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Author Report for: Wu S

Title: Alteration of gut microbiota after heat acclimation may reduce organ damage by regulating immune factors during heat stress
Liu S, Wen D, Feng C, Yu C, Gu Z, Wang L, Zhang Z, Li W, Wu S and Xue L <3 more author(s)> Liu S, Wen D, Feng C, Yu C, Gu Z, Wang L, Zhang Z, Li W, Wu S, Liu Y, Duan C, Zhuang R, Xue L (- 3)
Ref: Front Microbiol, 14:1114233, 2023 : PubMed
Abstract


ESTHER: Liu_2023_Front.Microbiol_14_1114233
PubMedSearch: Liu 2023 Front.Microbiol 14 1114233
PubMedID: 36910226

Abstract

INTRODUCTION: Heat-related illnesses can lead to morbidity, which are anticipated to increase frequency with predictions of increased global surface temperatures and extreme weather events. Although heat acclimation training (HAT) could prevent heat-related diseases, the mechanisms underlying HAT-promoting beneficial changes in organ function, immunity, and gut microbes remain unclear. METHODS: In the current study, we recruited 32 healthy young soldiers and randomly divided them into 4 teams to conduct HATs for 10 days: the equipment-assisted training team at high temperature (HE); the equipment-assisted training team under normal hot weather (NE); the high-intensity interval training team at high temperature (HIIT), and the control team without training. A standard heat tolerance test (HTT) was conducted before (HTT-1st) and after (HTT-2nd) the training to judge whether the participants met the heat acclimation (HA) criteria. RESULTS: We found that the participants in both HE and NE teams had significantly higher acclimation rates (HA/total population) than whom in the HIIT team. The effects of HAT on the participants of the HE team outperformed that of the NE team. In the HA group, the differences of physiological indicators and plasma organ damage biomarkers (ALT, ALP, creatinine, LDH, alpha-HBDH and cholinesterase) before and after HTT-2nd were significantly reduced to those during HTT-1st, but the differences of immune factors (IL-10, IL-6, CXCL2, CCL4, CCL5, and CCL11) elevated. The composition, metabolism, and pathogenicity of gut microbes changed significantly, with a decreased proportion of potentially pathogenic bacteria (Escherichia-Shigella and Lactococcus) and increased probiotics (Dorea, Blautia, and Lactobacillus) in the HA group. Training for a longer time in a high temperature and humidity showed beneficial effects for intestinal probiotics. CONCLUSION: These findings revealed that pathogenic gut bacteria decrease while probiotics increase following HA, with elevated immune factors and reduced organ damage during heat stress, thereby improving the body's heat adaption.



        

Title: Salicylic acid attenuates brassinosteroid signaling via protein de-S-acylation
Liu X, Chen Z, Huang L, Ouyang Y, Wang Z, Wu S, Ye W, Yu B, Zhang Y and Lai J <1 more author(s)> Liu X, Chen Z, Huang L, Ouyang Y, Wang Z, Wu S, Ye W, Yu B, Zhang Y, Yang C, Lai J (- 1)
Ref: EMBO j, :e112998, 2023 : PubMed
Abstract


ESTHER: Liu_2023_EMBO.J__e112998
PubMedSearch: Liu 2023 EMBO.J e112998
PubMedID: 37211868
Gene_locus related to this paper: arath-AT5G20520

Abstract

Brassinosteroids (BRs) are important plant hormones involved in many aspects of development. Here, we show that BRASSINOSTEROID SIGNALING KINASEs (BSKs), key components of the BR pathway, are precisely controlled via de-S-acylation mediated by the defense hormone salicylic acid (SA). Most Arabidopsis BSK members are substrates of S-acylation, a reversible protein lipidation that is essential for their membrane localization and physiological function. We establish that SA interferes with the plasma membrane localization and function of BSKs by decreasing their S-acylation levels, identifying ABAPT11 (ALPHA/BETA HYDROLASE DOMAIN-CONTAINING PROTEIN 17-LIKE ACYL PROTEIN THIOESTERASE 11) as an enzyme whose expression is quickly induced by SA. ABAPT11 de-S-acylates most BSK family members, thus integrating BR and SA signaling for the control of plant development. In summary, we show that BSK-mediated BR signaling is regulated by SA-induced protein de-S-acylation, which improves our understanding of the function of protein modifications in plant hormone cross talk.



        

Title: Serum alkaline phosphatase was independently associated with depression in patients with cerebrovascular disease
Tao X, Yang C, He J, Liu Q, Wu S, Tang W, Wang J
Ref: Front Psychiatry, 14:1184673, 2023 : PubMed
Abstract


ESTHER: Tao_2023_Front.Psychiatry_14_1184673
PubMedSearch: Tao 2023 Front.Psychiatry 14 1184673
PubMedID: 37469359

Abstract

BACKGROUND AND PURPOSE: Blood markers have important value in the diagnosis of depressive disorders. Serum alkaline phosphatase (ALP) not only predicts stroke recurrence and poor functional prognosis in cerebrovascular disease (CVD) patients but also increases significantly in middle-aged women with depression. Thus, it has not been reported whether serum ALP is associated with the development of depression and/or vascular depression (VDe) in CVD patients. METHODS: This was a cross-sectional study of 353 CVD patients (stroke patients, n = 291; cerebral small vessel disease (CSVD) patients, n = 62). Baseline demographic information, fasting blood markers (such as blood counts, liver function, kidney function and lipids), and brain CT/MRI scans were collected. CVD patients were divided into non-depression, suspected vascular depression (SVD), and positive vascular depression (PVD) groups according to their Hamilton Rating Scale for Depression (HAMD) scores. Univariate analysis of baseline data, blood markers, and the prevalence of lesions (> 1.5 cm) was performed. Subsequently, the diagnostic performance of the univariate and combined variables for SVD and PVD was analyzed using binary logistic regression. The diagnostic value of the multivariate model for VDe was analyzed by ordinal logistic regression. RESULTS: (1) Serum ALP (p = 0.003) and hypersensitive C-reactive protein (hs-CRP, p = 0.001) concentrations increased as HAMD scores increased, and the prevalence of brain atrophy (p = 0.016) and lesions in the basal ganglia (p = 0.001) and parietal (p = 0.001), temporal (p = 0.002), and frontal lobes (p = 0.003) also increased, whereas the concentrations of hemoglobin (Hb, p = 0.003), cholinesterase (ChE, p = 0.001), and high-density lipoprotein cholesterol (HDL-C, p = 0.005) declined. Among these variables, hs-CRP (r = 0.218, p < 0.001) had a weak positively association with HAMD scores, and ChE (r = -0.226, p < 0.001) had a weak negative association. (2) The combination of Hb, hs-CRP, ChE, ALP, and HDL-C improved diagnostic performance for VDe [AUC = 0.775, 95% CI (0.706, 0.844), p < 0.001]. (3) Hb (OR = 0.986, p = 0.049), ChE (OR = 0.999, p = 0.020), ALP (OR = 1.017, p = 0.003), and basal ganglia lesions (OR = 2.197, p < 0.001) were important factors impacting VDe development. After adjusting for Hb, hs-CRP, ChE, HDL-C, lesions in the above mentioned four locations, sex, age and the prevalence of CSVD and brain atrophy, ALP [OR = 1.016, 95% CI (1.005, 1.027), p = 0.004] was independently associated with VDe. CONCLUSION: Hb, hs-CRP, ChE, ALP, and HDL-C concentrations are potential blood markers of depression in CVD patients and, when combined, may improve diagnostic performance for VDe. Serum ALP was independently associated with VDe in patients with CVD.



        

Title: Reusable carboxylesterase immobilized in ZIF for efficient degradation of chlorpyrifos in enviromental water
Wang B, Chen J, Wu S, Fang J, Li Q, Wang G
Ref: Pestic Biochem Physiol, 194:105519, 2023 : PubMed
Abstract


ESTHER: Wang_2023_Pestic.Biochem.Physiol_194_105519
PubMedSearch: Wang 2023 Pestic.Biochem.Physiol 194 105519
PubMedID: 37532333
Gene_locus related to this paper: strco-estli
Inhibitor(s) related to this paper: Chlorpyrifos

Abstract

The past few decades have witnessed biodegradation of pesticides as a significant method in remediation of the environment for its specificity, efficiency and biocompatibility. However, the tolerability and recyclability of the enzymes in pesticide degradation and the development of enzymes that biodegrad pesticides are still urgent problems to be solved so far. Herein, a novel hyper-thermostable and chlorpyrifos-hydrolyzing carboxylesterase EstC was immobilized by biomineralization using zeolitic imidazolate framework (ZIF), one of the metal-organic frameworks (MOFs) with highly diverse structure and porosity. Compared with free enzyme, EstC@ZIF with a cruciate flower-like morphology presented scarcely variation in catalytic efficiency and generally improved the tolerance to organic solvents or detergents. Furthermore, there was scarcely decrease in the catalytic efficiency of EstC@ZIF and it also showed good reusability with about 50% residual activity after 12 continuous uses. Notably, EstC@ZIF could be used in actual water environment with an excellent value of degradation rate of 90.27% in 120 min, and the degradation efficiency remained about 50% after 9 repetitions. The present strategy of immobilizing carboxylesterase to treat pesticide-contaminated water broadens the method of immobilized enzymes on MOFs, and envisions its recyclable applicability in globe environmental remediation.



        

Title: Strigolactones positively regulate Verticillium wilt resistance in cotton via crosstalk with other hormones
Yi F, An G, Song A, Cheng K, Liu J, Wang C, Wu S, Wang P, Zhu J and Cai Y <11 more author(s)> Yi F, An G, Song A, Cheng K, Liu J, Wang C, Wu S, Wang P, Zhu J, Liang Z, Chang Y, Chu Z, Cai C, Zhang X, Chen A, Xu J, Burritt DJ, Herrera-Estrella L, Tran LP, Li W, Cai Y (- 11)
Ref: Plant Physiol, :, 2023 : PubMed
Abstract


ESTHER: Yi_2023_Plant.Physiol__
PubMedSearch: Yi 2023 Plant.Physiol
PubMedID: 36718522

Abstract

Verticillium wilt caused by Verticillium dahliae is a serious vascular disease in cotton (Gossypium spp.). V. dahliae induces the expression of the CAROTENOID CLEAVAGE DIOXYGENASE 7 (GauCCD7) gene involved in strigolactone (SL) biosynthesis in Gossypium australe, suggesting a role for SLs in Verticillium wilt resistance. We found that the SL analog rac-GR24 enhanced while the SL biosynthesis inhibitor TIS108 decreased cotton resistance to Verticillium wilt. Knock-down of GbCCD7 and GbCCD8b genes in island cotton (Gossypium barbadense) decreased resistance, whereas overexpression of GbCCD8b in upland cotton (Gossypium hirsutum) increased resistance to Verticillium wilt. Additionally, Arabidopsis (Arabidopsis thaliana) SL mutants defective in CCD7 and CCD8 putative orthologs were susceptible, whereas both Arabidopsis GbCCD7- and GbCCD8b-overexpressing plants were more resistant to Verticillium wilt than wild-type (WT) plants. Transcriptome analyses showed that several genes related to the jasmonic acid (JA)- and abscisic acid (ABA)-signaling pathways, such as MYELOCYTOMATOSIS 2 (GbMYC2) and ABA-INSENSITIVE 5, respectively, were up-regulated in the roots of WT cotton plants in responses to rac-GR24 and V. dahliae infection but down-regulated in the roots of both GbCCD7- and GbCCD8b-silenced cotton plants. Furthermore, GbMYC2 suppressed the expression of GbCCD7 and GbCCD8b by binding to their promoters, which might regulate the homeostasis of SLs in cotton through a negative feedback loop. We also found that GbCCD7- and GbCCD8b-silenced cotton plants were impaired in V. dahliae-induced reactive oxygen species (ROS) accumulation. Taken together, our results suggest that SLs positively regulate cotton resistance to Verticillium wilt through crosstalk with the JA and ABA-signaling pathways and by inducing ROS accumulation.



        

Title: Biosensor and chemo-enzymatic one-pot cascade applications to detect and transform PET-derived terephthalic acid in living cells
Bayer T, Pfaff L, Branson Y, Becker A, Wu S, Bornscheuer UT, Wei R
Ref: iScience, 25:104326, 2022 : PubMed
Abstract


ESTHER: Bayer_2022_iScience_25_104326
PubMedSearch: Bayer 2022 iScience 25 104326
PubMedID: 35602945

Abstract

Plastic waste imposes a serious problem to the environment and society. Hence, strategies for a circular plastic economy are demanded. One strategy is the engineering of polyester hydrolases toward higher activity for the biotechnological recycling of polyethylene terephthalate (PET). To provide tools for the rapid characterization of PET hydrolases and the detection of degradation products like terephthalic acid (TPA), we coupled a carboxylic acid reductase (CAR) and the luciferase LuxAB. CAR converted TPA into the corresponding aldehydes in Escherichia coli, which yielded bioluminescence that not only semiquantitatively reflected amounts of TPA in hydrolysis samples but is suitable as a high-throughput screening assay to assess PET hydrolase activity. Furthermore, the CAR-catalyzed synthesis of terephthalaldehyde was combined with a reductive amination cascade in a one-pot setup yielding the corresponding diamine, suggesting a new strategy for the transformation of TPA as a product obtained from PET biodegradation.



        

Title: Sertoli cell survival and barrier function are regulated by miR-181c/d-Pafah1b1 axis during mammalian spermatogenesis
Feng Y, Chen D, Wang T, Zhou J, Xu W, Xiong H, Bai R, Wu S, Li J, Li F
Ref: Cell Mol Life Sciences, 79:498, 2022 : PubMed
Abstract


ESTHER: Feng_2022_Cell.Mol.Life.Sci_79_498
PubMedSearch: Feng 2022 Cell.Mol.Life.Sci 79 498
PubMedID: 36008729

Abstract

Sertoli cells contribute to the formation of the blood-testis barrier (BTB), which is necessary for normal spermatogenesis. Recently, microRNAs (miRNAs) have emerged as posttranscriptional regulatory elements in BTB function during spermatogenesis. Our previous study has shown that miR-181c or miR-181d (miR-181c/d) is highly expressed in testes from boars at 60 days old compared with at 180 days old. Herein, we found that overexpression of miR-181c/d via miR-181c/d mimics in murine Sertoli cells (SCs) or through injecting miR-181c/d-overexpressing lentivirus in murine testes perturbs BTB function by altering BTB-associated protein distribution at the Sertoli cell-cell interface and F-actin organization, but this in vivo perturbation disappears approximately 6 weeks after the final treatment. We also found that miR-181c/d represses Sertoli cell proliferation and promotes its apoptosis. Moreover, miR-181c/d regulates Sertoli cell survival and barrier function by targeting platelet-activating factor acetylhydrolase 1b regulatory subunit 1 (Pafah1b1) gene. Furthermore, miR-181c/d suppresses PAFAH1B1 expression, reduces the complex of PAFAH1B1 with IQ motif-containing GTPase activating protein 1, and inhibits CDC42/PAK1/LIMK1/Cofilin pathway which is required for F-actin stabilization. In total, our results reveal the regulatory axis of miR-181c/d-Pafah1b1 in cell survival and barrier function of Sertoli cells and provide additional insights into miRNA functions in mammalian spermatogenesis.



        

Title: Maize domestication phenotypes reveal strigolactone networks coordinating grain size evolution with kernel-bearing cupule architecture
Guan JC, Li C, Flint-Garcia S, Suzuki M, Wu S, Saunders JW, Dong L, Bouwmeester HJ, McCarty DR, Koch KE
Ref: Plant Cell, :, 2022 : PubMed
Abstract


ESTHER: Guan_2022_Plant.Cell__
PubMedSearch: Guan 2022 Plant.Cell
PubMedID: 36573016

Abstract

The maize (Zea mays) ear represents one of the most striking domestication phenotypes in any crop species, with the cob conferring an exceptional yield advantage over the ancestral form of teosinte. Remodeling of the grain-bearing surface required profound developmental changes. However, the underlying mechanisms remain unclear and can only be partly attributed to the known domestication gene Teosinte glume architecture 1 (Tga1). Here we show that a more complete conversion involves strigolactones (SLs), and that these are prominent players not only in the Tga1 phenotype, but also other domestication features of the ear and kernel. Genetic combinations of a teosinte tga1 allele with three SL-related mutants progressively enhanced ancestral morphologies. The SL mutants, in addition to modulating the tga1 phenotype, also reshaped kernel-bearing pedicels and cupules in a teosinte-like manner. Genetic and molecular evidence are consistent with SL regulation of TGA1, including direct interaction of TGA1 with components of the SL-signaling system shown here to mediate TGA1 availability by sequestration. Roles of the SL network extend to enhancing maize seed size and, importantly, coordinating increased kernel growth with remodeling of protective maternal tissues. Collectively, our data show that SLs have central roles in releasing kernels from restrictive maternal encasement and coordinating other factors that increase kernel size, physical support, and their exposure on the grain-bearing surface.



        

Title: Antinociceptive Effects and Interaction Mechanisms of Intrathecal Pentazocine and Neostigmine in Two Different Pain Models in Rats
Huang H, Bai X, Zhang K, Guo J, Wu S, Ouyang H
Ref: Pain Res Manag, 2022:4819910, 2022 : PubMed
Abstract


ESTHER: Huang_2022_Pain.Res.Manag_2022_4819910
PubMedSearch: Huang 2022 Pain.Res.Manag 2022 4819910
PubMedID: 35646201

Abstract

BACKGROUND: Pentazocine produces a wide variety of actions in the treatment of perioperative analgesia. Neostigmine is a cholinesterase inhibitor used to antagonize the residual effects of muscle relaxants and also produces an analgesic effect. OBJECTIVES: To investigate the analgesic effects of intrathecally injected pentazocine and neostigmine and their interaction. METHODS: Sprague-Dawley rats were used to test the analgesic effect of pentazocine and neostigmine using the paw formalin pain model and the incision mechanical allodynia model. Pentazocine (3, 10, 30, and 100 microg), neostigmine (0.3, 1, 3, and 10 microg) or a pentazocine-neostigmine mixture were separately injected to evaluate their antinociceptive effects alone on the treatment groups. The corresponding control group received an intrathecal injection containing the same volume of saline. The formalin pain test, or the plantar incision pain behavior test were performed 30 minutes later. Isobolographic analysis was used to evaluate the interaction between pentazocine and neostigmine. Intrathecally administered selective mu-opioid receptor antagonist CTAP, selective kappa-opioid receptor antagonist nor-Binaltorphimine (nor-BNI), nonselective opioid receptor antagonist naloxone, and muscarinic acetylcholine receptor antagonist atropine were also used to test the possible interaction mechanism. These antagonists were used 30 minutes before the pentazocine and neostigmine mixtures which were intrathecally injected. RESULTS: Intrathecally administered pentazocine (3, 10, 30, and 100 microg) and neostigmine (0.3, 1, 3, and 10 microg) alone had a marked dose-related impact on suppressing the biphasic responses in the formalin test. Pentazocine (3, 10, 30, and 100 microg) and neostigmine (0.3, 1, 3, and 10 microg) alone attenuated the mechanical allodynia in a plantar incision model in a dose-dependent manner. Isobolographic analysis revealed that the mixture of intrathecal pentazocine and neostigmine synergistically decreased both phase I and II activity in the formalin test and mechanical allodynia in the plantar incision model. Pretreatment of intrathecally administered nor-BNI, naloxone, atropine, but not CTAP, antagonized the analgesic effect of the pentazocine-neostigmine mixture. CONCLUSIONS: All of these results suggest that the combined application of pentazocine and neostigmine is an effective way to relieve pain from formalin and acute incision mechanical allodynia. The synergistic effect between pentazocine and neostigmine is mostly attributed to the kappa-opioid receptor and the cholinergic receptor in the spinal cord.



        

Title: Development of a pH-Responsive, SO(4)(2-)-loaded Fe and N co-doped carbon quantum dots-based fluorescent method for highly sensitive detection of glyphosate
Peng Z, Zeng M, Wu S, Yan Z, Rui J, Qiu P, Wang X
Ref: Anal Chim Acta, 1221:340110, 2022 : PubMed
Abstract


ESTHER: Peng_2022_Anal.Chim.Acta_1221_340110
PubMedSearch: Peng 2022 Anal.Chim.Acta 1221 340110
PubMedID: 35934352

Abstract

A novel sulfate-loaded iron-nitrogen co-doped carbon quantum dots (SO(4)(2-)-CQDs)-based fluorescent method was synthesized by the facile and environmentally friendly pyrolysis of persimmon frost (carbon source) and (NH(4))(2)Fe(SO(4))(2).6H(2)O. After SMMC-7721 cells were incubated with the SO(4)(2-)-CQDs for 24 h, more than 95% of the cells remained viable, even at a high concentration of the SO(4)(2-)-CQDs, indicating excellent biocompatibility and low toxicity. In addition, it was able to be taken up by the cells to emit their bright blue fluorescence after excitation at 365 nm, indicating suitable cell permeability. The SO(4)(2-)-CQDs also exhibited a unique response to changes in pH, which was applied in the detection of OPs by relying on the production of acetic acid from the hydrolysis of acetylcholine (ACh) by acetylcholinesterase (AChE), which decreased the pH and engendered an increase in the fluorescence of the SO(4)(2-)-CQDs; however, the inhibition of AChE by glyphosate resulted in little influence on fluorescence intensity due to the lack of acetic acid produced. This mechanism was the basis for the development of a sensitive assay for the detection of glyphosate. The resulting assay had a limit of detection of 0.066 ng/mL. Furthermore, the method was successfully applied for the precise and accurate monitoring of the concentration, distribution, and variation of glyphosate residues in chives and cultivated soil. Therefore, the proposed method was anticipated to provide a promising alternative for other detection methods to enable the reliable analysis of OPs in food products.



        

Title: Invasive Plants Have Higher Resistance to Native Generalist Herbivores Than Exotic Noninvasive Congeners
Wu S, Chen L, Zhou Y, Xiao F, Liu D, Wang Y
Ref: Environ Entomol, :, 2022 : PubMed
Abstract


ESTHER: Wu_2022_Environ.Entomol__
PubMedSearch: Wu 2022 Environ.Entomol
PubMedID: 36545824

Abstract

Research on the invasive plant Phytolacca americana (L.) mostly focuses on its medicinal value and enrichment of heavy metals. However, little is known regarding its impact on native herbivorous insects. In this study, we explored the effects of P. americana and the exotic noninvasive Phytolacca icosandra (L.) on the Spodoptera litura (Fabricius) (native tobacco cutworm) via bioassay, oviposition preference, detoxifying enzyme activity analysis, and phytochemical determination. We found that the oviposition preference index (OPI) of S. litura feeding on P. icosandra was higher than that of P. americana. The developmental duration of S. litura feeding on P. icosandra was shorter than that of P. americana. Additionally, the Acetylcholinesterase (AchE) and Glutathione-S-transferase (GST) activities of S. litura feeding on P. americana were higher than that of S. litura feeding on artificial diets or P. icosandra. The content of lignin and flavonoids in P. americana was relatively high, whereas starch content was relatively low. These findings suggest invasive plants have higher resistance to herbivores, thereby suffering less damage than exotic noninvasive plants.



        

Title: Comparative genomics of Sarcoptes scabiei provide new insights into adaptation to permanent parasitism and within-host species divergence
Xu J, Wang Q, Wang S, Huang W, Xie Y, Gu X, He R, Peng X, Wu S, Yang G
Ref: Transbound Emerg Dis, :, 2022 : PubMed
Abstract


ESTHER: Xu_2022_Transbound.Emerg.Dis__
PubMedSearch: Xu 2022 Transbound.Emerg.Dis
PubMedID: 36134513

Abstract

Sarcoptic scabiei is the causative agent of a highly contagious skin disease in humans and more than 100 mammals. Here, we report the first chromosome-level reference genome of S. scabiei isolated from rabbits, with a contig N50 size of 5.92 Mb, a total assembled length of 57.30 Mb, -12.65% repetitive sequences, and 9,333 predicted protein-coding genes. The phylogenetic tree based on 1,338 shared high-confidence single-copy orthologous genes estimated that the mammalian ectoparasite S. scabiei and the plant-feeding mite Tetranychus urticae separated approximately 340 million years ago. Both neighbor-joining tree and principal component analysis of 20 mite populations isolated from four hosts (humans, pigs, dogs and rabbits) distributed in three countries (China, Australia and the US) consistently supported the genetic subdivisions according to host species rather than geographical location. The demographic history of S. scabiei reconstructed by multiple sequentially Markovian coalescent analysis suggested that S. scabiei isolated from rabbits, humans, dogs, and pigs diverged -5,000 years ago. Investigation of the homeobox (Hox) genes revealed that S. scabiei contains eight of 10 canonical Hox genes that are present in the arthropod ancestor, and the absence of the Abd-A gene may correlate with the long gap between their front and back legs. Comparative genomics demonstrated that genes specific to scabies mites were mainly enriched in nutrition digestive systems and genes in the families that involved detoxification (cytochrome P450, carboxyl/cholinesterases, and the ATP-binding cassette transporter C group) were extremely contracted compared with that of other mites analyzed in this study. Selective sweep analysis of mite populations from either two of the four host species revealed that the strongest selective sweep signals were mainly enriched in cysteine-type peptidase activity and apoptosis. The results provided clues for the mechanisms of S. scabiei adaptation to a permanent parasitic lifestyle and knowledge that would enable further control of this highly contagious skin disease. This article is protected by copyright. All rights reserved.



        

Title: Study on pathological and clinical characteristics of chronic HBV infected patients with HBsAg positive, HBV DNA negative, HBeAg negative
Zeng Z, Liu R, Cao W, Yang L, Lin Y, Bi X, Jiang T, Deng W, Wang S and Li M <13 more author(s)> Zeng Z, Liu R, Cao W, Yang L, Lin Y, Bi X, Jiang T, Deng W, Wang S, Lu H, Sun F, Shen G, Chang M, Lu Y, Wu S, Hao H, Xu M, Chen X, Hu L, Zhang L, Wan G, Xie Y, Li M (- 13)
Ref: Front Immunol, 13:1113070, 2022 : PubMed
Abstract


ESTHER: Zeng_2022_Front.Immunol_13_1113070
PubMedSearch: Zeng 2022 Front.Immunol 13 1113070
PubMedID: 36685494

Abstract

AIMS: Study of clinical characteristics of hepatitis B virus deoxyribonucleic acid (HBV DNA)-negative, hepatitis B surface antigen (HBsAg)-positive, hepatitis B e antigen (HBeAg)-negative patients based on liver histopathology. METHODS: We retrospectively enrolled patients with chronic HBV infection diagnosis at Beijing Ditan Hospital from May 2008 to November 2020. To study the differences between patients with significant hepatic histopathology and those without significant hepatic histopathology. And to study the independent factors of significant hepatic histopathology. RESULTS: 85 HBV DNA-negative and HBeAg-negative patients were 37.90 +/- 10.30 years old, 23.50% of patients with grade of inflammation (G) >1, 35.30% of patients with liver fibrosis stage (S) >1, 44.70% patients were diagnosed with significant hepatic histopathology. Compared to the no significant hepatic histopathology group, another group had older age (41.70 +/- 10.70 vs 34.80 +/- 8.87 years, t=-3.28, P=0.002), higher total bilirubin (TBIL) [14.9(10.3, 22.4) vs 11(8.9, 14.4) micromol/L, z=-2.26, P=0.024], lower cholinesterase (CHE) (t=-2.86, P=0.005, 7388.00 +/- 2156.00 vs 8988.00 +/- 2823.00 U/L) and lower platelet (PLT) (t=2.75, P=0.007, 157.00 +/- 61.40 vs 194.00 +/- 61.00 10^9/L). Abnormal ALT patients are more likely to have significant hepatic histopathology (z=5.44, P=0.020, 66.70% vs 337.50%). G had significant correlation with CHE (P=0.008, r=-0.23), alanine aminotransferase (ALT) (P=0.041, r=0.18), aspartate aminotransferase (AST) (P=0.001, r=0.29). S had significant correlation with TBIL (P = 0.008, r = 0.23), age (P < 0.001, r = 0.32), international normalized ratio (INR) (P = 0.04, r = 0.23), CHE (P < 0.001, r = -0.30), PLT (P < 0.001, r = -0.40) and prothrombin time activity (PTA) (P = 0.046, r = -0.22). Multivariate logistic analysis indicated only age (95%CI=1.014~1.130, OR=1.069, P=0.013) was an impact factor for significant hepatic histopathology. The cutoff point of age was 34.30 years. CONCLUSIONS: A large proportion of chronic HBV infection patients with HBeAg-negative and HBV DNA-negative still have chronic hepatitis. Age is an independent factor for significant hepatic histopathology.



        

Title: Huperzine-A Improved Animal Behavior in Cuprizone-Induced Mouse Model by Alleviating Demyelination and Neuroinflammation
Zhang H, Wang D, Sun J, Wang Y, Wu S, Wang J
Ref: Int J Mol Sci, 23:16182, 2022 : PubMed
Abstract


ESTHER: Zhang_2022_Int.J.Mol.Sci_23_16182
PubMedSearch: Zhang 2022 Int.J.Mol.Sci 23 16182
PubMedID: 36555825

Abstract

Huperzine A (HupA) is a natural acetylcholinesterase inhibitor (AChEI) with the advantages of high efficiency, selectivity as well as reversibility and can exhibit significant therapeutic effects against certain neurodegenerative diseases. It is also beneficial in reducing the neurological impairment and neuroinflammation of experimental autoimmune encephalomyelitis (EAE), a classic model for multiple sclerosis (MS). However, whether HupA can directly regulate oligodendrocyte differentiation and maturation and promote remyelination has not been investigated previously. In this study, we have analyzed the potential protective effects of HupA on the demylination model of MS induced by cuprizone (CPZ). It was found that HupA significantly attenuated anxiety-like behavior, as well as augmented motor and cognitive functions in CPZ mice. It also decreased demyelination and axonal injury in CPZ mice. Moreover, in CPZ mice, HupA increased mRNA levels of the various anti-inflammatory cytokines (Arg1, CD206) while reducing the levels of different pro-inflammatory cytokines (iNOS, IL-1beta, IL-18, CD16, and TNF-alpha). Mecamylamine, a nicotinic acetylcholinergic receptor antagonist, could effectively reverse the effects of HupA. Therefore, we concluded that HupA primarily exerts its therapeutic effects on multiple sclerosis through alleviating demyelination and neuroinflammation.



        

Title: Pancreatic Cancer Cell-Derived Exosomes Promote Lymphangiogenesis by Downregulating ABHD11-AS1 Expression
Zhou X, Zhong F, Yan Y, Wu S, Wang H, Liu J, Li F, Cui D, Xu M
Ref: Cancers (Basel), 14:, 2022 : PubMed
Abstract


ESTHER: Zhou_2022_Cancers.(Basel)_14_
PubMedSearch: Zhou 2022 Cancers.(Basel) 14
PubMedID: 36230535
Gene_locus related to this paper: human-ABHD11

Abstract

Research on pancreatic cancer microbiomes has attracted attention in recent years. The current view is that enriched microbial communities in pancreatic cancer tissues may affect pancreatic cancer metastasis, including lymph node (LN) metastasis. Similar to carriers of genetic information between cells, such as DNA, mRNA, protein, and non-coding RNA, exosomes are of great importance in early LN metastasis in tumors, including pancreatic cancer. Our previous study showed that the long non-coding RNA ABHD11-AS1 was highly expressed in tissues of patients with pancreatic cancer, and was correlated with patient survival time. However, the role of ABHD11-AS1 in pancreatic cancer LN metastasis has rarely been studied. Hence, in this paper we confirmed that exosomes derived from pancreatic cancer cells could promote lymphangiogenesis in vitro and in vivo, and that the mechanism was related to the downregulation of ABHD11-AS1 expression in lymphatic endothelial cells, and to the enhancement of their ability to proliferate, migrate, and form tubes. These findings preliminarily show a new mechanism by which pancreatic cancer cells regulate peripheral lymphangiogenesis, providing a new therapeutic strategy for inhibiting LN metastasis in pancreatic cancer.



        

Title: Characterization of a carboxylesterase with hyper-thermostability and alkali-stability from Streptomyces lividans TK24
Chang X, Wu S, Chen J, Xiong S, Wang P, Shi X, Wang A, Wang B
Ref: Extremophiles, :, 2021 : PubMed
Abstract


ESTHER: Chang_2021_Extremophiles__
PubMedSearch: Chang 2021 Extremophiles
PubMedID: 33515353
Gene_locus related to this paper: strco-SCO2123

Abstract

A gene (estA', 804 bp) from Streptomyces lividans TK24 was artificially synthesized and successfully overexpressed as a 6His-tagged fusion protein in Escherichia coli. It encoded a carboxylesterase (EstA) that composed of 267 amino acids with a predicted molecular weight of 28.56 kDa. Multiple sequence alignment indicated that EstA has typical characteristics of esterases, including a catalytic triad (Ser93-Asp194-His224) and a conserved pentapeptide motif (Gly91-Leu92-Ser93-Met94-Gly95). Simultaneously, phylogenetic analysis indicated that EstA belongs to family VI. Biochemical characterization displayed its optimum enzyme activity was at 55 and pH 8.5. Additionally, EstA exhibited higher activity towards short carbon substrates and showed the outstanding catalytic efficiency for pNPA2 with k(cat)/K(m) of 2296.14 +/- 10.35 s(-1) mM(-1). Notably, EstA has hyper-thermostability and good alkali stability. The activity of EstA did not change obviously when incubated at 50 and 100 for 337 and 1 h, independently. Besides, by incubating at 100 for 6 h, EstA remained about half of its initial activity. Moreover, EstA showed stability at pH ranging from 8.0 to 11.0, and about 90% residual enzyme activity was reserved by being treated at pH 8.0 or 9.0 for 80 h, especially. Such multiple features prepare EstA for a potential candidate in the field of biological catalysis of some industrial applications under harsh conditions.



        

Title: Characterization of Two Unique Cold-Active Lipases Derived from a Novel Deep-Sea Cold Seep Bacterium
Guo C, Zheng R, Cai R, Sun C, Wu S
Ref: Microorganisms, 9:, 2021 : PubMed
Abstract


ESTHER: Guo_2021_Microorganisms_9_
PubMedSearch: Guo 2021 Microorganisms 9
PubMedID: 33920298

Abstract

The deep ocean microbiota has unexplored potential to provide enzymes with unique characteristics. In order to obtain cold-active lipases, bacterial strains isolated from the sediment of the deep-sea cold seep were screened, and a novel strain gcc21 exhibited a high lipase catalytic activity, even at the low temperature of 4 degreesC. The strain gcc21 was identified and proposed to represent a new species of Pseudomonas according to its physiological, biochemical, and genomic characteristics; it was named Pseudomonas marinensis. Two novel encoding genes for cold-active lipases (Lipase 1 and Lipase 2) were identified in the genome of strain gcc21. Genes encoding Lipase 1 and Lipase 2 were respectively cloned and overexpressed in E. coli cells, and corresponding lipases were further purified and characterized. Both Lipase 1 and Lipase 2 showed an optimal catalytic temperature at 4 degreesC, which is much lower than those of most reported cold-active lipases, but the activity and stability of Lipase 2 were much higher than those of Lipase 1 under different tested pHs and temperatures. In addition, Lipase 2 was more stable than Lipase 1 when treated with different metal ions, detergents, potential inhibitors, and organic solvents. In a combination of mutation and activity assays, catalytic triads of Ser, Asp, and His in Lipase 1 and Lipase 2 were demonstrated to be essential for maintaining enzyme activity. Phylogenetic analysis showed that both Lipase 1 and Lipase 2 belonged to lipase family III. Overall, our results indicate that deep-sea cold seep is a rich source for novel bacterial species that produce potentially unique cold-active enzymes.



        

Title: Multiple transcriptomic profiling: potential novel metabolism-related genes predict prepubertal testis damage caused by DEHP exposure
Kang L, Chen J, Wang J, Zhao T, Wei Y, Wu Y, Han L, Zheng X, Shen L and Wu S <2 more author(s)> Kang L, Chen J, Wang J, Zhao T, Wei Y, Wu Y, Han L, Zheng X, Shen L, Long C, Wei G, Wu S (- 2)
Ref: Environ Sci Pollut Res Int, :, 2021 : PubMed
Abstract


ESTHER: Kang_2021_Environ.Sci.Pollut.Res.Int__
PubMedSearch: Kang 2021 Environ.Sci.Pollut.Res.Int
PubMedID: 34595713

Abstract

The toxic effect of di(2-ethylhexyl) phthalate (DEHP) on prepubertal testes was examined in this study. We treated 3-week-old male mice with 4.8 mg/kg/day (milligram/kilogram/day) (no observed adverse effect level), 30 mg/kg/day (high exposure dose relative to humans), 100 mg/kg/day (level causing a reproductive system disorder), and 500 mg/kg/day (dose causing a multigenerational reproductive system disorder) of DEHP via gavage. Obvious abnormalities in the testicular organ coefficient, spermatogenic epithelium, and testosterone levels occurred in the 500 mg/kg DEHP group. Ribonucleic acid sequencing (RNA-seq) showed that differentially expressed genes (DEGs) in each group could enrich reproduction and reproductive process terms according to the gene ontology (GO) results, and coenrichment of metabolism pathway was observed by the Reactome pathway analysis. Through the analysis of common genes in the metabolism pathway, we discovered that DEHP exposure at 4.8 to 500 mg/kg or 100 mg/kg caused the same damages to the prepubertal testis. In general, we identified two key transcriptional biomarkers (fatty acid binding protein 3 (Fabp3) and carboxylesterase (Ces) 1d), which provided new insight into the gene regulatory mechanism associated with DEHP exposure and will contribute to the prediction and diagnosis of prepuberty testis injury caused by DEHP.



        

Title: Old pesticide, new use: Smart and safe enantiomer of isocarbophos in locust control
Kong Y, Ji C, Qu J, Chen Y, Wu S, Zhu X, Niu L, Zhao M
Ref: Ecotoxicology & Environmental Safety, 225:112710, 2021 : PubMed
Abstract


ESTHER: Kong_2021_Ecotoxicol.Environ.Saf_225_112710
PubMedSearch: Kong 2021 Ecotoxicol.Environ.Saf 225 112710
PubMedID: 34481357

Abstract

Locust plagues are still worldwide problems. Selecting active enantiomers from current chiral insecticides is necessary for controlling locusts and mitigating the pesticide pollution in agricultural lands. Herein, two enantiomers of isocarbophos (ICP) were separated and the enantioselectivity in insecticidal activity against the pest Locusta migratoria manilensis (L. migratoria) and mechanisms were investigated. The significant difference of LD(50) between (+)-ICP (0.609 mg/kg bw) and (-)-ICP (79.412 mg/kg bw) demonstrated that (+)-ICP was a more effective enantiomer. The enantioselectivity in insecticidal activity of ICP enantiomers could be attributed to the selective affinity to acetylcholinesterase (AChE). Results of in vivo and in vitro assays suggested that AChE was more sensitive to (+)-ICP. In addition, molecular docking showed that the -CDOKER energies of (+)-ICP and (-)-ICP were 25.6652 and 24.4169, respectively, which suggested a stronger affinity between (+)-ICP and AChE. Significant selectivity also occurred in detoxifying enzymes activities (carboxylesterases (CarEs) and glutathione S-transferases (GSTs)) and related gene expressions. Suppression of detoxifying enzymes activities with (+)-ICP treatment suggested that (-)-ICP may induce the detoxifying enzyme-mediated ICP resistance. A more comprehensive understanding of the enantioselectivity of ICP is necessary for improving regulation and risk assessment of ICP.



        

Title: Functional Haplotype of LIPC Induces Triglyceride-Mediated Suppression of HDL-C Levels According to Genome-Wide Association Studies
Liao YH, Er LK, Wu S, Ko YL, Teng MS
Ref: Genes (Basel), 12:, 2021 : PubMed
Abstract


ESTHER: Liao_2021_Genes.(Basel)_12_
PubMedSearch: Liao 2021 Genes.(Basel) 12
PubMedID: 33499410

Abstract

Hepatic lipase (encoded by LIPC) is a glycoprotein in the triacylglycerol lipase family and mainly synthesized in and secreted from the liver. Previous studies demonstrated that hepatic lipase is crucial for reverse cholesterol transport and modulating metabolism and the plasma levels of several lipoproteins. This study was conducted to investigate the suppression effect of high-density lipoprotein cholesterol (HDL-C) levels in a genome-wide association study and explore the possible mechanisms linking triglyceride (TG) to LIPC variants and HDL-C. Genome-wide association data for TG and HDL-C were available for 4657 Taiwan-biobank participants. The prevalence of haplotypes in the LIPC promoter region and their effects were calculated. The cloned constructs of the haplotypes were expressed transiently in HepG2 cells and evaluated in a luciferase reporter assay. Genome-wide association analysis revealed that HDL-C was significantly associated with variations in LIPC after adjusting for TG. Three haplotypes (H1: TCG, H2: CTA and H3: CCA) in LIPC were identified. H2: CTA was significantly associated with HDL-C levels and H1: TCG suppressed HDL-C levels when a third factor, TG, was included in mediation analysis. The luciferase reporter assay further showed that the H2: CTA haplotype significantly inhibited luciferase activity compared with the H1: TCG haplotype. In conclusion, we identified a suppressive role for TG in the genome-wide association between LIPC and HDL-C. A functional haplotype of hepatic lipase may reduce HDL-C levels and is suppressed by TG.



        

Title: Antioxidant Effects of Sophora davidi (Franch.) Skeels on d-Galactose-Induced Aging Model in Mice via Activating the SIRT1/p53 Pathway
Lin B, Xu D, Wu S, Qi S, Xu Y, Liu X, Zhang X, Chen C
Ref: Front Pharmacol, 12:754554, 2021 : PubMed
Abstract


ESTHER: Lin_2021_Front.Pharmacol_12_754554
PubMedSearch: Lin 2021 Front.Pharmacol 12 754554
PubMedID: 34938181

Abstract

This study investigated the protective effect of Sophora davidi (Franch.) Skeels fruits extract (SDE) on d-galactose-induced acute aging in mice. Ultra performance liquid chromatography coupled with tine-of-flight mass spectrometry (UPLC-Q-TOF/MS) was performed to identify the composition of compounds in SDE. KM mice were divided stochastically into the normal control group (NC, saline), d-galactose (D-gal) model group, vitamin C (Vc) group (positive control), low-, medium-and high-dose SDE treat groups. After 28 days administration and fasting overnight, the serum, liver, and brain samples of mice were collected. The levels of inducible nitric oxide synthase (iNOS), acetylcholinesterase (AChE) activity in the brain, malondialdehyde (MDA) and reduced glutathione (GSH) content, superoxide dismutase (SOD) and total antioxidant capacity (T-AOC) activity in the liver and brain were measured. Immunohistochemistry was applied to detect silent information regulator 1 (SIRT1) and p53 protein expression in the liver and brain, and quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression of nuclear factor kappaB (NF-kappaB), tumor necrosis factor (TNF-alpha), interleukin-6 (IL-6), interleukin-1beta (IL-1beta), and anti-aging factor Klotho in the liver and brain. The results showed that UPLC-Q-TOF/MS identified 78 compounds in SDE. SDE could reduce the iNOS activity in serum and AChE activity in the brain, upregulate the levels of SOD, T-AOC and GSH in liver and brain, and debase the MDA content in liver and brain. SDE could downregulate the mRNA expressions of TNF-alpha, NF-kB, IL-1beta, and IL-6 in the liver and brain, and elevate the mRNA expression of Klotho. SDE improved the pathological changes of the liver and brain induced by D-gal, increased the expression of SIRT1 protein in the liver and brain, and inhibited the expression of p53 protein induced by D-gal. To summarize, SDE demonstrated clear anti-aging effect, and its mechanism may be relevant to the activation of the SIRT1/p53 signal pathway.



        

Title: Monitoring of parathion methyl using a colorimetric gold nanoparticle-based acetylcholinesterase assay
Liu B, Wu L, Peng Z, Wu S, Qiu P
Ref: Spectrochim Acta A Mol Biomol Spectrosc, :120665, 2021 : PubMed
Abstract


ESTHER: Liu_2021_Spectrochim.Acta.A.Mol.Biomol.Spectrosc__120665
PubMedSearch: Liu 2021 Spectrochim.Acta.A.Mol.Biomol.Spectrosc 120665
PubMedID: 34865979

Abstract

A colorimetric gold nanoparticles (AuNPs)-based acetylcholinesterase (AChE) assay was designed for the first time to measure the concentration of parathion-methyl (PM) in lake water samples. In this assay, the analyte PM inhibited the hydrolysis of acetylthiocholine (ATCh) by AChE, preventing the formation of thiocholine (TCh) that would otherwise react with the AuNPs catalyst and deactivate the catalyst. Therefore, in the presence of PM, the AuNPs catalyzed the oxidation of the 3,3',5,5'-tetramethylbenzidine (TMB) colorimetric indicator to oxTMB, inducing a visual color change from colorless to blue. However, in the absence of PM, AChE hydrolyzed ATCh to TCh, which then reacted with the AuNPs, preventing the oxidation of TMB to oxTMB and rendering the solution colorless. Therefore, the change in the color of the analyte solution indicated the presence of PM, and the absorbance of the resulting solution was measured by UV-Vis spectroscopy to calculate the concentration of PM after generation of a calibration curve. This method was then employed using the smartphone app Color Picker, which converted the color information from the photos of the solution into digital red (R), green (G), and blue (B) values. The ratio of green (G) to blue (B) (G/B) was then plotted against the corresponding concentration to calculate the standard curve, whose regression equation was expressed by y = -0.012x + 1.02 (ng/mL), and the coefficient of determination (R(2)) was 0.97. In addition, this method was also used to determine the amount of PM in real lake water samples with recovery of 90.2-133.3%.



        

Title: Mechanisms of Congenital Myasthenia Caused by Three Mutations in the COLQ Gene
Luo X, Wang C, Lin L, Yuan F, Wang S, Wang Y, Wang A, Wu S, Lan X and Chen Y <9 more author(s)> Luo X, Wang C, Lin L, Yuan F, Wang S, Wang Y, Wang A, Wu S, Lan X, Xu Q, Yin R, Cheng H, Zhang Y, Xi J, Zhang J, Sun X, Yan J, Zeng F, Chen Y (- 9)
Ref: Front Pediatr, 9:679342, 2021 : PubMed
Abstract


ESTHER: Luo_2021_Front.Pediatr_9_679342
PubMedSearch: Luo 2021 Front.Pediatr 9 679342
PubMedID: 34912755

Abstract

The gene encoding collagen like tail subunit of asymmetric acetylcholinesterase (COLQ) is responsible for the transcription of three strands of collagen of acetylcholinesterase, which is attached to the endplate of neuromuscular junctions. Mutations in the COLQ gene are inherited in an autosomal-recessive manner and can lead to type V congenital myasthenia syndrome (CMS), which manifests as decreased muscle strength at birth or shortly after birth, respiratory failure, restricted eye movements, drooping of eyelids, and difficulty swallowing. Here we reported three variants within COLQ in two unrelated children with CMS. An intronic variant (c.393+1G>A) and a novel missense variant (p.Q381P) were identified as compound heterozygous in a 13-month-old boy, with the parents being carriers of each. An intragenic deletion including exons 14 and 15 was found in a homozygous state in a 12-year-old boy. We studied the relative expression of the COLQ and AChE gene in the probands' families, performed three-dimensional protein structural analysis, and analyzed the conservation of the missense mutation c.1142A>C (p.Q381P). The splicing mutation c.393+1G>A was found to affect the normal splicing of COLQ exon 5, resulting in a 27-bp deletion. The missense mutation c.1142A>C (p.Q381P) was located in a conserved position in different species. We found that homozygous deletion of COLQ exons 14-15 resulted in a 241-bp deletion, which decreased the number of amino acids and caused a frameshift translation. COLQ expression was significantly lower in the probands than in the probands' parents and siblings, while AChE expression was significantly higher. Moreover, the mutations were found to cause significant differences in the predicted three-dimensional structure of the protein. The splicing mutation c.393+1G>A, missense mutation c.1A>C (p.Q381P), and COLQ exon 14-15 deletion could cause CMS.



        

Title: Design and Synthesis of Highly Potent and Specific ABHD6 Inhibitors
Malamas MS, Lamani M, Farah SI, Mohammad KA, Miyabe CY, Rajarshi G, Wu S, Zvonok N, Chandrashekhar H and Makriyannis A <1 more author(s)> Malamas MS, Lamani M, Farah SI, Mohammad KA, Miyabe CY, Rajarshi G, Wu S, Zvonok N, Chandrashekhar H, Wood J, Makriyannis A (- 1)
Ref: ChemMedChem, :, 2021 : PubMed
Abstract


ESTHER: Malamas_2021_ChemMedChem__
PubMedSearch: Malamas 2021 ChemMedChem
PubMedID: 34486233
Gene_locus related to this paper: human-ABHD6, mouse-ABHD6

Abstract

Fine-tuning than complete disruption of 2-arachidonoylglycerol (2-AG) metabolism in the brain represents a promising pharmacological approach to limit potential untoward effects associated with complete blockade of monoacylglycerol lipase (MGL), the primary hydrolase of 2-AG. This could be achieved through a/b-hydrolase domain containing 6 (ABHD6) inhibition, which will provide a smaller and safer contribution to 2-AG regulation in the brain. Pharmacological studies with ABHD6 inhibitors have recently been reported, where modulation of ABHD6 activity either through CB1R-dependent or CB1R-independent processes showed promise in preclinical models of epilepsy, neuropathic pain and inflammation. Furthermore in the periphery, ABHD6 modulates 2-AG and other fatty acid monoacylglycerols (MAGs) and is implicated in Type-2 diabetes, metabolic syndrome and potentially other diseases. Herein, we report the discovery of single-digit nanomolar potent and highly specific ABHD6 inhibitors with >1000-fold selectivity against MGL and FAAH. The new ABHD6 inhibitors provide early leads to develop therapeutics for neuroprotection and the treatment of inflammation and diabetes.



        

Title: Effect of chain length and branching on the in vitro metabolism of a series of parabens in human liver S9, human skin S9, and human plasma
Obringer C, Wu S, Troutman J, Karb M, Lester C
Ref: Regul Toxicol Pharmacol, :104918, 2021 : PubMed
Abstract


ESTHER: Obringer_2021_Regul.Toxicol.Pharmacol__104918
PubMedSearch: Obringer 2021 Regul.Toxicol.Pharmacol 104918
PubMedID: 33741472

Abstract

Parabens are antimicrobial compounds used as preservatives in cosmetics, foods, and pharmaceuticals. Paraben exposure occurs through a variety of routes including dermal absorption, ingestion, and inhalation. Ester bond hydrolysis has been shown to be the predominant biotransformation for this chemical class. Here we evaluated a series of parabens of increasing alkyl chain length and branching in addition to the aryl side chain of phenyl paraben (PhP). We evaluated the parabens under full Michaelis-Menten parameters to obtain intrinsic clearance values and found different trends between human liver and skin, which correlate with the predominant esterase enzymes in those matrices, respectively. In liver, where carboxylesterase 1 (CES1) is the predominant esterase enzyme, the shorter chain parabens were more readily metabolized, while in skin, where carboxylesterase 2 (CES2) is the predominant esterase enzyme, the longer chain parabens were more readily metabolized. Alkyl chain branching reduced the hydrolysis rates relative to those for the straight chain compounds, while the addition of a phenyl group, as in PhP, showed an increase in hydrolysis, producing the highest observed hydrolysis rate for skin. These data summarize the structure-metabolism relationship for a series of parabens and contribute to the safety assessment of this class of compounds.



        

Title: Novel amide derivatives containing an imidazo[1,2-a]pyridine moiety: Design, synthesis as potential nematicidal and antibacterial agents
Wei C, Huang J, Luo Y, Wang S, Wu S, Xing Z, Chen J
Ref: Pestic Biochem Physiol, 175:104857, 2021 : PubMed
Abstract


ESTHER: Wei_2021_Pestic.Biochem.Physiol_175_104857
PubMedSearch: Wei 2021 Pestic.Biochem.Physiol 175 104857
PubMedID: 33993975

Abstract

To discover new nematicides, a series of novel amide derivatives containing an imidazo[1,2-a]pyridine moeity were designed and synthesized. Among the title compounds, compounds 3 and 27 exhibited good nematicidal activities against Aphelenchoides besseyi (rice white-tip nematode), with LC(50) values against of 27.3 and 35.9 mg/L, respectively, which were superior to that of fosthiazate (45.4 mg/L). Meanwhile, the LC(50) value of compound 27 against Caenorhabditis elegans was 5.7 mg/L, which was superior to that of fosthiazate (77.2 mg/L). Compound 27 not only binds well to acetylcholinesterase (AChE) of nematodes, but also has a good inhibitory activity against AChE. Thus, AChE may be a potential target of compound 27 against nematodes. Unexpectedly, compound 28 exhibited excellent antibacterial activities with EC(50) values of 1.2 and 3.1 mg/L against Xanthomonas oryzae pv. oryzae (Xoo) and Xanthomonas oryzae pv. oryzicola (Xoc), respectively, which were superior to those of bismerthiazol (68.6 and 77.1 mg/L) and thiodiazole copper (80.8 and 96.6 mg/L). The curative and protective activities of compound 28 against bacterial leaf blight were 37.0% and 36.8% at 50 mg/L, respectively, which were higher than those of thiodiazole copper (16.1% and 15.5%). In addition, compound 28 may inhibit the growth of Xoo by affecting the production of cell membranes and extracellular polysaccharides. Amide derivatives containing an imidazo[1,2-a]pyridine moeity can be used as good lead-structures to discover new nematicidal and antibacterial agents in the future.



        

Title: A Unique Sulfotransferase-Involving Strigolactone Biosynthetic Route in Sorghum
Wu S, Li Y
Ref: Front Plant Sci, 12:793459, 2021 : PubMed
Abstract


ESTHER: Wu_2021_Front.Plant.Sci_12_793459
PubMedSearch: Wu 2021 Front.Plant.Sci 12 793459
PubMedID: 34970291

Abstract

LOW GERMINATION STIMULANT 1 (LGS1) plays an important role in strigolactones (SLs) biosynthesis and Striga resistance in sorghum, but the catalytic function remains unclear. Using the recently developed SL-producing microbial consortia, we examined the activities of sorghum MORE AXILLARY GROWTH1 (MAX1) analogs and LGS1. Surprisingly, SbMAX1a (cytochrome P450 711A enzyme in sorghum) synthesized 18-hydroxy-carlactonoic acid (18-hydroxy-CLA) directly from carlactone (CL) through four-step oxidations. The further oxidated product orobanchol (OB) was also detected in the microbial consortium. Further addition of LGS1 led to the synthesis of both 5-deoxystrigol (5DS) and 4-deoxyorobanchol (4DO). Further biochemical characterization found that LGS1 functions after SbMAX1a by converting 18-hydroxy-CLA to 5DS and 4DO possibly through a sulfonation-mediated pathway. The unique functions of SbMAX1 and LGS1 imply a previously unknown synthetic route toward SLs.



        

Title: Biocatalysis: Enzymatic Synthesis for Industrial Applications
Wu S, Snajdrova R, Moore JC, Baldenius K, Bornscheuer UT
Ref: Angew Chem Int Ed Engl, 60:88, 2021 : PubMed
Abstract


ESTHER: Wu_2021_Angew.Chem.Int.Ed.Engl_60_88
PubMedSearch: Wu 2021 Angew.Chem.Int.Ed.Engl 60 88
PubMedID: 32558088

Abstract

Biocatalysis has found numerous applications in various fields as an alternative to chemical catalysis. The use of enzymes in organic synthesis, especially to make chiral compounds for pharmaceuticals as well for the flavors and fragrance industry, are the most prominent examples. In addition, biocatalysts are used on a large scale to make specialty and even bulk chemicals. This review intends to give illustrative examples in this field with a special focus on scalable chemical production using enzymes. It also discusses the opportunities and limitations of enzymatic syntheses using distinct examples and provides an outlook on emerging enzyme classes.



        

Title: Double-enzymes-mediated fluorescent assay for sensitive determination of organophosphorus pesticides based on the quenching of upconversion nanoparticles by Fe(3)
Lin X, Yu Q, Yang W, He C, Zhou Y, Duan N, Wu S
Ref: Food Chem, 345:128809, 2020 : PubMed
Abstract


ESTHER: Lin_2020_Food.Chem_345_128809
PubMedSearch: Lin 2020 Food.Chem 345 128809
PubMedID: 33338834

Abstract

Herein, a new double-enzymes-modulated fluorescent assay based on the quenching of upconversion nanoparticles (UCNPs) by Fe(3+) was constructed for sensitive determination of OPs. OPs can inhibit the activity of acetylcholinesterase to reduce the production of choline and further lead to the lack of H(2)O(2) in the presence of choline oxidase. Therefore, Fe(2+) cannot be converted into Fe(3+), resulting in "turn-on" fluorescence of UCNPs. Under optimal conditions, an excellent linear correlation between the inhibition efficiency and the logarithm of the chlorpyrifos concentration was achieved with a detection limit (LOD) of 6.7 ng/mL in the range of 20-2000 ng/mL. The recovery for chlorpyrifos in apples and cucumbers was 89.5-97.1%. The results were consistent with those obtained by GC-MS. Overall, the integration of UCNPs into the double-enzymes-mediated Fe(3+)/Fe(2+) conversion endows this method with desirable rapidity, sensitivity, selectivity, stability, operational simplicity, and strong anti-interference capability, holding great potential in the application of food safety.



        

Title: A sensitive fluorescent assay for the determination of parathion-methyl using AHNSA probe with MnO(2) nanosheets
Liu B, Peng Z, Wu S, He T, Qiu P
Ref: Spectrochim Acta A Mol Biomol Spectrosc, 247:119146, 2020 : PubMed
Abstract


ESTHER: Liu_2020_Spectrochim.Acta.A.Mol.Biomol.Spectrosc_247_119146
PubMedSearch: Liu 2020 Spectrochim.Acta.A.Mol.Biomol.Spectrosc 247 119146
PubMedID: 33186817

Abstract

In this paper, a novel fluorescence assay has been constructed for the determination of parathion-methyl (PM) by using 4-amino-3-hydroxy-1-naphthalenesulfonic acid (AHNSA) as probe. MnO(2) nanosheets (MnO(2) NS) could quench the fluorescence of AHNSA, while Mn(2+), the reduction product of MnO(2) NS, has no influence on it, resulting in fluorescence recovery. This is because that MnO(2) NS have oxidized characteristic, and they can react with choline (TCh), which is the product of acetylthiocholine (ATCh) catalyzed by acetylcholinesterase (AChE). In the presence of OPs, the activity of AChE was inhibited, accompanied by the restraint of the redox reaction of MnO(2) NS, therefore the fluorescence of AHNSA was quenched. Under the optimized experimental conditions, a linear range of PM was determined to be 0.4-40 ng/mL (R(2) = 0.997) by the proposed method with the limit of detection for 0.18 ng/mL (S/N = 3). The assay was successfully applied to the determination of PM in lake water, which average recoveries were between 86.5% and 114.4%.



        

Title: Surgical Choice for Different Types of Gallbladder Adenomyomatosis: An Initial Experience of 20 Years Laparoscopic Cholecystectomy
Pang L, Wu S, Kong J
Ref: Surg Laparosc Endosc Percutan Tech, :, 2020 : PubMed
Abstract


ESTHER: Pang_2020_Surg.Laparosc.Endosc.Percutan.Tech__
PubMedSearch: Pang 2020 Surg.Laparosc.Endosc.Percutan.Tech
PubMedID: 32108730

Abstract

OBJECTIVES: The objective of this study was to compare the difference of clinical biochemical statistics in different types of gallbladder adenomyomatosis (GA). To investigate the different effects of patients between the 3 different types of GA. MATERIALS AND METHODS: Retrospective analysis of the clinical data of the adenomyomatosis patients that come from our hospital between 2010 to 2018. According to the preoperative image (all cases are performed as elective surgery), it could be divided into 3 groups: group A: fundal (localized) type; group B: segmental type; group C: diffuse type. The number of each group is 136, 27, 17. We analyze the biochemical statistics (total bilirubin, direct bilirubin, serum bile acid, alanine aminotransferase, aspartate aminotransferase, cholinesterase, etc.) of the 3 groups to explore the difference in operative mode, operative time and prognosis between these 3 groups. RESULTS: (1) In the liver function statistics, aspartate aminotransferase has the statistical significance (F=4.974, P=0.012); (2) And the diffuse adenomyomatosis might have a higher bile acid (F=6.048, P=0.005); (3) The segmental and diffuse adenomyomatosis is easier to be combined with stones (F=19.226, P<0.001); (4) The fundal adenomyomatosis seems to have a better prognosis: fewer hospital stay (F=4.519, P=0.018), fewer drainage time (F=6.575, P=0.004) and fewer complications (chi=29.429, P<0.001). CONCLUSIONS: GA is a disease characterized by epithelial proliferation and hypertrophy of the muscles of the gallbladder wall with an outpouching of the mucosa into or through the thickened muscular layer and cannot be regarded as a precancerous lesion based on available evidence. As for asymptomatic GA, conservative treatment is recommended with ultrasound examinations twice a year. The fundal type GA can be treated by partial laparoscopic cholecystectomy. The segmental and diffuse-type should undergo a total laparoscopic cholecystectomy.



        

Title: Identification and characterization of a novel phthalate-degrading hydrolase from a soil metagenomic library
Qiu J, Zhang Y, Shi Y, Jiang J, Wu S, Li L, Shao Y, Xin Z
Ref: Ecotoxicology & Environmental Safety, 190:110148, 2020 : PubMed
Abstract


ESTHER: Qiu_2020_Ecotoxicol.Environ.Saf_190_110148
PubMedSearch: Qiu 2020 Ecotoxicol.Environ.Saf 190 110148
PubMedID: 31911388
Gene_locus related to this paper: 9zzzz-EstJ6

Abstract

Phthalate esters have raised public concerns owing to their effects on the environment and human health. We identified a novel phthalate-degrading hydrolase, EstJ6, from a metagenomic library using function-driven screening. Phylogenetic analysis indicated that EstJ6 is a member of family IV esterases. EstJ6 hydrolyzed various dialkyl and monoalkyl phthalate esters, and exhibited high hydrolytic activity (128 U/mg) toward dibutyl phthalate at 40 degrees C and pH 7.5. EstJ6 hydrolyzed not only common phthalate esters with simple side chains but also diethylhexyl phthalate and monoethylhexyl phthalate, which have complex and long side chains. Site-directed mutagenesis indicated that the catalytic triad residues of EstJ6 consists of Ser146, Glu240, and His270. EstJ6 is therefore a promising biodegradation enzyme, and our study illustrates the advantages of a metagenomic approach in identifying enzyme-coding genes for agricultural, food, and biotechnological applications.



        

Title: Biodegradation of bis(2-hydroxyethyl) terephthalate by a newly isolated Enterobacter sp. HY1 and characterization of its esterase properties
Qiu L, Yin X, Liu T, Zhang H, Chen G, Wu S
Ref: J Basic Microbiol, 60:699, 2020 : PubMed
Abstract


ESTHER: Qiu_2020_J.Basic.Microbiol_60_699
PubMedSearch: Qiu 2020 J.Basic.Microbiol 60 699
PubMedID: 32510669

Abstract

Bis(2-hydroxyethyl) terephthalate (BHET) is an important compound produced from poly(ethylene terephthalate) (PET) cleavage. It was selected as the representative substance for the study of PET degradation. A bacterial strain HY1 that could degrade BHET was isolated and identified as Enterobacter sp. The optimal temperature and pH for BHET biodegradation were determined to be 30 degreesC and 8.0, respectively. The half-life of degradation was 70.20h at an initial BHET concentration of 1,000mg/L. The results of metabolites' analysis by liquid chromatograph-mass spectrometer revealed that BHET was first converted to mono-(2-hydroxyethyl) terephthalate (MHET) and then to terephthalic acid. Furthermore, an esterase-encoding gene, estB, was cloned from strain HY1, and the expressed enzyme EstB was characterized. The esterase has a molecular mass of approximately 25.13kDa, with an isoelectric point of 4.68. Its optimal pH and temperature were pH 8.0 and 40 degreesC, respectively. The analysis of the enzymatic products showed that EstB could hydrolyze one ester bond of BHET to MHET. To the best of authors' knowledge, this is the first report on the biodegradation characteristics of BHET by a member of the Enterobacter genus.



        

Title: Characterization of a novel hyper-thermostable and chlorpyrifos-hydrolyzing carboxylesterase EstC: A representative of the new esterase family XIX
Wang B, Wu S, Chang X, Chen J, Ma J, Wang P, Zhu G
Ref: Pestic Biochem Physiol, 170:104704, 2020 : PubMed
Abstract


ESTHER: Wang_2020_Pestic.Biochem.Physiol_170_104704
PubMedSearch: Wang 2020 Pestic.Biochem.Physiol 170 104704
PubMedID: 32980065
Gene_locus related to this paper: strco-estli
Inhibitor(s) related to this paper: Chlorpyrifos

Abstract

Carboxylesterases have widely been used in a series of industrial applications, especially, the detoxification of pesticide residues. In the present study, EstC, a novel carboxylesterase from Streptomyces lividans TK24, was successfully heterogeneously expressed, purified and characterized. Phylogenetic analysis showed that EstC can be assigned as the first member of a novel family XIX. Multiple sequence alignment indicated that EstC has highly conserved structural features, including a catalytic triad formed by Ser155, Asp248 and His278, as well as a canonical Gly-His-Ser-Ala-Gly pentapeptide. Biochemical characterization indicated that EstC exhibited maximal activity at pH 9.0 (Tris-HCl buffer) and 55 degC. It also showed higher activity towards short-chain substrates, with the highest activity for p-nitrophenyl acetate (pNPA2) (K(m) = 0.31 +/- 0.02 mM, k(cat)/K(m) = 1923.35 +/- 9.62 s(-1) mM(-1)) compared to other pNP esters used in this experiment. Notably, EstC showed hyper-thermostability and good alkali stability. The activity of EstC had no significant changes when it was incubated under 55 degC for 100 h and reached half-life after incubation at 100 degC for 8 h. Beyond that, EstC also showed stability at pH ranging from 6.0 to 11.0 and about 90% residual activity still reserved after treatment at pH 8.0 or 9.0 for 26 h, especially. Furthermore, EstC had outstanding potential for bioremediation of chlorpyrifos-contaminated environment. The recombinant enzyme (0.5 U mL(-1)) could hydrolyze 79.89% chlorpyrifos (5 mg L(-1)) at 37 degC within 80 min. These properties will make EstC have a potential application value in various industrial productions and detoxification of chlorpyrifos residues.



        

Title: A new fluorescent probe for sensing of biothiols and screening of acetylcholinesterase inhibitors
Wu S, Li Y, Deng T, Wang X, Hu S, Peng G, Huang XA, Ling Y, Liu F
Ref: Org Biomol Chem, :, 2020 : PubMed
Abstract


ESTHER: Wu_2020_Org.Biomol.Chem__
PubMedSearch: Wu 2020 Org.Biomol.Chem
PubMedID: 32167516

Abstract

A new N2O-type BODIPY probe (LF-Bop) has been proposed for the selective and sensitive detection of biologically relevant small molecular thiols. This detection is based on the Michael addition reaction between the thiol and nitrostyrene groups in the probe, which decreases the quenching effect from the nitro group, thus resulting in the recovery of the deep-red fluorescence from the BODIPY structure. The results show that LF-Bop is able to detect all tested free thiols through a fluorescence turn-on assay. The lowest limit of detection (LOD) for glutathione was found to be down to nanomolar levels (220 nM). Based on this probe, we have developed a new fluorescence assay for the screening of acetylcholinesterase inhibitors. In total, 11 natural and synthetic alkaloids have been evaluated. Both experimental measurements and theoretical molecular docking results reveal that both natural berberine and its synthetic derivative dihydroberberine are potential inhibitors of acetylcholinesterase.



        

Title: Schizophreniaassociated microRNA148b3p regulates COMT and PRSS16 expression by targeting the ZNF804A gene in human neuroblastoma cells
Wu S, Wang P, Tao R, Yang P, Yu X, Li Y, Shao Q, Nie F, Ha J and Ma J <2 more author(s)> Wu S, Wang P, Tao R, Yang P, Yu X, Li Y, Shao Q, Nie F, Ha J, Zhang R, Tian Y, Ma J (- 2)
Ref: Mol Med Rep, 22:1429, 2020 : PubMed
Abstract


ESTHER: Wu_2020_Mol.Med.Rep_22_1429
PubMedSearch: Wu 2020 Mol.Med.Rep 22 1429
PubMedID: 32626976
Gene_locus related to this paper: human-PRSS16

Abstract

Zinc finger protein 804A (ZNF804A) has been identified by genomewide association studies as a robust risk gene in schizophrenia, but how ZNF804A contributes to schizophrenia and its upstream regulation remains unknown. Previous studies have indicated that microRNAs (miRs) are key factors that regulate the expression levels of their target genes. The present study revealed significantly increased expression of miR148b3p in the peripheral blood of patients with firstonset schizophrenia compared with healthy controls, and bioinformatics analysis predicted that the ZNF804A gene is a target of miR148b3p. Therefore, the present study investigated the possible upstream regulation of ZNF804A by miR148b3p in the human neuroblastoma SHSY5Y cell line, and assessed the implications for schizophrenia. The results revealed significantly reversed expression levels of miR148b3p (P=0.0051) and ZNF804A (P=0.0218) in the peripheral blood of patients with firstonset schizophrenia compared with healthy individuals. Furthermore, it was demonstrated that miR148b3p directly targeted ZNF804A via binding to conserved target sites in the 3'untranslated region of ZNF804A mRNA, where it inhibited the endogenous expression of ZNF804A at both the mRNA (P=0.048) and protein levels (P=0.013) in SHSY5Y cells. Furthermore, miR148b3p was revealed to regulate the expression levels of catecholOmethyltransferase (COMT) and serine protease 16 (PRSS16) by targeting ZNF804A in SHSY5Y cells. Collectively, the present results indicated that there was a direct upstream regulation of the schizophrenia risk gene ZNF804A by miR148b3p, which contributed to the regulation of the downstream genes COMT and PRSS16. Thus, the miR148b3p/ZNF804A/COMT/PRSS16 pathway may play an important role in the pathophysiology of schizophrenia, and may serve as a potential target in drug discovery and gene therapy for this disorder.



        

Title: Identification of ovalbumin-derived peptides as multi-target inhibitors of AChE, BChE and BACE1
Yu Z, Dong W, Wu S, Shen J, Zhao W, Ding L, Liu J, Zheng F
Ref: J Sci Food Agric, :, 2020 : PubMed
Abstract


ESTHER: Yu_2020_J.Sci.Food.Agric__
PubMedSearch: Yu 2020 J.Sci.Food.Agric
PubMedID: 31997357

Abstract

BACKGROUND: Alzheimer's disease (AD) is a kind of progressive neurodegenerative disease that occurs to the elderly. But there is no ideal treatment for AD. Thus, the purpose of this study is to identify anti-AD peptides from ovalbumin. RESULTS: The potential tripeptides IEK, LYR and CIK were selected for molecular docking. The '-CDOCKER_Energy' value of the best docking position of the tripeptide IEK, LYR and CIK interacting with acetylcholinesterase (AChE) were - 93.8119, -86.9556 and - 73.6370 kcal/mol, respectively. The '-CDOCKER_Energy' values for interaction with butyrylcholinesterase (BChE) were - 96.6386, -80.8392 and - 87.4341 kcal/mol, respectively. Most importantly, the '-CDOCKER_Energy' values for interaction with beta-site amyloid precursor protein cleavage enzyme1 (BACE1) were - 85.5903, -71.3342 and - 68.4290 kcal/mol, respectively. Overall, in vitro assays results demonstrated that peptide CIK exhibited impressive inhibitory activities against AChE, BChE, and BACE1, with the IC50 value of 6.76, 7.72, and 34.48 muM, respectively. Especially, CIK can be contacted with some peripheral anion sites (PAS) and catalytic sites on AChE, BChE and BACE1. CONCLUSION: Tripeptide CIK can effectively inhibit the activities of AChE, BChE and BACE1. Therefore, tripeptide CIK has the potential to effectively treat AD. This article is protected by copyright. All rights reserved.



        

Title: Ethanol extracts from Cinnamomum camphora seed kernel: Potential bioactivities as affected by alkaline hydrolysis and simulated gastrointestinal digestion
Zhang G, Yan X, Wu S, Ma M, Yu P, Gong D, Deng S, Zeng Z
Ref: Food Res Int, 137:109363, 2020 : PubMed
Abstract


ESTHER: Zhang_2020_Food.Res.Int_137_109363
PubMedSearch: Zhang 2020 Food.Res.Int 137 109363
PubMedID: 33233066

Abstract

The aim of the study was to evaluate the changes of potential bioactivities of ethanol extracts (EE) from Cinnamomum camphora seed kernel (CCSK) after alkaline hydrolysis and simulated gastrointestinal digestion. A total of 13 compounds in EE, mainly phenolics and saponins were tentatively identified using HPLC-ESI-QTOF-MS(2) analysis. The total phenolic and total flavonoid contents in EE decreased by 30.6%, 1%, 33% and 11.8% after hydrolysis and digestion, respectively. The total saponins content decreased by 17% after hydrolysis while increased by 48% after digestion. The total condensed tannin contents increased by 70.3% and 17.2% after hydrolysis and digestion, respectively. The 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2'-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid (ABTS), cupric ion reducing activity (CUPRAC), ferric reducing antioxidant power (FRAP) and metal chelating activity (MCA) were used to determine antioxidant activity. Overall, the changes of antioxidant activities by hydrolysis and digestion were consistent with the changes of their total phenolic and flavonoid contents. The alpha-amylase and alpha-glucosidase inhibitory activities in EE increased by 817% and 33.3% after digestion while decreased by 12.3% and 19% after hydrolysis, respectively. Although the inhibitory activities of cholinesterase, tyrosinase and xanthine oxidase were decreased by hydrolysis and digestion, most of these activities were retained. These results showed that CCSK ethanol extracts had strong bioactivities and were reasonably stable to alkali and digestive enzymes.



        

Title: Structure of a gut microbial diltiazem-metabolizing enzyme suggests possible substrate binding mode
Zhou S, Ko TP, Huang JW, Liu W, Zheng Y, Wu S, Wang Q, Xie Z, Liu Z and Guo RT <1 more author(s)> Zhou S, Ko TP, Huang JW, Liu W, Zheng Y, Wu S, Wang Q, Xie Z, Liu Z, Chen CC, Guo RT (- 1)
Ref: Biochemical & Biophysical Research Communications, :, 2020 : PubMed
Abstract


ESTHER: Zhou_2020_Biochem.Biophys.Res.Commun__
PubMedSearch: Zhou 2020 Biochem.Biophys.Res.Commun
PubMedID: 32423809

Abstract

When administrated orally, the vasodilating drug diltiazem can be metabolized into diacetyl diltiazem in the presence of Bacteroides thetaiotaomicron, a human gut microbe. The removal of acetyl group from the parent drug is carried out by the GDSL/SGNH-family hydrolase BT4096. Here the crystal structure of the enzyme was solved by mercury soaking and single-wavelength anomalous diffraction. The protein folds into two parts. The N-terminal part comprises the catalytic domain which is similar to other GDSL/SGNH hydrolases. The flanking C-terminal part is made up of a beta-barrel subdomain and an alpha-helical subdomain. Structural comparison shows that the catalytic domain is most akin to acetyl-xylooligosaccharide esterase and allows a plausible binding mode of diltiazem to be proposed. The beta-barrel subdomain is similar in topology to the immunoglobulin-like domains, including some carbohydrate-binding modules, of various bacterial glycoside hydrolases. Consequently, BT4096 might originally function as an oligosaccharide deacetylase with additional subdomains that could enhance substrate binding, and it acts on diltiazem just by accident.



        

Title: Preparation of DHA-Rich Medium- and Long-Chain Triacylglycerols by Lipase-Catalyzed Acidolysis of Microbial Oil from Schizochytrium sp.with Medium-Chain Fatty Acids
Zou X, Ye L, He X, Wu S, Zhang H, Jin Q
Ref: Appl Biochem Biotechnol, 191:1294, 2020 : PubMed
Abstract


ESTHER: Zou_2020_Appl.Biochem.Biotechnol_191_1294
PubMedSearch: Zou 2020 Appl.Biochem.Biotechnol 191 1294
PubMedID: 32096059

Abstract

DHA-rich medium- and long-chain triacylglycerols (MLCT) were produced by lipase-catalyzed acidolysis of microbial oil from Schizochytrium sp. with medium-chain fatty acids (MCFA). Four commercial lipases, i.e., NS40086, Novozym 435, Lipozyme RM IM, and Lipozyme TL IM were screened based on their activity and fatty acid specificity. The selected conditions for MLCT synthesis were Lipozyme RM IM as catalyst, reaction time 6 h, lipase load 8 wt%, substrate molar ratio (MCFA/microbial oil) 3:1, and temperature 55 degreeC. Under the selected conditions, the lipase could be reused successively for 17 cycles without significant loss of lipase activity. The obtained product contained 27.53% MCFA, 95.29% at sn-1,3 positions, and 44.70% DHA, 69.77% at sn-2 position. Fifty-nine types of triacylglycerols (TAG) were identified, in which 35 types of TAG contained MCFA, the content accounting for 55.35%. This product enriched with DHA at sn-2 position and MCFA at sn-1,3 positions can improve its digestion and absorption under an infant's digestive system, and thus has potential to be used in infant formula to increase the bioavailability of DHA.



        

Title: Identification of a Novel Feruloyl Esterase by Functional Screening of a Soil Metagenomic Library
Li X, Guo J, Hu Y, Yang Y, Jiang J, Nan F, Wu S, Xin Z
Ref: Appl Biochem Biotechnol, 187:424, 2019 : PubMed
Abstract


ESTHER: Li_2019_Appl.Biochem.Biotechnol_187_424
PubMedSearch: Li 2019 Appl.Biochem.Biotechnol 187 424
PubMedID: 29968147

Abstract

A cosmid metagenomic library containing 1.3 x 10(5) clones was created from a soil sample. A novel gene (fae-xuan) encoding a feruloyl esterase was identified through functional screening. Primary sequence analysis showed that the gene consisted of 759 base pairs and encoded a protein of 252 amino acids. The gene was expressed in Escherichia coli BL21 (DE3) and the corresponding purified recombinant enzyme exhibited a molecular weight of 29 kDa. The FAE-Xuan showed high activity (40.0 U/mg) toward methyl ferulate with an optimal temperature and pH of 30 degreesC and 5.0, respectively. Besides methyl ferulate, FAE-Xuan can also hydrolyze methyl sinapate and methyl p-coumarate. The substrate utilization preferences and phylogenetic analysis indicated that FAE-Xuan belongs to type A FAE. FAE-Xuan was quite stable over a broad pH range from 3.0 to 10.0. The activity reduced remarkably in presence of Cu(2+). FAE-Xuan can enhance the quantity of ferulic acid from de-starched wheat bran in presence of xylanase. The work presented here highlighted the effectiveness of metagenomic strategy in identifying novel FAEs with diverse properties for potential use in industrial production.



        

Title: A Novel VIII Carboxylesterase with High Hydrolytic Activity Against Ampicillin from a Soil Metagenomic Library
Nan F, Jiang J, Wu S, Zhang Y, Qiu J, Qiao B, Li S, Xin Z
Ref: Mol Biotechnol, 61:892, 2019 : PubMed
Abstract


ESTHER: Nan_2019_Mol.Biotechnol_61_892
PubMedSearch: Nan 2019 Mol.Biotechnol 61 892
PubMedID: 31664703

Abstract

A novel carboxylesterase gene, named dlfae4, was discovered and sequenced from a soil metagenomic library. The dlfae4 gene was composed of 1017 base pairs encoding 338 amino acid residues with a predicted molecular mass of 37.2 kDa. DLFae4 exhibited strong hydrolytic activity towards methyl ferulate under optimum pH and temperature conditions (pH 8.6, 50 degrees C) and displayed remarkable thermostability, with residual activity as high as 50% after incubation for 3 h at 60 degrees C. A family VIII esterase DLFae4 was found to contain a typical serine residue within the S-X-X-K motif, which serves as a catalytic nucleophile in class C beta-lactamases and family VIII esterases. As a consequence of its high sequence similarity with beta-lactamases, DLFae4 exhibited significant hydrolytic activity towards ampicillin. In addition, DLFae4 was found to be the first known member of family VIII carboxylesterases with phthalate-degrading ability. Site-directed mutagenesis studies revealed that Ser11, Lys14, and Tyr121 residues play an essential catalytic role in DLFae4. These new findings, which are of great importance for further in-depth research and engineering development of carboxylesterases, should advance the implementation of biotechnological applications.



        

Title: ABHD5 blunts the sensitivity of colorectal cancer to fluorouracil via promoting autophagic uracil yield
Ou J, Peng Y, Yang W, Zhang Y, Hao J, Li F, Chen Y, Zhao Y, Xie X and Liang H <8 more author(s)> Ou J, Peng Y, Yang W, Zhang Y, Hao J, Li F, Chen Y, Zhao Y, Xie X, Wu S, Zha L, Luo X, Xie G, Wang L, Sun W, Zhou Q, Li J, Liang H (- 8)
Ref: Nat Commun, 10:1078, 2019 : PubMed
Abstract


ESTHER: Ou_2019_Nat.Commun_10_1078
PubMedSearch: Ou 2019 Nat.Commun 10 1078
PubMedID: 30842415
Gene_locus related to this paper: human-ABHD5

Abstract

The efficacy of Fluorouracil (FU) in the treatment of colorectal cancer (CRC) is greatly limited by drug resistance. Autophagy has been implicated in chemoresistance, but the role of selective autophagic degradation in regulating chemoresistance remains unknown. In this study, we revealed a critical role of ABHD5 in charging CRC sensitivity to FU via regulating autophagic uracil yield. We demonstrated that ABHD5 localizes to lysosome and interacts with PDIA5 to prevent PDIA5 from interacting with RNASET2 and inactivating RNASET2. ABHD5 deficiency releases PDIA5 to directly interact with RNASET2 and leave RNASET2 in an inactivate state, which impairs RNASET2-mediated autophagic uracil yield and promotes CRC cells to uptake FU as an exogenous uracil, thus increasing their sensitivity to FU. Our findings for the first time reveal a novel role of ABHD5 in regulating lysosome function, highlighting the significance of ABHD5 as a compelling biomarker predicting the sensitivity of CRCs to FU-based chemotherapy.



        

Title: Pharmacokinetics, excretion and metabolites analysis of DL0410, a dualacting cholinesterase inhibitor and histamine3 receptor antagonist
Pang X, Zhao Y, Song J, Kang, Wu S, Wang L, Liu A, Du G
Ref: Mol Med Rep, 20:1103, 2019 : PubMed
Abstract


ESTHER: Pang_2019_Mol.Med.Rep_20_1103
PubMedSearch: Pang 2019 Mol.Med.Rep 20 1103
PubMedID: 31173186
Inhibitor(s) related to this paper: DL0410

Abstract

DL0410, a dualaction cholinesterase inhibitor and histamine3 receptor antagonist with a novel structural scaffold, may be a potential candidate for the treatment of Alzheimer's disease (AD). To the best of the authors' knowledge, this is the first study to demonstrate a reliable method for the measurement of DL0410 in rat plasma, brain, bile, urine and feces samples, and identification of its primary metabolites. The pharmacokinetic properties of DL0410 were analyzed by liquid chromatographymass spectrometry at oral doses of 25, 50 and 100 mg/kg and intravenous dose of 5 mg/kg. The investigation of the excretion and metabolism of DL0410 was determined following liquidliquid extraction for biliary, urinary and fecal samples. Finally, the cytochrome (CY)P450 isoforms involved in the production of DL0410 metabolites with recombinant human cytochrome P450 enzymes were characterized. The results suggested that DL0410 was not well absorbed; however, was distributed to the entorhinal cortex and hippocampus of the brain. A total of two common metabolites of the reduction of DL0140 in the bile, urine and feces were identified and CYP2D6 was involved in this reaction. The pharmacokinetic results of DL0410 provided information for the illustration of its pharmacodynamic properties, mechanism of action and promoted its continued evaluation as a therapeutic agent for AD treatment.



        

Title: Pleiotropic association of LIPC variants with lipid and urinary 8-hydroxy deoxyguanosine levels in a Taiwanese population
Teng MS, Wu S, Hsu LA, Tzeng IS, Chou HH, Su CW, Ko YL
Ref: Lipids Health Dis, 18:111, 2019 : PubMed
Abstract


ESTHER: Teng_2019_Lipids.Health.Dis_18_111
PubMedSearch: Teng 2019 Lipids.Health.Dis 18 111
PubMedID: 31077211

Abstract

BACKGROUND: Hepatic lipase (HL, encoded by LIPC) is a glycoprotein primarily synthesized and secreted by hepatocytes. Previous studies had demonstrated that HL is crucial for reverse cholesterol transport and affects the metabolism, composition, and level of several lipoproteins. In current study, we investigated the association of LIPC (Lipase C, Hepatic Type) variants with circulating and urinary biomarker levels by using subgroup and mediation analyses. METHODS: A total of 572 participants from Taiwan were genotyped for three LIPC single nucleotide polymorphisms (SNPs) by using TaqMan assay. Fasting levels of glucose, lipid profile, inflammation markers, urine creatinine and 8-hydroxy deoxyguanosine (8-OHdG) were measured. The chi-square test, 2-sample t test and Analysis of variance (ANOVA) were used to examine differences among variables and genotype frequencies. RESULTS: SNPs rs2043085 and rs1532085 were significantly associated with urinary 8-OHdG levels, whereas all three SNPs were more significantly associated with Triglycerides (TG) or HDL-cholesterol (HDL-C) levels after additional adjustment for HDL-C or TG levels, respectively. Subgroup analyses revealed that the association of the LIPC SNPs with the levels of serum TG, HDL-C, and urinary 8-OHdG were predominantly observed in the men but not in the women. Differential associations of the LIPC SNPs with various lipid levels were observed in participants with different adiposity statuses. Mediation analyses indicated that TG levels acted as a suppressor masking the association of the LIPC genotypes with HDL-C levels, particularly in the men (Sobel test, all P < 0.01). CONCLUSION: Our data revealed that interaction and suppression effects mediated the pleiotropic association of the LIPC variants. The effects of the LIPC SNPs depended on sex, adiposity status, and TG levels. Thus, our findings can provide a method for identifying high-risk populations of cardiovascular diseases for clinical diagnosis.



        

Title: Design, synthesis, and evaluation of isoflavone analogs as multifunctional agents for the treatment of Alzheimer's disease
Wang D, Hu M, Li X, Zhang D, Chen C, Fu J, Shao S, Shi G, Zhou Y and Zhang T <1 more author(s)> Wang D, Hu M, Li X, Zhang D, Chen C, Fu J, Shao S, Shi G, Zhou Y, Wu S, Zhang T (- 1)
Ref: Eur Journal of Medicinal Chemistry, 168:207, 2019 : PubMed
Abstract


ESTHER: Wang_2019_Eur.J.Med.Chem_168_207
PubMedSearch: Wang 2019 Eur.J.Med.Chem 168 207
PubMedID: 30822710

Abstract

A series of novel isoflavone analogs were designed, synthesized, and evaluated as multitarget-directed ligands for the treatment of Alzheimer's disease. In vitro evaluations revealed that some ligands had multifunctional profiles, including potent blockage of histamine 3 receptor (H3R), excellent inhibition of acetylcholinesterase (AChE), neuroprotective effects and anti-neuroinflammatory properties. Among these derivatives, compound 9b exhibited the highest ability to block H3R (IC50=0.27muM) and good inhibitory activity against AChE (IC50=0.08muM). Additionally, compound 9b showed obvious neuroprotective effect on SH-SY5Y by preventing copper-induced neuronal damage and potent anti-neuroinflammatory activity by inhibiting the production of inflammatory factors on BV-2cells. A molecular modeling study revealed that 9b acts as a mixed-type inhibitor that interacts simultaneously with H3R and AChE. Moreover, in vivo data revealed that compound 9b did not cause acute toxicity in mice at doses up to 1000mg/kg, and had desirable pharmacokinetic properties, as well as a good blood-brain barrier (BBB) permeability (log BB=1.24+/-0.07). Further studies demonstrated that chronic oral treatment with 9b significantly improved cognitive dysfunction in scopolamine-induced AD mice in the step-down passive avoidance test. Taken together, the present study showed that compound 9b is a promising multifunctional drug candidate for the treatment of Alzheimer's disease.



        

Title: Enhancing the atypical esterase promiscuity of the gamma-lactamase Sspg from Sulfolobus solfataricus by substrate screening
Wang J, Zhao H, Zhao G, Chen D, Tao Y, Wu S
Ref: Applied Microbiology & Biotechnology, 103:4077, 2019 : PubMed
Abstract


ESTHER: Wang_2019_Appl.Microbiol.Biotechnol_103_4077
PubMedSearch: Wang 2019 Appl.Microbiol.Biotechnol 103 4077
PubMedID: 30955078

Abstract

Promiscuous enzymes can be modified by protein engineering, which enables the catalysis of non-native substrates. gamma-lactamase Sspg from Sulfolobus solfataricus is an enzyme with high activity, high stability, and pronounced tolerance of high concentrations of the gamma-lactam substrate. These characteristics suggest Sspg as a robust enzymatic catalyst for the preparation of optically pure gamma-lactam. This study investigated the modification of this enzyme to expand its application toward resolving chiral esters. gamma-Lactamase-esterase conversion was performed by employing a three-step method: initial sequence alignment, followed by substrate screening, and protein engineering based on the obtained substrate-enzyme docking results. This process of fine-tuning of chemical groups on substrates has been termed "substrate screening." Steric hindrance and chemical reactivity of the substrate are major concerns during this step, since both are determining factors for the enzyme-substrate interaction. By employing this three-step method, gamma-lactamase Sspg was successfully converted into an esterase with high enantioselectivity towards phenylglycidate substrates (E value > 300). However, since both wild-type Sspg and Sspg mutants did not hydrolyze para-nitrophenyl substrates (pNPs), this esterase activity was termed "atypical esterase activity." The gamma-lactamase activity and stability of the Sspg mutants were not severely compromised. The proposed method can be applied to find novel multi-functional enzyme catalysts within existing enzyme pools.



        

Title: Molecular characterization of ABHD5 gene promoter in intramuscular preadipocytes of Qinchuan cattle: Roles of Evi1 and C/EBPalpha
Wang X, Khan R, Raza SHA, Li A, Zhang Y, Liang C, Yang W, Wu S, Zan L
Ref: Gene, 690:38, 2019 : PubMed
Abstract


ESTHER: Wang_2019_Gene_690_38
PubMedSearch: Wang 2019 Gene 690 38
PubMedID: 30583026
Gene_locus related to this paper: bovin-q0vcc8

Abstract

The genetic regulation of lipolytic enzyme is closely related to carcass quality traits through deposition of intramuscular fat (marbling) in beef cattle breeds. The alpha/beta hydrolase domain containing 5 (ABHD5) is an accelerating factor of adipose triglyceride lipase (ATGL), which plays a key role in triglyceride metabolism. In this study, we determined that bovine ABHD5 gene was highly expressed in adult bovine adipose tissue. To elucidate the molecular mechanisms involved in bovine ABHD5 regulation, we cloned and characterized the promoter region of ABHD5. Applying 5'-rapid amplification of cDNA end analysis (RACE), we identified transcriptional start site (TSS) found in the predicted CpG island within promoter region of ABHD5 gene. Using the recombinant dual fluorescent reporter vectors, the fragment of -109/+307 was identified as proximal minimum core promoter region of ABHD5 in bovine intramuscular adipocytes. Site directed mutagenesis and electrophoretic mobility shift assay (EMSA) confirmed the role of two transcription factors, namely Ectopic viral integration site-1 (Evi1) and CCAAT/enhancer binding protein alpha (C/EBPalpha), in the regulation of ABHD5 gene. Taken together these findings we can conclude that ABHD5 gene regulated by Evi1 and C/EBPalpha could be used as potential marker in marker assisted selection for the improvement of Qinchuan cattle breed for carcass quality traits.



        

Title: STAT3-induced upregulation of lncRNA ABHD11-AS1 promotes tumour progression in papillary thyroid carcinoma by regulating miR-1301-3p/STAT3 axis and PI3K/AKT signalling pathway
Wen J, Wang H, Dong T, Gan P, Fang H, Wu S, Li J, Zhang Y, Du R, Zhu Q
Ref: Cell Prolif, 52:e12569, 2019 : PubMed
Abstract


ESTHER: Wen_2019_Cell.Prolif_52_e12569
PubMedSearch: Wen 2019 Cell.Prolif 52 e12569
PubMedID: 30657221
Gene_locus related to this paper: human-ABHD11

Abstract

OBJECTIVES: Emerging evidences indicated the importance of long non-coding RNAs (lncRNAs) in the tumorigenesis and deterioration of malignant tumours. To our knowledge, the study about lncRNAs in papillary thyroid carcinoma (PTC) is still inadequate. ABHD11-AS1 was highly expressed in the PTC samples of The Cancer Genome Atlas database. This study focused on the biological function and mechanism of lncRNA ABHD11-AS1 in PTC. MATERIALS AND METHODS: qRT-PCR analysis was used to examine the expression of ABHD11-AS1 in PTC tissues and cell lines. The prognostic significance of ABHD11-AS1 for the patients with PTC was analysed with Kaplan-Meier analysis. The effects of ABHD11-AS1 knockdown on the cell proliferation and metastasis were evaluated by in vitro functional assays and in vivo experiments. The molecular mechanism which contributed to the oncogenic role of ABHD11-AS1 in PTC was explored by conducting mechanism experiments. Rescue assays were carried out for final demonstration. RESULTS: High expression of ABHD11-AS1 predicted poor prognosis for patients with PTC and promoted cell proliferation and metastasis in vitro and in vivo. ABHD11-AS1 was activated by the transcription factor STAT3. ABHD11-AS1 positively regulated PI3K/AKT signalling pathway. ABHD11-AS1 acted as a competitive endogenous (ce) RNA to upregulate STAT3 by sponging miR-1301-3p. CONCLUSIONS: STAT3-induced lncRNA ABHD11-AS1 promoted PTC progression by regulating PI3K/AKT signalling pathway and miR-1301-3p/STAT3 axis.



        

Title: Molecular cloning, expression and characterization of a novel feruloyl esterase from a soil metagenomic library with phthalate-degrading activity
Wu S, Nan F, Jiang J, Qiu J, Zhang Y, Qiao B, Li S, Xin Z
Ref: Biotechnol Lett, 41:995, 2019 : PubMed
Abstract


ESTHER: Wu_2019_Biotechnol.Lett_41_995
PubMedSearch: Wu 2019 Biotechnol.Lett 41 995
PubMedID: 31102076
Gene_locus related to this paper: pseai-a0a222d555

Abstract

OBJECTIVES: To discover novel feruloyl esterases (FAEs) by the function-driven screening procedure from soil metagenome. RESULTS: A novel FAE gene bds4 was isolated from a soil metagenomic library and over-expressed in Escherichia coli. The recombinant enzyme BDS4 was purified to homogeneity with a predicted molecular weight of 38.8 kDa. BDS4 exhibited strong activity (57.05 U/mg) toward methyl ferulate under the optimum pH and temperature of 8.0 and 37 degrees C. Based on its amino acid sequence and model substrates specificity, BDS4 was classified as a type-C FAE. The quantity of the releasing ferulic acid can be enhanced significantly in the presence of xylanase compared with BDS4 alone from de-starched wheat bran. In addition, BDS4 can also hydrolyze several phthalates such as diethyl phthalate, dimethyl phthalate and dibutyl phthalate. CONCLUSION: The current investigation discovered a novel FAE with phthalate-degrading activity and highlighted the usefulness of metagenomic approaches as a powerful tool for discovery of novel FAEs.



        

Title: Selection of Reference Genes for Expression Analysis in Chinese Medicinal Herb Huperzia serrata
Yang M, Wu S, You W, Jaisi A, Xiao Y
Ref: Front Pharmacol, 10:44, 2019 : PubMed
Abstract


ESTHER: Yang_2019_Front.Pharmacol_10_44
PubMedSearch: Yang 2019 Front.Pharmacol 10 44
PubMedID: 30774594

Abstract

Huperzine A (HupA) is a powerful and selective inhibitor of acetylcholinesterase. It has attracted widespread attention endangering the ultimate plant sources of Lycopodiaceae family. In this study, we used Huperzia serrata, extensively used in Traditional Chinese medicine (TCM), a slow growing vascular plant as the model plant of the Lycopodiaceae family to develop and validate the reference genes. We aim to use gene expression platform to understand the gene expression of different tissues and developmental stages of this medicinal herb. Eight candidate reference genes were selected based on RNA-seq data and evaluated with qRT-PCR. The expression of L/ODC and cytochrome P450s genes known for their involvement in lycopodium alkaloid biosynthesis, were also studied to validate the selected reference genes. The most stable genes were TBP, GAPDH, and their combination (TBP + GAPDH). We report for the first time the reference gene of H. serrata's different tissues which would provide important insights into understanding their biological functions comparing other Lycopodiaceae plants and facilitate a good biopharming approach.



        

Title: Clinical spectrum and genetic landscape for hereditary spastic paraplegias in China
Dong EL, Wang C, Wu S, Lu YQ, Lin XH, Su HZ, Zhao M, He J, Ma LX and Lin X <2 more author(s)> Dong EL, Wang C, Wu S, Lu YQ, Lin XH, Su HZ, Zhao M, He J, Ma LX, Wang N, Chen WJ, Lin X (- 2)
Ref: Mol Neurodegener, 13:36, 2018 : PubMed
Abstract


ESTHER: Dong_2018_Mol.Neurodegener_13_36
PubMedSearch: Dong 2018 Mol.Neurodegener 13 36
PubMedID: 29980238

Abstract

BACKGROUND: Hereditary spastic paraplegias (HSP) is a heterogeneous group of rare neurodegenerative disorders affecting the corticospinal tracts. To date, more than 78 HSP loci have been mapped to cause HSP. However, both the clinical and mutational spectrum of Chinese patients with HSP remained unclear. In this study, we aim to perform a comprehensive analysis of clinical phenotypes and genetic distributions in a large cohort of Chinese HSP patients, and to elucidate the primary pathogenesis in this population. METHODS: We firstly performed next-generation sequencing targeting 149 genes correlated with HSP in 99 index cases of our cohort. Multiplex ligation-dependent probe amplification testing was further carried out among those patients without known disease-causing gene mutations. We simultaneously performed a retrospective study on the reported patients exhibiting HSP in other Chinese cohorts. All clinical and molecular characterization from above two groups of Chinese HSP patients were analyzed and summarized. Eventually, we further validated the cellular changes in fibroblasts of two major spastic paraplegia (SPG) patients (SPG4 and SPG11) in vitro. RESULTS: Most patients of ADHSP (94%) are pure forms, whereas most patients of ARHSP (78%) tend to be complicated forms. In ADHSP, we found that SPG4 (79%) was the most prevalent, followed by SPG3A (11%), SPG6 (4%) and SPG33 (2%). Subtle mutations were the common genetic cause for SPG4 patients and most of them located in AAA cassette domain of spastin protein. In ARHSP, the most common subtype was SPG11 (53%), followed by SPG5 (32%), SPG35 (6%) and SPG46 (3%). Moreover, haplotype analysis showed a unique haplotype was shared in 14 families carrying c.334C > T (p.R112(*)) mutation in CYP7B1 gene, suggesting the founder effect. Functionally, we observed significantly different patterns of mitochondrial dynamics and network, decreased mitochondrial membrane potential (deltam), increased reactive oxygen species and reduced ATP content in SPG4 fibroblasts. Moreover, we also found the enlargement of LAMP1-positive organelles and abnormal accumulation of autolysosomes in SPG11 fibroblasts. CONCLUSIONS: Our study present a comprehensive clinical spectrum and genetic landscape for HSP in China. We have also provided additional evidences for mitochondrial and autolysosomal-mediated pathways in the pathogenesis of HSP.



        

Title: ( R)- N-(1-Methyl-2-hydroxyethyl)-13-( S)-methyl-arachidonamide (AMG315): A Novel Chiral Potent Endocannabinoid Ligand with Stability to Metabolizing Enzymes
Liu Y, Ji L, Eno M, Kudalkar S, Li AL, Schimpgen M, Benchama O, Morales P, Xu S and Nikas SP <13 more author(s)> Liu Y, Ji L, Eno M, Kudalkar S, Li AL, Schimpgen M, Benchama O, Morales P, Xu S, Hurst D, Wu S, Mohammad KA, Wood JT, Zvonok N, Papahatjis DP, Zhou H, Honrao C, Mackie K, Reggio P, Hohmann AG, Marnett LJ, Makriyannis A, Nikas SP (- 13)
Ref: Journal of Medicinal Chemistry, 61:8639, 2018 : PubMed
Abstract


ESTHER: Liu_2018_J.Med.Chem_61_8639
PubMedSearch: Liu 2018 J.Med.Chem 61 8639
PubMedID: 30196704

Abstract

The synthesis of potent metabolically stable endocannabinoids is challenging. Here we report a chiral arachidonoyl ethanolamide (AEA) analogue, namely, (13 S,1' R)-dimethylanandamide (AMG315, 3a), a high affinity ligand for the CB1 receptor ( Ki of 7.8 +/- 1.4 nM) that behaves as a potent CB1 agonist in vitro (EC50 = 0.6 +/- 0.2 nM). (13 S,1' R)-dimethylanandamide is the first potent AEA analogue with significant stability for all endocannabinoid hydrolyzing enzymes as well as the oxidative enzymes COX-2. When tested in vivo using the CFA-induced inflammatory pain model, 3a behaved as a more potent analgesic when compared to endogenous AEA or its hydrolytically stable analogue AM356. This novel analogue will serve as a very useful endocannabinoid probe.



        

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
Abstract


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: Association between FASN gene polymorphisms ultrasound carcass traits and intramuscular fat in Qinchuan cattle
Raza SHA, Gui L, Khan R, Schreurs NM, Xiaoyu W, Wu S, Mei C, Wang L, Ma X and Zan L <5 more author(s)> Raza SHA, Gui L, Khan R, Schreurs NM, Xiaoyu W, Wu S, Mei C, Wang L, Ma X, Wei D, Guo H, Zhang S, Wang X, Kaleri HA, Zan L (- 5)
Ref: Gene, 645:55, 2018 : PubMed
Abstract


ESTHER: Raza_2018_Gene_645_55
PubMedSearch: Raza 2018 Gene 645 55
PubMedID: 29273553
Gene_locus related to this paper: bovin-fas

Abstract

Fatty acid synthase (FASN) is an enzyme involved with fat deposition and fatty acid composition in cattle. This study was conducted to detect single nucleotide polymorphisms (SNPs) of the FASN gene and explore their relationships with ultrasound carcass traits in order to assess the potential use of the FASN gene for the breeding selection of Qinchuan cattle for desirable carcass traits. The frequencies of SNP g.12740C>T, g.13192T>C and g.13232C>T were identified in 525 individual Qinchuan cattle which were also assessed for backfat depth, eye muscle area and intramuscular fat by ultrasound. According to the PIC values, g.13192T>C possessed an intermediate polymorphism (0.25T, g.12740C>T possessed low polymorphism (PIC<0.25). Chi-square tests showed that g.13192T>C were in Hardy-Weinberg disequilibrium (c2C was associated with a greater eye muscle area and the TT genotype at g.13232C>T was associated with greater intramuscular fat. When these genotypes were combined there was no difference in eye muscle area and intramuscular fat between the diplotypes. The H2H2 diplotype was associated with carcass traits that are likely to provide economic advantage in Qinchuan cattle. Variations in the FASN genes and their corresponding genotypes may be considered as molecular markers for economic traits in cattle breeding.



        

Title: Di-branched triphenylamine dye sensitized TiO2 nanocomposites with good photo-stability for sensitive photoelectrochemical detection of organophosphate pesticides
Song J, Wu S, Xing P, Zhao Y, Yuan J
Ref: Anal Chim Acta, 1001:24, 2018 : PubMed
Abstract


ESTHER: Song_2018_Anal.Chim.Acta_1001_24
PubMedSearch: Song 2018 Anal.Chim.Acta 1001 24
PubMedID: 29291803
Inhibitor(s) related to this paper: TPHP

Abstract

Herein, a di-branched di-anchoring dye, T(TA)2, with triphenylamine as electron donor, thiophene as electron transfer pi-bridge, and acrylic acid as both acceptor and anchoring groups, was synthesized and coupled with TiO2 nanoparticles for the highly sensitive photoelectrochemical (PEC) assay of organophosphate pesticides (OPs). The T(TA)2 exhibited good anchoring stability to TiO2 nanoparticles in neutral buffer solutions. Under 2h continual irradiation, the T(TA)2-TiO2 nanocomposites respectively kept 99.7% and 85.9% of their initial photocurrents in neutral Tris-HCl and phosphate buffer solutions. Neither degradation nor desorption of T(TA)2 from TiO2 nanoparticles was observed during the continual irradiation in the Tris-HCl solutions. The stability was not only superior to its analogues either possessing one branch, with cyanoacrylic acid as anchoring groups, or without thiophene in the pi-bridge, but also better than the Ru(II) complex N719 and the porphyrin dye sensitized TiO2 nanocomposites. The nanocomposites also showed highly photocatalytic ability towards the oxidation of ascorbic acid and thiocholine (TCh). Since the latter is the enzymatic hydrolysis product of acetylcholinesterase (AChE) and the activity of AChE can be inhibited by OPs, the T(TA)2-TiO2/FTO was further used for PEC assay of OPs. Using parathion as a model analyte, the PEC method showed a wide linear range from 2x10(-12)-4x10(-6)gmL(-1) and an extremely low limit of detection of 5.6x10(-13)gmL(-1). Regarding these good analytical performances, this study may provide some guidance and pave the way for the applications of dye-TiO2 nanocomposites in a lot of PEC devices required to be performed in aqueous solutions.



        

Title: Clinical diagnostic significance of prealbumin, cholinesterase and retinol binding protein in liver cirrhosis combined with encephalopathy
Tan L, Meng Y, Zeng T, Wang Q, Long T, Wu S, Guan X, Fu H, Zheng W and Cao L <5 more author(s)> Tan L, Meng Y, Zeng T, Wang Q, Long T, Wu S, Guan X, Fu H, Zheng W, Tian Y, Chen J, Yu J, Wu Y, Li H, Cao L (- 5)
Ref: Br J Biomed Sci, :1, 2018 : PubMed
Abstract


ESTHER: Tan_2018_Br.J.Biomed.Sci__1
PubMedSearch: Tan 2018 Br.J.Biomed.Sci 1
PubMedID: 30392460

Abstract

OBJECTIVE: Hepatic encephalopathy is a common consequence of liver cirrhosis, but diagnosis can be difficult as it is based on clinical criteria alone. We hypothesised that serum prealbumin, cholinesterase and retinol binding protein (RBP) can help support the diagnosis of hepatic encephalopathy. METHODS: We enrolled 306 cirrhotic patients (110 with encephalopathy), 100 chronic hepatitis B patients and 50 healthy controls, measuring routine liver function tests (ALT, AST, GGT, ALP, and bilirubin), albumin, prothrombin time, prealbumin, cholinesterase and RBP by routine methods. Logistic regression analysis and areas under the receiver operating characteristic curves (AUCs) were used to find predictive factors for hepatic encephalopathy. RESULTS: There were differences in all laboratory indices between the three groups (all p < 0.001). In univariate analysis, albumin, prothrombin time, prealbumin, cholinesterase and RBP were significantly altered in those with encephalopathy (p < 0.01), but only prealbumin, cholinesterase and RBP levels were significant predictors in multivariate analysis, and each was linked to the severity of liver fibrosis defined by the Child-Pugh score (all p < 0.001). The AUCs (95% CI) of prealbumin, cholinesterase and RBP for diagnosing liver cirrhosis with hepatic encephalopathy were comparable at 0.85 (81-90), 0.81 (0.76-0.85) and 0.81 (0.76-0.86), respectively (all p < 0.01). CONCLUSIONS: Serum prealbumin, cholinesterase and RBP levels are of potential clinical value in diagnosis of liver cirrhosis complicated by encephalopathy.



        

Title: Joint toxic effects of triazophos and imidacloprid on zebrafish (Danio rerio)
Wu S, Li X, Liu X, Yang G, An X, Wang Q, Wang Y
Ref: Environ Pollut, 235:470, 2018 : PubMed
Abstract


ESTHER: Wu_2018_Environ.Pollut_235_470
PubMedSearch: Wu 2018 Environ.Pollut 235 470
PubMedID: 29316522

Abstract

Pesticide contamination is more often found as a mixture of different pesticides in water bodies rather than individual compounds. However, regulatory risk evaluation is mostly based on the effects of individual pesticides. In the present study, we aimed to investigate the individual and joint toxicities of triazophos (TRI) and imidacloprid (IMI) to the zebrafish (Danio rerio) using acute indices and various sublethal endpoints. Results from 96-h semi-static test indicated that the LC50 values of TRI to D. rerio at multiple life stages (embryonic, larval, juvenile and adult stages) ranged from 0.49 (0.36-0.71) to 4.99 (2.06-6.81) mg a.i. L(-1), which were higher than those of IMI ranging from 26.39 (19.04-38.01) to 128.9 (68.47-173.6) mg a.i. L(-1). Pesticide mixtures of TRI and IMI displayed synergistic response to zebrafish embryos. Activities of carboxylesterase (CarE) and catalase (CAT) were significantly changed in most of the individual and joint exposures of pesticides compared with the control group. The expressions of 26 genes related to oxidative stress, cellular apoptosis, immune system, hypothalamic-pituitary-thyroid and hypothalamic-pituitary-gonadal axis at the mRNA level revealed that zebrafish embryos were affected by the individual or joint pesticides, and greater changes in the expressions of six genes (Mn-sod, CXCL-CIC, Dio1, Dio2, tsh and vtg1) were observed when exposed to joint pesticides compared with their individual pesticides. Taken together, the synergistic effects indicated that it was highly important to incorporate joint toxicity studies, especially at low concentrations, when assessing the risk of pesticides.



        

Title: Anti-Alzheimers activity and molecular mechanism of albumin-derived peptides against AChE and BChE
Yu Z, Wu S, Zhao W, Ding L, Fan Y, Shiuan D, Liu J, Chen F
Ref: Food Funct, 9:1173, 2018 : PubMed
Abstract


ESTHER: Yu_2018_Food.Funct_9_1173
PubMedSearch: Yu 2018 Food.Funct 9 1173
PubMedID: 29363710

Abstract

Alzheimer's disease (AD) is a global health issue affecting millions of elderly people worldwide. The aim of the present study was to identify novel anti-AD peptides isolated from albumin. Anti-AD activities of the peptides were evaluated via inhibitory activities on acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Furthermore, the potential molecular mechanisms of the KLPGF/AChE were investigated by CDOCKER of Discovery studio 2017. The results revealed that peptide KLPGF could effectively inhibit AChE with an inhibition rate of 61.23% at a concentration of 50 mug mL(-1). In addition, the peptide KLPGF came in contact with acylation sites and peripheral anion sites of AChE. The present study demonstrates that the peptide KLPGF could become a potential functional food intervention in AD.



        

Title: Cholinesterase inhibitors for the treatment of delirium in non-ICU settings
Yu A, Wu S, Zhang Z, Dening T, Zhao S, Pinner G, Xia J, Yang D
Ref: Cochrane Database Syst Rev, 6:CD012494, 2018 : PubMed
Abstract


ESTHER: Yu_2018_Cochrane.Database.Syst.Rev_6_CD012494
PubMedSearch: Yu 2018 Cochrane.Database.Syst.Rev 6 CD012494
PubMedID: 29952000

Abstract

BACKGROUND: Delirium is a common clinical syndrome defined as alterations in attention with an additional disturbance in cognition or perception, which develop over a short period of time and tend to fluctuate during the course of the episode. Delirium is commonly treated in hospitals or community settings and is often associated with multiple adverse outcomes such as increased cost, morbidity, and even mortality. The first-line intervention involves a multicomponent non-pharmacological approach that includes ensuring effective communication and reorientation in addition to providing reassurance or a suitable care environment. There are currently no drugs approved specifically for the treatment of delirium. Clinically, however, various medications are employed to provide symptomatic relief, such as antipsychotic medications and cholinesterase inhibitors, among others. OBJECTIVES: To evaluate the effectiveness and safety of cholinesterase inhibitors for treating people with established delirium in a non-intensive care unit (ICU) setting. SEARCH METHODS: We searched ALOIS, which is the Cochrane Dementia and Cognitive Improvement Group's Specialised Register, on 26 October 2017. We also cross-checked the reference lists of included studies to identify any potentially eligible trials. SELECTION CRITERIA: We included randomised controlled trials, published or unpublished, reported in English or Chinese, which compared cholinesterase inhibitors to placebo or other drugs intended to treat people with established delirium in a non-ICU setting. DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures expected by Cochrane. The primary outcomes were duration of delirium, severity of delirium, and adverse events. The secondary outcomes were use of rescue medications, persistent cognitive impairment, length of hospitalisation, institutionalisation, mortality, cost of intervention, leaving the study early, and quality of life. For dichotomous outcomes, we calculated the risk ratio (RR) with 95% confidence intervals (CIs); for continuous outcomes we calculated the mean difference (MD) with 95% CIs. We assessed the quality of evidence using GRADE to generate a 'Summary of findings' table. MAIN RESULTS: We included one study involving 15 participants from the UK. The included participants were diagnosed with delirium based on the Confusion Assessment Method (CAM) criteria. Eight males and seven females were included, with a mean age of 82.5 years. Seven of the 15 participants had comorbid dementia at baseline. The risk of bias was low in all domains.The study compared rivastigmine with placebo. We did not find any clear differences between the two groups in terms of duration of delirium (MD -3.6, 95% CI -15.6 to 8.4), adverse events (nausea, RR 0.30, 95% CI 0.01 to 6.29), use of rescue medications (RR 0.13, 95% CI 0.01 to 2.1), mortality (RR 0.10, 95% CI 0.01 to 1.56), and leaving the study early (RR 0.88, 95% CI 0.07 to 11.54). Evidence was not available regarding the severity of delirium, persistent cognitive impairment, length of hospitalisation, cost of intervention, or other predefined secondary outcomes.The quality of evidence is low due to the very small sample size. AUTHORS' CONCLUSIONS: There is insufficient evidence to support or refute the use of cholinesterase inhibitors for the treatment of delirium in non-ICU settings. No clear benefits or harms associated with cholinesterase inhibitors were observed when compared with placebo due to the lack of data. More trials are required.



        

Title: Evaluation of Novel Dual Acetyl- and Butyrylcholinesterase Inhibitors as Potential Anti-Alzheimer's Disease Agents Using Pharmacophore, 3D-QSAR, and Molecular Docking Approaches
Pang X, Fu H, Yang S, Wang L, Liu AL, Wu S, Du GH
Ref: Molecules, 22:, 2017 : PubMed
Abstract


ESTHER: Pang_2017_Molecules_22_
PubMedSearch: Pang 2017 Molecules 22
PubMedID: 28933746

Abstract

DL0410, containing biphenyl and piperidine skeletons, was identified as an acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitor through high-throughput screening assays, and further studies affirmed its efficacy and safety for Alzheimer's disease treatment. In our study, a series of novel DL0410 derivatives were evaluated for inhibitory activities towards AChE and BuChE. Among these derivatives, compounds 6-1 and 7-6 showed stronger AChE and BuChE inhibitory activities than DL0410. Then, pharmacophore modeling and three-dimensional quantitative structure activity relationship (3D-QSAR) models were performed. The R(2) of AChE and BuChE 3D-QSAR models for training set were found to be 0.925 and 0.883, while that of the test set were 0.850 and 0.881, respectively. Next, molecular docking methods were utilized to explore the putative binding modes. Compounds 6-1 and 7-6 could interact with the amino acid residues in the catalytic anionic site (CAS) and peripheral anionic site (PAS) of AChE/BuChE, which was similar with DL0410. Kinetics studies also suggested that the three compounds were all mixed-types of inhibitors. In addition, compound 6-1 showed better absorption and blood brain barrier permeability. These studies provide better insight into the inhibitory behaviors of DL0410 derivatives, which is beneficial for rational design of AChE and BuChE inhibitors in the future.



        

Title: Effects of P-Glycoprotein on the Transport of DL0410, a Potential Multifunctional Anti-Alzheimer Agent
Pang X, Wang L, Kang, Zhao Y, Wu S, Liu AL, Du GH
Ref: Molecules, 22:, 2017 : PubMed
Abstract


ESTHER: Pang_2017_Molecules_22_2
PubMedSearch: Pang 2017 Molecules 22 2
PubMedID: 28757552
Inhibitor(s) related to this paper: DL0410

Abstract

In our study, we attempted to investigate the influences of P-glycoprotein (P-gp) on DL0410, a novel synthetic molecule for Alzheimer's disease (AD) treatment, for intestinal absorption and blood-brain barrier permeability in vitro and related binding mechanisms in silico. Caco-2, MDCK, and MDCK-MDR1 cells were utilized for transport studies, and homology modelling of human P-gp was built for further docking study to uncover the binding mode of DL0410. The results showed that the apparent permeability (Papp) value of DL0410 was approximately 1 x 10(-6) cm/s, indicating the low permeability of DL0410. With the presence of verapamil, the directional transport of DL0410 disappeared in Caco-2 and MDCK-MDR1 cells, suggesting that DL0410 should be a substrate of P-gp, which was also confirmed by P-gp ATPase assay. In addition, DL0410 could competitively inhibit the transport of Rho123, a P-gp known substrate. According to molecular docking, we also found that DL0410 could bind to the drug binding pocket (DBP), but not the nucleotide binding domain (NBD). In conclusion, DL0410 was a substrate as well as a competitive inhibitor of P-gp, and P-gp had a remarkable impact on the intestine and brain permeability of DL0410, which is of significance for drug research and development.



        

Title: Karyotype Stability and Unbiased Fractionation in the Paleo-Allotetraploid Cucurbita Genomes
Sun H, Wu S, Zhang G, Jiao C, Guo S, Ren Y, Zhang J, Zhang H, Gong G and Xu Y <7 more author(s)> Sun H, Wu S, Zhang G, Jiao C, Guo S, Ren Y, Zhang J, Zhang H, Gong G, Jia Z, Zhang F, Tian J, Lucas WJ, Doyle JJ, Li H, Fei Z, Xu Y (- 7)
Ref: Mol Plant, 10:1293, 2017 : PubMed
Abstract


ESTHER: Sun_2017_Mol.Plant_10_1293
PubMedSearch: Sun 2017 Mol.Plant 10 1293
PubMedID: 28917590
Gene_locus related to this paper: cucma-a0a6j1jlb1, cucma-a0a6j1i8e2

Abstract

The Cucurbita genus contains several economically important species in the Cucurbitaceae family. Here, we report high-quality genome sequences of C. maxima and C. moschata and provide evidence supporting an allotetraploidization event in Cucurbita. We are able to partition the genome into two homoeologous subgenomes based on different genetic distances to melon, cucumber, and watermelon in the Benincaseae tribe. We estimate that the two diploid progenitors successively diverged from Benincaseae around 31 and 26 million years ago (Mya), respectively, and the allotetraploidization happened at some point between 26 Mya and 3 Mya, the estimated date when C. maxima and C. moschata diverged. The subgenomes have largely maintained the chromosome structures of their diploid progenitors. Such long-term karyotype stability after polyploidization has not been commonly observed in plant polyploids. The two subgenomes have retained similar numbers of genes, and neither subgenome is globally dominant in gene expression. Allele-specific expression analysis in the C. maxima x C. moschata interspecific F(1) hybrid and their two parents indicates the predominance of trans-regulatory effects underlying expression divergence of the parents, and detects transgressive gene expression changes in the hybrid correlated with heterosis in important agronomic traits. Our study provides insights into polyploid genome evolution and valuable resources for genetic improvement of cucurbit crops.



        

Title: Design, Synthesis, and Biological Evaluation of a New Series of Biphenyl/Bibenzyl Derivatives Functioning as Dual Inhibitors of Acetylcholinesterase and Butyrylcholinesterase
Wang DM, Feng B, Fu H, Liu AL, Wang L, Du GH, Wu S
Ref: Molecules, 22:, 2017 : PubMed
Abstract


ESTHER: Wang_2017_Molecules_22_
PubMedSearch: Wang 2017 Molecules 22
PubMedID: 28117700

Abstract

Alzheimer's disease (AD), the most common form of dementia in adults, is a progressive neurodegenerative disorder of the brain characterized by loss of memory and steady deterioration of cognition. Here, a series of symmetrical molecules containing biphenyl/bibenzyl scaffolds (12-36) were designed, synthesized, and evaluated for their ability to inhibit both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). A biological evaluation showed that most of these biphenyl derivatives were potent AChE and BuChE inhibitors. Among them, compound 15 displayed the greatest ability to inhibit BuChE (IC50 = 0.74 microM) and was also a good AChE inhibitor (IC50 = 1.18 microM). Compound 19 was not only a potent AChE inhibitor (IC50 = 0.096 microM), but also a mild BuChE inhibitor (IC50 =1.25 microM). Overall, these results suggested that compound 19 may be a promising agent in the treatment of AD.



        

Title: Association between L55M polymorphism in Paraoxonase 1 and cancer risk: a meta-analysis based on 21 studies
Chen L, Lu W, Fang L, Xiong H, Wu X, Zhang M, Wu S, Yu D
Ref: Onco Targets Ther, 9:1151, 2016 : PubMed
Abstract


ESTHER: Chen_2016_Onco.Targets.Ther_9_1151
PubMedSearch: Chen 2016 Onco.Targets.Ther 9 1151
PubMedID: 27019599

Abstract

L55M polymorphism in Paraoxonase 1 (PON1) has been regarded as a risk factor for many cancer types. Nevertheless, the results remain controversial and inconclusive. We therefore performed a meta-analysis of all eligible case-control studies to evaluate the association between L55M polymorphism and cancer risk. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of the associations. Finally, a total of 5,627 cases and 6,390 controls, arising from 21 case-control studies, were enrolled in our study. Significant associations between PON1-L55M polymorphism and overall cancer risk were identified in all genetic models. In the stratified analyses by cancer type, PON1-L55M polymorphism was a risk factor for breast cancer in all genetic models, prostate cancer in the heterozygote model (ML vs LL: OR =1.304, 95% CI =1.049-1.620, P heterogeneity=0.067), and ovarian cancer in the recessive model (MM vs ML/LL: OR =1.526, 95% CI =1.110-2.097, P heterogeneity=0.464). Similarly, an increased risk was also identified for the Caucasian population in the heterozygote comparison and homozygote models, and hospital-based controls in all genetic models. To sum up, our study suggests that the PON1-L55M allele increased the risk of cancer. Future well-designed studies with larger sample sizes are warranted to further verify these findings.



        

Title: ABHD5 interacts with BECN1 to regulate autophagy and tumorigenesis of colon cancer independent of PNPLA2
Peng Y, Miao H, Wu S, Yang W, Zhang Y, Xie G, Xie X, Li J, Shi C and Ou J <4 more author(s)> Peng Y, Miao H, Wu S, Yang W, Zhang Y, Xie G, Xie X, Li J, Shi C, Ye L, Sun W, Wang L, Liang H, Ou J (- 4)
Ref: Autophagy, 12:2167, 2016 : PubMed
Abstract


ESTHER: Peng_2016_Autophagy_12_2167
PubMedSearch: Peng 2016 Autophagy 12 2167
PubMedID: 27559856
Gene_locus related to this paper: human-ABHD5

Abstract

Autophagy critically contributes to metabolic reprogramming and chromosomal stability. It has been reported that monoallelic loss of the essential autophagy gene BECN1 (encoding BECN1/Beclin 1) promotes cancer development and progression. However, the mechanism by which BECN1 is inactivated in malignancy remains largely elusive. We have previously reported a tumor suppressor role of ABHD5 (abhydrolase domain containing 5), a co-activator of PNPLA2 (patatin like phospholipase domain containing 2) in colorectal carcinoma (CRC). Here we report a noncanonical role of ABHD5 in regulating autophagy and CRC tumorigenesis. ABHD5 directly competes with CASP3 for binding to the cleavage sites of BECN1, and consequently prevents BECN1 from being cleaved by CASP3. ABHD5 deficiency provides CASP3 an advantage to cleave and inactivate BECN1, thus impairing BECN1-induced autophagic flux and augmenting genomic instability, which subsequently promotes tumorigenesis. Notably, clinical data also confirm that ABHD5 proficiency is significantly correlated with the expression levels of BECN1, LC3-II and CASP3 in human CRC tissues. Our findings suggest that ABHD5 possesses a PNPLA2-independent function in regulating autophagy and tumorigenesis, further establishing the tumor suppressor role of ABHD5, and offering an opportunity to develop new approaches aimed at preventing CRC carcinogenesis.



        

Title: Facilitating the Evolution of Esterase Activity from a Promiscuous Enzyme (Mhg) with Catalytic Functions of Amide Hydrolysis and Carboxylic Acid Perhydrolysis by Engineering the Substrate Entrance Tunnel
Yan X, Wang J, Sun Y, Zhu J, Wu S
Ref: Applied Environmental Microbiology, 82:6748, 2016 : PubMed
Abstract


ESTHER: Yan_2016_Appl.Environ.Microbiol_82_6748
PubMedSearch: Yan 2016 Appl.Environ.Microbiol 82 6748
PubMedID: 27613682
Gene_locus related to this paper: 9mico-e3svs0

Abstract

Promiscuous enzymes are generally considered to be starting points in the evolution of offspring enzymes with more specific or even novel catalytic activities, which is the molecular basis of producing new biological functions. Mhg, a typical alpha/beta fold hydrolase, was previously reported to have both gamma-lactamase and perhydrolase activities. However, despite having high structural similarity to and sharing an identical catalytic triad with an extensively studied esterase from Pseudomonas fluorescens, this enzyme did not show any esterase activity. Molecular docking and sequence analysis suggested a possible role for the entry of the binding pocket in blocking the entrance tunnel, preventing the ester compounds from entering into the pocket. By engineering the entrance tunnel with only one or two amino acid substitutions, we successfully obtained five esterase variants of Mhg. The variants exhibited a very broad substrate acceptance, hydrolyzing not only the classical p-nitrophenol esters but also various types of chiral esters, which are widely used as drug intermediates. Site 233 at the entrance tunnel of Mhg was found to play a pivotal role in modulating the three catalytic activities by adjusting the size and shape of the tunnel, with different amino acid substitutions at this site facilitating different activities. Remarkably, the variant with the L233G mutation was a very specific esterase without any gamma-lactamase and perhydrolase activities. Considering the amino acid conservation and differentiation, this site could be a key target for future protein engineering. In addition, we demonstrate that engineering the entrance tunnel is an efficient strategy to regulate enzyme catalytic capabilities. IMPORTANCE: Promiscuous enzymes can act as starting points in the evolution of novel catalytic activities, thus providing a molecular basis for the production of new biological functions. In this study, we identified a critical amino acid residue (Leu233) at the entry of the substrate tunnel of a promiscuous enzyme, Mhg. We found that substitution of this residue with smaller amino acids such as Gly, Ala, Ser, or Pro endowed the enzyme with novel esterase activity. Different amino acids at this site can facilitate different catalytic activities. These findings exhibited universal significance in this subset of alpha/beta fold hydrolases, including Mhg. Furthermore, we demonstrate that engineering the entrance tunnel is an efficient strategy to evolve new enzyme catalytic capabilities. Our study has important implications for the regulation of enzyme catalytic promiscuity and development of protein engineering methodologies.



        

Title: DL0410, a novel dual cholinesterase inhibitor, protects mouse brains against Abeta-induced neuronal damage via the Akt/JNK signaling pathway
Zhou D, Zhou W, Song JK, Feng ZY, Yang RY, Wu S, Wang L, Liu AL, Du GH
Ref: Acta Pharmacol Sin, 37:1401, 2016 : PubMed
Abstract


ESTHER: Zhou_2016_Acta.Pharmacol.Sin_37_1401
PubMedSearch: Zhou 2016 Acta.Pharmacol.Sin 37 1401
PubMedID: 27498773
Inhibitor(s) related to this paper: DL0410

Abstract

AIM: 1,1'-([1,1'-Biphenyl]-4,4'-diyl)bis(3-(piperidin-1-yl)propan-1-one)dihydrochlorid e (DL0410) is a novel synthetic dual acetylcholinesterase (AChE)/butyrocholinesterase (BuChE) inhibitor, which has shown a potential therapeutic effect on Alzheimer's disease (AD). In this study we examined whether DL0410 produced neuroprotective effects in an AD cellular model and an Abeta1-42-induced amnesia mouse model.
METHODS: The in vitro inhibitory activities against AChE and BuChE were estimated using Ellman's assay. Copper-induced toxicity in APPsw-SY5Y cells was used as AD cellular model, the cell viability was assessed using MTS assay, and cell apoptosis was evaluated based on mitochondrial membrane potential detection. Abeta1-42-induced amnesia mouse model was made in male mice by injecting aggregated Abeta1-42 (2 mug in 2 muL 0.1% DMSO) into the right cerebral ventricle. Before and after Abeta1-42 injection, the mice were orally administered DL0410 (1, 3, 9 mg.kg-1.d-1) or rivastigmine (2 mg.kg-1.d-1) for 3 and 11 d, respectively. Memory impairments were examined using Morris water maze (MWM) test and passive avoidance test. The expression levels of APP, CREB, BDNF, JNK and Akt in the mouse brains were measured with either immunohistochemistry or Western blotting.
RESULTS: DL0410 exhibited in vitro inhibitory abilities against AChE and BuChE with IC50 values of 0.286+/-0.004 and 3.962+/-0.099 mumol/L, respectively, which were comparable to those of donepezil and rivastigmine. In APPsw-SY5Y cells, pretreatment with DL0410 (1, 3, and 10 mumol/L) decreased the phosphorylation of JNK and increased the phosphorylation of Akt, markedly decreased copper-stimulated Abeta1-42 production, reversed the loss of mitochondrial membrane potential, and dose-dependently increased the cell viability. In Abeta1-42-treated mice, DL0410 administration significantly ameliorated learning and memory deficits in MWM test and passive avoidance test. Furthermore, DL0410 administration markedly decreased Abeta1-40/42 deposits in mouse cerebral cortices, and significantly up-regulated neurotrophic CREB/BDNF. Meanwhile, Akt/JNK signaling pathway may play a key role in the neuroprotective effect of DL0410. CONCLUSION: DL0410 ameliorates cognitive deficit and exerts neuronal protection in AD models, implicating this compound as a candidate drug for the prevention and therapy of AD.



        

Title: A ratiometric fluorescent system for carboxylesterase detection with AIE dots as FRET donors
Wu Y, Huang S, Zeng F, Wang J, Yu C, Huang J, Xie H, Wu S
Ref: Chem Commun (Camb), 51:12791, 2015 : PubMed
Abstract


ESTHER: Wu_2015_Chem.Commun.(Camb)_51_12791
PubMedSearch: Wu 2015 Chem.Commun.(Camb) 51 12791
PubMedID: 26165151

Abstract

A ratiometric fluorescent system for CaE detection with AIE dots as the FRET donors was designed. Upon enzymatic reaction, electrostatic interaction between the cationic TPE-N(+) dots and the enzymatic reaction product - the negatively charged fluorescein molecules - allows the FRET process to proceed, thus affording the ratiometric fluorescence CaE assay.



        

Title: A point mutation in the acetylcholinesterase-1 gene is associated with chlorpyrifos resistance in the plant bug Apolygus lucorum
Wu S, Zuo K, Kang Z, Yang Y, Oakeshott JG, Wu Y
Ref: Insect Biochemistry & Molecular Biology, 65:75, 2015 : PubMed
Abstract


ESTHER: Wu_2015_Insect.Biochem.Mol.Biol_65_75
PubMedSearch: Wu 2015 Insect.Biochem.Mol.Biol 65 75
PubMedID: 26363297
Gene_locus related to this paper: apolu-ACHE1

Abstract

Control of Chinese Apolygus lucorum relies heavily on organophosphate insecticides. Here we describe resistance to the organophosphate chlorpyrifos in an A. lucorum strain, BZ-R, which was developed from a field-collected strain (BZ) by selection with chlorpyrifos in the laboratory. BZ-R showed 21-58 fold resistance to chlorpyrifos compared with the laboratory reference strain LSF and another susceptible strain, BZ-S, derived from BZ. BZ-R also showed several fold resistance to two other organophosphates and a carbamate. No synergism of chlorpyrifos by metabolic enzyme inhibitors nor any increase in detoxifying enzyme activities were observed in BZ-R. No sequence differences in acetylcholinesterase-2 were found to be associated with the resistance but the frequency of an alanine to serine substitution at position 216 of acetylcholinesterase-1 was 100% in BZ-R, approximately 21-23% in SLF and BZ, and 0% in BZ-S. A single generation treatment of chlorpyrifos on the BZ strain also increased its frequency of the serine substitution to 64%. Recombinantly expressed acetylcholinesterase-1 carrying the serine substitution was about five fold less sensitive to inhibition by chlorpyrifos oxon than the wild-type enzyme. Quantitative real-time PCR found no differences in ace1 or ace2 expression levels among the strains tested. Thus the chlorpyrifos resistance is strongly associated with the serine substituted acetylcholinesterase-1. An equivalent substitution has been found to confer resistance to many organophosphate and carbamate insecticides in four other insect species.



        

Title: DL0410 can reverse cognitive impairment, synaptic loss and reduce plaque load in APP/PS1 transgenic mice
Yang RY, Zhao G, Wang DM, Pang XC, Wang SB, Fang JS, Li C, Liu AL, Wu S, Du GH
Ref: Pharmacol Biochem Behav, 139:15, 2015 : PubMed
Abstract


ESTHER: Yang_2015_Pharmacol.Biochem.Behav_139_15
PubMedSearch: Yang 2015 Pharmacol.Biochem.Behav 139 15
PubMedID: 26476132
Inhibitor(s) related to this paper: DL0410

Abstract

Cholinesterase inhibitors are first-line therapy for Alzheimer's disease (AD). DL0410 is an AChE/BuChE dual inhibitor with a novel new structural scaffold. It has been demonstrated that DL0410 could improve memory deficits in both Abeta1-42-induced and scopolamine-induced amnesia in mice. In the present study, the therapeutic effect of DL0410 and its action mechanism were investigated in APP/PS1 transgenic mice. Six-month old APP/PS1 transgenic mice were orally administered with DL0410 (3, 10, 30mg/kg/day). After 60days, several behavioural tests, including the Morris water maze and step-down tests, were used to investigate the effects of DL0410 on mice behaviours. All the behavioural experimental results showed that DL0410 significantly ameliorated memory deficits. Meanwhile, DL0410 attenuated neural cell damage and reduced senile plaques significantly in the hippocampus of APP/PS1 transgenic mice. In addition, DL0410 significantly decreased Abeta plaques, while increasing the number of synapses and the thickness of PSD in the hippocampus. We also found DL0410 decreased the expression of APP, NMDAR1B and the phosphorylation level of NMDAR2B, and increased the phosphorylation level of CAMKII and the expression of PSD-95. In this study, the results of behavioural tests demonstrated for the first time that DL0410 could improve learning and memory dysfunction in APP/PS1 transgenic mice. The mechanism of its beneficial effects might be related to cholinesterase inhibition, Abeta plaques inhibition, improvement of synapse loss by regulating of expression of proteins related to synapses. As a result, DL0410 could be considered as a candidate drug for the therapy of AD.



        

Title: Simultaneous enantioselective determination of isocarbophos and its main metabolite isocarbophos oxon in rice, soil, and water by chiral liquid chromatography and tandem mass spectrometry
Yao Z, Lin M, Xu M, Wang T, Ping X, Wu S, Wang Q, Zhang H
Ref: J Sep Sci, 38:1663, 2015 : PubMed
Abstract


ESTHER: Yao_2015_J.Sep.Sci_38_1663
PubMedSearch: Yao 2015 J.Sep.Sci 38 1663
PubMedID: 25755196
Inhibitor(s) related to this paper: Isocarbophos

Abstract

An efficient enantioselective method for the simultaneous determination of isocarbophos and its main metabolite isocarbophos oxon in rice, soil, and water was developed using liquid chromatography with tandem mass spectrometry. The enantioseparation was performed on a Chiralpak AD-3R column at 30 degrees C using gradient elution. Target compounds were extracted from soil and rice using acetonitrile with omission of a clean-up procedure, while a C18 solid-phase extraction column was used for water samples. Quantification was achieved using matrix-matched calibration. The overall mean recoveries for isocarbophos and isocarbophos oxon enantiomers from the five matrices were 89.7-103 and 90.1-98.7%, with relative standard deviations of 2.1-5.4 and 2.5-4.7%, respectively. Moreover, the absolute configurations of isocarbophos oxon enantiomers were determined by liquid chromatography with tandem mass spectrometry through incubation of each isocarbophos enantiomer in soil, the first eluting enantiomer being confirmed as (R)-(-)-isocarbophos oxon. The proposed method was applied to real soil samples and satisfactory results were obtained.



        

Title: Quantitative Proteomics Analysis of the Hepatitis C Virus Replicon High-Permissive and Low-Permissive Cell Lines
Ye F, Xin Z, Han W, Fan J, Yin B, Wu S, Yang W, Yuan J, Qiang B and Peng X <1 more author(s)> Ye F, Xin Z, Han W, Fan J, Yin B, Wu S, Yang W, Yuan J, Qiang B, Sun W, Peng X (- 1)
Ref: PLoS ONE, 10:e0142082, 2015 : PubMed
Abstract


ESTHER: Ye_2015_PLoS.One_10_e0142082
PubMedSearch: Ye 2015 PLoS.One 10 e0142082
PubMedID: 26544179

Abstract

Chronic hepatitis C virus (HCV) infection is one of the leading causes of severe hepatitis. The molecular mechanisms underlying HCV replication and pathogenesis remain unclear. The development of the subgenome replicon model system significantly enhanced study of HCV. However, the permissiveness of the HCV subgenome replicon greatly differs among different hepatoma cell lines. Proteomic analysis of different permissive cell lines might provide new clues in understanding HCV replication. In this study, to detect potential candidates that might account for the differences in HCV replication. Label-free and iTRAQ labeling were used to analyze the differentially expressed protein profiles between Huh7.5.1 wt and HepG2 cells. A total of 4919 proteins were quantified in which 114 proteins were commonly identified as differentially expressed by both quantitative methods. A total of 37 differential proteins were validated by qRT-PCR. The differential expression of Glutathione S-transferase P (GSTP1), Ubiquitin carboxyl-terminal hydrolase isozyme L1 (UCHL1), carboxylesterase 1 (CES1), vimentin, Proteasome activator complex subunit1 (PSME1), and Cathepsin B (CTSB) were verified by western blot. And over-expression of CTSB or knock-down of vimentin induced significant changes to HCV RNA levels. Additionally, we demonstrated that CTSB was able to inhibit HCV replication and viral protein translation. These results highlight the potential role of CTSB and vimentin in virus replication.



        

Title: Inhibition of acetylcholinesterase by two genistein derivatives: kinetic analysis, molecular docking and molecular dynamics simulation
Fang J, Wu P, Yang R, Gao L, Li C, Wang D, Wu S, Liu AL, Du GH
Ref: Acta Pharm Sin B, 4:430, 2014 : PubMed
Abstract


ESTHER: Fang_2014_Acta.Pharm.Sin.B_4_430
PubMedSearch: Fang 2014 Acta.Pharm.Sin.B 4 430
PubMedID: 26579414

Abstract

In this study two genistein derivatives (G1 and G2) are reported as inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), and differences in the inhibition of AChE are described. Although they differ in structure by a single methyl group, the inhibitory effect of G1 (IC50=264 nmol/L) on AChE was 80 times stronger than that of G2 (IC50=21,210 nmol/L). Enzyme-kinetic analysis, molecular docking and molecular dynamics (MD) simulations were conducted to better understand the molecular basis for this difference. The results obtained by kinetic analysis demonstrated that G1 can interact with both the catalytic active site and peripheral anionic site of AChE. The predicted binding free energies of two complexes calculated by the molecular mechanics/generalized born surface area (MM/GBSA) method were consistent with the experimental data. The analysis of the individual energy terms suggested that a difference between the net electrostatic contributions (DeltaE ele+DeltaG GB) was responsible for the binding affinities of these two inhibitors. Additionally, analysis of the molecular mechanics and MM/GBSA free energy decomposition revealed that the difference between G1 and G2 originated from interactions with Tyr124, Glu292, Val294 and Phe338 of AChE. In conclusion, the results reveal significant differences at the molecular level in the mechanism of inhibition of AChE by these structurally related compounds.



        

Title: Heart failure and dipeptidyl peptidase-4 inhibitors
Krum H, Skiba M, Wu S, Hopper I
Ref: Eur J Heart Fail, 16:603, 2014 : PubMed
Abstract


ESTHER: Krum_2014_Eur.J.Heart.Fail_16_603
PubMedSearch: Krum 2014 Eur.J.Heart.Fail 16 603
PubMedID: 24687300



        

Title: Protective effects of aloe-emodin on scopolamine-induced memory impairment in mice and HO-induced cytotoxicity in PC12 cells
Tao L, Xie J, Wang Y, Wang S, Wu S, Wang Q, Ding H
Ref: Bioorganic & Medicinal Chemistry Lett, 24:5385, 2014 : PubMed
Abstract


ESTHER: Tao_2014_Bioorg.Med.Chem.Lett_24_5385
PubMedSearch: Tao 2014 Bioorg.Med.Chem.Lett 24 5385
PubMedID: 25453793

Abstract

Aloe-emodin (AE) is one of the most important active components of Rheum officinale Baill. The present study aimed to investigate that AE could attenuate scopolamine-induced cognitive deficits via inhibiting acetylcholinesterase (AChE) activity and modulating oxidative stress. Kunming (KM) mice were received intraperitoneal injection of scopolamine (2mg/kg) to induce cognitive impairment. Learning and memory performance were assessed in the Morris water maze (MWM). After behavioral testing, the mice were sacrificed and their hippocampi were removed for biochemical assays (superoxide dismutase (SOD), glutathione peroxidase (GPx), malondialdehyde (MDA), AChE and acetylcholine (ACh)). In vitro, we also performed the AChE activity assay and H2O2-induced PC12 cells toxicity assay. After 2h exposure to 200muM H2O2 in PC12 cells, the cytotoxicity were evaluated by cell viability (MTT), nitric oxide (NO)/lactate dehydrogenase (LDH) release and intracellular reactive oxygen species (ROS) production. Our results confirmed that AE showed significant improvement in cognitive deficit in scopolamine-induced amnesia animal model. Besides, it increased SOD, GPx activities and ACh content, while decreased the level of MDA and AChE activity in AE treated mice. In addition, AE was found to inhibit AChE activity (IC50=18.37mug/ml) in a dose-dependent manner. Furthermore, preincubation of PC12 cells with AE could prevent cytotoxicity induced by H2O2 and reduce significantly extracellular release of NO, LDH and intracellular accumulation of ROS. The study indicated that AE could have neuroprotective effects against Alzheimer's disease (AD) via inhibiting the activity of AChE and modulating oxidative stress.



        

Title: Surface Display of Recombinant Drosophila melanogaster Acetylcholinesterase for Detection of Organic Phosphorus and Carbamate Pesticides
Li J, Qian B, Yin J, Wu S, Zhuan F, Xu S, Salazar JK, Zhang W, Wang H
Ref: PLoS ONE, 8:e72986, 2013 : PubMed
Abstract


ESTHER: Li_2013_PLoS.One_8_e72986
PubMedSearch: Li 2013 PLoS.One 8 e72986
PubMedID: 24039837

Abstract

Acetylcholinesterase (AChE) is commonly used for the detection of organophosphate (OP) and carbamate (CB) insecticides. However, the cost of this commercially available enzyme is high, making high-throughput insecticide detection improbable. In this study we constructed a new AChE yeast expression system in Saccharomyces cerevisiae for the expression of a highly reactive recombinant AChE originating from Drosophila melanogaster (DmAChE). Specifically, the coding sequence of DmAChE was fused with the 3'-terminal half of an alpha-agglutinin anchor region, along with an antigen tag for the detection of the recombinant protein. The target sequence was cloned into the yeast expression vector pYes-DEST52, and the signal peptide sequence was replaced with a glucoamylase secretion region for induced expression. The resultant engineered vector was transformed into S. cerevisiae. DmAChE was expressed and displayed on the cell surface after galactose induction. Our results showed that the recombinant protein displayed activity comparable to the commercial enzyme. We also detected different types of OP and CB insecticides through enzyme inhibition assays, with the expressed DmAChE showing high sensitivity. These results show the construction of a new yeast expression system for DmAChE, which can subsequently be used for detecting OP and CB insecticides with reduced economic costs.



        

Title: Diverse roles of strigolactone signaling in maize architecture and the uncoupling of a branching-specific subnetwork
Guan JC, Koch KE, Suzuki M, Wu S, Latshaw S, Petruff T, Goulet C, Klee HJ, McCarty DR
Ref: Plant Physiol, 160:1303, 2012 : PubMed
Abstract


ESTHER: Guan_2012_Plant.Physiol_160_1303
PubMedSearch: Guan 2012 Plant.Physiol 160 1303
PubMedID: 22961131

Abstract

Strigolactones (SLs) control lateral branching in diverse species by regulating transcription factors orthologous to Teosinte branched1 (Tb1). In maize (Zea mays), however, selection for a strong central stalk during domestication is attributed primarily to the Tb1 locus, leaving the architectural roles of SLs unclear. To determine how this signaling network is altered in maize, we first examined effects of a knockout mutation in an essential SL biosynthetic gene that encodes CAROTENOID CLEAVAGE DIOXYGENASE8 (CCD8), then tested interactions between SL signaling and Tb1. Comparative genome analysis revealed that maize depends on a single CCD8 gene (ZmCCD8), unlike other panicoid grasses that have multiple CCD8 paralogs. Function of ZmCCD8 was confirmed by transgenic complementation of Arabidopsis (Arabidopsis thaliana) max4 (ccd8) and by phenotypic rescue of the maize mutant (zmccd8::Ds) using a synthetic SL (GR24). Analysis of the zmccd8 mutant revealed a modest increase in branching that contrasted with prominent pleiotropic changes that include (1) marked reduction in stem diameter, (2) reduced elongation of internodes (independent of carbon supply), and (3) a pronounced delay in development of the centrally important, nodal system of adventitious roots. Analysis of the tb1 zmccd8 double mutant revealed that Tb1 functions in an SL-independent subnetwork that is not required for the other diverse roles of SL in development. Our findings indicate that in maize, uncoupling of the Tb1 subnetwork from SL signaling has profoundly altered the balance between conserved roles of SLs in branching and diverse aspects of plant architecture.



        

Title: Overexpressed esterases in a fenvalerate resistant strain of the cotton bollworm, Helicoverpa armigera
Wu S, Yang Y, Yuan G, Campbell PM, Teese MG, Russell RJ, Oakeshott JG, Wu Y
Ref: Insect Biochemistry & Molecular Biology, 41:14, 2011 : PubMed
Abstract


ESTHER: Wu_2011_Insect.Biochem.Mol.Biol_41_14
PubMedSearch: Wu 2011 Insect.Biochem.Mol.Biol 41 14
PubMedID: 20875855
Gene_locus related to this paper: helam-h9zvh4

Abstract

Enhanced detoxification is the major mechanism responsible for pyrethroid resistance in Chinese populations of Helicoverpa armigera. Previous work has shown that enhanced oxidation contributes to resistance in the fenvalerate-selected Chinese strain, YGF. The current study provides evidence that enhanced hydrolysis by esterase isozymes also contributes to the resistance in this strain. The average esterase activity of third instar YGF larvae was 1.9-fold compared with that of a susceptible SCD strain. Much of this difference was attributed to isozymes at two zones which hydrolysed the model carboxylester substrate 1-naphthyl acetate and also a 1-naphthyl analogue of fenvalerate. A preparation enriched for enzymes migrating to one of these zones from YGF was shown to hydrolyse fenvalerate with a specific activity of about 2.9 nmol/min/mg. This material was also matched by mass spectrometry with four putative carboxylesterase genes, all of which clustered within a phylogenetic clade of secreted midgut esterases. Quantitative PCR on these four genes showed several-fold greater expression in tissues of YGF compared to SCD but no differences was found in the number of copies of the genes between the strains.



        

Title: Ultra-sensitive biosensor based on mesocellular silica foam for organophosphorous pesticide detection
Wu S, Zhang L, Qi L, Tao S, Lan X, Liu Z, Meng C
Ref: Biosensors & Bioelectronics, 26:2864, 2011 : PubMed
Abstract


ESTHER: Wu_2011_Biosens.Bioelectron_26_2864
PubMedSearch: Wu 2011 Biosens.Bioelectron 26 2864
PubMedID: 21185711

Abstract

A sensitive amperometric acetylcholinesterase (AChE) biosensor was fabricated based on mesocellular silica foam (MSF), which functioned as both an enzyme immobilization matrix and a solid phase extraction (SPE) material for the preconcentration of target molecules. The hydrophilic interface, the good mechanical/chemical stability, and the suitable pore dimension of MSF provided the entrapped AChE a good environment to well maintain its bioactivity at basic condition. The AChE immobilized in MSF showed improved catalytic ability for the hydrolysis of acetylthiocholine, as evidenced by the increasing of the oxidation current of thiocholine, the enzymatic catalytic hydrolysis production of acetylthiocholine. In addition, the MSF with large surface area showed a modest adsorption capacity for monocrotophos, a model organophosphate used in this study, via the hydrogen bond or physical adsorption interaction. The combination of the SPE and the good enzyme immobilization ability in MSF significantly promoted the sensitivity of the biosensor, and the limit of detection has lowered to 0.05 ng/mL. The biosensor exhibited accuracy, good reproducibility, and acceptable stability when used for garlic samples analysis. The strategy may provide a new method to fabricate highly sensitive biosensors for the detection of ultra-trace organophosphorous pesticide infield.



        

Title: Controlled immobilization of acetylcholinesterase on improved hydrophobic gold nanoparticle/Prussian blue modified surface for ultra-trace organophosphate pesticide detection
Wu S, Lan X, Zhao W, Li Y, Zhang L, Wang H, Han M, Tao S
Ref: Biosensors & Bioelectronics, 27:82, 2011 : PubMed
Abstract


ESTHER: Wu_2011_Biosens.Bioelectron_27_82
PubMedSearch: Wu 2011 Biosens.Bioelectron 27 82
PubMedID: 21752626

Abstract

An ultrasensitive amperometric acetylcholinesterase (AChE) biosensor was fabricated by controlled immobilization of AChE on gold nanoparticles/poly(dimethyldiallylammonium chloride) protected Prussian blue (Au-PDDA-PB) nanocomposite modified electrode surface for the detection of organophorous pesticide. The Au-PDDA-PB membrane served as an excellent matrix for the immobilization of enzyme, which not only enhanced electron transfer but also possessed a relatively large surface area. In addition, the surface hydrophilicity of the Au-PDDA-PB nanocomposite was finely controlled in the static water contact angle range of 25.6-78.1 degrees by adjusting the ratio of gold nanoparticles to PDDA-PB. On an optimized hydrophobic surface, the AChE adopts an orientation with both good activity and stability, which has been proven by electrochemical methods. Benefit from the advantages of the Au-PDDA-PB nanocomposite and the good activity and stability of AChE, the biosensor shows significantly improved sensitivity to monocrotophos, a typical highly toxic organophorous pesticide, with wide linear range (1.0-1000 pg/mL and 1.0-10 ng/mL) and an ultra-low detection limit of 0.8 pg/mL. The biosensor exhibits accuracy, good reproducibility and stability. This strategy may therefore provide useful information for the controlled immobilization of protein and the design of highly sensitive biosensors.



        

Title: Reverse genetic identification of CRN1 and its distinctive role in chlorophyll degradation in Arabidopsis
Ren G, Zhou Q, Wu S, Zhang Y, Zhang L, Huang J, Sun Z, Kuai B
Ref: J Integr Plant Biol, 52:496, 2010 : PubMed
Abstract


ESTHER: Ren_2010_J.Integr.Plant.Biol_52_496
PubMedSearch: Ren 2010 J.Integr.Plant.Biol 52 496
PubMedID: 20537045
Gene_locus related to this paper: arath-Q9FFZ1

Abstract

Recent identification of NYE1/SGR1 brought up a new era for the exploration of the regulatory mechanism of Chlorophyll (Chl) degradation. Cluster analysis of senescence associated genes with putative chloroplast targeting sequences revealed several genes sharing a similar expression pattern with NYE1. Further characterization of available T-DNA insertion lines led to the discovery of a novel stay-green gene CRN1 (Co-regulated with NYE1). Chl breakdown was significantly restrained in crn1-1 under diversified senescence scenarios, which is comparable with that in acd1-20, but much more severe than that in nye1-1. Notably, various Chl binding proteins, especially trimeric LHCP II, were markedly retained in crn1-1 four days after dark-treatment, possibly due to a lesion in disassociation of protein-pigment complex. Nevertheless, the photochemical efficiency of PSII in crn1-1 declined, even more rapidly, two days after dark-treatment, compared to those in Col-0 and nye1-1. Our results suggest that CRN1 plays a crucial role in Chl degradation, and that loss of its function produces various side-effects, including those on the breakdown of Ch-protein complex and the maintenance of the residual photosynthetic capability during leaf senescence.



        

Title: Cloning and characterization of acetylcholinesterase 1 genes from insecticide-resistant field populations of Liposcelis paeta Pearman (Psocoptera: Liposcelididae)
Wu S, Li M, Tang PA, Felton GW, Wang JJ
Ref: Insect Biochemistry & Molecular Biology, 40:415, 2010 : PubMed
Abstract


ESTHER: Wu_2010_Insect.Biochem.Mol.Biol_40_415
PubMedSearch: Wu 2010 Insect.Biochem.Mol.Biol 40 415
PubMedID: 20385234
Gene_locus related to this paper: 9neop-D2KI31

Abstract

The psocid, Liposcelis paeta Pearman, is an increasingly important polyphagous pest of stored products worldwide. Intensive use of organophosphorous insecticides for pest control has facilitated resistance development in psocids in China. Three insecticide-resistant field populations of L. paeta were collected from Nanyang city of Henan Province (NY), and Wuzhou (WZ) and Hezhou (HZ) cities of Guangxi Province, China. Previous studies have shown that psocids have different susceptibilities to insecticides. In addition, their AChE susceptibilities to paraoxon-ethyl and demeton-S-methyl also differed from each other. Acetylcholinesterase 1, which is one of the major targets for organophosphate insecticides, has been fully cloned and sequenced from these populations of L. paeta. Comparison of both nucleotide and deduced amino acid sequences revealed nucleotide polymorphisms among L. paeta ace 1 genes from different populations, but none of these polymorphisms correspond to the active sites in AChE 1 from other insects. The results of comparative quantitative real-time PCR indicated that the relative expression level of HZ ace 1 gene was the highest among three populations, which was 1.20 and 1.02-fold higher than those of NY and WZ populations, respectively. This may due to an epigenetic inheritance phenomenon, which allows organisms to respond to a particular environment through changes in gene expression.



        

Title: Efficacy, safety and tolerability of rivastigmine capsules in patients with probable vascular dementia: the VantagE study
Ballard C, Sauter M, Scheltens P, He Y, Barkhof F, van Straaten EC, van der Flier WM, Hsu C, Wu S, Lane R
Ref: Curr Med Res Opin, 24:2561, 2008 : PubMed
Abstract


ESTHER: Ballard_2008_Curr.Med.Res.Opin_24_2561
PubMedSearch: Ballard 2008 Curr.Med.Res.Opin 24 2561
PubMedID: 18674411

Abstract

OBJECTIVE: The aim was to evaluate the efficacy, safety and tolerability of rivastigmine capsules in patients diagnosed with probable vascular dementia (VaD). METHODS: VantagE (Vascular Dementia trial studying Exelon) was a 24-week, multicentre, double-blind study. VaD patients aged 50-85 years were randomized to rivastigmine capsules (3-12 mg/day) or placebo. Efficacy assessments included global and cognitive performances, activities of daily living and neuropsychiatric symptoms. Adverse events were recorded. Additional exploratory analyses determined whether heterogeneity in pathologies and symptoms extended to differential treatment effects. TRIAL REGISTRATION: NCT00099216. RESULTS: 710 patients were randomized. Rivastigmine demonstrated superiority over placebo on three measures of cognitive performance (Vascular Dementia Assessment Scale, Alzheimer's Disease Assessment Scale cognitive subscale, Mini-Mental State Examination; all p< or = 0.05, intent-to-treat population [ITT]), but not other outcomes. Predominant adverse events were nausea and vomiting. Exploratory analyses indicated that older patients (> or =75 years old), assumed more likely to also have Alzheimer's disease (AD) pathology, demonstrated significant cognitive responses to rivastigmine and a safety profile similar to that seen in AD patients. Younger patients, assumed less likely to have concomitant AD pathology, showed no efficacy response and were associated with slight elevations of blood pressure, cerebrovascular accidents and mortality. Rivastigmine-placebo differences in patients with, versus those without, medial temporal atrophy (also suggestive of concomitant AD) showed a numerical difference similar to that seen between the older versus younger patients, but did not attain statistical significance. CONCLUSION: Consistent with trials evaluating other cholinesterase inhibitors, rivastigmine did not provide consistent efficacy in probable VaD. The efficacy apparent on cognitive outcomes was derived from effects in older patients likely to have concomitant Alzheimer pathology. This is supportive of an existing argument that the putative cholinergic deficit in VaD reflects the presence of concomitant Alzheimer pathology.



        

Title: Comparison of acetylcholinesterase from three field populations of Liposcelis paeta Pearman (Psocoptera: Liposcelididae): Implications of insecticide resistance
Ren Y, Wei X-Q, Wu S, Dou W, Wang J-J
Ref: Pesticide Biochemistry and Physiology, 90:196, 2008 : PubMed
Abstract


ESTHER: Ren_2008_Pestic.Biochem.Physiol_90_196
PubMedSearch: Ren 2008 Pestic.Biochem.Physiol 90 196
Gene_locus related to this paper: 9neop-D2KI31

Abstract

The toxicological and biochemical characteristics of acetylcholinesterases (AChE) in Liposcelis paeta Pearman were investigated in three field populations collected from Nanyang city of Henan Province (NY), Wuzhou (WZ) and Hezhou (HZ) Cities of Guangxi Province, China. The result of bioassay showed that the LC50s of the NY (281.4802 mg/m2) and the WZ (285.0655 mg/m2) to dichlorvos were 1.156-fold and 1.171-fold higher than that of the HZ (243.5197 mg/m2), respectively. Compared to NY population, the activity per insect and the specific activity of AChE in WZ and HZ populations were significantly higher, and significant kinetic differences among the three populations were also observed. The apparent Michaelis-Menten constant (Km) for acetylthiocholine iodide (ATChI) was obviously lower in NY than that in WZ and HZ populations, indicating a higher affinity to the substrate ATChI in the NY population. The affinity to the substrate ATChI between WZ and HZ population was also significantly different. As for Vmax, the values of WZ and HZ populations were significantly greater when compared to that for NY population, suggesting a possible over expression of AChE in the former two populations. The inhibition studies of AChE indicated that paraoxon-ethyl, demeton-S-methyl, carbaryl, and eserine all possessed some inhibitory effects on AChE in L. paeta. The results of I50S suggested that when compared to the other two populations, while AChE from HZ population was less sensitive to paraoxon-ethyl and demeton-S-methyl. The contradiction with the result of the bioassay might be due to the different insecticides used in the bioassay. Although both carbaryl and eserine had excellent inhibitory effects, there was no significant difference among the three populations. The statistical analysis of the bimolecular rate constants (ki) was consistent with the above situation that carbamates expressed remarkable inhibitory effects. It was noticeable that NY population was most sensitive to carbaryl while least to eserine. The differences in AChE among three populations may attribute to the difference in control practices for psocids between Henan and Guangxi Provinces.



        

Title: Improved PCR method for the creation of saturation mutagenesis libraries in directed evolution: application to difficult-to-amplify templates
Sanchis J, Fernandez L, Carballeira JD, Drone J, Gumulya Y, Hobenreich H, Kahakeaw D, Kille S, Lohmer R and Reetz MT <7 more author(s)> Sanchis J, Fernandez L, Carballeira JD, Drone J, Gumulya Y, Hobenreich H, Kahakeaw D, Kille S, Lohmer R, Peyralans JJ, Podtetenieff J, Prasad S, Soni P, Taglieber A, Wu S, Zilly FE, Reetz MT (- 7)
Ref: Applied Microbiology & Biotechnology, 81:387, 2008 : PubMed
Abstract


ESTHER: Sanchis_2008_Appl.Microbiol.Biotechnol_81_387
PubMedSearch: Sanchis 2008 Appl.Microbiol.Biotechnol 81 387
PubMedID: 18820909

Abstract

Saturation mutagenesis constitutes a powerful method in the directed evolution of enzymes. Traditional protocols of whole plasmid amplification such as Stratagene's QuikChange sometimes fail when the templates are difficult to amplify. In order to overcome such restrictions, we have devised a simple two-primer, two-stage polymerase chain reaction (PCR) method which constitutes an improvement over existing protocols. In the first stage of the PCR, both the mutagenic primer and the antiprimer that are not complementary anneal to the template. In the second stage, the amplified sequence is used as a megaprimer. Sites composed of one or more residues can be randomized in a single PCR reaction, irrespective of their location in the gene sequence.The method has been applied to several enzymes successfully, including P450-BM3 from Bacillus megaterium, the lipases from Pseudomonas aeruginosa and Candida antarctica and the epoxide hydrolase from Aspergillus niger. Here, we show that megaprimer size as well as the direction and design of the antiprimer are determining factors in the amplification of the plasmid. Comparison of the results with the performances of previous protocols reveals the efficiency of the improved method.



        

Title: A novel enantioselective epoxide hydrolase for (R)-phenyl glycidyl ether to generate (R)-3-phenoxy-1,2-propanediol
Wu S, Shen J, Zhou X, Chen J
Ref: Applied Microbiology & Biotechnology, 76:1281, 2007 : PubMed
Abstract


ESTHER: Wu_2007_Appl.Microbiol.Biotechnol_76_1281
PubMedSearch: Wu 2007 Appl.Microbiol.Biotechnol 76 1281
PubMedID: 17710393
Gene_locus related to this paper: tsupd-d5us69

Abstract

Bacillus sp. Z018, a novel strain producing epoxide hydrolase, was isolated from soil. The epoxide hydrolase catalyzed the stereospecific hydrolysis of (R)-phenyl glycidyl ether to generate (R)-3-phenoxy-1,2-propanediol. Epoxide hydrolase from Bacillus sp. Z018 was inducible, and (R)-phenyl glycidyl ether was able to act as an inducer. The fermentation conditions for epoxide hydrolase were 35 degrees C, pH 7.5 with glucose and NH(4)Cl as the best carbon and nitrogen source, respectively. Under optimized conditions, the biotransformation yield of 45.8% and the enantiomeric excess of 96.3% were obtained for the product (R)-3-phenoxy-1,2-propanediol.



        

Title: The Genomes of Oryza sativa: a history of duplications
Yu J, Wang J, Lin W, Li S, Li H, Zhou J, Ni P, Dong W, Hu S and Yang H <88 more author(s)> Yu J, Wang J, Lin W, Li S, Li H, Zhou J, Ni P, Dong W, Hu S, Zeng C, Zhang J, Zhang Y, Li R, Xu Z, Li X, Zheng H, Cong L, Lin L, Yin J, Geng J, Li G, Shi J, Liu J, Lv H, Li J, Deng Y, Ran L, Shi X, Wang X, Wu Q, Li C, Ren X, Li D, Liu D, Zhang X, Ji Z, Zhao W, Sun Y, Zhang Z, Bao J, Han Y, Dong L, Ji J, Chen P, Wu S, Xiao Y, Bu D, Tan J, Yang L, Ye C, Xu J, Zhou Y, Yu Y, Zhang B, Zhuang S, Wei H, Liu B, Lei M, Yu H, Li Y, Xu H, Wei S, He X, Fang L, Huang X, Su Z, Tong W, Tong Z, Ye J, Wang L, Lei T, Chen C, Chen H, Huang H, Zhang F, Li N, Zhao C, Huang Y, Li L, Xi Y, Qi Q, Li W, Hu W, Tian X, Jiao Y, Liang X, Jin J, Gao L, Zheng W, Hao B, Liu S, Wang W, Yuan L, Cao M, McDermott J, Samudrala R, Wong GK, Yang H (- 88)
Ref: PLoS Biol, 3:e38, 2005 : PubMed
Abstract


ESTHER: Yu_2005_PLoS.Biol_3_e38
PubMedSearch: Yu 2005 PLoS.Biol 3 e38
PubMedID: 15685292
Gene_locus related to this paper: orysa-Q7XTC5, orysa-Q852M6, orysa-Q8GSE8, orysa-Q9S7P1, orysa-Q9FYP7, orysa-Q5ZBH3, orysa-Q5ZA26, orysa-Q5JLP6, orysa-Q8H5P9, orysa-Q8H5P5, orysa-Q7F1Y5, orysa-Q949C9, orysa-cbp1, orysa-cbp3, orysa-cbpx, orysa-Q33B71, orysa-Q8GSJ3, orysa-LPL1, orysa-Q6YSZ8, orysa-Q8S5X5, orysa-Q8LIG3, orysa-Q6K7F5, orysa-Q7F1B1, orysa-Q8H4S9, orysa-Q69UB1, orysa-Q9FW17, orysa-Q337C3, orysa-Q7F959, orysa-Q84QZ6, orysa-Q84QY7, orysa-Q851E3, orysa-Q6YTH5, orysa-Q0JK71, orysa-Q8S1D9, orysa-Q5N8V4, orysa-Q0JCY4, orysa-Q8GTK2, orysa-B9EWJ8, orysa-Q8H3K6, orysa-Q6ZDG8, orysa-Q6ZDG6, orysa-Q6ZDG5, orysa-Q6ZDG4, orysa-Q5NAI4, orysa-Q658B2, orysa-Q5JMQ8, orysa-Q5QMD9, orysa-Q5N7L1, orysa-Q8RYV9, orysa-Q8H3R3, orysa-Q5SNH3, orysa-Q8W0F0, orysa-pir7a, orysa-pir7b, orysa-q2qlm4, orysa-q2qm78, orysa-q2qm82, orysa-q2qn31, orysa-q2qnj4, orysa-q2qnt9, orysa-q2qur1, orysa-q2qx94, orysa-q2qyi1, orysa-q2qyj1, orysa-q2r051, orysa-q2r077, orysa-q2ram0, orysa-q2rat1, orysa-q2rbb3, orysa-Q4VWY7, orysa-q5na00, orysa-q5nbu1, orysa-Q5QLC0, orysa-q5smv5, orysa-Q5VP27, orysa-q5vrt2, orysa-q5w6c5, orysa-q5z5a3, orysa-q5z9i2, orysa-q5z417, orysa-q5z901, orysa-Q5ZAM8, orysa-Q5ZBI5, orysa-Q5ZCR3, orysa-q6atz0, orysa-q6ave2, orysa-q6f358, orysa-q6h6s1, orysa-q6h7i6, orysa-q6i5q3, orysa-q6i5u7, orysa-q6j657, orysa-q6k3d9, orysa-q6k4q2, orysa-q6k880, orysa-q6l5b6, orysa-Q6L5F5, orysa-q6l556, orysj-q6yse8, orysa-q6yy42, orysa-q6yzk1, orysa-q6z8b1, orysa-q6z995, orysa-q6zc62, orysa-q6zia4, orysa-q6zjq6, orysa-q7x7y5, orysa-Q7XC50, orysa-q7xej4, orysa-q7xem8, orysa-q7xkj9, orysa-q7xr62, orysa-q7xr63, orysa-q7xr64, orysa-q7xsg1, orysa-q7xsq2, orysa-q7xts6, orysa-q7xv53, orysa-Q7XVB5, orysa-Q8L562, orysa-Q8LQS5, orysa-Q8RZ40, orysa-Q8RZ79, orysa-Q8S0U8, orysa-Q8S0V0, orysa-Q8S125, orysa-Q8SAY7, orysa-Q8SAY9, orysa-Q8W3C6, orysa-Q8W3F2, orysa-Q8W3F4, orysa-Q8W3F6, orysa-Q9LHX5, orysa-q33aq0, orysa-q53lh1, orysa-q53m20, orysa-q53nd8, orysa-q60e79, orysa-q60ew8, orysa-q67iz2, orysa-q67iz3, orysa-q67iz7, orysa-q67iz8, orysa-q67j02, orysa-q67j05, orysa-q67j07, orysa-q67j09, orysa-q67j10, orysa-q67tr6, orysa-q67tv0, orysa-q67uz1, orysa-q67v34, orysa-q67wz5, orysa-q69j38, orysa-q69k08, orysa-q69md7, orysa-q69me0, orysa-q69pf3, orysa-q69ti3, orysa-q69xr2, orysa-q69y12, orysa-q69y21, orysa-q75hy2, orysa-q75i01, orysa-Q94JD7, orysa-Q0J0A4, orysa-q651a8, orysa-q651z3, orysa-q652g4, orysa-q688m0, orysa-q688m8, orysa-q688m9, orysa-Q6H8G1, orysi-a2wn01, orysi-a2xc83, orysi-a2yh83, orysi-a2z179, orysi-a2zef2, orysi-b8a7e6, orysi-b8a7e7, orysi-b8bfe5, orysi-b8bhp9, orysj-a3b9l8, orysj-b9eub8, orysj-b9eya5, orysj-b9fi05, orysj-b9fkb0, orysj-b9fn42, orysj-b9gbb7, orysj-cgep, orysj-PLA7, orysj-q0d4u5, orysj-q0djj0, orysj-q0jaf0, orysj-q5jl22, orysj-q5jlw7, orysj-q5z419, orysj-q6h7q9, orysj-q6yvk6, orysj-q6z6i1, orysj-q7f8x1, orysj-q7xcx3, orysj-q9fwm6, orysj-q10j20, orysj-q10ss2, orysj-q69uw6, orysj-q94d71, orysj-q338c0, orysi-b8bly4, orysj-b9gbs4, orysi-a2zb88, orysj-b9gbs1, orysi-b8b698, orysj-pla4, orysj-pla1

Abstract

We report improved whole-genome shotgun sequences for the genomes of indica and japonica rice, both with multimegabase contiguity, or almost 1,000-fold improvement over the drafts of 2002. Tested against a nonredundant collection of 19,079 full-length cDNAs, 97.7% of the genes are aligned, without fragmentation, to the mapped super-scaffolds of one or the other genome. We introduce a gene identification procedure for plants that does not rely on similarity to known genes to remove erroneous predictions resulting from transposable elements. Using the available EST data to adjust for residual errors in the predictions, the estimated gene count is at least 38,000-40,000. Only 2%-3% of the genes are unique to any one subspecies, comparable to the amount of sequence that might still be missing. Despite this lack of variation in gene content, there is enormous variation in the intergenic regions. At least a quarter of the two sequences could not be aligned, and where they could be aligned, single nucleotide polymorphism (SNP) rates varied from as little as 3.0 SNP/kb in the coding regions to 27.6 SNP/kb in the transposable elements. A more inclusive new approach for analyzing duplication history is introduced here. It reveals an ancient whole-genome duplication, a recent segmental duplication on Chromosomes 11 and 12, and massive ongoing individual gene duplications. We find 18 distinct pairs of duplicated segments that cover 65.7% of the genome; 17 of these pairs date back to a common time before the divergence of the grasses. More important, ongoing individual gene duplications provide a never-ending source of raw material for gene genesis and are major contributors to the differences between members of the grass family.



        

Title: A single residual replacement improves the folding and stability of recombinant cassava hydroxynitrile lyase in E. coil
Yan G, Cheng S, Zhao G, Wu S, Liu Y, Sun W
Ref: Biotechnol Lett, 25:1041, 2003 : PubMed
Abstract


ESTHER: Yan_2003_Biotechnol.Lett_25_1041
PubMedSearch: Yan 2003 Biotechnol.Lett 25 1041
PubMedID: 12889812
Gene_locus related to this paper: manes-hnl

Abstract

Substitution of Ser113 for Gly113 in the cap domain of hydroxynitrile lyase from Manihot esculenta (MeHNL) was performed by site-directed mutagenesis to improve its self-generated folding and stability under denaturation conditions. The yield of the recombinant mutant HNL1 (mut-HNL1), which had higher specific activity than the wild type HNL0 (wt-HNL0), was increased by 2 to 3-fold. Thermostability of MeHNL was also enhanced, probably due to an increase in content of the beta-strand secondary structure according to CD analysis. Our data in this report suggest that Ser113 significantly contributes to the in vivo folding and stability of MeHNL and demonstrates an economic advantage of mut-HNL1 over the wt-HNL0.



        

Title: Structure and function engineered Pseudomonas mendocina lipase
Boston M, Requadt C, Danko S, Jarnagin A, Ashizawa E, Wu S, Poulose AJ, Bott R
Ref: Methods Enzymol, 284:298, 1997 : PubMed
Abstract


ESTHER: Boston_1997_Methods.Enzymol_284_298
PubMedSearch: Boston 1997 Methods.Enzymol 284 298
PubMedID: 9379942
Gene_locus related to this paper: pseme-LIPA, psemy-a4y035



        

Title: Ser-His-Glu triad forms the catalytic site of the lipase from Geotrichum candidum
Schrag JD, Li YG, Wu S, Cygler M
Ref: Nature, 351:761, 1991 : PubMed
Abstract


ESTHER: Schrag_1991_Nature_351_761
PubMedSearch: Schrag 1991 Nature 351 761
PubMedID: 2062369
Gene_locus related to this paper: geoca-1lipa

Abstract

The Ser-His-Asp triad is a well known structural feature of the serine proteases. It has also been directly observed in the catalytic sites of two lipases, whose high-resolution three-dimensional structures have been determined 1,2. Lipases show a wide variety of sizes, substrate and positional specificities, and catalytic rates 3. They achieve maximal catalytic rates at oil-water interfaces. The fungus Geotrichum candidum produces several different forms of lipases, two of which have been purified to homogeneity 4,5. Two lipase genes have been identified, cloned and sequenced 6,7. Both code for proteins of 544 amino acids with a total relative molecular mass of about 60,000 (Mr 60K). The two forms are 86% identical. Their isoelectric points differ slightly, being between 4.3 and 4.6. About 7% of the total Mr is carbohydrate. Until now, only a low resolution structure of GCL has been reported 8, but no high resolution structure has followed. We now report the three-dimensional structure of a lipase from G. candidum (GCL) at 2.2 A resolution. Unlike the other lipases and serine proteases, the catalytic triad of GCL is Ser-His-Glu, with glutamic acid replacing the usual aspartate. Although the sequence similarity with the other two lipases is limited to the region near the active-site serine, there is some similarity in their three-dimensional structures. The GCL is also an alpha/beta protein with a central mixed beta sheet whose topology is similar to that of the N-terminal domain of human pancreatic lipase. As in the other lipases 1,2, the catalytic site is buried under surface loops. Sequence comparisons with proteins from the cholinesterase family suggest that they also contain the Ser-His-Glu triad.