-v7awu7 Abstract Common bean (Phaseolus vulgaris L.) is the most important grain legume for human consumption and has a role in sustainable agriculture owing to its ability to fix atmospheric nitrogen. We assembled 473 Mb of the 587-Mb genome and genetically anchored 98% of this sequence in 11 chromosome-scale pseudomolecules. We compared the genome for the common bean against the soybean genome to find changes in soybean resulting from polyploidy. Using resequencing of 60 wild individuals and 100 landraces from the genetically differentiated Mesoamerican and Andean gene pools, we confirmed 2 independent domestications from genetic pools that diverged before human colonization. Less than 10% of the 74 Mb of sequence putatively involved in domestication was shared by the two domestication events. We identified a set of genes linked with increased leaf and seed size and combined these results with quantitative trait locus data from Mesoamerican cultivars. Genes affected by domestication may be useful for genomics-enabled crop improvement. Title: Oral intake of hydrogen-rich water ameliorated chlorpyrifos-induced neurotoxicity in rats Wang T, Zhao L, Liu M, Xie F, Ma X, Zhao P, Liu Y, Li J, Wang M and Zhang Y <1 more author(s)> Wang T, Zhao L, Liu M, Xie F, Ma X, Zhao P, Liu Y, Li J, Wang M, Yang Z, Zhang Y (- 1) Ref: Toxicol Appl Pharmacol, 280:169, 2014 : PubMed ESTHER: Wang_2014_Toxicol.Appl.Pharmacol_280_169 PubMedSearch: Wang 2014 Toxicol.Appl.Pharmacol 280 169 PubMedID: 24967689 Abstract Chronic exposure to low-levels of organophosphate (OP) compounds, such as chlorpyrifos (CPF), induces oxidative stress and could be related to neurological disorders. Hydrogen has been identified as a novel antioxidant which could selectively scavenge hydroxyl radicals. We explore whether intake of hydrogen-rich water (HRW) can protect Wistar rats from CPF-induced neurotoxicity. Rats were gavaged daily with 6.75mg/kg body weight (1/20 LD50) of CPF and given HRW by oral intake. Nissl staining and electron microscopy results indicated that HRW intake had protective effects on the CPF-induced damage of hippocampal neurons and neuronal mitochondria. Immunostaining results showed that the increased glial fibrillary acidic protein (GFAP) expression in astrocytes induced by CPF exposure can be ameliorated by HRW intake. Moreover, HRW intake also attenuated CPF-induced oxidative stress as evidenced by enhanced level of MDA, accompanied by an increase in GSH level and SOD and CAT activity. Acetylcholinesterase (AChE) activity tests showed significant decrease in brain AChE activity after CPF exposure, and this effect can be ameliorated by HRW intake. An in vitro study demonstrated that AChE activity was more intense in HRW than in normal water with or without chlorpyrifos-oxon (CPO), the metabolically-activated form of CPF. These observations suggest that HRW intake can protect rats from CPF-induced neurotoxicity, and the protective effects of hydrogen may be mediated by regulating the oxidant and antioxidant status of rats. Furthermore, this work defines a novel mechanism of biological activity of hydrogen by directly increasing the AChE activity. Title: Genome characteristics reveal the impact of lichenization on lichen-forming fungus Endocarpon pusillum Hedwig (Verrucariales, Ascomycota) Wang YY, Liu B, Zhang XY, Zhou QM, Zhang T, Li H, Yu YF, Zhang XL, Hao XY and Wei JC <2 more author(s)> Wang YY, Liu B, Zhang XY, Zhou QM, Zhang T, Li H, Yu YF, Zhang XL, Hao XY, Wang M, Wang L, Wei JC (- 2) Ref: BMC Genomics, 15:34, 2014 : PubMed ESTHER: Wang_2014_BMC.Genomics_15_34 PubMedSearch: Wang 2014 BMC.Genomics 15 34 PubMedID: 24438332 Gene_locus related to this paper: endpu-u1ggx3, endpu-u1hiw6, endpu-u1gx33, endpu-u1hli9, endpu-u1hmu1, endpu-u1htc7, endpu-u1gu60 Abstract BACKGROUND: Lichen is a classic mutualistic organism and the lichenization is one of the fungal symbioses. The lichen-forming fungus Endocarpon pusillum is living in symbiosis with the green alga Diplosphaera chodatii Bialsuknia as a lichen in the arid regions. Title: Aryl-aldehyde formation in fungal polyketides: discovery and characterization of a distinct biosynthetic mechanism Wang M, Beissner M, Zhao H Ref: Chemical Biology, 21:257, 2014 : PubMed ESTHER: Wang_2014_Chem.Biol_21_257 PubMedSearch: Wang 2014 Chem.Biol 21 257 PubMedID: 24412543 Gene_locus related to this paper: asptn-5moas, asptn-azpb5 Abstract Aryl-aldehydes are a common feature in fungal polyketides, which are considered to be exclusively generated by the R domain of nonreducing polyketide synthases (NR-PKSs). However, by cloning and heterologous expression of both cryptic NR-PKS and nonribosomal peptide synthase (NRPS)-like genes from Aspergillus terreus in Saccharomyces cerevisiae, we identified a distinct mechanism for aryl-aldehyde formation in which a NRPS-like protein activates and reduces an aryl-acid produced by the accompanying NR-PKS to an aryl-aldehyde. Bioinformatics study indicates that such a mechanism may be widely used throughout the fungi kingdom. Title: Changes in monoclonal HLA-DR antigen expression in acute organophosphorus pesticide-poisoned patients Xia C, Wang M, Liang Q, Yun L, Kang H, Fan L, Wang D, Zhang G Ref: Exp Ther Med, 7:137, 2014 : PubMed ESTHER: Xia_2014_Exp.Ther.Med_7_137 PubMedSearch: Xia 2014 Exp.Ther.Med 7 137 PubMedID: 24348778 Abstract The aim of this study was to investigate changes in human leukocyte antigen (HLA)-DR expression of peripheral blood mononuclear cells (MNCs) in patients with acute organophosphorus pesticide poisoning (AOPP). HLA-DR antigen expression of peripheral blood MNCs was examined in 75 patients with AOPP, including 36 patients without multiple organ dysfunction syndrome (non-MODS) and 39 patients with multiple organ dysfunction syndrome (MODS), as well as in 30 healthy individuals using flow cytometry assay. The associations between HLA-DR antigen expression and certain parameters were analyzed, including acute physiology and chronic health evaluation II (APACHE II) score, serum cholinesterase (ChE) activity, cardiac troponin I (cTnI), cardiac enzymes, and liver and kidney function. The mean fluorescence intensity (MCF) of HLA-DR expression in the AOPP group (21.59+/-5.36) was significantly lower than that in the control group (27.85+/-4.86) (P<0.001). The MCF in the MODS group (18.17+/-4.23) was lower than that in the non-MODS group (25.15+/-6.15). In addition, the MCF of the deceased patients (15.29+/-3.97) was lower than that of the surviving patients (22.34+/-2.76) (P<0.001). The MCF of patients with AOPP and MODS was positively correlated with serum ChE (P<0.01) and negatively correlated with the APACHE II score, creatine kinase isoenzyme, cTnI, lactate dehydrogenase, alanine aminotransferase, aspartate aminotransferase, blood urea nitrogen and serum creatinine (P<0.05). In conclusion, HLA-DR expression in patients with AOPP was significantly decreased compared with that in healthy individuals; HLA-DR expression may therefore be a good indicator for evaluating AOPP, MODS disease severity, immune function, efficacy of prognosis and prognosis. Examination of HLA-DR antigen expression may be of crucial clinical value. Title: DWARF3 participates in an SCF complex and associates with DWARF14 to suppress rice shoot branching Zhao J, Wang T, Wang M, Liu Y, Yuan S, Gao Y, Yin L, Sun W, Peng L and Li X <2 more author(s)> Zhao J, Wang T, Wang M, Liu Y, Yuan S, Gao Y, Yin L, Sun W, Peng L, Zhang W, Wan J, Li X (- 2) Ref: Plant Cell Physiol, 55:1096, 2014 : PubMed ESTHER: Zhao_2014_Plant.Cell.Physiol_55_1096 PubMedSearch: Zhao 2014 Plant.Cell.Physiol 55 1096 PubMedID: 24616269 Abstract Strigolactones (SLs) are a novel class of plant hormones that inhibit shoot branching. Currently, two proteins in rice are thought to play crucial roles in SL signal transduction. DWARF14 (D14), an alpha/beta hydrolase, is responsible for SL perception, while DWARF3 (D3), an F-box protein with leucine-rich repeats, is essential for SL signal transduction. However, how these two proteins transmit SL signals to downstream factors remains unclear. Here, we characterized a high-tillering dwarf rice mutant, gsor300097, which is insensitive to GR24, a synthetic analog of SL. Mapping and sequencing analysis showed that gsor300097 is a novel allelic mutant of D3, in which a nonsense mutation truncates the protein from 720 to 527 amino acids. The D3 gene was strongly expressed in root, leaf, shoot base and panicle. Nuclear-localized F-box protein D3 played a role in the SCF complex by interacting with OSK1, OSK5 or OSK20 and OsCullin1. In addition, D3 associated with D14 in a GR24-dependent manner in vivo. Taken together, our findings suggested that D3 assembled into an SCF(D3) complex and associated with D14 to suppress rice shoot branching. Title: Genome Sequencing of Ralstonia solanacearum FQY_4, Isolated from a Bacterial Wilt Nursery Used for Breeding Crop Resistance Cao Y, Tian B, Liu Y, Cai L, Wang H, Lu N, Wang M, Shang S, Luo Z, Shi J Ref: Genome Announc, 1:, 2013 : PubMed ESTHER: Cao_2013_Genome.Announc_1_E00125 PubMedSearch: Cao 2013 Genome.Announc 1 E00125 PubMedID: 23661471 Gene_locus related to this paper: ralso-PCAD Abstract Ralstonia solanacearum strain FQY_4 was isolated from a bacterial wilt nursery, which is used for breeding crops for Ralstonia resistance in China. Here, we report the complete genome sequence of FQY_4 and its comparison with other published R. solanacearum genomes, especially with the strains GMI1000 and Y45 in the same group. Title: Whole-genome sequencing of Oryza brachyantha reveals mechanisms underlying Oryza genome evolution Chen J, Huang Q, Gao D, Wang J, Lang Y, Liu T, Li B, Bai Z, Luis Goicoechea J and Chen M <30 more author(s)> Chen J, Huang Q, Gao D, Wang J, Lang Y, Liu T, Li B, Bai Z, Luis Goicoechea J, Liang C, Chen C, Zhang W, Sun S, Liao Y, Zhang X, Yang L, Song C, Wang M, Shi J, Liu G, Liu J, Zhou H, Zhou W, Yu Q, An N, Chen Y, Cai Q, Wang B, Liu B, Min J, Huang Y, Wu H, Li Z, Zhang Y, Yin Y, Song W, Jiang J, Jackson SA, Wing RA, Chen M (- 30) Ref: Nat Commun, 4:1595, 2013 : PubMed ESTHER: Chen_2013_Nat.Commun_4_1595 PubMedSearch: Chen 2013 Nat.Commun 4 1595 PubMedID: 23481403 Gene_locus related to this paper: orysa-Q6ZDG3, orysa-q6h415, orysj-q6yse8, orysa-q33aq0, orybr-j3l7k2, orybr-j3m138, orybr-j3l6m8, orybr-j3m3b3, orybr-j3l8d1, orybr-j3kza5, orybr-j3mnb5, orybr-j3n4p4, orybr-j3lg73, orybr-j3l342, orybr-j3msi2, orybr-j3nb83, orybr-j3mpc5 Abstract The wild species of the genus Oryza contain a largely untapped reservoir of agronomically important genes for rice improvement. Here we report the 261-Mb de novo assembled genome sequence of Oryza brachyantha. Low activity of long-terminal repeat retrotransposons and massive internal deletions of ancient long-terminal repeat elements lead to the compact genome of Oryza brachyantha. We model 32,038 protein-coding genes in the Oryza brachyantha genome, of which only 70% are located in collinear positions in comparison with the rice genome. Analysing breakpoints of non-collinear genes suggests that double-strand break repair through non-homologous end joining has an important role in gene movement and erosion of collinearity in the Oryza genomes. Transition of euchromatin to heterochromatin in the rice genome is accompanied by segmental and tandem duplications, further expanded by transposable element insertions. The high-quality reference genome sequence of Oryza brachyantha provides an important resource for functional and evolutionary studies in the genus Oryza. Title: Development of a biosensor based on immobilization of acetylcholinesterase on NiO nanoparticles-carboxylic graphene-nafion modified electrode for detection of pesticides Yang L, Wang G, Liu Y, Wang M Ref: Talanta, 113:135, 2013 : PubMed ESTHER: Yang_2013_Talanta_113_135 PubMedSearch: Yang 2013 Talanta 113 135 PubMedID: 23708635 Abstract A sensitive amperometric acetylcholinesterase (AChE) biosensor based on NiO nanoparticles (NiO NPs), carboxylic graphene (CGR) and nafion (NF) modified glassy carbon electrode (GCE) has been developed. NiO NPs-CGR-NF nanocomposites with excellent conductivity, catalysis and biocompatibility offered an extremely hydrophilic surface for AChE adhesion. The AChE biosensor showed favorable affinity to acetylthiocholine chloride (ATCl) and could catalyze the hydrolysis of ATCl with an apparent Michaelis-Menten constant value of 135muM. Under optimum conditions, the biosensor detected methyl parathion and chlorpyrifos in the linear range from 1.0x10(-13) to 1x10(-10)M and from 1.0x10(-10) to 1x10(-8)M with the detection limits 5x10(-14)M. The biosensor detected carbofuran in the linear range from 1.0x10(-12) to 1x10(-10)M and from 1.0x10(-10) to 1x10(-8)M with the detection limit of 5x10(-13)M. The developed biosensor exhibited good sensitivity, stability and reproducibility, thus providing a promising tool for analysis of enzyme inhibitors. Title: Development of a stable biosensor based on a SiO2 nanosheet-Nafion-modified glassy carbon electrode for sensitive detection of pesticides Yang L, Wang GC, Liu YJ, An JJ, Wang M Ref: Anal Bioanal Chem, 405:2545, 2013 : PubMed ESTHER: Yang_2013_Anal.Bioanal.Chem_405_2545 PubMedSearch: Yang 2013 Anal.Bioanal.Chem 405 2545 PubMedID: 23354570 Abstract SiO(2) nanosheets (SNS) have been prepared by a chemical method using montmorillonite as raw material and were characterized by scanning electron microscopy and X-ray diffraction. SiO(2) nanosheet-Nafion nanocomposites with excellent conductivity, catalytic activity, and biocompatibility provided an extremely hydrophilic surface for biomolecule adhesion. Chitosan was used as a cross-linker to immobilize acetylcholinesterase (AChE), and Nafion was used as a protective membrane to efficiently improve the stability of the AChE biosensor. The AChE biosensor showed favorable affinity for acetylthiocholine chloride and catalyzed the hydrolysis of acetylthiocholine chloride with an apparent Michaelis-Menten constant of 134 muM to form thiocholine, which was then oxidized to produce a detectable and fast response. Based on the inhibition by pesticides of the enzymatic activity of AChE, detection of the amperometric response from thiocholine on the biosensor is a simple and effective way to biomonitor exposure to pesticides. Under optimum conditions, the biosensor detected methyl parathion, chlorpyrifos, and carbofuran at concentrations ranging from 1.0 x 10(-12) to 1 x 10(-10) M and from 1.0 x 10(-10) to 1 x 10(-8) M. The detection limits for methyl parathion, chlorpyrifos, and carbofuran were 5 x 10(-13) M. The biosensor developed exhibited good sensitivity, stability, reproducibility, and low cost, thus providing a new promising tool for analysis of enzyme inhibitors. Title: Nicotinic alpha7 receptors enhance NMDA cognitive circuits in dorsolateral prefrontal cortex Yang Y, Paspalas CD, Jin LE, Picciotto MR, Arnsten AF, Wang M Ref: Proc Natl Acad Sci U S A, 110:12078, 2013 : PubMed ESTHER: Yang_2013_Proc.Natl.Acad.Sci.U.S.A_110_12078 PubMedSearch: Yang 2013 Proc.Natl.Acad.Sci.U.S.A 110 12078 PubMedID: 23818597 Abstract The cognitive function of the highly evolved dorsolateral prefrontal cortex (dlPFC) is greatly influenced by arousal state, and is gravely afflicted in disorders such as schizophrenia, where there are genetic insults in alpha7 nicotinic acetylcholine receptors (alpha7-nAChRs). A recent behavioral study indicates that ACh depletion from dlPFC markedly impairs working memory [Croxson PL, Kyriazis DA, Baxter MG (2011) Nat Neurosci 14(12):1510-1512]; however, little is known about how alpha7-nAChRs influence dlPFC cognitive circuits. Goldman-Rakic [Goldman-Rakic (1995) Neuron 14(3):477-485] discovered the circuit basis for working memory, whereby dlPFC pyramidal cells excite each other through glutamatergic NMDA receptor synapses to generate persistent network firing in the absence of sensory stimulation. Here we explore alpha7-nAChR localization and actions in primate dlPFC and find that they are enriched in glutamate network synapses, where they are essential for dlPFC persistent firing, with permissive effects on NMDA receptor actions. Blockade of alpha7-nAChRs markedly reduced, whereas low-dose stimulation selectively enhanced, neuronal representations of visual space. These findings in dlPFC contrast with the primary visual cortex, where nAChR blockade had no effect on neuronal firing [Herrero JL, et al. (2008) Nature 454(7208):1110-1114]. We additionally show that alpha7-nAChR stimulation is needed for NMDA actions, suggesting that it is key for the engagement of dlPFC circuits. As ACh is released in cortex during waking but not during deep sleep, these findings may explain how ACh shapes differing mental states during wakefulness vs. sleep. The results also explain why genetic insults to alpha7-nAChR would profoundly disrupt cognitive experience in patients with schizophrenia. Title: Mind the gap: upgrading genomes with Pacific Biosciences RS long-read sequencing technology English AC, Richards S, Han Y, Wang M, Vee V, Qu J, Qin X, Muzny DM, Reid JG and Gibbs RA <1 more author(s)> English AC, Richards S, Han Y, Wang M, Vee V, Qu J, Qin X, Muzny DM, Reid JG, Worley KC, Gibbs RA (- 1) Ref: PLoS ONE, 7:e47768, 2012 : PubMed ESTHER: English_2012_PLoS.ONE_7_E47768 PubMedSearch: English 2012 PLoS.ONE 7 E47768 PubMedID: 23185243 Gene_locus related to this paper: drome-GH02439 Abstract Many genomes have been sequenced to high-quality draft status using Sanger capillary electrophoresis and/or newer short-read sequence data and whole genome assembly techniques. However, even the best draft genomes contain gaps and other imperfections due to limitations in the input data and the techniques used to build draft assemblies. Sequencing biases, repetitive genomic features, genomic polymorphism, and other complicating factors all come together to make some regions difficult or impossible to assemble. Traditionally, draft genomes were upgraded to "phase 3 finished" status using time-consuming and expensive Sanger-based manual finishing processes. For more facile assembly and automated finishing of draft genomes, we present here an automated approach to finishing using long-reads from the Pacific Biosciences RS (PacBio) platform. Our algorithm and associated software tool, PBJelly, (publicly available at https://sourceforge.net/projects/pb-jelly/) automates the finishing process using long sequence reads in a reference-guided assembly process. PBJelly also provides "lift-over" co-ordinate tables to easily port existing annotations to the upgraded assembly. Using PBJelly and long PacBio reads, we upgraded the draft genome sequences of a simulated Drosophila melanogaster, the version 2 draft Drosophila pseudoobscura, an assembly of the Assemblathon 2.0 budgerigar dataset, and a preliminary assembly of the Sooty mangabey. With 24x mapped coverage of PacBio long-reads, we addressed 99% of gaps and were able to close 69% and improve 12% of all gaps in D. pseudoobscura. With 4x mapped coverage of PacBio long-reads we saw reads address 63% of gaps in our budgerigar assembly, of which 32% were closed and 63% improved. With 6.8x mapped coverage of mangabey PacBio long-reads we addressed 97% of gaps and closed 66% of addressed gaps and improved 19%. The accuracy of gap closure was validated by comparison to Sanger sequencing on gaps from the original D. pseudoobscura draft assembly and shown to be dependent on initial reference quality. Title: Benzopyranones from the endophytic fungus Hyalodendriella sp. Ponipodef12 and their bioactivities Meng X, Mao Z, Lou J, Xu L, Zhong L, Peng Y, Zhou L, Wang M Ref: Molecules, 17:11303, 2012 : PubMed ESTHER: Meng_2012_Molecules_17_11303 PubMedSearch: Meng 2012 Molecules 17 11303 PubMedID: 23011274 Abstract The endophytic fungus Hyalodendriella sp. Ponipodef12 was isolated from the hybrid 'Neva' of Populus deltoides Marsh x P. nigra L. In this study, four benzopyranones were isolated from the ethyl acetate extract of Hyalodendriella sp. Ponipodef12, and identified as palmariol B (1), 4-hydroxymellein (2), alternariol 9-methyl ether (3), and botrallin (4) by means of physicochemical and spectroscopic analysis. All the compounds were evaluated for their antibacterial, antifungal, antinematodal and acetylcholinesterase inhibitory activities. 4-Hydroxymellein (2) exhibited stronger antibacterial activity than the other compounds. Palmariol B (1) showed stronger antimicrobial, antinematodal and acetylcholinesterase inhibitory activities than alternariol 9-methyl ether (3) which indicated that the chlorine substitution at position 2 may contribute to its bioactivity. The results indicate the potential of this endophytic fungus as a source of bioactive benzopyranones. Title: 6-Deoxyerythronolide B synthase thioesterase-catalyzed macrocyclization is highly stereoselective Pinto A, Wang M, Horsman M, Boddy CN Ref: Org Lett, 14:2278, 2012 : PubMed ESTHER: Pinto_2012_Org.Lett_14_2278 PubMedSearch: Pinto 2012 Org.Lett 14 2278 PubMedID: 22519860 Abstract Macrocyclic polyketide natural products are an indispensable source of therapeutic agents. The final stage of their biosynthesis, macrocyclization, is catalyzed regio- and stereoselectively by a thioesterase. A panel of substrates were synthesized to test their specificity for macrocyclization by the erythromycin polyketide synthase TE (DEBS TE) in vitro. It was shown that DEBS TE is highly stereospecific, successfully macrocyclizing a 14-member ring substrate with an R configured O-nucleophile, and highly regioselective, generating exclusively the 14-member lactone over the 12-member lactone. Title: The immunomodulation of acetylcholinesterase in zhikong scallop Chlamys farreri Shi X, Zhou Z, Wang L, Yue F, Wang M, Yang C, Song L Ref: PLoS ONE, 7:e30828, 2012 : PubMed ESTHER: Shi_2012_PLoS.ONE_7_E30828 PubMedSearch: Shi 2012 PLoS.ONE 7 E30828 PubMedID: 22292052 Gene_locus related to this paper: 9biva-h6u1i3 Abstract BACKGROUND: Acetycholinesterase (AChE; EC 3.1.1.7) is an essential hydrolytic enzyme in the cholinergic nervous system, which plays an important role during immunomodulation in vertebrates. Though AChEs have been identified in most invertebrates, the knowledge about immunomodulation function of AChE is still quite meagre in invertebrates. METHODOLOGY: A scallop AChE gene was identified from Chlamys farreri (designed as CfAChE), and its open reading frame encoded a polypeptide of 522 amino acids. A signal peptide, an active site triad, the choline binding site and the peripheral anionic sites (PAS) were identified in CfAChE. The recombinant mature polypeptide of CfAChE (rCfAChE) was expressed in Pichia pastoris GS115, and its activity was 71.3+/-1.3 U mg(-1) to catalyze the hydrolysis of acetylthiocholine iodide. The mRNA transcripts of CfAChE were detected in haemocytes, hepatopancreas, adductor muscle, mantle, gill, kidney and gonad, with the highest expression level in hepatopancreas. The relative expression level of CfAChE mRNA in haemocytes was both up-regulated after LPS (0.5 mg mL(-1)) and human TNF-alpha (50 ng mL(-1)) stimulations, and it reached the highest level at 12 h (10.4-fold, P<0.05) and 1 h (3.2-fold, P<0.05), respectively. After Dichlorvos (DDVP) (50 mg L(-1)) stimulation, the CfAChE activity in the supernatant of haemolymph decreased significantly from 0.16 U mg(-1) at 0 h to 0.03 U mg(-1) at 3 h, while the expression level of lysozyme in the haemocytes was up-regulated and reached the highest level at 6 h, which was 3.0-fold (P<0.05) of that in the blank group. CONCLUSIONS: The results collectively indicated that CfAChE had the acetylcholine-hydrolyzing activity, which was in line with the potential roles of AChE in the neuroimmune system of vertebrates which may help to re-balance the immune system after immune response. Title: Complete genome sequence of Riemerella anatipestifer reference strain Wang X, Zhu D, Wang M, Cheng A, Jia R, Zhou Y, Chen Z, Luo Q, Liu F and Chen XY <1 more author(s)> Wang X, Zhu D, Wang M, Cheng A, Jia R, Zhou Y, Chen Z, Luo Q, Liu F, Wang Y, Chen XY (- 1) Ref: Journal of Bacteriology, 194:3270, 2012 : PubMed ESTHER: Wang_2012_J.Bacteriol_194_3270 PubMedSearch: Wang 2012 J.Bacteriol 194 3270 PubMedID: 22628503 Abstract Riemerella anatipestifer is an infectious pathogen causing serositis in ducks. We had the genome of the R. anatipestifer reference strain ATCC 11845 sequenced. The completed draft genome consists of one circular chromosome with 2,164,087 bp. There are 2,101 genes in the draft, and its GC content is 35.01%. Title: [Effect of sailuotong capsule on intervening cognitive dysfunction of multi-infarct dementia in rats] Xu L, Lin CR, Liu JX, Ren JX, Li JM, Wang M, Li HH, Song WT, Yao MJ, Wang GR Ref: Zhongguo Zhong Yao Za Zhi, 37:2943, 2012 : PubMed ESTHER: Xu_2012_Zhongguo.Zhong.Yao.Za.Zhi_37_2943 PubMedSearch: Xu 2012 Zhongguo.Zhong.Yao.Za.Zhi 37 2943 PubMedID: 23270238 Abstract OBJECTIVE: To study the effect of Sailuotong capsule (Sailuotong) on learning and memory functions of multi-infarct dementia (MID) rats and its mechanism. METHOD: All SD rats were divided into five groups, namely the sham operation group, the model group, the positive group, the low dosage Sailuotong-treated group and the high dosage Sailuotong-treated group. The multi-infarct dementia model was established by injecting the micro-sphere vascular occlusive agent. On the 10th day after the successful operation, the rats were administered intragastrically with distilled water, memantine hydrochloride (20 mg x kg(-1)) and Sailuotong (16.5 mg x kg(-1) and 33.0 mg x kg(-1)) once a day for 60 days respectively, in order to detect the effect of Sailuotong in different doses on the latent period and route length in Morris water maze and the activities of choline acetyltransferase (ChAT) and acetylcholinesterase (AchE) in brain tissues. RESULT: Compared with the sham operation rats, it had been observed that the latent period and route length of MID rats in Morris water maze were significantly increased (P < 0.05 or P < 0.01), and the activity of ChAT in brain tissues was significantly decreased (P < 0.05). After the intervention with Sailuotong for sixty days, the latent period and route length of MID rats in Morris water maze significantly shrank (P < 0.05 or P < 0.01). Additionally, Sailuotong decreased AchE activity, while increasing ChAT activity in brain tissues of MID rats (P < 0.05 or P < 0.01). CONCLUSION: Sailuotong capsule can improve cognitive dysfunction of MID rats to some extent. Its mechanism may be related to its different regulation of activities of ChAT and AchE in brain tissues. Title: Draft genome sequence of CBS 2479, the standard type strain of Trichosporon asahii Yang RY, Li HT, Zhu H, Zhou GP, Wang M, Wang L Ref: Eukaryot Cell, 11:1415, 2012 : PubMed ESTHER: Yang_2012_Eukaryot.Cell_11_1415 PubMedSearch: Yang 2012 Eukaryot.Cell 11 1415 PubMedID: 23104369 Abstract Trichosporon asahii is one of the important opportunistic pathogenic fungi. Here, we first report the draft nuclear chromosome genome sequence and mitochondrial genome sequence of T. asahii CBS 2479, which is a standard strain of T. asahii that was isolated from a progressive psoriatic lesion. COG analysis predicted that 3,131 genes were assigned to 23 functional categories and that 628 genes were predicted to have a general function. Title: Genome sequence of the Trichosporon asahii environmental strain CBS 8904 Yang RY, Li HT, Zhu H, Zhou GP, Wang M, Wang L Ref: Eukaryot Cell, 11:1586, 2012 : PubMed ESTHER: Yang_2012_Eukaryot.Cell_11_1586 PubMedSearch: Yang 2012 Eukaryot.Cell 11 1586 PubMedID: 23193141 Abstract This is the first report of the genome sequence of Trichosporon asahii environmental strain CBS 8904, which was isolated from maize cobs. Comparison of the genome sequence with that of clinical strain CBS 2479 revealed that they have >99% chromosomal and mitochondrial sequence identity, yet CBS 8904 has 368 specific genes. Analysis of clusters of orthologous groups predicted that 3,307 genes belong to 23 functional categories and 703 genes were predicted to have a general function. Title: The ecoresponsive genome of Daphnia pulex Colbourne JK, Pfrender ME, Gilbert D, Thomas WK, Tucker A, Oakley TH, Tokishita S, Aerts A, Arnold GJ and Boore JL <59 more author(s)> Colbourne JK, Pfrender ME, Gilbert D, Thomas WK, Tucker A, Oakley TH, Tokishita S, Aerts A, Arnold GJ, Basu MK, Bauer DJ, Caceres CE, Carmel L, Casola C, Choi JH, Detter JC, Dong Q, Dusheyko S, Eads BD, Frohlich T, Geiler-Samerotte KA, Gerlach D, Hatcher P, Jogdeo S, Krijgsveld J, Kriventseva EV, Kultz D, Laforsch C, Lindquist E, Lopez J, Manak JR, Muller J, Pangilinan J, Patwardhan RP, Pitluck S, Pritham EJ, Rechtsteiner A, Rho M, Rogozin IB, Sakarya O, Salamov A, Schaack S, Shapiro H, Shiga Y, Skalitzky C, Smith Z, Souvorov A, Sung W, Tang Z, Tsuchiya D, Tu H, Vos H, Wang M, Wolf YI, Yamagata H, Yamada T, Ye Y, Shaw JR, Andrews J, Crease TJ, Tang H, Lucas SM, Robertson HM, Bork P, Koonin EV, Zdobnov EM, Grigoriev IV, Lynch M, Boore JL (- 59) Ref: Science, 331:555, 2011 : PubMed ESTHER: Colbourne_2011_Science_331_555 PubMedSearch: Colbourne 2011 Science 331 555 PubMedID: 21292972 Gene_locus related to this paper: dappu-e9fut0, dappu-e9fut9, dappu-e9fvw6, dappu-e9fxt4, dappu-e9fyr6, dappu-e9fzg6, dappu-e9g1e2, dappu-e9g1e6, dappu-e9g1e7, dappu-e9g1e8, dappu-e9g1v3, dappu-e9g1z2, dappu-e9gb99, dappu-e9gba0, dappu-e9gcb4, dappu-e9gdv5, dappu-e9gdv7, dappu-e9gi24, dappu-e9gj77, dappu-e9gja7, dappu-e9gmp5, dappu-e9gmr0, dappu-e9gn32, dappu-e9gp76, dappu-e9gp82, dappu-e9gp98, dappu-e9gp99, dappu-e9gvl2, dappu-e9gzn7, dappu-e9h1p4, dappu-e9h2c8, dappu-e9h2c9, dappu-e9h6x9, dappu-e9h6y4, dappu-e9h7w9, dappu-e9h8r4, dappu-e9hd06, dappu-e9hh56, dappu-e9hh57, dappu-e9hh59, dappu-e9hmp4, dappu-e9hp64, dappu-e9hp65, dappu-e9hpy8, dappu-e9htg8, dapul-ACHE1, dapul-ACHE2, dappu-e9gnj1, dappu-e9gu36, dappu-e9hpc4, dappu-e9gb07, dappu-e9glp6, dappu-e9glp5, dappu-e9gjv2, dappu-e9h0c7, dappu-e9g4g2, dappu-e9gw69, dappu-e9h3h9, dappu-e9g545, dappu-e9gw71, dappu-e9gw68, dappu-e9h3e7, dappu-e9gfg9, dappu-e9fvy6, dappu-e9hgt2 Abstract We describe the draft genome of the microcrustacean Daphnia pulex, which is only 200 megabases and contains at least 30,907 genes. The high gene count is a consequence of an elevated rate of gene duplication resulting in tandem gene clusters. More than a third of Daphnia's genes have no detectable homologs in any other available proteome, and the most amplified gene families are specific to the Daphnia lineage. The coexpansion of gene families interacting within metabolic pathways suggests that the maintenance of duplicated genes is not random, and the analysis of gene expression under different environmental conditions reveals that numerous paralogs acquire divergent expression patterns soon after duplication. Daphnia-specific genes, including many additional loci within sequenced regions that are otherwise devoid of annotations, are the most responsive genes to ecological challenges. Title: The HindIII polymorphism in the lipoprotein lipase gene predicts type 2 diabetes risk among Chinese adults Qi Y, Liu J, Wang W, Wang M, Sun JY, Li Y, Wu ZS, Zhao D Ref: Clinica Chimica Acta, 412:1229, 2011 : PubMed ESTHER: Qi_2011_Clin.Chim.Acta_412_1229 PubMedSearch: Qi 2011 Clin.Chim.Acta 412 1229 PubMedID: 21419757 Abstract OBJECTIVE: We aimed to investigate the polymorphism HindIII of the lipoprotein lipase (LPL) gene to explore whether it had a potential role in susceptibility to type 2 diabetes mellitus (T2DM) among Han Chinese, and whether this effect was influenced by regulating LPL or other risk factors. METHODS: Overall, 654 Han Chinese adults were selected from a community-based cross-sectional study using a stratified cluster random sampling. Genotyping was performed using the PCR-RFLP technique, and the metabolic variables were measured using standard methods. RESULTS: Individuals with the HindIII H-/H- genotype tended to have higher pre-heparin LPL (PrLPL) and lower triglyceride levels but an unexpected higher prevalence of T2DM compared with the H+/H+ genotype carriers. The association between the H-/H- genotype and T2DM risk remained unchanged across all subgroups of lipids/glucose-related RF. In a recessive model, the H-/H- genotype conferred a 2.12-fold increased risk [odds ratio (OR): 3.12; 95% confidence interval (CI): 1.18-8.27] for T2DM after controlling for age and sex, and increased further after additionally adjusting for traditional RFs, and PrLPL (OR=4.45; 95% CI=1.51-13.07). CONCLUSIONS: This study indicated that Chinese adults with the LPL gene HindIII H-/H- genotype had a significantly increased risk of T2DM, even if they had favorable lipid profiles. Title: Synthesis of carbon-11-labeled bivalent beta-carbolines as new PET agents for imaging of cholinesterase in Alzheimer's disease Wang M, Zheng DX, Gao M, Hutchins GD, Zheng QH Ref: Appl Radiat Isot, 69:678, 2011 : PubMed ESTHER: Wang_2011_Appl.Radiat.Isot_69_678 PubMedSearch: Wang 2011 Appl.Radiat.Isot 69 678 PubMedID: 21256758 Abstract Carbon-11-labeled bivalent beta-carbolines, 9,9'-(pentane-1,5-diyl)bis(2-[(11)C]methyl-9H-pyrido[3,4-b]indol-2-ium)iodide ([(11)C]2a), 9,9'-(nonane-1,9-diyl)bis(2-[(11)C]methyl-9H-pyrido[3,4-b]indol-2-ium)iodide ([(11)C]2b), 9,9'-(dodecane-1,12-diyl)bis(2-[(11)C]methyl-9H-pyrido[3,4-b]indol-2-ium)iodide ([(11)C]2c) and 1,9-bis(2-[(11)C]methyl-3,4-dihydro-1H-pyrido[3,4-b]indol-9(2H)-yl)nonane ([(11)C]3), were prepared by N-[(11)C]methylation of their corresponding amine precursors using [(11)C]CH(3)I and isolated by either a simplified solid-phase extraction (SPE) method or HPLC in 40-60% radiochemical yields based on [(11)C]CO(2) and decay corrected to end of bombardment (EOB). The overall synthesis time from EOB was 20-30min, the radiochemical purity was >99%, and the specific activity at end of synthesis (EOS) was 185-370 GBq/umol. Title: Over-expression of human lipoprotein lipase in mouse mammary glands leads to reduction of milk triglyceride and delayed growth of suckling pups Wang Y, Tong J, Li S, Zhang R, Chen L, Zheng M, Wang M, Liu G, Dai Y and Li N <1 more author(s)> Wang Y, Tong J, Li S, Zhang R, Chen L, Zheng M, Wang M, Liu G, Dai Y, Zhao Y, Li N (- 1) Ref: PLoS ONE, 6:e20895, 2011 : PubMed ESTHER: Wang_2011_PLoS.One_6_e20895 PubMedSearch: Wang 2011 PLoS.One 6 e20895 PubMedID: 21698114 Abstract BACKGROUND: The mammary gland is a conserved site of lipoprotein lipase expression across species and lipoprotein lipase attachment to the luminal surface of mammary gland vascular endothelial cells has been implicated in the direction of circulating triglycerides into milk synthesis during lactation. PRINCIPAL FINDINGS: Here we report generation of transgenic mice harboring a human lipoprotein lipase gene driven by a mammary gland-specific promoter. Lipoprotein lipase levels in transgenic milk was raised to 0.16 mg/ml, corresponding to an activity of 8772.95 mU/ml. High lipoprotein lipase activity led to a significant reduction of triglyceride concentration in milk, but other components were largely unchanged. Normal pups fed with transgenic milk showed inferior growth performances compared to those fed with normal milk. CONCLUSION: Our study suggests a possibility to reduce the triglyceride content of cow milk using transgenic technology. Title: Metabolomic analysis of the toxic effects of chronic exposure to low-level dichlorvos on rats using ultra-performance liquid chromatography-mass spectrometry Yang J, Sun X, Feng Z, Hao D, Wang M, Zhao X, Sun C Ref: Toxicol Lett, 206:306, 2011 : PubMed ESTHER: Yang_2011_Toxicol.Lett_206_306 PubMedSearch: Yang 2011 Toxicol.Lett 206 306 PubMedID: 21889581 Abstract The purpose of the current study was to assess the effects of long-term exposure to low levels of DDVP on the biochemical parameters and metabolic profiles of rats. Three different doses (2.4, 7.2, and 21.6 mg/kg body weight/day) of DDVP were administered to rats through their drinking water over 24 weeks. Significant changes in blood cholinesterase, creatinine, urea nitrogen, aspartate aminotransferase, alanine aminotransferase, and albumin concentrations were observed in the middle and high dose groups. Changes in the concentration of some urine metabolites were detected via ultra performance liquid chromatography-mass spectrometry (UPLC-MS). Dimethyl phosphate (DMP), which was exclusively detected in the treated groups, can be an early, sensitive biomarker for DDVP exposure. Moreover, DDVP treatment resulted in an increase in the lactobionic acid, estrone sulfate, and indoxyl sulfic concentrations, and a decrease in citric acid, suberic acid, gulonic acid, urea, creatinine, and uric acid. These results suggest that chronic exposure to low-level DDVP can cause a disturbance in carbohydrate and fatty acid metabolism, the antioxidant system, etc. Therefore, an analysis of the metabolic profiles can contribute to the understanding of the adverse effects of long-term exposure to low doses of DDVP. Title: The Medicago genome provides insight into the evolution of rhizobial symbioses Young ND, Debelle F, Oldroyd GE, Geurts R, Cannon SB, Udvardi MK, Benedito VA, Mayer KF, Gouzy J and Roe BA <114 more author(s)> Young ND, Debelle F, Oldroyd GE, Geurts R, Cannon SB, Udvardi MK, Benedito VA, Mayer KF, Gouzy J, Schoof H, Van de Peer Y, Proost S, Cook DR, Meyers BC, Spannagl M, Cheung F, De Mita S, Krishnakumar V, Gundlach H, Zhou S, Mudge J, Bharti AK, Murray JD, Naoumkina MA, Rosen B, Silverstein KA, Tang H, Rombauts S, Zhao PX, Zhou P, Barbe V, Bardou P, Bechner M, Bellec A, Berger A, Berges H, Bidwell S, Bisseling T, Choisne N, Couloux A, Denny R, Deshpande S, Dai X, Doyle JJ, Dudez AM, Farmer AD, Fouteau S, Franken C, Gibelin C, Gish J, Goldstein S, Gonzalez AJ, Green PJ, Hallab A, Hartog M, Hua A, Humphray SJ, Jeong DH, Jing Y, Jocker A, Kenton SM, Kim DJ, Klee K, Lai H, Lang C, Lin S, Macmil SL, Magdelenat G, Matthews L, McCorrison J, Monaghan EL, Mun JH, Najar FZ, Nicholson C, Noirot C, O'Bleness M, Paule CR, Poulain J, Prion F, Qin B, Qu C, Retzel EF, Riddle C, Sallet E, Samain S, Samson N, Sanders I, Saurat O, Scarpelli C, Schiex T, Segurens B, Severin AJ, Sherrier DJ, Shi R, Sims S, Singer SR, Sinharoy S, Sterck L, Viollet A, Wang BB, Wang K, Wang M, Wang X, Warfsmann J, Weissenbach J, White DD, White JD, Wiley GB, Wincker P, Xing Y, Yang L, Yao Z, Ying F, Zhai J, Zhou L, Zuber A, Denarie J, Dixon RA, May GD, Schwartz DC, Rogers J, Quetier F, Town CD, Roe BA (- 114) Ref: Nature, 480:520, 2011 : PubMed ESTHER: Young_2011_Nature_480_520 PubMedSearch: Young 2011 Nature 480 520 PubMedID: 22089132 Gene_locus related to this paper: medtr-b7fki4, medtr-b7fmi1, medtr-g7itl1, medtr-g7iu67, medtr-g7izm0, medtr-g7j641, medtr-g7jtf8, medtr-g7jtg2, medtr-g7jtg4, medtr-g7kem3, medtr-g7kml3, medtr-g7ksx5, medtr-g7leb3, medtr-q1s5d8, medtr-q1s9m3, medtr-q1t171, medtr-g7k9e1, medtr-g7k9e3, medtr-g7k9e5, medtr-g7k9e8, medtr-g7k9e9, medtr-g7lbp2, medtr-g7lch3, medtr-g7ib94, medtr-g7ljk8, medtr-g7i6w5, medtr-g7kvg4, medtr-g7iam1, medtr-g7iam3, medtr-g7l754, medtr-g7jr41, medtr-g7l4f5, medtr-g7l755, medtr-a0a072vyl4, medtr-g7jwk8, medtr-a0a072vhg0, medtr-a0a072vrv9, medtr-g7kmk5, medtr-a0a072uuf6, medtr-a0a072urp3, medtr-g7zzc3, medtr-g7ie19, medtr-g7kst7, medtr-a0a072u5k5, medtr-a0a072v056, medtr-scp1 Abstract Legumes (Fabaceae or Leguminosae) are unique among cultivated plants for their ability to carry out endosymbiotic nitrogen fixation with rhizobial bacteria, a process that takes place in a specialized structure known as the nodule. Legumes belong to one of the two main groups of eurosids, the Fabidae, which includes most species capable of endosymbiotic nitrogen fixation. Legumes comprise several evolutionary lineages derived from a common ancestor 60 million years ago (Myr ago). Papilionoids are the largest clade, dating nearly to the origin of legumes and containing most cultivated species. Medicago truncatula is a long-established model for the study of legume biology. Here we describe the draft sequence of the M. truncatula euchromatin based on a recently completed BAC assembly supplemented with Illumina shotgun sequence, together capturing approximately 94% of all M. truncatula genes. A whole-genome duplication (WGD) approximately 58 Myr ago had a major role in shaping the M. truncatula genome and thereby contributed to the evolution of endosymbiotic nitrogen fixation. Subsequent to the WGD, the M. truncatula genome experienced higher levels of rearrangement than two other sequenced legumes, Glycine max and Lotus japonicus. M. truncatula is a close relative of alfalfa (Medicago sativa), a widely cultivated crop with limited genomics tools and complex autotetraploid genetics. As such, the M. truncatula genome sequence provides significant opportunities to expand alfalfa's genomic toolbox. Title: Endocannabinoids generated by Ca2+ or by metabotropic glutamate receptors appear to arise from different pools of diacylglycerol lipase Zhang L, Wang M, Bisogno T, Di Marzo V, Alger BE Ref: PLoS ONE, 6:e16305, 2011 : PubMed ESTHER: Zhang_2011_PLoS.One_6_e16305 PubMedSearch: Zhang 2011 PLoS.One 6 e16305 PubMedID: 21305054 Abstract The identity and subcellular sources of endocannabinoids (eCBs) will shape their ability to affect synaptic transmission and, ultimately, behavior. Recent discoveries support the conclusion that 2-arachidonoyl glycerol, 2-AG, is the major signaling eCB, however, some important issues remain open. 2-AG can be synthesized by a mechanism that is strictly Ca(2+)-dependent, and another that is initiated by G-protein coupled receptors (GPCRs) and facilitated by Ca(2+). An important question is whether or not the 2-AG in these cases is synthesized by the same pool of diacylglycerol lipase alpha (DAGLalpha). Using whole-cell voltage-clamp techniques in CA1 pyramidal cells in acute in vitro rat hippocampal slices, we investigated two mechanistically distinct eCB-mediated responses to address this issue. We now report that pharmacological inhibitors of DGLalpha have quantitatively different effects on eCB-mediated responses triggered by different stimuli, suggesting that functional, and perhaps physical, distinctions among pools of DAGLalpha exist. Title: The sequence and de novo assembly of the giant panda genome Li R, Fan W, Tian G, Zhu H, He L, Cai J, Huang Q, Cai Q, Li B and Yang H <103 more author(s)> Li R, Fan W, Tian G, Zhu H, He L, Cai J, Huang Q, Cai Q, Li B, Bai Y, Zhang Z, Zhang Y, Wang W, Li J, Wei F, Li H, Jian M, Nielsen R, Li D, Gu W, Yang Z, Xuan Z, Ryder OA, Leung FC, Zhou Y, Cao J, Sun X, Fu Y, Fang X, Guo X, Wang B, Hou R, Shen F, Mu B, Ni P, Lin R, Qian W, Wang G, Yu C, Nie W, Wang J, Wu Z, Liang H, Min J, Wu Q, Cheng S, Ruan J, Wang M, Shi Z, Wen M, Liu B, Ren X, Zheng H, Dong D, Cook K, Shan G, Zhang H, Kosiol C, Xie X, Lu Z, Li Y, Steiner CC, Lam TT, Lin S, Zhang Q, Li G, Tian J, Gong T, Liu H, Zhang D, Fang L, Ye C, Zhang J, Hu W, Xu A, Ren Y, Zhang G, Bruford MW, Li Q, Ma L, Guo Y, An N, Hu Y, Zheng Y, Shi Y, Li Z, Liu Q, Chen Y, Zhao J, Qu N, Zhao S, Tian F, Wang X, Wang H, Xu L, Liu X, Vinar T, Wang Y, Lam TW, Yiu SM, Liu S, Huang Y, Yang G, Jiang Z, Qin N, Li L, Bolund L, Kristiansen K, Wong GK, Olson M, Zhang X, Li S, Yang H (- 103) Ref: Nature, 463:311, 2010 : PubMed ESTHER: Li_2010_Nature_463_311 PubMedSearch: Li 2010 Nature 463 311 PubMedID: 20010809 Gene_locus related to this paper: ailme-ABH15, ailme-ACHE, ailme-BCHE, ailme-d2gtv3, ailme-d2gty9, ailme-d2gu87, ailme-d2gu97, ailme-d2gve7, ailme-d2gwu1, ailme-d2gx08, ailme-d2gyt0, ailme-d2gz36, ailme-d2gz37, ailme-d2gz38, ailme-d2gz39, ailme-d2gz40, ailme-d2h5r9, ailme-d2h7b7, ailme-d2h9c9, ailme-d2h794, ailme-d2hau7, ailme-d2hau8, ailme-d2hcd9, ailme-d2hdi6, ailme-d2heu6, ailme-d2hga4, ailme-d2hqw5, ailme-d2hs98, ailme-d2hsx4, ailme-d2hti6, ailme-d2htv3, ailme-d2htz6, ailme-d2huc7, ailme-d2hwj8, ailme-d2hwy7, ailme-d2hxm1, ailme-d2hyc8, ailme-d2hyv2, ailme-d2hz11, ailme-d2hza3, ailme-d2hzr4, ailme-d2i1l4, ailme-d2i2g8, ailme-g1l7m3, ailme-g1lu36, ailme-g1m769, ailme-g1mc29, ailme-g1mdj8, ailme-g1mdr5, ailme-g1mfp4, ailme-g1mfx5, ailme-g1lj41, ailme-g1lm28, ailme-g1l3u1, ailme-g1l7l1, ailme-g1m5i3, ailme-g1l2f6, ailme-g1lji5, ailme-g1lqk3, ailme-g1l8s9, ailme-d2h717, ailme-d2h718, ailme-d2h719, ailme-d2h720, ailme-g1m5v0, ailme-g1m5y7, ailme-g1lkt7, ailme-g1l2a1, ailme-g1lsc8, ailme-g1lrp4, ailme-d2gv02, ailme-g1mik5, ailme-g1ljr1, ailme-g1lxw7, ailme-d2h8b5, ailme-d2h2r2, ailme-d2h9w7, ailme-g1meh3, ailme-g1m719 Abstract Using next-generation sequencing technology alone, we have successfully generated and assembled a draft sequence of the giant panda genome. The assembled contigs (2.25 gigabases (Gb)) cover approximately 94% of the whole genome, and the remaining gaps (0.05 Gb) seem to contain carnivore-specific repeats and tandem repeats. Comparisons with the dog and human showed that the panda genome has a lower divergence rate. The assessment of panda genes potentially underlying some of its unique traits indicated that its bamboo diet might be more dependent on its gut microbiome than its own genetic composition. We also identified more than 2.7 million heterozygous single nucleotide polymorphisms in the diploid genome. Our data and analyses provide a foundation for promoting mammalian genetic research, and demonstrate the feasibility for using next-generation sequencing technologies for accurate, cost-effective and rapid de novo assembly of large eukaryotic genomes. Title: Genome sequencing and analysis of the model grass Brachypodium distachyon. Vogel JP, Garvin DF, Mockler TC, Schmutz J, Rokhsar D, Bevan MW, Barry K, Lucas S, Harmon-Smith M and Baxter I <127 more author(s)> Vogel JP, Garvin DF, Mockler TC, Schmutz J, Rokhsar D, Bevan MW, Barry K, Lucas S, Harmon-Smith M, Lail K, Tice H, Grimwood J, McKenzie N, Huo N, Gu YQ, Lazo GR, Anderson OD, You FM, Luo MC, Dvorak J, Wright J, Febrer M, Idziak D, Hasterok R, Lindquist E, Wang M, Fox SE, Priest HD, Filichkin SA, Givan SA, Bryant DW, Chang JH, Wu H, Wu W, Hsia AP, Schnable PS, Kalyanaraman A, Barbazuk B, Michael TP, Hazen SP, Bragg JN, Laudencia-Chingcuanco D, Weng Y, Haberer G, Spannagl M, Mayer K, Rattei T, Mitros T, Lee SJ, Rose JK, Mueller LA, York TL, Wicker T, Buchmann JP, Tanskanen J, Schulman AH, Gundlach H, Bevan M, de Oliveira AC, Maia Lda C, Belknap W, Jiang N, Lai J, Zhu L, Ma J, Sun C, Pritham E, Salse J, Murat F, Abrouk M, Bruggmann R, Messing J, Fahlgren N, Sullivan CM, Carrington JC, Chapman EJ, May GD, Zhai J, Ganssmann M, Gurazada SG, German M, Meyers BC, Green PJ, Tyler L, Wu J, Thomson J, Chen S, Scheller HV, Harholt J, Ulvskov P, Kimbrel JA, Bartley LE, Cao P, Jung KH, Sharma MK, Vega-Sanchez M, Ronald P, Dardick CD, De Bodt S, Verelst W, Inz D, Heese M, Schnittger A, Yang X, Kalluri UC, Tuskan GA, Hua Z, Vierstra RD, Cui Y, Ouyang S, Sun Q, Liu Z, Yilmaz A, Grotewold E, Sibout R, Hematy K, Mouille G, Hofte H, Michael T, Pelloux J, O'Connor D, Schnable J, Rowe S, Harmon F, Cass CL, Sedbrook JC, Byrne ME, Walsh S, Higgins J, Li P, Brutnell T, Unver T, Budak H, Belcram H, Charles M, Chalhoub B, Baxter I (- 127) Ref: Nature, 463:763, 2010 : PubMed ESTHER: Vogel_2010_Nature_463_763 PubMedSearch: Vogel 2010 Nature 463 763 PubMedID: 20148030 Gene_locus related to this paper: bradi-i1grm0, bradi-i1gx82, bradi-i1hb80, bradi-i1hkv6, bradi-i1hpu6, bradi-i1i3e4, bradi-i1i9i0, bradi-i1i435, bradi-i1ix93, bradi-i1gsk6, bradi-i1hk44, bradi-i1hk45, bradi-i1hnk7, bradi-i1hsd5, bradi-i1huy4, bradi-i1huy9, bradi-i1huz0, bradi-i1gxx9, bradi-i1hl25, bradi-i1hcw7, bradi-i1hyv6, bradi-i1hyb5, bradi-i1hvr8, bradi-i1hmu2, bradi-i1hf05, bradi-i1gry7, bradi-i1hf06, bradi-i1i5z8, bradi-i1icy3, bradi-i1j1h3, bradi-i1h1e3, bradi-i1hvr9, bradi-a0a0q3r7i7, bradi-i1i377, bradi-i1hjg5, bradi-i1h3i9, bradi-i1gsg5, bradi-a0a0q3mph9, bradi-i1h682, bradi-a0a0q3lc91 Title: Oxidative damage effects in the copepod Tigriopus japonicus Mori experimentally exposed to nickel Wang M, Wang G Ref: Ecotoxicology, 19:273, 2010 : PubMed ESTHER: Wang_2010_Ecotoxicology_19_273 PubMedSearch: Wang 2010 Ecotoxicology 19 273 PubMedID: 19821026 Abstract Tigriopus japonicus Mori has been recognized as a good model for toxicological testing of marine pollutants. Recently, a large number of genes have been identified from this copepod, and their mRNA expression has been studied independently against exposure to marine pollutants; however, biochemical-response information is relatively scarce. The response of T. japonicus to nickel (Ni) additions was examined under laboratory-controlled conditions in 12 days exposure. Superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione-S-transferase (GST), acetylcholinesterase (AchE), reduced glutathione (GSH), the ratio of reduced to oxidized glutathione (GSH/GSSG) and metallothionein (MT) were analyzed for Ni treatments (0, 0.125, 0.25, 0.75 and 3.0 mg/L) after 1, 4, 7 and 12 days. The thiobarbituric reactive species assay was used to evaluate lipid peroxidation (LPO) level in copepods after exposure. The results showed that Ni remarkably affected the biochemical parameters (SOD, GPx, GST, GSH, and GSH/GSSG) after certain exposure durations. However, the copepod's LPO level was significantly decreased under metal treatments after exposure, hinting that the factors involved in LPO might not significantly depend on the operations and functions in the antioxidant system. Ni exhibited the neurotoxicity to copepods, because its use obviously elevated AchE activity. During exposure, Ni initially displayed an inhibition effect but induced MT synthesis in T. japonicus by day 12, probably being responsible for metal detoxification. Thus, Ni had intervened in the detoxification process and antioxidant system of this copepod, and it could be used as a suitable bioindicator of Ni exposure via measuring SOD, GPx, GST, and MT as biomarkers. Title: Studies on protective effects of human paraoxonases 1 and 3 on atherosclerosis in apolipoprotein E knockout mice Zhang C, Peng W, Wang M, Zhu J, Zang Y, Shi W, Zhang J, Qin J Ref: Gene Therapy, 17:626, 2010 : PubMed ESTHER: Zhang_2010_Gene.Ther_17_626 PubMedSearch: Zhang 2010 Gene.Ther 17 626 PubMedID: 20182519 Abstract Paraoxonase (PON) possesses antiatherogenic potentials, but the distinct functions of PON members in alleviating atherosclerosis are not yet clear. This study aimed to evaluate the protective effects of hPON1 and hPON3 against atherosclerosis, and thereby exploring their synergistic mechanism in atherosclerosis development. We generated the recombinant adenovirus AdPON1 and AdPON3, which were capable of expressing hPON1 and hPON3. After AdPON1 and AdPON3 were injected intravenously into 5-week-old apolipoprotein E knockout mice, abundant hPON1 and hPON3 mRNA expression levels were detected. However, increase in serum lactonase activity was detected only in AdPON1-treated mice. Serum antioxidation and anti-inflammation capabilities in AdPON1-treated mice, reflected by malondialdehyde, total antioxidant capability and tumor necrosis factor-alpha levels, were greatly enhanced, whereas those in AdPON3-treated mice were not significantly affected. Nevertheless, histological analysis revealed that adenovirus-mediated expression of hPON1, hPON3 or both of them reduced atherosclerotic plaque area to a similar extent. Although no synergistic mechanism was detected in reducing arterial lesion size, hPON1 and hPON3 showed synergistic effects on promoting macrophage cholesterol efflux. In conclusion, hPON1 and hPON3 exhibited similar potentials in reducing arterial lesion size, but they exerted antiatherogenic effects in distinct ways. Title: The genome of the cucumber, Cucumis sativus L Huang S, Li R, Zhang Z, Li L, Gu X, Fan W, Lucas WJ, Wang X, Xie B and Du Y <77 more author(s)> Huang S, Li R, Zhang Z, Li L, Gu X, Fan W, Lucas WJ, Wang X, Xie B, Ni P, Ren Y, Zhu H, Li J, Lin K, Jin W, Fei Z, Li G, Staub J, Kilian A, van der Vossen EA, Wu Y, Guo J, He J, Jia Z, Tian G, Lu Y, Ruan J, Qian W, Wang M, Huang Q, Li B, Xuan Z, Cao J, Asan, Wu Z, Zhang J, Cai Q, Bai Y, Zhao B, Han Y, Li Y, Li X, Wang S, Shi Q, Liu S, Cho WK, Kim JY, Xu Y, Heller-Uszynska K, Miao H, Cheng Z, Zhang S, Wu J, Yang Y, Kang H, Li M, Liang H, Ren X, Shi Z, Wen M, Jian M, Yang H, Zhang G, Yang Z, Chen R, Ma L, Liu H, Zhou Y, Zhao J, Fang X, Fang L, Liu D, Zheng H, Zhang Y, Qin N, Li Z, Yang G, Yang S, Bolund L, Kristiansen K, Li S, Zhang X, Wang J, Sun R, Zhang B, Jiang S, Du Y (- 77) Ref: Nat Genet, 41:1275, 2009 : PubMed ESTHER: Huang_2009_Nat.Genet_41_1275 PubMedSearch: Huang 2009 Nat.Genet 41 1275 PubMedID: 19881527 Gene_locus related to this paper: cucsa-a0a0a0ktw5, cucsa-a0a0a0lnt6, cucsa-a0a0a0kpn7, cucsa-a0a0a0lvt9, cucsa-a0a0a0kdx8, cucsa-a0a0a0m228, cucsa-a0a0a0kz31, cucsa-a0a0a0k5t5, cucsa-a0a0a0kfs7, cucsa-a0a0a0kjj7, cucsa-a0a0a0kzs7, cucsa-a0a0a0l0a6, cucsa-a0a0a0l4w4, cucsa-a0a0a0lpz0, cucsa-a0a0a0ls66 Abstract Cucumber is an economically important crop as well as a model system for sex determination studies and plant vascular biology. Here we report the draft genome sequence of Cucumis sativus var. sativus L., assembled using a novel combination of traditional Sanger and next-generation Illumina GA sequencing technologies to obtain 72.2-fold genome coverage. The absence of recent whole-genome duplication, along with the presence of few tandem duplications, explains the small number of genes in the cucumber. Our study establishes that five of the cucumber's seven chromosomes arose from fusions of ten ancestral chromosomes after divergence from Cucumis melo. The sequenced cucumber genome affords insight into traits such as its sex expression, disease resistance, biosynthesis of cucurbitacin and 'fresh green' odor. We also identify 686 gene clusters related to phloem function. The cucumber genome provides a valuable resource for developing elite cultivars and for studying the evolution and function of the plant vascular system. Title: A novel nicotinic acetylcholine receptor subtype in basal forebrain cholinergic neurons with high sensitivity to amyloid peptides Liu Q, Huang Y, Xue F, Simard AR, DeChon J, Li G, Zhang J, Lucero L, Wang M and Wu J <4 more author(s)> Liu Q, Huang Y, Xue F, Simard AR, DeChon J, Li G, Zhang J, Lucero L, Wang M, Sierks M, Hu G, Chang Y, Lukas RJ, Wu J (- 4) Ref: Journal of Neuroscience, 29:918, 2009 : PubMed ESTHER: Liu_2009_J.Neurosci_29_918 PubMedSearch: Liu 2009 J.Neurosci 29 918 PubMedID: 19176801 Abstract Nicotinic acetylcholine receptors (nAChRs) containing alpha7 subunits are thought to assemble as homomers. alpha7-nAChR function has been implicated in learning and memory, and alterations of alpha7-nAChR have been found in patients with Alzheimer's disease (AD). Here we report findings consistent with a novel, naturally occurring nAChR subtype in rodent, basal forebrain cholinergic neurons. In these cells, alpha7 subunits are coexpressed, colocalize, and coassemble with beta2 subunit(s). Compared with homomeric alpha7-nAChRs from ventral tegmental area neurons, functional, presumably heteromeric alpha7beta2-nAChRs on cholinergic neurons freshly dissociated from medial septum/diagonal band (MS/DB) exhibit relatively slow kinetics of whole-cell current responses to nicotinic agonists and are more sensitive to the beta2 subunit-containing nAChR-selective antagonist, dihydro-beta-erythroidine (DHbetaE). Interestingly, presumed, heteromeric alpha7beta2-nAChRs are highly sensitive to functional inhibition by pathologically relevant concentrations of oligomeric, but not monomeric or fibrillar, forms of amyloid beta(1-42) (Abeta(1-42)). Slow whole-cell current kinetics, sensitivity to DHbetaE, and specific antagonism by oligomeric Abeta(1-42) also are characteristics of heteromeric alpha7beta2-nAChRs, but not of homomeric alpha7-nAChRs, heterologously expressed in Xenopus oocytes. Moreover, choline-induced currents have faster kinetics and less sensitivity to Abeta when elicited from MS/DB neurons derived from nAChR beta2 subunit knock-out mice rather than from wild-type mice. The presence of novel, functional, heteromeric alpha7beta2-nAChRs on basal forebrain cholinergic neurons and their high sensitivity to blockade by low concentrations of oligomeric Abeta(1-42) suggests possible mechanisms for deficits in cholinergic signaling that could occur early in the etiopathogenesis of AD and might be targeted by disease therapies. Title: A rapid and efficient method for directed screening of lipase-producing Burkholderia cepacia complex strains with organic solvent tolerance from rhizosphere Shu Z, Lin R, Jiang H, Zhang Y, Wang M, Huang J Ref: J Biosci Bioeng, 107:658, 2009 : PubMed ESTHER: Shu_2009_J.Biosci.Bioeng_107_658 PubMedSearch: Shu 2009 J.Biosci.Bioeng 107 658 PubMedID: 19447345 Abstract Lipase from Burkholderia cepacia strain is one of the most versatile biocatalysts and is used widely in many biotechnological application fields including detergent additives, the resolution of racemic compounds, etc. Based on the known whole genomic information of B. cepacia strain, both ampicillin and kanamycin were added to the TB-T medium to screen B. cepacia complex stains from rhizosphere soil samples. The selected colonies from the modified TB-T medium were then qualitatively determined the ability to produce extracellular lipase on the rhodamine B-olive oil agar plates. A total of 35 lipolytic pseudo-B. cepacia complex strains were isolated and the positive rate of lipolytic bacteria was 65%. Among them, 15 pseudo-B. cepacia complex strains showed tolerance to benzene, n-hexane and n-heptane at concentration of 10% (V/V) and were identified by the recA gene sequence. All of the 14 lipolytic bacteria were identified as B. cepacia complex strains except that the recA gene sequence of one lipolytic bacterium, strain ZMB009, was not obtained. Title: Continuous colorimetric assay for acetylcholinesterase and inhibitor screening with gold nanoparticles Wang M, Gu X, Zhang G, Zhang D, Zhu D Ref: Langmuir, 25:2504, 2009 : PubMed ESTHER: Wang_2009_Langmuir_25_2504 PubMedSearch: Wang 2009 Langmuir 25 2504 PubMedID: 19154124 Abstract We report herein a new colorimetric assay method for acetylcholinesterase (AChE) activity and its inhibitor screening by making use of the following facts: (1) the aggregation of gold nanoparticles (Au-NPs) results in the red-shift of the plasmon absorption due to interparticle plasmon interactions and (2) AChE can catalyze the hydrolysis of acetylthiocholine into thiocholine which can induce the aggregation of Au-NPs. With this convenient method, the activity of AChE with a concentration as low as 0.6 mU/mL can be assayed. Moreover, this assay method is also useful for screening inhibitors of AChE. Given its simplicity and easy-operation, this method may extend to high-throughput screening of AChE inhibitors and relevant drug discovery. Title: Convenient and continuous fluorometric assay method for acetylcholinesterase and inhibitor screening based on the aggregation-induced emission Wang M, Gu X, Zhang G, Zhang D, Zhu D Ref: Analytical Chemistry, 81:4444, 2009 : PubMed ESTHER: Wang_2009_Anal.Chem_81_4444 PubMedSearch: Wang 2009 Anal.Chem 81 4444 PubMedID: 19374428 Abstract A new convenient and continuous fluorometric assay method for acetylcholinesterase (AChE) and its inhibitor screening is successfully established with the ensemble of 1 [a TPE (tetraphenylethylene) compound with two sulfonate (-SO(3)(-)) units] and myristoylcholine (an amphiphilic compound as a good substrate of AChE). This new assay method is designed by making use of the aggregation-induced emission (AIE) feature of TPE compounds. Both dynamic light scattering (DLS) and fluorescence confocal microscopic measurements indicated the formation of aggregation complex for the ensemble of 1 and myristoylcholine and further disassembly of the aggregation complex after introducing AChE. The analysis for AChE can be carried out continuously, and AChE with concentration as low as 0.5 U/mL can be assayed. The results also clearly demonstrate the usefulness of this convenient assay method for kinetic study of AChE-catalyzed myristoylcholine hydrolysis and screening inhibitors of AChE. Given its simplicity and easy operation, this method may extend to high-throughput screening of AChE inhibitors and relevant Alzheimer's disease (AD) drug discovery. Title: Structural basis and enzymatic mechanism of the biosynthesis of C9- from C10-monoterpenoid indole alkaloids Yang L, Hill M, Wang M, Panjikar S, Stockigt J Ref: Angew Chem Int Ed Engl, 48:5211, 2009 : PubMed ESTHER: Yang_2009_Angew.Chem.Int.Ed.Engl_48_5211 PubMedSearch: Yang 2009 Angew.Chem.Int.Ed.Engl 48 5211 PubMedID: 19496101 Gene_locus related to this paper: rause-pnae Inhibitor(s) related to this paper: 16-epi-Vellosimine Abstract Cutting carbons: The three-dimensional structure of polyneuridine aldehyde esterase (PNAE) gives insight into the enzymatic mechanism of the biosynthesis of C(9)- from C(10)-monoterpenoid indole alkaloids (see scheme). PNAE is a very substrate-specific serine esterase. It harbors the catalytic triad S87-D216-H244, and is a new member of the alpha/beta-fold hydrolase superfamily. Its novel function leads to the diversification of alkaloid structures. Title: Immobilization of acetylcholinesterase based on the controllable adsorption of carbon nanotubes onto an alkanethiol monolayer for carbaryl sensing Du D, Wang M, Cai J, Tao Y, Tu H, Zhang A Ref: Analyst, 133:1790, 2008 : PubMed ESTHER: Du_2008_Analyst_133_1790 PubMedSearch: Du 2008 Analyst 133 1790 PubMedID: 19082085 Abstract A simple method to immobilize acetylcholinesterase (AChE) on the controllable adsorption of multiwalled carbon nanotubes (MWCNTs) onto an alkanethiol self-assembled monolayer (C(6)H(13)SH SAM) modified Au electrode was proposed. The surface coverage of the MWCNTs was readily controlled by adjusting the immersion time for the adsorption of the MWCNTs. Atomic force microscopy (AFM), cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) were used to monitor these controllable fabrication processes. The MWCNTs adsorbed onto the SAM surface substantially restores the heterogeneous electron transfer between the bare Au electrode and the redox system in the solution phase that is almost totally blocked by the SAM of C(6)H(13)SH, and as a result, the prepared MWCNT-SAM-modified electrode possesses good electrode reactivity without a remarkable barrier to heterogeneous electron transfer. Due to the inherent conductive properties of MWCNTs, the immobilized AChE exhibited high affinity to its substrate and produced a detectable and fast response. Thus, a sensitive, efficient and stable amperometric sensor for quantitative determination of carbaryl was developed. The inhibition of carbaryl was proportional to its concentration ranging from 0.001 to 1 microg mL(-1) and 2 to 15 microg mL(-1), with a detection limit of 0.6 ng mL(-1). The determination of carbaryl in garlic samples showed acceptable accuracy, which provided a new promising tool for analysis of enzyme inhibitors. Title: Facile synthesis of new carbon-11 labeled conformationally restricted rivastigmine analogues as potential PET agents for imaging AChE and BChE enzymes Wang M, Wang JQ, Gao M, Zheng QH Ref: Appl Radiat Isot, 66:506, 2008 : PubMed ESTHER: Wang_2008_Appl.Radiat.Isot_66_506 PubMedSearch: Wang 2008 Appl.Radiat.Isot 66 506 PubMedID: 18155915 Abstract Rivastigmine is a newer-generation inhibitor with a dual inhibitory action on both acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes, and is used for the treatment of AChE- and BChE-related diseases such as brain Alzheimer's disease and cardiovascular disease. New carbon-11 labeled conformationally restricted rivastigmine analogues radiolabeled quaternary ammonium triflate salts, (3aR,9bS)-1-[(11)C]methyl-1-methyl-6-(methylcarbamoyloxy)-2,3,3a,4,5,9b-hexahydro -1H-benzo[g]indolium triflate ([(11)C]8) and (3aR,9bS)-1-[(11)C]methyl-1-methyl-6-(heptylcarbamoyloxy)-2,3,3a,4,5,9b-hexahydro -1H-benzo[g]indolium triflate ([(11)C]9), were designed and synthesized as potential positron emission tomography (PET) agents for imaging AChE and BChE enzymes. The appropriate precursors were labeled with [(11)C]CH(3)OTf through N-[(11)C]methylation, and the target tracers were isolated by solid-phase extraction (SPE) using a cation-exchange CM Sep-Pak cartridge in 40-50% radiochemical yields decay corrected to end of bombardment (EOB), 15-20 min overall synthesis time, and 148-222 GBq/micromol specific activity at EOB. Title: The genome of a lepidopteran model insect, the silkworm Bombyx mori Xia Q, Wang J, Zhou Z, Li R, Fan W, Cheng D, Cheng T, Qin J, Duana J and Morishita S <88 more author(s)> Xia Q, Wang J, Zhou Z, Li R, Fan W, Cheng D, Cheng T, Qin J, Duana J, Xu H, Li Q, Li N, Wang M, Dai F, Liu C, Lin Y, Zhao P, Zhang H, Liu S, Zha X, Li C, Zhao A, Pan M, Pan G, Shen Y, Gao Z, Wang Z, Wang G, Wu Z, Hou Y, Chai C, Yu Q, He N, Zhang Z, Li S, Yang H, Lu C, Xiang Z, Mita K, Kasahara M, Nakatani Y, Yamamoto K, Abe H, Ahsan B, Daimoni T, Doi K, Fujii T, Fujiwara H, Fujiyama A, Futahashi R, Hashimotol S, Ishibashi J, Iwami M, Kadono-Okuda K, Kanamori H, Kataoka H, Katsuma S, Kawaoka S, Kawasaki H, Kohara Y, Kozaki T, Kuroshu RM, Kuwazaki S, Matsushima K, Minami H, Nagayasu Y, Nakagawa T, Narukawa J, Nohata J, Ohishi K, Ono Y, Osanai-Futahashi M, Ozaki K, Qu W, Roller L, Sasaki S, Sasaki T, Seino A, Shimomura M, Shin-I T, Shinoda T, Shiotsuki T, Suetsugu Y, Sugano S, Suwa M, Suzuki Y, Takiya S, Tamura T, Tanaka H, Tanaka Y, Touhara K, Yamada T, Yamakawa M, Yamanaka N, Yoshikawa H, Zhong YS, Shimada T, Morishita S (- 88) Ref: Insect Biochemistry & Molecular Biology, 38:1036, 2008 : PubMed ESTHER: Xia_2008_Insect.Biochem.Mol.Biol_38_1036 PubMedSearch: Xia 2008 Insect.Biochem.Mol.Biol 38 1036 PubMedID: 19121390 Gene_locus related to this paper: bommo-a0mnw6, bommo-a1yw85, bommo-a9ls22, bommo-ACHE1, bommo-ACHE2, bommo-b0fgv8, bommo-b1q137, bommo-b1q139, bommo-b1q140, bommo-b1q141, bommo-b2zdz0, bommo-b3gef6, bommo-b3gef7, bommo-b3gs55, bommo-b3gs56, bommo-d2ktu3, bommo-d2ktu5, bommo-d9ile0, bommo-e1cga5, bommo-e1cga6, bommo-g8fpz6, bommo-h9iu43, bommo-h9iu46, bommo-h9iu47.1, bommo-h9iu47.2, bommo-h9iue5, bommo-h9ivg2, bommo-h9iwj7, bommo-h9iwj8, bommo-h9ix58, bommo-h9ixi1.1, bommo-h9ixi1.2, bommo-h9iy47, bommo-h9izw1, bommo-h9j0s4, bommo-h9j1y0, bommo-h9j3r0, bommo-h9j3w6, bommo-h9j3w7, bommo-h9j5t0, bommo-h9j8g3, bommo-h9j9k9, bommo-h9j066, bommo-h9j067, bommo-h9j593, bommo-h9j594, bommo-h9j990, bommo-h9jde8, bommo-h9jde9, bommo-h9jdf0, bommo-h9jds4, bommo-h9jle7, bommo-h9jn83, bommo-h9jn85, bommo-h9jrg2, bommo-h9jyh9, bommo-JHE, bommo-m1rmh6, bommo-q1hq05, bommo-q4tte1, bommo-h9j592, bommo-h9j604, bommo-h9jpm8, bommo-h9iss4, bommo-h9j2c7 Abstract Bombyx mori, the domesticated silkworm, is a major insect model for research, and the first lepidopteran for which draft genome sequences became available in 2004. Two independent data sets from whole-genome shotgun sequencing were merged and assembled together with newly obtained fosmid- and BAC-end sequences. The remarkably improved new assembly is presented here. The 8.5-fold sequence coverage of an estimated 432 Mb genome was assembled into scaffolds with an N50 size of approximately 3.7 Mb; the largest scaffold was 14.5 million base pairs. With help of a high-density SNP linkage map, we anchored 87% of the scaffold sequences to all 28 chromosomes. A particular feature was the high repetitive sequence content estimated to be 43.6% and that consisted mainly of transposable elements. We predicted 14,623 gene models based on a GLEAN-based algorithm, a more accurate prediction than the previous gene models for this species. Over three thousand silkworm genes have no homologs in other insect or vertebrate genomes. Some insights into gene evolution and into characteristic biological processes are presented here and in other papers in this issue. The massive silk production correlates with the existence of specific tRNA clusters, and of several sericin genes assembled in a cluster. The silkworm's adaptation to feeding on mulberry leaves, which contain toxic alkaloids, is likely linked to the presence of new-type sucrase genes, apparently acquired from bacteria. The silkworm genome also revealed the cascade of genes involved in the juvenile hormone biosynthesis pathway, and a large number of cuticular protein genes. Title: Antiobesity properties of two African plants (Afromomum meleguetta and Spilanthes acmella) by pancreatic lipase inhibition Ekanem AP, Wang M, Simon JE, Moreno DA Ref: Phytother Res, 21:1253, 2007 : PubMed ESTHER: Ekanem_2007_Phytother.Res_21_1253 PubMedSearch: Ekanem 2007 Phytother.Res 21 1253 PubMedID: 17705140 Abstract Ethanol extracts of seeds of Afromomum meleguetta and flower buds of Splilanthes acmella presented pancreatic lipase inhibitory activities in a concentration related manner under in vitro conditions. The two plants were extracted with 70% ethanol by sonication, fractionated on silica gel and tested at concentrations in the range 0.75-2.0 mg/mL. Lipase inhibitory activities of 90% and 40% were observed in A. meleguetta and S. acmella, respectively. The two plants have potentials as candidates for weight reduction and obesity control. Title: Crystal structure of homoserine O-acetyltransferase from Leptospira interrogans Wang M, Liu L, Wang Y, Wei Z, Zhang P, Li Y, Jiang X, Xu H, Gong W Ref: Biochemical & Biophysical Research Communications, 363:1050, 2007 : PubMed ESTHER: Wang_2007_Biochem.Biophys.Res.Commun_363_1050 PubMedSearch: Wang 2007 Biochem.Biophys.Res.Commun 363 1050 PubMedID: 17927957 Gene_locus related to this paper: lepin-METX Abstract Homoserine O-acetyltransferase (HTA, EC 2.3.1.31) initiates methionine biosynthesis pathway by catalyzing the transfer of acetyl group from acetyl-CoA to homoserine. This study reports the crystal structure of HTA from Leptospira interrogans determined at 2.2A resolution using selenomethionyl single-wavelength anomalous diffraction method. HTA is modular and consists of two structurally distinct domains--a core alpha/beta domain containing the catalytic site and a helical bundle called the lid domain. Overall, the structure fold belongs to alpha/beta hydrolase superfamily with the characteristic 'catalytic triad' residues in the active site. Detailed structure analysis showed that the catalytic histidine and serine are both present in two conformations, which may be involved in the catalytic mechanism for acetyl transfer. Title: Small-molecule compounds that modulate lipolysis in adipose tissue: targeting strategies and molecular classes Wang M, Fotsch C Ref: Chemical Biology, 13:1019, 2006 : PubMed ESTHER: Wang_2006_Chem.Biol_13_1019 PubMedSearch: Wang 2006 Chem.Biol 13 1019 PubMedID: 17052606 Abstract Lipolysis is an important pathway in maintaining energy homeostasis through the degradation of triglycerides in adipose tissue and the release of fatty acids into the circulation as an energy source. However, an elevated level of circulating fatty acids leads to unfavorable metabolic effects such as insulin resistance and dyslipidemia. Cell surface receptors and intracellular components of the lipolytic pathway have been targeted to develop antilipolytic agents, among which are G-protein-coupled receptor agonists and lipase inhibitors. In addition, molecules that stimulate lipolysis have been tested in clinical trials as a treatment for obesity. Together, these molecules represent a diverse group of regulators for this pathway. This review will discuss strategies to target lipolysis and the major issues with representative small-molecule modulators of this pathway. Title: In vitro SAR of (5-(2H)-isoxazolonyl) ureas, potent inhibitors of hormone-sensitive lipase Lowe DB, Magnuson S, Qi N, Campbell AM, Cook J, Hong Z, Wang M, Rodriguez M, Achebe F and Clairmont KB <7 more author(s)> Lowe DB, Magnuson S, Qi N, Campbell AM, Cook J, Hong Z, Wang M, Rodriguez M, Achebe F, Kluender H, Wong WC, Bullock WH, Salhanick AI, Witman-Jones T, Bowling ME, Keiper C, Clairmont KB (- 7) Ref: Bioorganic & Medicinal Chemistry Lett, 14:3155, 2004 : PubMed ESTHER: Lowe_2004_Bioorg.Med.Chem.Lett_14_3155 PubMedSearch: Lowe 2004 Bioorg.Med.Chem.Lett 14 3155 PubMedID: 15149665 Inhibitor(s) related to this paper: BAY Abstract A series of (5-(2H)-isoxazolonyl) ureas were developed as nanomolar inhibitors of hormone-sensitive lipase, an enzyme of potential importance in the treatment of diabetes. Title: NDRG1 is necessary for p53-dependent apoptosis Stein S, Thomas EK, Herzog B, Westfall MD, Rocheleau JV, Jackson RS, 2nd, Wang M, Liang P Ref: Journal of Biological Chemistry, 279:48930, 2004 : PubMed ESTHER: Stein_2004_J.Biol.Chem_279_48930 PubMedSearch: Stein 2004 J.Biol.Chem 279 48930 PubMedID: 15377670 Gene_locus related to this paper: human-NDRG1 Abstract Although a number of target genes for the tumor suppressor p53 have been described, the mechanism of p53-dependent apoptosis is incompletely understood. Thus, it is essential to identify and characterize additional target genes that could mediate apoptosis. In the study reported here, we isolated a p53-regulated gene named NDRG1 (N-Myc down-regulated gene 1). Its expression is induced by DNA damage in a p53-dependent fashion. The promoter region of the NDRG1 gene contains a p53 binding site that confers p53-dependent transcriptional activation via a heterologous reporter. RNA interference and inducible gene expression approaches suggest that NDRG1 is necessary but not sufficient for p53-mediated caspase activation and apoptosis. This report further supports the notion that p53 controls a network of genes that are required for its apoptotic function. Title: A complete gene cluster from Streptomyces nanchangensis NS3226 encoding biosynthesis of the polyether ionophore nanchangmycin Sun Y, Zhou X, Dong H, Tu G, Wang M, Wang B, Deng Z Ref: Chemical Biology, 10:431, 2003 : PubMed ESTHER: Sun_2003_Chem.Biol_10_431 PubMedSearch: Sun 2003 Chem.Biol 10 431 PubMedID: 12770825 Gene_locus related to this paper: strna-NANE Abstract The PKS genes for biosynthesis of the polyether nanchangmycin are organized to encode two sets of proteins (six and seven ORFs, respectively), but are separated by independent ORFs that encode an epimerase, epoxidase, and epoxide hydrolase, and, notably, an independent ACP. One of the PKS modules lacks a corresponding ACP. We propose that the process of oxidative cyclization to form the polyether structure occurs when the polyketide chain is still anchored on the independent ACP before release. 4-O-methyl-L-rhodinose biosynthesis and its transglycosylation involve four putative genes, and regulation of nanchangmycin biosynthesis seems to involve activation as well as repression. In-frame deletion of a KR6 domain generated the nanchangmycin aglycone with loss of 4-O-methyl-L-rhodinose and antibacterial activity, in agreement with the assignments of the PKS domains catalyzing specific biosynthetic steps. Title: The genome sequence of the malaria mosquito Anopheles gambiae Holt RA, Subramanian GM, Halpern A, Sutton GG, Charlab R, Nusskern DR, Wincker P, Clark AG, Ribeiro JM and Hoffman SL <113 more author(s)> Holt RA, Subramanian GM, Halpern A, Sutton GG, Charlab R, Nusskern DR, Wincker P, Clark AG, Ribeiro JM, Wides R, Salzberg SL, Loftus B, Yandell M, Majoros WH, Rusch DB, Lai Z, Kraft CL, Abril JF, Anthouard V, Arensburger P, Atkinson PW, Baden H, de Berardinis V, Baldwin D, Benes V, Biedler J, Blass C, Bolanos R, Boscus D, Barnstead M, Cai S, Center A, Chaturverdi K, Christophides GK, Chrystal MA, Clamp M, Cravchik A, Curwen V, Dana A, Delcher A, Dew I, Evans CA, Flanigan M, Grundschober-Freimoser A, Friedli L, Gu Z, Guan P, Guigo R, Hillenmeyer ME, Hladun SL, Hogan JR, Hong YS, Hoover J, Jaillon O, Ke Z, Kodira C, Kokoza E, Koutsos A, Letunic I, Levitsky A, Liang Y, Lin JJ, Lobo NF, Lopez JR, Malek JA, McIntosh TC, Meister S, Miller J, Mobarry C, Mongin E, Murphy SD, O'Brochta DA, Pfannkoch C, Qi R, Regier MA, Remington K, Shao H, Sharakhova MV, Sitter CD, Shetty J, Smith TJ, Strong R, Sun J, Thomasova D, Ton LQ, Topalis P, Tu Z, Unger MF, Walenz B, Wang A, Wang J, Wang M, Wang X, Woodford KJ, Wortman JR, Wu M, Yao A, Zdobnov EM, Zhang H, Zhao Q, Zhao S, Zhu SC, Zhimulev I, Coluzzi M, della Torre A, Roth CW, Louis C, Kalush F, Mural RJ, Myers EW, Adams MD, Smith HO, Broder S, Gardner MJ, Fraser CM, Birney E, Bork P, Brey PT, Venter JC, Weissenbach J, Kafatos FC, Collins FH, Hoffman SL (- 113) Ref: Science, 298:129, 2002 : PubMed ESTHER: Holt_2002_Science_298_129 PubMedSearch: Holt 2002 Science 298 129 PubMedID: 12364791 Gene_locus related to this paper: anoga-a0nb77, anoga-a0nbp6, anoga-a0neb7, anoga-a0nei9, anoga-a0nej0, anoga-a0ngj1, anoga-a7ut12, anoga-a7uuz9, anoga-ACHE1, anoga-ACHE2, anoga-agCG44620, anoga-agCG44666, anoga-agCG45273, anoga-agCG45279, anoga-agCG45511, anoga-agCG46741, anoga-agCG47651, anoga-agCG47655, anoga-agCG47661, anoga-agCG47690, anoga-agCG48797, anoga-AGCG49362, anoga-agCG49462, anoga-agCG49870, anoga-agCG49872, anoga-agCG49876, anoga-agCG50851, anoga-agCG51879, anoga-agCG52383, anoga-agCG54954, anoga-AGCG55021, anoga-agCG55401, anoga-agCG55408, anoga-agCG56978, anoga-ebiG239, anoga-ebiG2660, anoga-ebiG5718, anoga-ebiG5974, anoga-ebiG8504, anoga-ebiG8742, anoga-glita, anoga-nrtac, anoga-q5tpv0, anoga-Q5TVS6, anoga-q7pm39, anoga-q7ppw9, anoga-q7pq17, anoga-Q7PQT0, anoga-q7q8m4, anoga-q7q626, anoga-q7qa14, anoga-q7qa52, anoga-q7qal7, anoga-q7qbj0, anoga-f5hl20, anoga-q7qkh2, anoga-a0a1s4h1y7, anoga-q7q887 Abstract Anopheles gambiae is the principal vector of malaria, a disease that afflicts more than 500 million people and causes more than 1 million deaths each year. Tenfold shotgun sequence coverage was obtained from the PEST strain of A. gambiae and assembled into scaffolds that span 278 million base pairs. A total of 91% of the genome was organized in 303 scaffolds; the largest scaffold was 23.1 million base pairs. There was substantial genetic variation within this strain, and the apparent existence of two haplotypes of approximately equal frequency ("dual haplotypes") in a substantial fraction of the genome likely reflects the outbred nature of the PEST strain. The sequence produced a conservative inference of more than 400,000 single-nucleotide polymorphisms that showed a markedly bimodal density distribution. Analysis of the genome sequence revealed strong evidence for about 14,000 protein-encoding transcripts. Prominent expansions in specific families of proteins likely involved in cell adhesion and immunity were noted. An expressed sequence tag analysis of genes regulated by blood feeding provided insights into the physiological adaptations of a hematophagous insect. Title: A comparison of whole-genome shotgun-derived mouse chromosome 16 and the human genome Mural RJ, Adams MD, Myers EW, Smith HO, Miklos GL, Wides R, Halpern A, Li PW, Sutton GG and Stephenson LD <169 more author(s)> Mural RJ, Adams MD, Myers EW, Smith HO, Miklos GL, Wides R, Halpern A, Li PW, Sutton GG, Nadeau J, Salzberg SL, Holt RA, Kodira CD, Lu F, Chen L, Deng Z, Evangelista CC, Gan W, Heiman TJ, Li J, Li Z, Merkulov GV, Milshina NV, Naik AK, Qi R, Shue BC, Wang A, Wang J, Wang X, Yan X, Ye J, Yooseph S, Zhao Q, Zheng L, Zhu SC, Biddick K, Bolanos R, Delcher AL, Dew IM, Fasulo D, Flanigan MJ, Huson DH, Kravitz SA, Miller JR, Mobarry CM, Reinert K, Remington KA, Zhang Q, Zheng XH, Nusskern DR, Lai Z, Lei Y, Zhong W, Yao A, Guan P, Ji RR, Gu Z, Wang ZY, Zhong F, Xiao C, Chiang CC, Yandell M, Wortman JR, Amanatides PG, Hladun SL, Pratts EC, Johnson JE, Dodson KL, Woodford KJ, Evans CA, Gropman B, Rusch DB, Venter E, Wang M, Smith TJ, Houck JT, Tompkins DE, Haynes C, Jacob D, Chin SH, Allen DR, Dahlke CE, Sanders R, Li K, Liu X, Levitsky AA, Majoros WH, Chen Q, Xia AC, Lopez JR, Donnelly MT, Newman MH, Glodek A, Kraft CL, Nodell M, Ali F, An HJ, Baldwin-Pitts D, Beeson KY, Cai S, Carnes M, Carver A, Caulk PM, Center A, Chen YH, Cheng ML, Coyne MD, Crowder M, Danaher S, Davenport LB, Desilets R, Dietz SM, Doup L, Dullaghan P, Ferriera S, Fosler CR, Gire HC, Gluecksmann A, Gocayne JD, Gray J, Hart B, Haynes J, Hoover J, Howland T, Ibegwam C, Jalali M, Johns D, Kline L, Ma DS, MacCawley S, Magoon A, Mann F, May D, McIntosh TC, Mehta S, Moy L, Moy MC, Murphy BJ, Murphy SD, Nelson KA, Nuri Z, Parker KA, Prudhomme AC, Puri VN, Qureshi H, Raley JC, Reardon MS, Regier MA, Rogers YH, Romblad DL, Schutz J, Scott JL, Scott R, Sitter CD, Smallwood M, Sprague AC, Stewart E, Strong RV, Suh E, Sylvester K, Thomas R, Tint NN, Tsonis C, Wang G, Williams MS, Williams SM, Windsor SM, Wolfe K, Wu MM, Zaveri J, Chaturvedi K, Gabrielian AE, Ke Z, Sun J, Subramanian G, Venter JC, Pfannkoch CM, Barnstead M, Stephenson LD (- 169) Ref: Science, 296:1661, 2002 : PubMed ESTHER: Mural_2002_Science_296_1661 PubMedSearch: Mural 2002 Science 296 1661 PubMedID: 12040188 Gene_locus related to this paper: mouse-ABH15, mouse-Ces3b, mouse-Ces4a, mouse-dpp4, mouse-FAP, mouse-Lipg, mouse-Q8C1A9, mouse-rbbp9, mouse-SERHL, mouse-SPG21, mouse-w4vsp6 Abstract The high degree of similarity between the mouse and human genomes is demonstrated through analysis of the sequence of mouse chromosome 16 (Mmu 16), which was obtained as part of a whole-genome shotgun assembly of the mouse genome. The mouse genome is about 10% smaller than the human genome, owing to a lower repetitive DNA content. Comparison of the structure and protein-coding potential of Mmu 16 with that of the homologous segments of the human genome identifies regions of conserved synteny with human chromosomes (Hsa) 3, 8, 12, 16, 21, and 22. Gene content and order are highly conserved between Mmu 16 and the syntenic blocks of the human genome. Of the 731 predicted genes on Mmu 16, 509 align with orthologs on the corresponding portions of the human genome, 44 are likely paralogous to these genes, and 164 genes have homologs elsewhere in the human genome; there are 14 genes for which we could find no human counterpart. 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: Histamine H(3) receptor-mediated inhibition of endogenous acetylcholine release from the isolated, vascularly perfused rat stomach Yokotani K, Murakami Y, Okada S, Wang M, Nakamura K Ref: European Journal of Pharmacology, 392:23, 2000 : PubMed ESTHER: Yokotani_2000_Eur.J.Pharmacol_392_23 PubMedSearch: Yokotani 2000 Eur.J.Pharmacol 392 23 PubMedID: 10748268 Abstract We studied the effects of histamine H(3) receptor ligands on the release of endogenous acetylcholine from the isolated, vascularly perfused rat stomach. The stomach was perfused via the celiac artery with modified Krebs-Ringer solution containing physostigmine. Released acetylcholine from the portal vein was electrochemically measured using high-performance liquid chromatography and an enzyme system. Vagus nerves were electrically stimulated twice for 2 min (0.5 or 2.5 Hz). Acetylcholine release evoked at 2.5 Hz was slightly inhibited by histamine and effectively potentiated by thioperamide, a histamine H(3) receptor antagonist. Acetylcholine release evoked at 0.5 Hz in the presence of atropine was not influenced by thioperamide, but effectively inhibited by histamine, R-alpha-methylhistamine or imetit, histamine H(3) receptor agonists. These inhibitory effects were abolished by thioperamide or pertussis toxin. These results suggest that histamine attenuates acetylcholine release from vagus nerves through histamine H(3) receptor-mediated and pertussis toxin-sensitive mechanisms in the rat stomach. | |||||||
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