Author

Biblio print

Tree Display

AceDB Schema

XML Display

Feedback

Author Report for: Yang G

Title: Selection and Identification of an ssDNA Aptamer for Fibroblast Activation Protein
Zhang X, Yang G, Zhao Y, Dai X, Liu W, Qu F, Huang Y
Ref: Molecules, 28:, 2023 : PubMed
Abstract


ESTHER: Zhang_2023_Molecules_28_
PubMedSearch: Zhang 2023 Molecules 28
PubMedID: 36838669

Abstract

As a type II transmembrane serine protease, fibroblast activation protein (FAP) is specifically expressed on the surface of fibroblasts associated with a variety of epithelial-derived malignancies such as pancreatic cancer, breast cancer, and colon cancer. It participates in the processes of tumorigenesis, progression, and immunosuppression. FAP constitutes an important target for tumor treatment; however, the current studies on FAP are mainly related to structural characteristics, enzymatic properties, and biological functions, and aptamers of FAP have not been investigated. In this work, by using recombinant human FAP as the target, five candidate aptamers, which are AptFAP-A1, AptFAP-A2, AptFAP-A3, AptFAP-A4, and AptFAP-A5, were selected by capillary electrophoresis-systematic evolution of ligands by exponential enrichment (CE-SELEX), and their secondary structures were predicted to be mainly stem-loop. Moreover, the CE-laser-induced fluorescence (LIF) method was used to determine the equilibrium dissociation constant K(D) values between the FAP protein and candidate aptamers, and the K(D) value was in the low molar range. Finally, Cy5-labeled aptamers were co-incubated with human pancreatic cancer-associated fibroblasts highly expressing FAP protein, and confocal microscopy imaging showed that aptamer AptFAP-A4 had the highest affinities with the cells. The FAP aptamers screened in this study provide a promising direction for the development of rapid tumor diagnosis and targeted therapy.



        

Title: Highly selective SERS detection of acetylcholinesterase in human blood based on catalytic reaction
Chen Y, Zhao W, Si J, Zheng Y, Tan H, Meng F, Yang G, Gu Y, Qu L
Ref: Anal Chim Acta, 1232:340495, 2022 : PubMed
Abstract


ESTHER: Chen_2022_Anal.Chim.Acta_1232_340495
PubMedSearch: Chen 2022 Anal.Chim.Acta 1232 340495
PubMedID: 36257753

Abstract

Acetylcholinesterase (AChE) is a key hydrolase in the cholinergic system, which directly determines the degradation of neurotransmitters. Therefore, it is a significant challenge to detect AChE in human blood with high sensitivity and selectivity in physiological and pathological processes. A novel nanoprobe by decorating the surface of gold nanoparticles with neostigmine (NE) AuNPs/NE was constructed for the AChE assay in serum. The principle is based on the specific recognition and cleavage of carbamate bonds in AuNPs/NE by AChE to form hydroxyl groups, resulting in changes of SERS spectra. The results show that 10 nm AuNPs/NE exhibit excellent catalytic activity for this reaction and the reaction rate is six times higher than that of 70 nm AuNPs/NE. Benefiting from the combined advantages of catalytic reaction specificity and molecular finger printing provided by SERS technology, AuNPs/NE exhibit high selectivity for AChE. The limit of detection (LOD) of this method for AChE activity was low to 0.02 U/mL. In addition, the spiked recovery of AChE in serum samples was 75.0%-119.2%. The proposed sensor also exhibits long-term stability and high biocompatibility with the increasing incubation time. More importantly, this work provides a new perspective for elucidating the role of AChE regulated by oxidative stress in the pathology of depression.



        

Title: Interrelationship between 2019-nCov receptor DPP4 and diabetes mellitus targets based on protein interaction network
Gao Q, Zhang W, Li T, Yang G, Zhu W, Chen N, Jin H
Ref: Sci Rep, 12:188, 2022 : PubMed
Abstract


ESTHER: Gao_2022_Sci.Rep_12_188
PubMedSearch: Gao 2022 Sci.Rep 12 188
PubMedID: 34996987

Abstract

Patients with diabetes are more likely to be infected with Coronavirus disease 2019 (COVID-19), and the risk of death is significantly higher than ordinary patients. Dipeptidyl peptidase-4 (DPP4) is one of the functional receptor of human coronavirus. Exploring the relationship between diabetes mellitus targets and DPP4 is particularly important for the management of patients with diabetes and COVID-19. We intend to study the protein interaction through the protein interaction network in order to find a new clue for the management of patients with diabetes with COVID-19. Diabetes mellitus targets were obtained from GeneCards database. Targets with a relevance score exceeding 20 were included, and DPP4 protein was added manually. The initial protein interaction network was obtained through String. The targets directly related to DPP4 were selected as the final analysis targets. Importing them into String again to obtain the protein interaction network. Module identification, gene ontology (GO) analysis and Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis were carried out respectively. The impact of DPP4 on the whole network was analyzed by scoring the module where it located. 43 DPP4-related proteins were finally selected from the diabetes mellitus targets and three functional modules were found by the cluster analysis. Module 1 was involved in insulin secretion and glucagon signaling pathway, module 2 and module 3 were involved in signaling receptor binding. The scoring results showed that LEP and apoB in module 1 were the highest, and the scores of INS, IL6 and ALB of cross module associated proteins of module 1 were the highest. DPP4 is widely associated with key proteins in diabetes mellitus. COVID-19 may affect DPP4 in patients with diabetes mellitus, leading to high mortality of diabetes mellitus combined with COVID-19. DPP4 inhibitors and IL-6 antagonists can be considered to reduce the effect of COVID-19 infection on patients with diabetes.



        

Title: Potentially tunable ratiometric electrochemiluminescence sensing based on conjugated polymer nanoparticle for organophosphorus pesticides detection
He Y, Yang G, Zhao J, Tan K, Yuan R, Chen S
Ref: J Hazard Mater, 432:128699, 2022 : PubMed
Abstract


ESTHER: He_2022_J.Hazard.Mater_432_128699
PubMedSearch: He 2022 J.Hazard.Mater 432 128699
PubMedID: 35325864

Abstract

In general, suitable double luminophores and their coreactants are necessary for constructing electrochemiluminescence (ECL) ratio strategy. However, the complexity of matching double luminophores and the stability and repeatability problem suffered by introducing exogenous coreactant would greatly limit the application of ratio detection. An original single-luminophore-based ECL ratio sensing was developed excluding any exogenous coreactants in this work. The poly [9,9-bis(3'-(N,N-dimethylamino)propyl)- 2,7-fluorene]-alt-2,7-(9,9-dioctylfluorene)] nanoparticles (PFN NPs) were explored to emit two anodic ECL signals. One centered at + 1.25 V (ECL-1) with the scanning potential of 0 ~ + 1.25 V and the other at + 1.95 V (ECL-2) with the scanning potential of 0 ~ + 1.95 V. ECL-1 showed a very strong emission without any exogenous coreactant. Importantly, hydrogen peroxide (H(2)O(2)) was able to efficiently weaken ECL-1 but strengthen ECL-2. When organophosphorus pesticides (OPs) were absent, the immobilized acetylcholinesterase-choline oxidase (AChE-ChOx) would catalyze the substrate acetylthiocholine chloride (ATCl) to produce H(2)O(2), resulting in a quenched ECL-1 and an enhanced ECL-2. With the introduction of OPs, ECL-1 increased while ECL-2 accordingly decreased as OPs prohibited production of H(2)O(2) by inhibiting activity of AChE. Highly sensitive ECL ratio detection for OPs was realized based on the change of the ratio of two signals. The dual anode emission properties of PFN NPs coupled with the opposite regulation of H(2)O(2) on the two signals paved a new avenue for potentially tunable ECL ratio sensing strategy, and showed enormous potential applications for OPs analysis.



        

Title: Effects of Lipase and Xylanase Pretreatment on the Structure and Pulping Properties of Wheat Straw
Jia Q, Chen J, Yang G, Liu K, Wang Y, Zhang K
Ref: Polymers (Basel), 14:, 2022 : PubMed
Abstract


ESTHER: Jia_2022_Polymers.(Basel)_14_
PubMedSearch: Jia 2022 Polymers.(Basel) 14
PubMedID: 36501524

Abstract

Based on the reduction of environmental pollution, a biological enzyme assisted alkali-oxygen pulping method was explored to improve the delignification efficiency and fiber accessibility of wheat straw and improve the properties of wheat straw pulp. In this paper, lipase and xylanase were used to pretreat wheat straw and the effects of different enzyme types and enzyme dosage on the microstructure and pulp properties of wheat straw were investigated and experimented. The results showed that the lipase can remove fat and wax on the surface of wheat straw, while xylanase degraded the hemicellulose components, such as xylan, of wheat straw fiber, destroyed the structure of the lignin-carbohydrate complex, increasing lignin removal as a result and enhancing the impregnating, diffusion and penetration of alkali. Compared with wheat straw without enzyme pretreatment, the skeleton of wheat straw pretreated by enzyme became looser, the internal cavity appeared and the wall cavity became thin and transparent. The fines decreased obviously and the length of fibers increased. After combined pretreatment with lipase (15 U.g(-1)) and xylanase (15 U.g(-1)), the pulping performance of wheat straw was improved and the tensile index (97.37 N.m.g(-1)), brightness (40.9% ISO) and yield (58.10%) of the pulp increased by 12.9%, 19.9% and 9.9%, respectively. It can be seen that enzyme pretreatment is a green and effective approach to improving the alkali-oxygen pulping performance of wheat straw.



        

Title: Anti-Alzheimer's disease active components screened out and identified from Hedyotis diffusa combining bioaffinity ultrafiltration LC-MS with acetylcholinesterase
Li J, Yang G, Shi W, Fang X, Han L, Cao Y
Ref: J Ethnopharmacol, :115460, 2022 : PubMed
Abstract


ESTHER: Li_2022_J.Ethnopharmacol__115460
PubMedSearch: Li 2022 J.Ethnopharmacol 115460
PubMedID: 35714878

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE: Hedyotis diffusa is a traditional ethnomedicinal plant in local communities in northeastern Asia and used to treat inflammation, nervous breakdown, among others. In recent years, it has been applied in the treatment of Alzheimer's disease (AD), while the specific chemical components responsible for the activity remain need to be explored. AIM OF THE STUDY: To prepare, screen and identify the potential anti-AD active components from Hedyotis diffusa. MATERIALS AND METHODS: The acetylcholinesterase (AChE) inhibitory activity of four different extracts of Hedyotis diffusa were initially assessed using a spectrophotometric Ellman's method. A more accurate LC-MS/MS screening method combining functional enzyme assay and affinity ultrafiltration (AU) screening assay was developed and applied for the screening of natural compound inhibitors of AChE from Hedyotis diffusa. The binding mode were further investigated between protein and ligands via molecular docking. Subsequently, CL4176, a transgenic nematode model for AD, was used for activity validation of one of these components. RESULTS: N-butanol extract of Hedyotis diffusa (NHD) appeared significant inhibitory activities on AChE, were chosen to delve deeper. Five bioactive components targeting AChE were screened out and identified using AU coupled to liquid chromatography-mass spectrometry. Molecular docking technique further confirmed the results of the screening assay. Finally, qurecetin-3-O-sophoroside (QS) was confirmed as a potent anti-AD agent by in vivo experiments in C. elegans. CONCLUSION: This study explores a new idea for screening anti-AD active components from traditional medicine. The findings provide a molecular structure and bioactivity basis for future potential applications of Hedyotis diffusa in medical industries.



        

Title: Development of indole-2-carbonyl piperazine urea derivatives as selective FAAH inhibitors for efficient treatment of depression and pain
Shang Y, Wang M, Hao Q, Meng T, Li L, Shi J, Yang G, Zhang Z, Yang K, Wang J
Ref: Bioorg Chem, 128:106031, 2022 : PubMed
Abstract


ESTHER: Shang_2022_Bioorg.Chem_128_106031
PubMedSearch: Shang 2022 Bioorg.Chem 128 106031
PubMedID: 36037600

Abstract

Fatty acid amide hydrolase (FAAH), aserinehydrolase with significant role in thehydrolysis of endocannabinoids, is a promising therapeutic target for peripheral and central nervous system related disorders, including pain, neuroinflammation and depression. Employing a structure-based approach, a novel series of indole-2-carbonyl piperazine urea derivatives were designed and synthesized as FAAH inhibitors for the treatment of pain-depression comorbidity. Among them, compound 4i emerged as the most potent inhibitor (IC(50) = 0.12 microM) with fine selectivity versus CES2, ABHD6, MAGL and the cannabinoid receptor, which also displayed superior metabolic stability in human liver microsome and an adequate pharmacokinetic profile in rodents. Treatment of depressed rats with 4i demonstrated favorable antidepressant-like effects not only by increasing the level of BDNF in the hippocampus but also by restraining the apoptosis of hippocampal neurons. Also, 4i effectively suppressed the LPS-induced neuroinflammation in vitro. Moreover, 4i exhibited potent analgesic activity, which indicated its promising therapeutical application for pain and depression. These meaningful results shed light on FAAH inhibitors as promising pain-depression comorbidity therapeutics.



        

Title: Lipase induced highly hydrophobic nanofibrillated cellulose film for strain sensor application
Wang Y, Wang Q, Liu S, Ji X, Yang G, Chen J
Ref: Carbohydr Polym, 284:119193, 2022 : PubMed
Abstract


ESTHER: Wang_2022_Carbohydr.Polym_284_119193
PubMedSearch: Wang 2022 Carbohydr.Polym 284 119193
PubMedID: 35287910

Abstract

An environmental-friendly lipase induced highly hydrophobic NFC film was fabricated through lipase induced dimethyl adipate (DA) esterification followed by silver nanowires (AgNWs) coating for strain sensor application. Due to the lipase activation, the substitution degree (DS(NMR)) of 0.18 was achieved, which was three times higher than that of the control sample (without lipase treatment of NFC-DA). As a result, the water contact angle (WCA) of lipase induced adipated-NFC film was reached to 105 +/- 3 degrees from 50 +/- 2.3 degrees of NFC-DA. In addition, the cellulose structure and performance were well maintained after lipase induced esterification, confirmed by AFM, SEM, TG/DTG, and XRD analysis. After AgNWs coating and annealing, the hydrophobic NFC film-based strain sensor exhibited excellent sensitivity towards human motion, such as finger/wrist movement in real-time, even under wet conditions. Overall, a highly hydrophobic NFC film-based strain sensor was fabricated, which has promising application in wearable devices for human motion monitoring.



        

Title: Lipase-Catalyzed Phospha-Michael Addition Reactions under Mild Conditions
Xu J, Cao P, Fan Z, Luo X, Yang G, Qu T, Gao J, Xu Y, Li F and Wang L <5 more author(s)> Xu J, Cao P, Fan Z, Luo X, Yang G, Qu T, Gao J, Xu Y, Li F, Ma J, Li J, Xie H, Wang C, Chen P, Wang L (- 5)
Ref: Molecules, 27:, 2022 : PubMed
Abstract


ESTHER: Xu_2022_Molecules_27_
PubMedSearch: Xu 2022 Molecules 27
PubMedID: 35684413 36431898

Abstract

Organophosphorus compounds are the core structure of many active natural products. The synthesis of these compounds is generally achieved by metal catalysis requiring specifically functionalized substrates or harsh conditions. Herein, we disclose the phospha-Michael addition reaction of biphenyphosphine oxide with various substituted beta-nitrostyrenes or benzylidene malononitriles. This biocatalytic strategy provides a direct route for the synthesis of C-P bonds with good functional group compatibility and simple and practical operation. Under the optimal conditions (styrene (0.5 mmol), biphenyphosphine oxide (0.5 mmol), Novozym 435 (300 U), and EtOH (1 mL)), lipase leads to the formation of organophosphorus compounds in yields up to 94% at room temperature. Furthermore, we confirm the role of the catalytic triad of lipase in this phospha-Michael addition reaction. This new biocatalytic system will have broad applications in organic synthesis.



        

Title: 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: Bifunctional Moderator-Powered Ratiometric Electrochemiluminescence Enzymatic Biosensors for Detecting Organophosphorus Pesticides Based on Dual-Signal Combined Nanoprobes
He Y, Hu F, Zhao J, Yang G, Zhang Y, Chen S, Yuan R
Ref: Analytical Chemistry, :, 2021 : PubMed
Abstract


ESTHER: He_2021_Anal.Chem__
PubMedSearch: He 2021 Anal.Chem
PubMedID: 34133127

Abstract

The bifunctional moderator is urgently needed in the field of ratiometric electrochemiluminescence (ECL) sensing since it can mediate simultaneously two ECL signals to conveniently realize their opposite change trend. This work designed a novel dual-signal combined nanoprobe with carboxyl-functionalized poly[(9,9-dioctylfluorenyl-2,7-diyl)-co-(1,4-benzo-{2,1',3}-thiadazole)] nanoparticles (c-PFBT NPs) as the anodic ECL probe and L-cysteine capped CdS quantum dots (L-CdS QDs) as the cathodic ECL probe, which performed a dual-signal output capability without any additional coreactants. More importantly, hydrogen peroxide (H(2)O(2)) produced in situ by enzyme-catalyzed reaction was developed as a bifunctional moderator for simultaneously regulating two signals. The dual-signal combined nanoprobe (c-PFBT NPs@CdS QDs) served as the matrix to immobilize acetylcholinesterase (AChE) and choline oxidase for organophosphorus (OPs) analysis. In the absence of OPs, H(2)O(2) was produced by catalyzing the substrate acetylthiocholine (ATCl) with enzymes and it quenched the anodic ECL signal from c-PFBT NPs and simultaneously promoted the cathodic ECL signal from L-CdS QDs. When OPs was present, the activity of AChE was inhibited, the anodic signal would increase, and the cathodic signal would accordingly decrease. The integration of the bifunctional moderator H(2)O(2) and dual-signal combined nanoprobe c-PFBT NPs@CdS QDs not only provides an attractive ECL platform for enzymatic sensing involving the generation or consumption of H(2)O(2) but also paves a new pathway for other ratiometric ECL systems involving enzyme catalytic amplification for detecting antigens, antibodies, DNA, RNA, etc.



        

Title: The relationship between pesticide exposure during critical neurodevelopment and autism spectrum disorder: A narrative review
He X, Tu Y, Song Y, Yang G, You M
Ref: Environ Research, 203:111902, 2021 : PubMed
Abstract


ESTHER: He_2021_Environ.Res_203_111902
PubMedSearch: He 2021 Environ.Res 203 111902
PubMedID: 34416252

Abstract

Agricultural pesticides have been one of the most extensively used compounds throughout the world. The main sources of contamination for humans are dietary intake and occupational exposure. The impairments caused by agricultural pesticide exposure have been a significant global public health problem. Recent studies have shown that low-level agricultural pesticide exposure during the critical period of neurodevelopment (pregnancy and lactation) is closely related to autism spectrum disorder (ASD). Inhibition of acetylcholinesterase, gut microbiota, neural dendrite morphology, synaptic function, and glial cells are targets for the effects of pesticides during nervous system development. In the present review, we summarize the associations between several highly used and frequently studied pesticides (e.g., glyphosate, chlorpyrifos, pyrethroids, and avermectins) and ASD. We also discusse future epidemiological and toxicological research directions on the relationship between pesticides and ASD.



        

Title: An In-Silico Comparative Study of Lipases from the Antarctic Psychrophilic Ciliate Euplotes focardii and the Mesophilic Congeneric Species Euplotes crassus: Insight into Molecular Cold-Adaptation
Yang G, Mozzicafreddo M, Ballarini P, Pucciarelli S, Miceli C
Ref: Mar Drugs, 19:, 2021 : PubMed
Abstract


ESTHER: Yang_2021_Mar.Drugs_19_
PubMedSearch: Yang 2021 Mar.Drugs 19
PubMedID: 33513970

Abstract

Cold-adapted enzymes produced by psychrophilic organisms have elevated catalytic activities at low temperatures compared to their mesophilic counterparts. This is largely due to amino acids changes in the protein sequence that often confer increased molecular flexibility in the cold. Comparison of structural changes between psychrophilic and mesophilic enzymes often reveal molecular cold adaptation. In the present study, we performed an in-silico comparative analysis of 104 hydrolytic enzymes belonging to the family of lipases from two evolutionary close marine ciliate species: The Antarctic psychrophilic Euplotes focardii and the mesophilic Euplotes crassus. By applying bioinformatics approaches, we compared amino acid composition and predicted secondary and tertiary structures of these lipases to extract relevant information relative to cold adaptation. Our results not only confirm the importance of several previous recognized amino acid substitutions for cold adaptation, as the preference for small amino acid, but also identify some new factors correlated with the secondary structure possibly responsible for enhanced enzyme activity at low temperatures. This study emphasizes the subtle sequence and structural modifications that may help to transform mesophilic into psychrophilic enzymes for industrial applications by protein engineering.



        

Title: Nos2 deficiency enhances carbon tetrachloride-induced liver injury in aged mice
Li D, Song Y, Wang Y, Guo Y, Zhang Z, Yang G, Wang G, Xu C
Ref: Iran J Basic Med Sci, 23:600, 2020 : PubMed
Abstract


ESTHER: Li_2020_Iran.J.Basic.Med.Sci_23_600
PubMedSearch: Li 2020 Iran.J.Basic.Med.Sci 23 600
PubMedID: 32742597

Abstract

OBJECTIVES: As a multifunctional molecule, NO has different effects on liver injury. The present work aimed to investigate the effects of Nos2 knockout (KO) on acute liver injury in aged mice treated with carbon tetrachloride (CCl(4)). MATERIALS AND METHODS: The acute liver injury model was produced by CCl(4) at 10 ml/kg body weight in 24-month-old Nos2 KO mice and wild type (WT) mice groups. The histological changes, transaminase and glutathione (GSH) contents, and the expressions of liver function genes superoxide dismutase (SOD2) and butyrylcholinesterase (BCHE), as well as apoptosis- and inflammation-associated genes were detected at 0, 6, 16, 20, 28, and 48 hr, respectively. RESULTS: Compared with WT aged mice, there are more fat droplets in liver tissues of Nos2 KO aged mice, and the serum levels of ALT and AST were elevated in the KO group; in addition, there was a decrease in the expression of SOD2 and BCHE and GSH content at multiple time-points. Furthermore, the expression of apoptosis protein CASPASE-3 was elevated from 20 to 48 hr, the same as CASPASE-9 at 28 and 48 hr and pro-apoptotic protein BAX at 6 and 28 hr, while the expression of apoptosis inhibitory protein BCL2 declined at 6 and 28 hr; at the same time the mRNA expressions of genes related to inflammation were increased at different extents in liver extracts of Nos2 KO aged mice. CONCLUSION: Nos2 KO exacerbated liver injury probably by elevated oxidative stress, apoptosis and inammation response in CCl(4)-induced aged mice liver intoxication model.



        

Title: LncRNA KCNQ1OT1 ameliorates the liver injury induced by acetaminophen through the regulation of miR-122-5p/CES2 axis
Pei J, Sun X, Yang G, Zhang S
Ref: Molecular & Cellular Biochemistry, 475:107, 2020 : PubMed
Abstract


ESTHER: Pei_2020_Mol.Cell.Biochem_475_107
PubMedSearch: Pei 2020 Mol.Cell.Biochem 475 107
PubMedID: 32779042

Abstract

Long noncoding RNAs (lncRNAs) have been shown to be implicated in acetaminophen (APAP)-induced liver injury (AILI). We applied this study to investigate the role and functional mechanism of KCNQ1 overlapping transcript 1 (KCNQ1OT1) in AILI. The AILI model was established by APAP treatment in mice. The liver injury was preliminarily evaluated by ALT and AST activities via the detection kits. The quantitative real-time polymerase chain reaction (qRT-PCR) was exploited for detecting the expression of KCNQ1OT1, microRNA-122-5p (miR-122-5p), and carboxylesterase 2 (CES2). Protein levels were analyzed via Western blot. 3-(4, 5-dimethylthiazol-2-y1)-2, 5-diphenyl tetrazolium bromide (MTT) assay, and flow cytometry were separately applied to determine cell proliferation and apoptosis rate. Inflammation was assessed by enzyme-linked immunosorbent assay (ELISA). Dual-luciferase reporter assay was implemented to testify the intergenic combination. The function of KCNQ1OT1 in vivo was explored through KCNQ1OT1 knockdown in mice. APAP triggered the downregulation of KCNQ1OT1 and CES2 in mice serums. KCNQ1OT1 upregulation could relieve the AILI in HepaRG cells, which were abrogated by CES2 downregulation. KCNQ1OT1 served as a sponge of miR-122-5p and miR-122-5p directly targeted CES2. KCNQ1OT1 overexpression abated the AILI through the miR-122-5p/CES2 axis in HepaRG cells in vitro and mice in vivo. The collective results clarified that KCNQ1OT1 weakened the AILI in vitro and in vivo by the miR-122-5p/CES2 axis, providing an explicit molecular mechanism and selectable therapeutic strategy of AILI.



        

Title: Aptamer-functionalized magnetic nanoparticles conjugated organic framework for immobilization of acetylcholinesterase and its application in inhibitors screening
Zhao L, Yang G, Li L, Zhu C, Ma Y, Qu F
Ref: Anal Chim Acta, 1140:228, 2020 : PubMed
Abstract


ESTHER: Zhao_2020_Anal.Chim.Acta_1140_228
PubMedSearch: Zhao 2020 Anal.Chim.Acta 1140 228
PubMedID: 33218485

Abstract

Construction of new enzyme reactor based on aptamer functionalized magnetic nanoparticles conjugated organic framework (COF) for acetylcholinesterase immobilization has been an enabling endeavor in this work. The aptamer against acetylcholinesterase was selected through a method based on capillary electrophoresis in one round. A new magnetic COF material rich of carboxyl groups was firstly synthesized, and its surface was then modified with the selected aptamer through covalently linking. Acetylcholinesterase was immobilized to fabricate the enzyme reactor Fe(3)O(4)@COF-Apt-AChE through the high affinity and specificity with its binding aptamer. The as constructed enzyme reactor was comprehensively characterized and the key factors that affected its catalysis efficiency were investigated in detail. Owing to the surface modification of the magnetic COF materials by aptamer for acetylcholinesterase immobilization, the immobilized enzyme exhibited improved substrates affinity. What's more, good reusability (more than 8 times) and prolonged stability (enzyme activity still kept at 90% after 42 days) were also achieved. Finally, the enzyme reactor could be applied in AChE inhibitors screening, which expanded its application capability. The proposed protocol not only paves a new way for fabrication of novel aptamer functionalized magnetic COF materials as enzyme reactors, but also indicates a broadened application of the integration of aptamer and its enzyme.



        

Title: FSH1 regulates the phenotype and pathogenicity of the pathogenic dermatophyte Microsporum canis
Zhang F, Tan C, Xu Y, Yang G
Ref: Int J Mol Med, 44:2047, 2019 : PubMed
Abstract


ESTHER: Zhang_2019_Int.J.Mol.Med_44_2047
PubMedSearch: Zhang 2019 Int.J.Mol.Med 44 2047
PubMedID: 31573050
Gene_locus related to this paper: artot-a0a516ux40

Abstract

Microsporum canis (M. canis) is a common pathogen that causes tinea capitis and is present worldwide. The incidence of M. canis infection, particularly tinea capitis, has been increasing in China. In our previous studies, family of serine hydrolases 1 (FSH1) was identified as a potential virulence factor in tinea capitis infection caused by M. canis. To determine the function of this gene in M. canis, FSH1 was knocked down using doublestranded RNA interference mediated by Agrobacterium tumefaciens. Reverse transcriptionquantitative PCR analysis was used to confirm gene knockdown. Loss of FSH1 expression by RNAi resulted in a minor phenotype alteration, but M. canis pathogenicity in guinea pig cutaneous infection was decreased compared with the wildtype strain. To the best of our knowledge, the present study is the first to demonstrate that FSH1 is associated with macroconidia septa formation and is an important contributor to M. canis virulence. These findings may advance the understanding of the function of the FSH1 gene and provide a foundation for future studies on macroconidia septa formation and pathogenicity of M. canis.



        

Title: Evaluation of joint effects of cyprodinil and kresoxim-methyl on zebrafish, Danio rerio
Wang Y, Dai D, Yu Y, Yang G, Shen W, Wang Q, Weng H, Zhao X
Ref: J Hazard Mater, 352:80, 2018 : PubMed
Abstract


ESTHER: Wang_2018_J.Hazard.Mater_352_80
PubMedSearch: Wang 2018 J.Hazard.Mater 352 80
PubMedID: 29574263

Abstract

Aquatic organisms are usually exposed to a mixture of pesticides instead of individual chemicals. However, risk assessment of pesticides is traditionally based on toxicity data of individual compounds. In this study, we aimed to examine the joint toxicity of two fungicides cyprodinil (CYP) and kresoxim-methyl (KRM) to zebrafish (Danio rerio) using a systematic experimental approach. Results from 96-h semi-static test indicated that the LC50 values of KRM to D. rerio at multiple life stages (embryonic, larval, juvenile and adult stages) ranged from 0.034 (0.015-0.073) to 0.61 (0.39-0.83) mg a.i. L(-1), which were higher than those of CYP ranging from 1.05 (0.88-1.52) to 4.42 (3.24-6.02) mg a.i. L(-1). Pesticide mixtures of CYP and KRM exhibited synergistic effect on embryonic zebrafish. The activities of carboxylesterase (CarE) and cytochrome P450 (Cyp450) were significantly altered in most of the individual and combined exposures compared with the control group. The expressions of seven genes (Mnsod, cyp17, crhr 2, crh, gnrhr 4, gnrhr 1 and hmgrb) were significantly altered upon exposure to combined pesticides compared with their individual pesticides. Collectively, these findings suggested joint effects should be considered in the risk assessment of pesticides and development of water quality criteria for the protection of aquatic environment.



        

Title: Multi-level ecotoxicological effects of imidacloprid on earthworm (Eisenia fetida)
Wang X, Zhu X, Peng Q, Wang Y, Ge J, Yang G, Cai L, Shen W
Ref: Chemosphere, 219:923, 2018 : PubMed
Abstract


ESTHER: Wang_2018_Chemosphere_219_923
PubMedSearch: Wang 2018 Chemosphere 219 923
PubMedID: 30572241

Abstract

As a neurotoxic insecticide, imidacloprid (IMI) has been widely used for crop protection. However, continuous application of such pesticide in the environment may damage the non-target organisms in soil. In the present study, we aimed to investigate the effects of IMI on earthworms in terms of survival, avoidance behavior, reproduction, detoxification enzyme activity and gene expression using a systematic experimental approach. The results showed that the 14-day LC50 value of IMI was 2.26 (2.09-2.43) mg a.i. kg(-1), and the 2-day AC50 value (concentration inducing an avoidance rate of 50%) of IMI was 1.34 (1.02-1.91) mg a.i. kg(-1) to E. fetida. For reproduction, the 56-day EC50 value of IMI was 0.87 (0.66-1.33) mg a.i. kg(-1) to E. fetida, and there was a positive correlation between the growth rate of earthworms and the number of juveniles in IMI treatments. Activities of carboxylesterase (CarE) and glutathione-S-transferases (GST) in earthworms were disturbed by IMI exposure. Moreover, effects of IMI on the CarE activity in earthworms were more severe and sensitive compared with the GST activity. The expressions of annetocin (ann) and calreticulin (crt) at the transcriptional level were decreased upon IMI exposure, reaching the lowest levels of 0.09 fold and 0.16 fold on day 7 and day 14, respectively. Transcriptionally controlled tumor protein (tctp), heat shock protein 70 (hsp70) and gst exhibited relatively obvious variations (up-regulation or down-regulation) when the exposure duration was extended. Taken together, these results comprehensively contributed to further understandings of the impacts of IMI on earthworms.



        

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: The Pseudomonas aeruginosa Type VI Secretion PGAP1-like Effector Induces Host Autophagy by Activating Endoplasmic Reticulum Stress
Jiang F, Wang X, Wang B, Chen L, Zhao Z, Waterfield NR, Yang G, Jin Q
Ref: Cell Rep, 16:1502, 2016 : PubMed
Abstract


ESTHER: Jiang_2016_Cell.Rep_16_1502
PubMedSearch: Jiang 2016 Cell.Rep 16 1502
PubMedID: 27477276
Gene_locus related to this paper: pseae-PA1510

Abstract

Pseudomonas aeruginosa is an opportunistic pathogen that regularly causes nosocomial infections in hospitalized patients. The type VI secretion system (T6SS) is responsible for the secretion of numerous virulence effector proteins that can both interfere with competing microbes and manipulate host cells.sHere, we report a detailed investigation of a P.saeruginosa H2-T6SS-dependent phospholipase effector, TplE, which acts as a trans-kingdom toxin. Delivery of TplE to the periplasmic space of rival bacteria leads to growth inhibition. Importantly, TplE, also contains a eukaryotic PGAP1-like domain, which targets the host ER apparatus, ultimately leading to disruption of the ER. TplE activity leads to the activation of the unfolded protein response (UPR) through the IRE1alpha-XBP1 pathway, enhancing autophagic flux. These findings indicate that this T6SS-delivered phospholipase effector is active against both prokaryotic and eukaryotic cellular targets, highlighting the T6SS as a versatile weapon in the Pseudomonas arsenal.



        

Title: Treatment effects of tanshinone IIA against intracerebroventricular streptozotocin induced memory deficits in mice
Liu C, Wu Y, Zha S, Liu M, Wang Y, Yang G, Ma K, Fei Y, Zhang Y and Qian Y <2 more author(s)> Liu C, Wu Y, Zha S, Liu M, Wang Y, Yang G, Ma K, Fei Y, Zhang Y, Hu X, Yang W, Qian Y (- 2)
Ref: Brain Research, 1631:137, 2016 : PubMed
Abstract


ESTHER: Liu_2016_Brain.Res_1631_137
PubMedSearch: Liu 2016 Brain.Res 1631 137
PubMedID: 26656068
Inhibitor(s) related to this paper: Tanshinone-IIA

Abstract

Our previous studies demonstrated that tanshinone IIA (tan IIA) has significant protective effects against the neurotoxicity induced by beta-amyloid protein (Abeta) in cultured cortical neurons and PC12 cells. This study was designed to investigate the protective effects of tan IIA against memory deficits induced by streptozotocin (STZ) in a model of sporadic Alzheimer's disease (AD). STZ was injected twice intracerebroventrically (3mg/kg ICV) on alternate days (day 1 and day 3) in mice. Daily treatment with tan IIA (20, 40, and 80mg/kg, i.g.) starting from the first dose of STZ for 28 days showed a dose dependent improvement in STZ induced memory deficits as assessed by Morris water maze (MWM) test. Nissl staining results confirmed the protective effects of tan IIA on cerebral cortical and hippocampal neurons damage induced by STZ. In addition, tan IIA markedly reduced STZ induced elevation in acetylcholinesterase (AChE) activity and malondialdehyde (MDA) level, and significantly inhibited STZ induced reduction in superoxide dismutases (SOD) and glutathione peroxidase (GSH-Px) activities in the parietal cortex and hippocampus. Moreover, tan IIA attenuated p38 mitogen activated protein kinase (MAPK) phosphorylation in the parietal cortex and hippocampus. These findings demonstrate that tan IIA prevents STZ induced memory deficits may be attributed to ameliorating neuronal damage, restoring cholinergic function, attenuating oxidative stress and blocking p38 MAPK signal pathway activation. Based on our previous studies, the present study provides further support for the potential use of tan IIA in the treatment of AD.



        

Title: Evolution of Digestive Enzymes and RNASE1 Provides Insights into Dietary Switch of Cetaceans
Wang Z, Xu S, Du K, Huang F, Chen Z, Zhou K, Ren W, Yang G
Ref: Molecular Biology Evolution, 33:3144, 2016 : PubMed
Abstract


ESTHER: Wang_2016_Mol.Biol.Evol_33_3144
PubMedSearch: Wang 2016 Mol.Biol.Evol 33 3144
PubMedID: 27651393
Gene_locus related to this paper: souch-a0a1d8i1n4

Abstract

Although cetaceans (whales, porpoises, and dolphins) have multi-chambered stomachs, feeding habits of modern cetaceans have dramatically changed from herbivorous to carnivorous. However, the genetic basis underlying this dietary switch remains unexplored. Here, we present the first systematic investigation of 10 digestive enzymes genes (i.e., CYP7A1, CTRC, LIPC, LIPF, PNLIP, PGC, PRSS1, SI, SLC5A1, and TMPRSS15) of representative cetaceans, and the evolutionary trajectory of RNASE1 in cetartiodactylans. Positive selections were detected with proteinases (i.e., CTRC, PRSS1, and TMPRSS15) and lipases (i.e., CYP7A1, LIPF, and PNLIP) suggesting that cetaceans have evolved an enhanced digestion capacity for proteins and lipids, the major nutritional components of their prey (fishes and invertebrates). In addition, it was found that RNASE1 gene duplicated after the cetartiodactylan speciation and two independent gene duplication events took place in Camelidae and Ruminantia. Positive selection was detected with RNASE1 of Camelidae and Bovidae, suggesting enhanced digestive efficiency in the ruminants. Remarkably, even though the ancestors of cetaceans were terrestrial artiodactyls that are herbivorous, modern cetaceans lost the pancreatic RNASE1 copy with digestive function, which is in accordance with the dietary change from herbivorous to carnivorous. In sum, this is the first study that provides new insights into the evolutionary mechanism of dietary switch in cetaceans.



        

Title: Conformational Tinkering Drives Evolution of a Promiscuous Activity through Indirect Mutational Effects
Yang G, Hong N, Baier F, Jackson CJ, Tokuriki N
Ref: Biochemistry, 55:4583, 2016 : PubMed
Abstract


ESTHER: Yang_2016_Biochemistry_55_4583
PubMedSearch: Yang 2016 Biochemistry 55 4583
PubMedID: 27444875

Abstract

How remote mutations can lead to changes in enzyme function at a molecular level is a central question in evolutionary biochemistry and biophysics. Here, we combine laboratory evolution with biochemical, structural, genetic, and computational analysis to dissect the molecular basis for the functional optimization of phosphotriesterase activity in a bacterial lactonase (AiiA) from the metallo-beta-lactamase (MBL) superfamily. We show that a 1000-fold increase in phosphotriesterase activity is caused by a more favorable catalytic binding position of the paraoxon substrate in the evolved enzyme that resulted from conformational tinkering of the active site through peripheral mutations. A nonmutated active site residue, Phe68, was displaced by -3 A through the indirect effects of two second-shell trajectory mutations, allowing molecular interactions between the residue and paraoxon. Comparative mutational scanning, i.e., examining the effects of alanine mutagenesis on different genetic backgrounds, revealed significant changes in the functional roles of Phe68 and other nonmutated active site residues caused by the indirect effects of trajectory mutations. Our work provides a quantitative measurement of the impact of second-shell mutations on the catalytic contributions of nonmutated residues and unveils the underlying intramolecular network of strong epistatic mutational relationships between active site residues and more remote residues. Defining these long-range conformational and functional epistatic relationships has allowed us to better understand the subtle, but cumulatively significant, role of second- and third-shell mutations in evolution.



        

Title: Relaxant action of plumula nelumbinis extract on mouse airway smooth muscle
Tan L, Chen W, Wei MY, Shen J, Yu MF, Yang G, Guo D, Qin G, Ji G, Liu QH
Ref: Evid Based Complement Alternat Med, 2015:523640, 2015 : PubMed
Abstract


ESTHER: Tan_2015_Evid.Based.Complement.Alternat.Med_2015_523640
PubMedSearch: Tan 2015 Evid.Based.Complement.Alternat.Med 2015 523640
PubMedID: 25763092

Abstract

The traditional herb Plumula Nelumbinis is widely used in the world because it has many biological activities, such as anti-inflammation, antioxidant, antihypertension, and butyrylcholinesterase inhibition. However, the action of Plumula Nelumbinis on airway smooth muscle (ASM) relaxation has not been investigated. A chloroform extract of Plumula Nelumbinis (CEPN) was prepared, which completely inhibited precontraction induced by high K(+) in a concentration-dependent manner in mouse tracheal rings, but it had no effect on resting tension. CEPN also blocked voltage-dependent L-type Ca(2+) channel- (VDCC-) mediated currents. In addition, ACh-induced precontraction was also completely blocked by CEPN and partially inhibited by nifedipine or pyrazole 3. Besides, CEPN partially reduced ACh-activated nonselective cation channel (NSCC) currents. Taken together, our data demonstrate that CEPN blocked VDCC and NSCC to inhibit Ca(2+) influx, resulting in relaxation of precontracted ASM. This finding indicates that CEPN would be a candidate of new potent bronchodilators.



        

Title: 'Obesity' is healthy for cetaceans? Evidence from pervasive positive selection in genes related to triacylglycerol metabolism
Wang Z, Chen Z, Xu S, Ren W, Zhou K, Yang G
Ref: Sci Rep, 5:14187, 2015 : PubMed
Abstract


ESTHER: Wang_2015_Sci.Rep_5_14187
PubMedSearch: Wang 2015 Sci.Rep 5 14187
PubMedID: 26381091
Gene_locus related to this paper: delle-a0a2y9m8t8, lipve-a0a0n6wyt2

Abstract

Cetaceans are a group of secondarily adapted marine mammals with an enigmatic history of transition from terrestrial to fully aquatic habitat and subsequent adaptive radiation in waters around the world. Numerous physiological and morphological cetacean characteristics have been acquired in response to this drastic habitat transition; for example, the thickened blubber is one of the most striking changes that increases their buoyancy, supports locomotion, and provides thermal insulation. However, the genetic basis underlying the blubber thickening in cetaceans remains poorly explored. Here, 88 candidate genes associated with triacylglycerol metabolism were investigated in representative cetaceans and other mammals to test whether the thickened blubber matched adaptive evolution of triacylglycerol metabolism-related genes. Positive selection was detected in 41 of the 88 candidate genes, and functional characterization of these genes indicated that these are involved mainly in triacylglycerol synthesis and lipolysis processes. In addition, some essential regulatory genes underwent significant positive selection in cetacean-specific lineages, whereas no selection signal was detected in the counterpart terrestrial mammals. The extensive occurrence of positive selection in triacylglycerol metabolism-related genes is suggestive of their essential role in secondary adaptation to an aquatic life, and further implying that 'obesity' might be an indicator of good health for cetaceans.



        

Title: The resurrection genome of Boea hygrometrica: A blueprint for survival of dehydration
Xiao L, Yang G, Zhang L, Yang X, Zhao S, Ji Z, Zhou Q, Hu M, Wang Y and He Y <14 more author(s)> Xiao L, Yang G, Zhang L, Yang X, Zhao S, Ji Z, Zhou Q, Hu M, Wang Y, Chen M, Xu Y, Jin H, Xiao X, Hu G, Bao F, Hu Y, Wan P, Li L, Deng X, Kuang T, Xiang C, Zhu JK, Oliver MJ, He Y (- 14)
Ref: Proc Natl Acad Sci U S A, 112:5833, 2015 : PubMed
Abstract


ESTHER: Xiao_2015_Proc.Natl.Acad.Sci.U.S.A_112_5833
PubMedSearch: Xiao 2015 Proc.Natl.Acad.Sci.U.S.A 112 5833
PubMedID: 25902549
Gene_locus related to this paper: 9lami-a0a2z7c6k4, 9lami-a0a2z7bgj4

Abstract

"Drying without dying" is an essential trait in land plant evolution. Unraveling how a unique group of angiosperms, the Resurrection Plants, survive desiccation of their leaves and roots has been hampered by the lack of a foundational genome perspective. Here we report the approximately 1,691-Mb sequenced genome of Boea hygrometrica, an important resurrection plant model. The sequence revealed evidence for two historical genome-wide duplication events, a compliment of 49,374 protein-coding genes, 29.15% of which are unique (orphan) to Boea and 20% of which (9,888) significantly respond to desiccation at the transcript level. Expansion of early light-inducible protein (ELIP) and 5S rRNA genes highlights the importance of the protection of the photosynthetic apparatus during drying and the rapid resumption of protein synthesis in the resurrection capability of Boea. Transcriptome analysis reveals extensive alternative splicing of transcripts and a focus on cellular protection strategies. The lack of desiccation tolerance-specific genome organizational features suggests the resurrection phenotype evolved mainly by an alteration in the control of dehydration response genes.



        

Title: Death receptor and mitochondria-mediated hepatocyte apoptosis underlies liver dysfunction in rats exposed to organic pollutants from drinking water
Yang G, Zhou Z, Cen Y, Gui X, Zeng Q, Ao Y, Li Q, Wang S, Li J, Zhang A
Ref: Drug Des Devel Ther, 9:4719, 2015 : PubMed
Abstract


ESTHER: Yang_2015_Drug.Des.Devel.Ther_9_4719
PubMedSearch: Yang 2015 Drug.Des.Devel.Ther 9 4719
PubMedID: 26316710

Abstract

Persistent organic pollutants in drinking water impose a substantial risk to the health of human beings, but the evidence for liver toxic effect and the underlying mechanism is scarce. This study aimed to examine the liver toxicity and elucidate the molecular mechanism of organic pollutants in drinking water in normal human liver cell line L02 cells and rats. The data showed that organic extraction from drinking water remarkably impaired rat liver function, evident from the increase in the serum level of alanine aminotransferase, aspartate aminotransferase, and cholinesterase, and decrease in the serum level of total protein and albumin. Organic extraction dose-dependently induced apoptotic cell death in rat liver and L02 cells. Administration of rats with organic extraction promoted death receptor signaling pathway through the increase in gene and protein expression level of Fas and FasL. Treatment of rats with organic extraction also induced mitochondria-mediated apoptosis via increasing the expression level of proapoptotic protein, Bax, but decreasing the expression level of antiapoptotic protein, Bcl-2, resulting in an upregulation of cytochrome c and activation of caspase cascade at both transcriptional and post-transcriptional levels. Moreover, organic extraction enhanced rat liver glutathione S-transferases activity and reactive oxygen species generation, and upregulated aryl hydrocarbon receptor and glutathione S-transferase A1 at both transcriptional and translational levels. Collectively, the results indicate that organic extraction from drinking water impairs liver function, with the involvement of death receptor and mitochondria-mediated apoptosis in rats. The results provide evidence and molecular mechanisms for organic pollutants in drinking water-induced liver dysfunction, which may help prevent and treat organic extraction-induced liver injury.



        

Title: Increase of Oleic Acid Content in Phosphatidylcholine through Lipase-catalyzed Interesterification: Optimization by Response Surface Methodology
Yang G, Yang L
Ref: J Oleo Sci, 64:673, 2015 : PubMed
Abstract


ESTHER: Yang_2015_J.Oleo.Sci_64_673
PubMedSearch: Yang 2015 J.Oleo.Sci 64 673
PubMedID: 25891113

Abstract

In order to obtain phosphatidylcholine (PC) with higher amount of oleic acid, the interesterification between soybean PC and Camellia oleifera oil (COO) rich in oleic acid catalyzed by lipase was studied in hexane. For this aim three commercially available immobilized lipases (Novozym 435, Lipozyme TLIM and Lipozyme RMIM) were assayed and Novozym 435 was finally selected for further optimization. The effects of the factors, such as PC concentration, substrate ratio, water amount, lipase dosage and temperature, on the oleic acid content in PC and PC recovery during the interesterification were investigated. The conditions of the interesterification were optimized using response surface methodology. The optimum conditions were as follows: lipase dosage 13 % (based on the mass of PC and COO), reaction temperature 55 degC, water amount 5% (based on the mass of PC), reaction time 8 h, PC concentration 0.3g/mL (PC/hexane), PC-to-COO ratio 1:3 (acyl groups in PC/acyl groups in COO, mol/mol). Under these conditions, oleic acid content and PC recovery were 40.8 +/- 0.5% and 69.0 +/- 2.8%, respectively. Analysis of variance (ANOVA) showed that the regression models were adequate for predicting the interesterifiction. The orders of reaction variables affecting on oleic acid content and PC recovery were water amount > reaction time > lipase dosage > reaction temperature, and water amount > reaction temperature > lipase dosage > reaction time, respectively.



        

Title: Lysophosphatidylcholine synthesis by lipase-catalyzed ethanolysis
Yang G, Yang R, Hu J
Ref: J Oleo Sci, 64:443, 2015 : PubMed
Abstract


ESTHER: Yang_2015_J.Oleo.Sci_64_443
PubMedSearch: Yang 2015 J.Oleo.Sci 64 443
PubMedID: 25766935

Abstract

Lysophosphatidylcholine (LPC) is amphiphilic substance, and possesses excellent physiological functions. In this study, LPC was prepared through ethanolysis of phosphatidylcholine (PC) in n-hexane or solvent free media catalyzed by Novozym 435 (from Candida antarctica), Lipozyme TLIM (from Thermomcyces lanuginosus) and Lipozyme RMIM (from Rhizomucor miehei). The results showed that three immobilized lipases from Candida Antarctica, Thermomcyces lanuginosus and Rhizomucor miehei could catalyze ethanolysis of PC efficiently. In n-hexane, the LPC conversions of ethanolysis of PC catalyzed by Novozyme 435, Lipozyme TLIM and Lipozyme RMIM could reach to 98.5 +/- 1.6%, 94.6 +/- 1.4% and 93.7 +/- 1.8%, respectively. In solvent free media, the highest LPC conversions of ethanolysis of PC catalyzed by Novozyme 435, Lipozyme TL IM and Lipozyme RM IM were 97.7 +/- 1.7%, 93.5 +/- 1.2% and 93.8 +/- 1.9%, respectively. The catalytic efficiencies of the three lipases were in the order of Novozyme 435 > Lipozyme TLIM > Lipozyme RMIM. Furthermore, their catalytic efficiencies in n-hexane were better than those in solvent free media.



        

Title: Novibacillus thermophilus gen. nov., sp. nov., a Gram-staining-negative and moderately thermophilic member of the family Thermoactinomycetaceae
Yang G, Chen J, Zhou S
Ref: Int J Syst Evol Microbiol, 65:2591, 2015 : PubMed
Abstract


ESTHER: Yang_2015_Int.J.Syst.Evol.Microbiol_65_2591
PubMedSearch: Yang 2015 Int.J.Syst.Evol.Microbiol 65 2591
PubMedID: 25951858
Gene_locus related to this paper: 9bacl-a0a1u9k3n4

Abstract

Two Gram-staining-negative, facultatively anaerobic bacterial strains, SG-1T and SG-2, were isolated from a saline soil sample and a compost sample, respectively. The cells were non-motile rods that occurred singly or in chains, and endospores were not observed under tested growth conditions. Optimum growth occurred at 50 degreesC, pH 7.5-8.0 and with 5-7% (w/v) NaCl. The DNA G+C content was 49.5-50.5mol%. The strains contained MK-7 as the predominant menaquinone and iso-C15 : 0 and anteiso-C15 : 0 as the major fatty acids. The polar lipids consisted mainly of diphosphatidylglycerol and phosphatidylglycerol. The cell-wall peptidoglycan type was A1gamma (meso-DAP direct). Phylogenetic analyses revealed that the new isolates belonged to the family Thermoactinomycetaceae, exhibiting low 16S rRNA gene sequence similarity (90.8-91.3%) to the nearest type strain, Mechercharimyces asporophorigenens YM11-542T, and formed a well-supported lineage that was clearly distinguished from all currently described genera in this family. Based on our polyphasic taxonomic characterization, we propose that strains SG-1T and SG-2 represent a novel genus and species within the family Thermoactinomycetaceae, for which we propose the name Novibacillus thermophilus gen. nov., sp. nov. The type strain of Novibacillus thermophilus is SG-1T ( = KCTC 33118T = CGMCC 1.12771T).



        

Title: Design of hyperthermophilic lipase chimeras by key motif-directed recombination
Zhou X, Gao L, Yang G, Liu D, Bai A, Li B, Deng Z, Feng Y
Ref: Chembiochem, 16:455, 2015 : PubMed
Abstract


ESTHER: Zhou_2015_Chembiochem_16_455
PubMedSearch: Zhou 2015 Chembiochem 16 455
PubMedID: 25530200

Abstract

Recombination of diverse natural evolved domains within a superfamily offers greater opportunity for enzyme function leaps. How to recombine protein modules from distant parents with less disruption in cross-interfaces is a challenging issue. Here, we identified the existence of a key motif, the sequence VVSVN(D)YR, within a structural motif psi loop in the alpha/beta-hydrolase fold superfamily, by using a MEME server and the PROMOTIF program. To obtain thermostable lipase-like enzymes, two chimeras were engineered at the key motif regions through recombination of domains from a mesophilic lipase and a hyperthermophilic esterase/peptidase with amino acid identity less than 21 %. The chimeras retained the desirable substrate preference of their mesophilic parent and exhibited more than 100-fold increased thermostability at 50 degrees C. Through site-directed mutation, we further improved activity of the chimera by 4.6-fold. The recombination strategy presented here enables the creation of novel catalysts.



        

Title: Enhanced Enzyme Kinetic Stability by Increasing Rigidity within the Active Site
Xie Y, An J, Yang G, Wu G, Zhang Y, Cui L, Feng Y
Ref: Journal of Biological Chemistry, 289:7994, 2014 : PubMed
Abstract


ESTHER: Xie_2014_J.Biol.Chem_289_7994
PubMedSearch: Xie 2014 J.Biol.Chem 289 7994
PubMedID: 24448805
Gene_locus related to this paper: canar-LipB

Abstract

Enzyme stability is an important issue for protein engineers. Understanding how rigidity in the active site affects protein kinetic stability will provide new insight into enzyme stabilization. In this study, we demonstrated enhanced kinetic stability of Candida antarctica lipase B (CalB) by mutating the structurally flexible residues within the active site. Six residues within 10 A of the catalytic Ser(105) residue with a high B factor were selected for iterative saturation mutagenesis. After screening 2200 colonies, we obtained the D223G/L278M mutant, which exhibited a 13-fold increase in half-life at 48 degrees C and a 12 degrees C higher T50(15), the temperature at which enzyme activity is reduced to 50% after a 15-min heat treatment. Further characterization showed that global unfolding resistance against both thermal and chemical denaturation also improved. Analysis of the crystal structures of wild-type CalB and the D223G/L278M mutant revealed that the latter formed an extra main chain hydrogen bond network with seven structurally coupled residues within the flexible alpha10 helix that are primarily involved in forming the active site. Further investigation of the relative B factor profile and molecular dynamics simulation confirmed that the enhanced rigidity decreased fluctuation of the active site residues at high temperature. These results indicate that enhancing the rigidity of the flexible segment within the active site may provide an efficient method for improving enzyme kinetic stability.



        

Title: Whole-genome sequencing of the snub-nosed monkey provides insights into folivory and evolutionary history
Zhou X, Wang B, Pan Q, Zhang J, Kumar S, Sun X, Liu Z, Pan H, Lin Y and Li R <24 more author(s)> Zhou X, Wang B, Pan Q, Zhang J, Kumar S, Sun X, Liu Z, Pan H, Lin Y, Liu G, Zhan W, Li M, Ren B, Ma X, Ruan H, Cheng C, Wang D, Shi F, Hui Y, Tao Y, Zhang C, Zhu P, Xiang Z, Jiang W, Chang J, Wang H, Cao Z, Jiang Z, Li B, Yang G, Roos C, Garber PA, Bruford MW, Li R (- 24)
Ref: Nat Genet, 46:1303, 2014 : PubMed
Abstract


ESTHER: Zhou_2014_Nat.Genet_46_1303
PubMedSearch: Zhou 2014 Nat.Genet 46 1303
PubMedID: 25362486
Gene_locus related to this paper: rhibe-a0a2k6jtl7, rhibe-ACHE, rhibe-a0a2k6k3y7, rhibe-a0a2k6k493, rhibe-a0a2k6lev4, rhibe-a0a2k6lfa5, rhibe-a0a2k6m6k8, rhiro-a0a2k6p1u8, rhiro-a0a2k6q1t8, rhiro-a0a2k6q1w3, rhibe-a0a2k6n5t9, rhibe-a0a2k6ju46, rhibe-a0a2k6kt48, rhibe-a0a2k6llm5, rhibe-a0a2k6lnt5, rhiro-a0a2k6qzp6, rhiro-a0a2k6q4a6, rhibe-a0a2k6kn93, rhibe-a0a2k6lm22, rhibe-a0a2k6jwp8, rhiro-a0a2k6qun2, rhiro-a0a2k6nj56, rhiro-a0a2k6n885, rhiro-a0a2k6nnj4, rhiro-a0a2k6n7n5, rhibe-a0a2k6jvz4, rhiro-a0a2k6nfk9, rhiro-a0a2k6qjv0, rhibe-a0a2k6jn19, rhibe-a0a2k6k333, rhibe-a0a2k6mff5

Abstract

Colobines are a unique group of Old World monkeys that principally eat leaves and seeds rather than fruits and insects. We report the sequencing at 146x coverage, de novo assembly and analyses of the genome of a male golden snub-nosed monkey (Rhinopithecus roxellana) and resequencing at 30x coverage of three related species (Rhinopithecus bieti, Rhinopithecus brelichi and Rhinopithecus strykeri). Comparative analyses showed that Asian colobines have an enhanced ability to derive energy from fatty acids and to degrade xenobiotics. We found evidence for functional evolution in the colobine RNASE1 gene, encoding a key secretory RNase that digests the high concentrations of bacterial RNA derived from symbiotic microflora. Demographic reconstructions indicated that the profile of ancient effective population sizes for R. roxellana more closely resembles that of giant panda rather than its congeners. These findings offer new insights into the dietary adaptations and evolutionary history of colobine primates.



        

Title: Dynamic adipocyte phosphoproteome reveals that Akt directly regulates mTORC2
Humphrey SJ, Yang G, Yang P, Fazakerley DJ, Stockli J, Yang JY, James DE
Ref: Cell Metab, 17:1009, 2013 : PubMed
Abstract


ESTHER: Humphrey_2013_Cell.Metab_17_1009
PubMedSearch: Humphrey 2013 Cell.Metab 17 1009
PubMedID: 23684622

Abstract

A major challenge of the post-genomics era is to define the connectivity of protein phosphorylation networks. Here, we quantitatively delineate the insulin signaling network in adipocytes by high-resolution mass spectrometry-based proteomics. These data reveal the complexity of intracellular protein phosphorylation. We identified 37,248 phosphorylation sites on 5,705 proteins in this single-cell type, with approximately 15% responding to insulin. We integrated these large-scale phosphoproteomics data using a machine learning approach to predict physiological substrates of several diverse insulin-regulated kinases. This led to the identification of an Akt substrate, SIN1, a core component of the mTORC2 complex. The phosphorylation of SIN1 by Akt was found to regulate mTORC2 activity in response to growth factors, revealing topological insights into the Akt/mTOR signaling network. The dynamic phosphoproteome described here contains numerous phosphorylation sites on proteins involved in diverse molecular functions and should serve as a useful functional resource for cell biologists.



        

Title: A near-infrared fluorophore for live-cell super-resolution microscopy of cellular proteins
Lukinavicius G, Umezawa K, Olivier N, Honigmann A, Yang G, Plass T, Mueller V, Reymond L, Correa IR, Jr. and Johnsson K <6 more author(s)> Lukinavicius G, Umezawa K, Olivier N, Honigmann A, Yang G, Plass T, Mueller V, Reymond L, Correa IR, Jr., Luo ZG, Schultz C, Lemke EA, Heppenstall P, Eggeling C, Manley S, Johnsson K (- 6)
Ref: Nat Chem, 5:132, 2013 : PubMed
Abstract


ESTHER: Lukinavicius_2013_Nat.Chem_5_132
PubMedSearch: Lukinavicius 2013 Nat.Chem 5 132
PubMedID: 23344448

Abstract

The ideal fluorescent probe for bioimaging is bright, absorbs at long wavelengths and can be implemented flexibly in living cells and in vivo. However, the design of synthetic fluorophores that combine all of these properties has proved to be extremely difficult. Here, we introduce a biocompatible near-infrared silicon-rhodamine probe that can be coupled specifically to proteins using different labelling techniques. Importantly, its high permeability and fluorogenic character permit the imaging of proteins in living cells and tissues, and its brightness and photostability make it ideally suited for live-cell super-resolution microscopy. The excellent spectroscopic properties of the probe combined with its ease of use in live-cell applications make it a powerful new tool for bioimaging.



        

Title: Characterization of the first eukaryotic cold-adapted patatin-like phospholipase from the psychrophilic Euplotes focardii: Identification of putative determinants of thermal-adaptation by comparison with the homologous protein from the mesophilic Euplotes crassus
Yang G, De Santi C, de Pascale D, Pucciarelli S, Miceli C
Ref: Biochimie, 95:1795, 2013 : PubMed
Abstract


ESTHER: Yang_2013_Biochimie_95_1795
PubMedSearch: Yang 2013 Biochimie 95 1795
PubMedID: 23796575

Abstract

The ciliated protozoon Euplotes focardii, originally isolated from the coastal seawaters of Terra Nova Bay in Antarctica, shows a strictly psychrophilic phenotype, including optimal survival and multiplication rates at 4-5 degrees C. This characteristic makes E. focardii an ideal model species for identifying the molecular bases of cold adaptation in psychrophilic organisms, as well as a suitable source of novel cold-active enzymes for industrial applications. In the current study, we characterized the patatin-like phospholipase from E. focardii (EfPLP), and its enzymatic activity was compared to that of the homologous protein from the mesophilic congeneric species Euplotes crassus (EcPLP). Both EfPLP and EcPLP have consensus motifs conserved in other patatin-like phospholipases. By analyzing both esterase and phospholipase A2 activity, we determined the thermostability and the optimal pH, temperature dependence and substrates of these enzymes. We demonstrated that EfPLP shows the characteristics of a psychrophilic phospholipase. Furthermore, we analyzed the enzymatic activity of three engineered versions of the EfPLP, in which unique residues of EfPLP, Gly80, Ala201 and Val204, were substituted through site-directed mutagenesis with residues found in the E. crassus homolog (Glu, Pro and Ile, respectively). Additionally, three corresponding mutants of EcPLP were also generated and characterized. These analyses showed that the substitution of amino acids with rigid and bulky charged/hydrophobic side chain in the psychrophilic EfPLP confers enzymatic properties similar to those of the mesophilic patatin-like phospholipase, and vice versa. This is the first report on the isolation and characterization of a cold-adapted patatin-like phospholipase from eukaryotes. The results reported in this paper support the idea that enzyme thermal-adaptation is based mainly on some amino acid residues that influence the structural flexibility of polypeptides and that EfPLP is an attractive biocatalyst for industrial processes at low temperatures.



        

Title: Expression of APP, BACE1, AChE and ChAT in an AD model in rats and the effect of donepezil hydrochloride treatment
Li Q, Chen M, Liu H, Yang L, Yang G
Ref: Mol Med Rep, 6:1450, 2012 : PubMed
Abstract


ESTHER: Li_2012_Mol.Med.Rep_6_1450
PubMedSearch: Li 2012 Mol.Med.Rep 6 1450
PubMedID: 23023803

Abstract

The aim of this study was to investigate the pathological changes in a rat model of Alzheimer's disease (AD) and the effect of donepezil hydrochloride (HCl) treatment. The rat model of AD was established by the bilateral injection of amyloid beta1-40 (Abeta1-40) into the hippocampus. Changes in spatial learning and memory functions were examined using the Morris water maze test and changes in catalase (CAT) and glutathione peroxidase (GSH-Px) activities were determined using chemical colorimetry. Moreover, the changes in acetylcholinesterase (AChE) and choline acetyltransferase (ChAT) expression were analyzed using immunohistochemical staining. The mRNA expression levels of the amyloid precursor protein (APP) and beta-secreted enzyme 1 (BACE1) were evaluated using RT-PCR. The effects of donepezil HCl on the aforementioned indices were also observed. The rat memories of the platform quadrants in the blank, sham and donepezil HCl groups were improved compared with those of the rats in the model group. The ratio of swim distance in the fourth platform quadrant (l4) to the total swim distance (l total) for the model group rats (l4/l total) was significantly decreased compared with that for the blank and sham group rats. Following donepezil HCl treatment, the ratio of l4/l total significantly increased. AD modeling caused a significant decrease in the CAT and GSH-Px activities in the brain tissues of the rats. The CAT and GSH-Px activities in the AD model rats significantly increased following donepezil HCl treatment. Moreover, donepezil HCl treatment significantly decreased the AChE, APP and BACE1 mRNA expression levels and increased the ChAT expression levels. Therefore, donepezil HCl was able to significantly decrease learning and memory damage in a rat model of AD.



        

Title: Role of the NC-loop in catalytic activity and stability in lipase from Fervidobacterium changbaicum
Li B, Yang G, Wu L, Feng Y
Ref: PLoS ONE, 7:e46881, 2012 : PubMed
Abstract


ESTHER: Li_2012_PLoS.One_7_e46881
PubMedSearch: Li 2012 PLoS.One 7 e46881
PubMedID: 23056508
Gene_locus related to this paper: 9them-a1yv97

Abstract

Flexible NC-loops between the catalytic domain and the cap domain of the alpha/beta hydrolase fold enzymes show remarkable diversity in length, sequence, and configuration. Recent investigations have suggested that the NC-loop might be involved in catalysis and substrate recognition in many enzymes from the alpha/beta hydrolase fold superfamily. To foster a deep understanding of its role in catalysis, stability, and divergent evolution, we here systemically investigated the function of the NC-loop (residues 131-151) in a lipase (FClip1) from thermophilic bacterium Fervidobacterium changbaicum by loop deletion, alanine-scanning mutagenesis and site-directed mutagenesis. We found that the upper part of the NC-loop (residues 131-138) was of great importance to enzyme catalysis. Single substitutions in this region could fine-tune the activity of FClip1 as much as 41-fold, and any deletions from this region rendered the enzyme completely inactive. The lower part of the NC-loop (residues 139-151) was capable of enduring extensive deletions without loss of activity. The shortened mutants in this region were found to show both improved activity and increased stability simultaneously. We therefore speculated that the NC-loop, especially the lower part, would be a perfect target for enzyme engineering to optimize the enzymatic properties, and might present a hot zone for the divergent evolution of alpha/beta hydrolases. Our findings may provide an opportunity for better understanding of the mechanism of divergent evolution in the alpha/beta hydrolase fold superfamily, and may also guide the design of novel biocatalysts for industrial applications.



        

Title: Solvent-free enzymatic transesterification of ethyl ferulate and monostearin: optimized by response surface methodology
Sun S, Song F, Bi Y, Yang G, Liu W
Ref: J Biotechnol, 164:340, 2012 : PubMed
Abstract


ESTHER: Sun_2012_J.Biotechnol_164_340
PubMedSearch: Sun 2012 J.Biotechnol 164 340
PubMedID: 23376620

Abstract

In this study, enzymatic transesterification of ethyl ferulate (EF) and monostearin for feruloylated lipids production was investigated. Enzyme screening and the effect of feruloyl acceptors on the transesterification were also studied. Effects of reaction variables (reaction temperatures, enzyme load, and reaction time) on the transesterification were optimized using response surface methodology (RSM). The optimum conditions were as follows: reaction temperature 74 degrees C, reaction time 23h, and enzyme load 20% (w/w, relative to the weight of substrates). Under these conditions, EF conversion was 98.3+/-1.1%, and the transesterification product was consisted of 19.2+/-2.1% glyceryl ferulate (FG), 32.9+/-1.9% diferuloylated glycerols (DFG), 36.6+/-2.2% feruloylated monoacylglycerols (FMAG), 9.1+/-2.0% feruloylated diacylglycerols (FDAG), and 0.5% ferulic acid (FA). Analysis of variance (ANOVA) showed that the regression equation was adequate for predicting EF conversion. The activation energies for hydrolysis to form FG+DFG and transesterification to form FMAG+FDAG were calculated as 22.45 and 51.05kJ/mol, respectively, based on Arrhenius law.



        

Title: Pdl1 is a putative lipase that enhances Photorhabdus toxin complex secretion
Yang G, Hernandez-Rodriguez CS, Beeton ML, Wilkinson P, ffrench-Constant RH, Waterfield NR
Ref: PLoS Pathog, 8:e1002692, 2012 : PubMed
Abstract


ESTHER: Yang_2012_PLoS.Pathog_8_e1002692
PubMedSearch: Yang 2012 PLoS.Pathog 8 e1002692
PubMedID: 22615559

Abstract

The Toxin Complex (TC) is a large multi-subunit toxin first characterized in the insect pathogens Photorhabdus and Xenorhabdus, but now seen in a range of pathogens, including those of humans. These complexes comprise three protein subunits, A, B and C which in the Xenorhabdus toxin are found in a 4:1:1 stoichiometry. Some TCs have been demonstrated to exhibit oral toxicity to insects and have the potential to be developed as a pest control technology. The lack of recognisable signal sequences in the three large component proteins hinders an understanding of their mode of secretion. Nevertheless, we have shown the Photorhabdus luminescens (Pl) Tcd complex has been shown to associate with the bacteria's surface, although some strains can also release it into the surrounding milieu. The large number of tc gene homologues in Pl make study of the export process difficult and as such we have developed and validated a heterologous Escherichia coli expression model to study the release of these important toxins. In addition to this model, we have used comparative genomics between a strain that releases high levels of Tcd into the supernatant and one that retains the toxin on its surface, to identify a protein responsible for enhancing secretion and release of these toxins. This protein is a putative lipase (Pdl1) which is regulated by a small tightly linked antagonist protein (Orf53). The identification of homologues of these in other bacteria, linked to other virulence factor operons, such as type VI secretion systems, suggests that these genes represent a general and widespread mechanism for enhancing toxin release in gram negative pathogens.



        

Title: Switch of substrate specificity of hyperthermophilic acylaminoacyl peptidase by combination of protein and solvent engineering
Liu C, Yang G, Wu L, Tian G, Zhang Z, Feng Y
Ref: Protein Cell, 2:497, 2011 : PubMed
Abstract


ESTHER: Liu_2011_Protein.Cell_2_497
PubMedSearch: Liu 2011 Protein.Cell 2 497
PubMedID: 21748600

Abstract

The inherent evolvability of promiscuous enzymes endows them with great potential to be artificially evolved for novel functions. Previously, we succeeded in transforming a promiscuous acylaminoacyl peptidase (apAAP) from the hyperthermophilic archaeon Aeropyrum pernix K1 into a specific carboxylesterase by making a single mutation. In order to fulfill the urgent requirement of thermostable lipolytic enzymes, in this paper we describe how the substrate preference of apAAP can be further changed from p-nitrophenyl caprylate (pNP-C8) to p-nitrophenyl laurate (pNP-C12) by protein and solvent engineering. After one round of directed evolution and subsequent saturation mutagenesis at selected residues in the active site, three variants with enhanced activity towards pNP-C12 were identified. Additionally, a combined mutant W474V/F488G/R526V/T560W was generated, which had the highest catalytic efficiency (k (cat)/K (m)) for pNP-C12, about 71-fold higher than the wild type. Its activity was further increased by solvent engineering, resulting in an activity enhancement of 280-fold compared with the wild type in the presence of 30% DMSO. The structural basis for the improved activity was studied by substrate docking and molecular dynamics simulation. It was revealed that W474V and F488G mutations caused a significant change in the geometry of the active center, which may facilitate binding and subsequent hydrolysis of bulky substrates. In conclusion, the combination of protein and solvent engineering may be an effective approach to improve the activities of promiscuous enzymes and could be used to create naturally rare hyperthermophilic enzymes.



        

Title: Deficiency of liver adipose triglyceride lipase in mice causes progressive hepatic steatosis
Wu JW, Wang SP, Alvarez F, Casavant S, Gauthier N, Abed L, Soni KG, Yang G, Mitchell GA
Ref: Hepatology, 54:122, 2011 : PubMed
Abstract


ESTHER: Wu_2011_Hepatology_54_122
PubMedSearch: Wu 2011 Hepatology 54 122
PubMedID: 21465509

Abstract

UNLABELLED: Accumulation of cytoplasmic triacylglycerol (TG) underlies hepatic steatosis, a major cause of cirrhosis. The pathways of cytoplasmic TG metabolism are not well known in hepatocytes, but evidence suggests an important role in lipolysis for adipose triglyceride lipase (ATGL). We created mice with liver-specific inactivation of Pnpla2, the ATGL gene. These ATGLLKO mice had severe progressive periportal macrovesicular and pericentral microvesicular hepatic steatosis (73, 150, and 226 mumol TG/g liver at 4, 8, and 12 months, respectively). However, plasma levels of glucose, TG, and cholesterol were similar to those of controls. Fasting 3-hydroxybutyrate level was normal, but in thin sections of liver, beta oxidation of palmitate was decreased by one-third in ATGLLKO mice compared with controls. Tests of very low-density lipoprotein production, glucose, and insulin tolerance and gluconeogenesis from pyruvate were normal. Plasma alanine aminotransferase levels were elevated in ATGLLKO mice, but histological estimates of inflammation and fibrosis and messenger RNA (mRNA) levels of tumor necrosis factor-alpha and interleukin-6 were similar to or lower than those in controls. ATGLLKO cholangiocytes also showed cytoplasmic lipid droplets, demonstrating that ATGL is also a major lipase in cholangiocytes. There was a 50-fold reduction of hepatic diacylglycerol acyltransferase 2 mRNA level and a 2.7-fold increase of lipolysosomes in hepatocytes (P < 0.001), suggesting reduced TG synthesis and increased lysosomal degradation of TG as potential compensatory mechanisms. CONCLUSION: Compared with the hepatic steatosis of obesity and diabetes, steatosis in ATGL deficiency is well tolerated metabolically. ATGLLKO mice will be useful for studying the pathophysiology of hepatic steatosis.



        

Title: Elevated adipose triglyceride lipase in newly diagnosed type 2 diabetes mellitus with hypertension
Xu S, Yang G, Yang M, Li S, Liu H, Li L
Ref: American Journal of Medicine Sci, 342:452, 2011 : PubMed
Abstract


ESTHER: Xu_2011_Am.J.Med.Sci_342_452
PubMedSearch: Xu 2011 Am.J.Med.Sci 342 452
PubMedID: 21709540

Abstract

INTRODUCTION: Adipose triglyceride lipase (ATGL) is a recently identified triacylglycerol lipase responsible for adiposity lipolysis. Its pathophysiologic role in humans remains unknown. MATERIAL AND METHODS: In this study, the authors investigated the levels of plasma ATGL among patients with type 2 diabetes mellitus (T2DM), patients with T2DM and hypertension and control subjects. They also assessed the association between plasma ATGL and body composition and metabolic parameters. RESULTS AND CONCLUSIONS: Plasma ATGL levels significantly increased in patients with T2DM and hypertension compared with those with T2DM (78.3 +/- 23.4 versus 65.1 +/- 22.8 mug/L, P < 0.01). No gender differences were found among plasma ATGL levels. Furthermore, they found that the plasma ATGL level was positively correlated with total cholesterol (r = 0.17, P < 0.05) and high-density lipoprotein C (r = 0.16, P < 0.05) in simple regression analysis of pooled data, whereas, in multiple stepwise regression analysis, diastolic blood pressure, total cholesterol and homeostasis model assessment of insulin resistance were independently related factors with plasma ATGL levels (Y = -13.662 + 0.343 x waist + 0.268 x diastolic blood pressure + 0.053 x 2hPin + 0.966 x homeostasis model assessment of insulin resistance). This work indicates the potential link of ATGL with the pathogenesis of insulin resistance and T2DM.



        

Title: The sequence and de novo assembly of the giant panda genome
Li R, Fan W, Tian G, Zhu H, He L, Cai J, Huang Q, Cai Q, Li B and Yang H <103 more author(s)> Li R, Fan W, Tian G, Zhu H, He L, Cai J, Huang Q, Cai Q, Li B, Bai Y, Zhang Z, Zhang Y, Wang W, Li J, Wei F, Li H, Jian M, Nielsen R, Li D, Gu W, Yang Z, Xuan Z, Ryder OA, Leung FC, Zhou Y, Cao J, Sun X, Fu Y, Fang X, Guo X, Wang B, Hou R, Shen F, Mu B, Ni P, Lin R, Qian W, Wang G, Yu C, Nie W, Wang J, Wu Z, Liang H, Min J, Wu Q, Cheng S, Ruan J, Wang M, Shi Z, Wen M, Liu B, Ren X, Zheng H, Dong D, Cook K, Shan G, Zhang H, Kosiol C, Xie X, Lu Z, Li Y, Steiner CC, Lam TT, Lin S, Zhang Q, Li G, Tian J, Gong T, Liu H, Zhang D, Fang L, Ye C, Zhang J, Hu W, Xu A, Ren Y, Zhang G, Bruford MW, Li Q, Ma L, Guo Y, An N, Hu Y, Zheng Y, Shi Y, Li Z, Liu Q, Chen Y, Zhao J, Qu N, Zhao S, Tian F, Wang X, Wang H, Xu L, Liu X, Vinar T, Wang Y, Lam TW, Yiu SM, Liu S, Huang Y, Yang G, Jiang Z, Qin N, Li L, Bolund L, Kristiansen K, Wong GK, Olson M, Zhang X, Li S, Yang H (- 103)
Ref: Nature, 463:311, 2010 : PubMed
Abstract


ESTHER: Li_2010_Nature_463_311
PubMedSearch: Li 2010 Nature 463 311
PubMedID: 20010809
Gene_locus related to this paper: ailme-ABH15, ailme-ACHE, ailme-BCHE, ailme-d2gtv3, ailme-d2gty9, ailme-d2gu87, ailme-d2gu97, ailme-d2gve7, ailme-d2gwu1, ailme-d2gx08, ailme-d2gyt0, ailme-d2gz36, ailme-d2gz37, ailme-d2gz38, ailme-d2gz39, ailme-d2gz40, ailme-d2h5r9, ailme-d2h7b7, ailme-d2h9c9, ailme-d2h794, ailme-d2hau7, ailme-d2hau8, ailme-d2hcd9, ailme-d2hdi6, ailme-d2heu6, ailme-d2hga4, ailme-d2hqw5, ailme-d2hs98, ailme-d2hsx4, ailme-d2hti6, ailme-d2htv3, ailme-d2htz6, ailme-d2huc7, ailme-d2hwj8, ailme-d2hwy7, ailme-d2hxm1, ailme-d2hyc8, ailme-d2hyv2, ailme-d2hz11, ailme-d2hza3, ailme-d2hzr4, ailme-d2i1l4, ailme-d2i2g8, ailme-g1l7m3, ailme-g1lu36, ailme-g1m769, ailme-g1mc29, ailme-g1mdj8, ailme-g1mdr5, ailme-g1mfp4, ailme-g1mfx5, ailme-g1lj41, ailme-g1lm28, ailme-g1l3u1, ailme-g1l7l1, ailme-g1m5i3, ailme-g1l2f6, ailme-g1lji5, ailme-g1lqk3, ailme-g1l8s9, ailme-d2h717, ailme-d2h718, ailme-d2h719, ailme-d2h720, ailme-g1m5v0, ailme-g1m5y7, ailme-g1lkt7, ailme-g1l2a1, ailme-g1lsc8, ailme-g1lrp4, ailme-d2gv02, ailme-g1mik5, ailme-g1ljr1, ailme-g1lxw7, ailme-d2h8b5, ailme-d2h2r2, ailme-d2h9w7, ailme-g1meh3, ailme-g1m719

Abstract

Using next-generation sequencing technology alone, we have successfully generated and assembled a draft sequence of the giant panda genome. The assembled contigs (2.25 gigabases (Gb)) cover approximately 94% of the whole genome, and the remaining gaps (0.05 Gb) seem to contain carnivore-specific repeats and tandem repeats. Comparisons with the dog and human showed that the panda genome has a lower divergence rate. The assessment of panda genes potentially underlying some of its unique traits indicated that its bamboo diet might be more dependent on its gut microbiome than its own genetic composition. We also identified more than 2.7 million heterozygous single nucleotide polymorphisms in the diploid genome. Our data and analyses provide a foundation for promoting mammalian genetic research, and demonstrate the feasibility for using next-generation sequencing technologies for accurate, cost-effective and rapid de novo assembly of large eukaryotic genomes.



        

Title: Comparative study of properties of immobilized lipase onto glutaraldehyde-activated amino-silica gel via different methods
Yang G, Wu J, Xu G, Yang L
Ref: Colloids Surf B Biointerfaces, 78:351, 2010 : PubMed
Abstract


ESTHER: Yang_2010_Colloids.Surf.B.Biointerfaces_78_351
PubMedSearch: Yang 2010 Colloids.Surf.B.Biointerfaces 78 351
PubMedID: 20399626

Abstract

The enzyme-aggregate coating method was performed to immobilize Arthrobacter sp. lipase in order to achieve better catalytic properties comparable to the conventional covalent attachment and covalent attachment plus cross-linking. The glutaraldehyde-activated amino-silica gel which was synthesized by sol-gel technique was used as the support, and the catalytic characteristics of the lipase preparations were tested in the asymmetric acylation of 4-hydroxy-3-methyl-2-(2-propenyl)-2-cyclopenten-1-one (HMPC) in organic solvents. The results showed that the immobilized lipase by enzyme-aggregate coating possessed both higher activity and stability than those by other methods, e.g. it obtained an activity of 82.6 U/g and remained 42% and 93% of the original activity after incubation in vinyl acetate at 60 degrees C for 16 h and 9 times recycles, respectively, while the covalently attached lipase got an activity of 67.4 U/g and left 33% and 73% of the original under the same conditions, and the enzyme prepared by covalent attachment plus cross-linking exhibited the lowest activity yield. Moreover, excellent enantioselectivity (E > or =400) was achieved by all the three prepared lipases in our paper (E=85 for the free enzyme).



        

Title: The genome of the cucumber, Cucumis sativus L
Huang S, Li R, Zhang Z, Li L, Gu X, Fan W, Lucas WJ, Wang X, Xie B and Du Y <77 more author(s)> Huang S, Li R, Zhang Z, Li L, Gu X, Fan W, Lucas WJ, Wang X, Xie B, Ni P, Ren Y, Zhu H, Li J, Lin K, Jin W, Fei Z, Li G, Staub J, Kilian A, van der Vossen EA, Wu Y, Guo J, He J, Jia Z, Tian G, Lu Y, Ruan J, Qian W, Wang M, Huang Q, Li B, Xuan Z, Cao J, Asan, Wu Z, Zhang J, Cai Q, Bai Y, Zhao B, Han Y, Li Y, Li X, Wang S, Shi Q, Liu S, Cho WK, Kim JY, Xu Y, Heller-Uszynska K, Miao H, Cheng Z, Zhang S, Wu J, Yang Y, Kang H, Li M, Liang H, Ren X, Shi Z, Wen M, Jian M, Yang H, Zhang G, Yang Z, Chen R, Ma L, Liu H, Zhou Y, Zhao J, Fang X, Fang L, Liu D, Zheng H, Zhang Y, Qin N, Li Z, Yang G, Yang S, Bolund L, Kristiansen K, Li S, Zhang X, Wang J, Sun R, Zhang B, Jiang S, Du Y (- 77)
Ref: Nat Genet, 41:1275, 2009 : PubMed
Abstract


ESTHER: Huang_2009_Nat.Genet_41_1275
PubMedSearch: Huang 2009 Nat.Genet 41 1275
PubMedID: 19881527
Gene_locus related to this paper: cucsa-a0a0a0ktw5, cucsa-a0a0a0lnt6, cucsa-a0a0a0kpn7, cucsa-a0a0a0lvt9, cucsa-a0a0a0kdx8, cucsa-a0a0a0m228, cucsa-a0a0a0kz31, cucsa-a0a0a0k5t5, cucsa-a0a0a0kfs7, cucsa-a0a0a0kjj7, cucsa-a0a0a0kzs7, cucsa-a0a0a0l0a6, cucsa-a0a0a0l4w4, cucsa-a0a0a0lpz0, cucsa-a0a0a0ls66

Abstract

Cucumber is an economically important crop as well as a model system for sex determination studies and plant vascular biology. Here we report the draft genome sequence of Cucumis sativus var. sativus L., assembled using a novel combination of traditional Sanger and next-generation Illumina GA sequencing technologies to obtain 72.2-fold genome coverage. The absence of recent whole-genome duplication, along with the presence of few tandem duplications, explains the small number of genes in the cucumber. Our study establishes that five of the cucumber's seven chromosomes arose from fusions of ten ancestral chromosomes after divergence from Cucumis melo. The sequenced cucumber genome affords insight into traits such as its sex expression, disease resistance, biosynthesis of cucurbitacin and 'fresh green' odor. We also identify 686 gene clusters related to phloem function. The cucumber genome provides a valuable resource for developing elite cultivars and for studying the evolution and function of the plant vascular system.



        

Title: Capecitabine, oxaliplatin and radiotherapy: a phase IB neoadjuvant study for esophageal cancer with gene expression analysis
Javle MM, Yang G, Nwogu CE, Wilding GE, O'Malley L, Vinjamaram S, Schiff MD, Nava HR, LeVea C and Pendyala L <3 more author(s)> Javle MM, Yang G, Nwogu CE, Wilding GE, O'Malley L, Vinjamaram S, Schiff MD, Nava HR, LeVea C, Clark KR, Prey JD, Smith PF, Pendyala L (- 3)
Ref: Cancer Invest, 27:193, 2009 : PubMed
Abstract


ESTHER: Javle_2009_Cancer.Invest_27_193
PubMedSearch: Javle 2009 Cancer.Invest 27 193
PubMedID: 19235592

Abstract


PURPOSE: To determine the maximal tolerated dose of capecitabine with oxaliplatin + radiotherapy in a phase I study of localized esophageal cancer. PATIENTS AND METHODS: Oxaliplatin (85 mg/m(2)) administered on days 1, 15, and 29. Capecitabine administered twice daily 5 days weekly; dose levels (DL) were 1, 1000; 2, 1250; and 3, 1500 mg/m(2) with 50.4 Gy radiation. RESULTS: Dose-limiting toxicity was reached at DL 3. Carboxylesterase expression in day 2 tumor specimens and induction correlated with response (p



        

Title: The adipose triglyceride lipase, adiponectin and visfatin are downregulated by tumor necrosis factor-alpha (TNF-alpha) in vivo
Li L, Yang G, Shi S, Yang M, Liu H, Boden G
Ref: Cytokine, 45:12, 2009 : PubMed
Abstract


ESTHER: Li_2009_Cytokine_45_12
PubMedSearch: Li 2009 Cytokine 45 12
PubMedID: 19026557

Abstract

Inflammatory cytokines have been linked to obesity-related insulin resistance. To investigate the effect of TNF-alpha, an inflammatory cytokine, on insulin action, C57BL/6J mice were treated with TNF-alpha for 7 days after which we examined the in vivo effects of TNF-alpha on glucose tolerance and insulin sensitivity with IV glucose tolerance tests and hyperinsulinemic-euglycemic clamps. In addition, we analyzed the in vivo effect of TNF-alpha on several metabolism-related genes and adipocytokines implicated in the development of insulin resistance. TNF-alpha treatment resulted in markedly increased fasting blood glucose, insulin and free fatty acids (FFA) levels and reduced glucose tolerance. During the clamps, the rates insulin-stimulated whole body (G(Rd)) and skeletal muscle glucose uptake (MGU) and insulin's ability to suppress hepatic glucose production (HGP) were decreased in TNF-alpha treated animals, indicating insulin resistance. In addition, both PPARgamma and ATGL mRNA expression in adipose tissues as well as ATGL protein levels in plasma were downregulated. Moreover, adipose mRNA expression and plasma protein levels of adiponectin and visfatin were significantly down-regulated. We conclude that the alterations of PPARgamma, ATGL, adiponectin and visfatin may contribute to the development of insulin resistance mediated by TNF-alpha.



        

Title: Glu88 in the non-catalytic domain of acylpeptide hydrolase plays dual roles: charge neutralization for enzymatic activity and formation of salt bridge for thermodynamic stability
Yang G, Bai A, Gao L, Zhang Z, Zheng B, Feng Y
Ref: Biochimica & Biophysica Acta, 1794:94, 2009 : PubMed
Abstract


ESTHER: Yang_2009_Biochim.Biophys.Acta_1794_94
PubMedSearch: Yang 2009 Biochim.Biophys.Acta 1794 94
PubMedID: 18930847

Abstract

Acylpeptide hydrolase of Aeropyrum pernix K1 is composed of a catalytic alpha/beta hydrolase domain and a non-catalytic beta-propeller domain. The Glu88 residue of the propeller domain is highly conserved in the prolyl oligopeptidase family and forms an inter-domain salt bridge with Arg526, a key residue for substrate binding. We have dissected the functions of Glu88 using site-directed mutagenesis, steady-state kinetics analyses, and molecular dynamics simulations. In E88A and E88A/R526K mutants, with a broken inter-domain salt bridge and a positive charge at position 526, catalytic activities for both a peptidase substrate and an esterase substrate were almost abolished. Analysis of the pH dependence of the mutants' reaction kinetics indicates that these mutations lead to changes in the electrostatic environment of the active site, which can be modulated by chloride ions. These findings indicate that the neutralization at position 526 is favorable for the activity of the enzyme, which is also verified by the catalytic behavior of E88A/R526V mutant. All mutants have lower thermodynamic stability than the wild-type. Therefore, Glu88 plays two major roles in the function of the enzyme: neutralizing the positive charge of Arg526, thereby increasing the enzymatic activity, and forming the Glu88-Arg526 salt bridge, thereby stabilizing the protein.



        

Title: Novel acetylcholinesterase inhibitors: Synthesis and structure-activity relationships of phthalimide alkyloxyphenyl N,N-dimethylcarbamate derivatives
Zhao Q, Yang G, Mei X, Yuan H, Ning J
Ref: Pesticide Biochemistry and Physiology, 95:131, 2009 : PubMed
Abstract


ESTHER: Zhao_2009_Pestic.Biochem.Physiol_95_131
PubMedSearch: Zhao 2009 Pestic.Biochem.Physiol 95 131

Abstract

Based on the multiple binding sites of acetylcholinesterase (AChE), a series of AChE inhibitors: phthalimide alkyloxyphenyl N,N-dimethylcarbamate were designed and synthesized. AChE inhibitory activity and structure-activity relationship of the compounds were researched also. The influence of structural variations on the inhibitory potency was carefully investigated by modifying different alkyloxy chain length and position between phthalimide and phenyl N,N-dimethylcarbamate (PDM). The biological properties of the series were investigated by considering the activity on isolated enzyme. Some of the newly synthesized derivatives, when tested on isolated AChE from head of housefly (Musca domestica), were more active than PDM. The compounds J1, J2 and K1-K8 demonstrated higher inhibitory activity (5- to 404-fold) for AChE than that of PDM. In particular, compound K1 displayed the best AChE inhibition (404-fold higher than PDM), which suggested that phthalimide group of K1 strongly bound at the residues lining the gorge while phenyl N,N-dimethylcarbamate bound at the catalytic site.



        

Title: Rapid Virulence Annotation (RVA): identification of virulence factors using a bacterial genome library and multiple invertebrate hosts
Waterfield NR, Sanchez-Contreras M, Eleftherianos I, Dowling A, Yang G, Wilkinson P, Parkhill J, Thomson N, Reynolds SE and ffrench-Constant RH <2 more author(s)> Waterfield NR, Sanchez-Contreras M, Eleftherianos I, Dowling A, Yang G, Wilkinson P, Parkhill J, Thomson N, Reynolds SE, Bode HB, Dorus S, ffrench-Constant RH (- 2)
Ref: Proc Natl Acad Sci U S A, 105:15967, 2008 : PubMed
Abstract


ESTHER: Waterfield_2008_Proc.Natl.Acad.Sci.U.S.A_105_15967
PubMedSearch: Waterfield 2008 Proc.Natl.Acad.Sci.U.S.A 105 15967
PubMedID: 18838673
Gene_locus related to this paper: phoaa-b6vks1, phoaa-b6vmd3

Abstract

Current sequence databases now contain numerous whole genome sequences of pathogenic bacteria. However, many of the predicted genes lack any functional annotation. We describe an assumption-free approach, Rapid Virulence Annotation (RVA), for the high-throughput parallel screening of genomic libraries against four different taxa: insects, nematodes, amoeba, and mammalian macrophages. These hosts represent different aspects of both the vertebrate and invertebrate immune system. Here, we apply RVA to the emerging human pathogen Photorhabdus asymbiotica using "gain of toxicity" assays of recombinant Escherichia coli clones. We describe a wealth of potential virulence loci and attribute biological function to several putative genomic islands, which may then be further characterized using conventional molecular techniques. The application of RVA to other pathogen genomes promises to ascribe biological function to otherwise uncharacterized virulence genes.



        

Title: Design of novel carbamate acetylcholinesterase inhibitors based on the multiple binding sites of acetylcholinesterase
Zhao Q, Yang G, Mei X, Yuan H, Ning J
Ref: Journal of Pesticide Science, 33:371, 2008 : PubMed
Abstract


ESTHER: Zhao_2008_J.Pestic.Sci_33_371
PubMedSearch: Zhao 2008 J.Pestic.Sci 33 371
Inhibitor(s) related to this paper: Metolcarb

Abstract

This work describes the design, synthesis, AChE inhibitory activity, and structure-activity relationship of compounds related to a recently discovered series of AChE inhibitors: phthalimide alkyloxyphenyl N-methylcarbamates. The influence of structural variations on inhibitory potency was carefully investigated by modifying different alkyloxy chain lengths and positions between phthalimide and phenyl N-methylcarbamate. The biological properties of the series were investigated in some detail by considering their activity on isolated enzymes. All of the newly synthesized derivatives, when tested on isolated AChE from the brain of the housefly (Musca domestica), were more active than phenyl N-methylcarbamate. In particular, compound I1 displayed the best AChE inhibition (352-fold higher than phenyl N-methylcarbamate, and 29-fold higher than metolcarb), which suggested that the phthalimide group of I1 bound strongly to the residues lining the gorge, and phenyl N-methylcarbamate bound at the catalytic sites.



        

Title: Computational design of a human butyrylcholinesterase mutant for accelerating cocaine hydrolysis based on the transition-state simulation
Gao D, Cho H, Yang W, Pan Y, Yang G, Tai HH, Zhan CG
Ref: Angew Chem Int Ed Engl, 45:653, 2006 : PubMed
Abstract


ESTHER: Gao_2006_Angew.Chem.Int.Ed.Engl_45_653
PubMedSearch: Gao 2006 Angew.Chem.Int.Ed.Engl 45 653
PubMedID: 16355430



        

Title: The complete genome of Rhodococcus sp. RHA1 provides insights into a catabolic powerhouse
McLeod MP, Warren RL, Hsiao WW, Araki N, Myhre M, Fernandes C, Miyazawa D, Wong W, Lillquist AL and Eltis LD <19 more author(s)> McLeod MP, Warren RL, Hsiao WW, Araki N, Myhre M, Fernandes C, Miyazawa D, Wong W, Lillquist AL, Wang D, Dosanjh M, Hara H, Petrescu A, Morin RD, Yang G, Stott JM, Schein JE, Shin H, Smailus D, Siddiqui AS, Marra MA, Jones SJ, Holt R, Brinkman FS, Miyauchi K, Fukuda M, Davies JE, Mohn WW, Eltis LD (- 19)
Ref: Proc Natl Acad Sci U S A, 103:15582, 2006 : PubMed
Abstract


ESTHER: McLeod_2006_Proc.Natl.Acad.Sci.U.S.A_103_15582
PubMedSearch: McLeod 2006 Proc.Natl.Acad.Sci.U.S.A 103 15582
PubMedID: 17030794
Gene_locus related to this paper: rhoob-c1ar27, rhoob-c1arb5, rhoob-c1asz4, rhoob-c1at13, rhoob-c1ata3, rhoob-c1atk8, rhoob-c1atq0, rhoob-c1ats8, rhoob-c1att5, rhoob-c1au11, rhoob-c1auh5, rhoob-c1aux1, rhoob-c1av24, rhoob-c1awr1, rhoob-c1axf2, rhoob-c1ayb0, rhoob-c1b0a8, rhoob-c1b0g7, rhoob-c1b0w8, rhoob-c1b1i6, rhoob-c1b7t4, rhoob-c1b8z9, rhoob-c1b9l2, rhoob-c1b9v1, rhoob-c1b9y1, rhoob-c1b930, rhoob-c1b931, rhoob-c1b932, rhoob-c1b996, rhoob-c1bbl3, rhoob-c1bbq4, rhoop-pcaL, rhosp-bphD2, rhosp-EtbD1, rhosr-q0rwt2, rhosr-q0rwv3, rhosr-q0rxc8, rhosr-q0ryc0, rhosr-q0ryn3, rhosr-q0rz46, rhosr-q0rz78, rhosr-q0s0s0, rhosr-q0s1l0, rhosr-q0s1m1, rhosr-q0s1n4, rhosr-q0s1x5, rhosr-q0s1x6, rhosr-q0s2i6, rhosr-q0s2n9, rhosr-q0s2t5, rhosr-q0s3c8, rhosr-q0s3s6, rhosr-q0s4f1, rhosr-q0s5h5, rhosr-q0s5m7, rhosr-q0s6a9, rhosr-q0s6b3, rhosr-q0s6b5, rhosr-q0s7i7, rhosr-q0s7r1, rhosr-q0s008, rhosr-q0s8b3, rhosr-q0s8f4, rhosr-q0s8p7, rhosr-q0s8z9, rhosr-q0s9l3, rhosr-q0s9m1, rhosr-q0s101, rhosr-q0s125, rhosr-q0s230, rhosr-q0s252, rhosr-q0s393, rhosr-q0s477, rhosr-q0s545, rhojr-q0s546, rhosr-q0s837, rhosr-q0s849, rhosr-q0sa25, rhosr-q0sa26, rhosr-q0sa61, rhosr-q0saa5, rhosr-q0san0, rhosr-q0saw3, rhosr-q0sbd3, rhosr-q0sc04, rhosr-q0scq2, rhosr-q0sd10, rhosr-q0sdb8, rhosr-q0sdh6, rhosr-q0sdr2, rhosr-q0sdr5, rhosr-q0sdt1, rhosr-q0sdu5, rhosr-q0sej4, rhosr-q0ses6, rhosr-q0set7, rhosr-q0sex8, rhosr-q0sf05, rhosr-q0sfh8, rhosr-q0sfl2, rhosr-q0sfz6, rhosr-q0sgc8, rhosr-q0sgj4, rhosr-q0sgv4, rhosr-q0sgw4, rhosr-q0sh74, rhosr-q0shd6, rhosr-q0shi2, rhosr-q0sjy0, rhosr-q0skn1, rhoob-c1b934, rhosr-q0sab7, rhosr-q0rwx4, rhoob-c1asm3, rhosr-q0ruu2, rhosr-q0s747, rhosr-q0ry47, rhosr-q0rwa1, rhosr-q0sj22, 9noca-j2j8s8, rhojr-q0sd80, rhojr-q0sf05

Abstract

Rhodococcus sp. RHA1 (RHA1) is a potent polychlorinated biphenyl-degrading soil actinomycete that catabolizes a wide range of compounds and represents a genus of considerable industrial interest. RHA1 has one of the largest bacterial genomes sequenced to date, comprising 9,702,737 bp (67% G+C) arranged in a linear chromosome and three linear plasmids. A targeted insertion methodology was developed to determine the telomeric sequences. RHA1's 9,145 predicted protein-encoding genes are exceptionally rich in oxygenases (203) and ligases (192). Many of the oxygenases occur in the numerous pathways predicted to degrade aromatic compounds (30) or steroids (4). RHA1 also contains 24 nonribosomal peptide synthase genes, six of which exceed 25 kbp, and seven polyketide synthase genes, providing evidence that rhodococci harbor an extensive secondary metabolism. Among sequenced genomes, RHA1 is most similar to those of nocardial and mycobacterial strains. The genome contains few recent gene duplications. Moreover, three different analyses indicate that RHA1 has acquired fewer genes by recent horizontal transfer than most bacteria characterized to date and far fewer than Burkholderia xenovorans LB400, whose genome size and catabolic versatility rival those of RHA1. RHA1 and LB400 thus appear to demonstrate that ecologically similar bacteria can evolve large genomes by different means. Overall, RHA1 appears to have evolved to simultaneously catabolize a diverse range of plant-derived compounds in an O(2)-rich environment. In addition to establishing RHA1 as an important model for studying actinomycete physiology, this study provides critical insights that facilitate the exploitation of these industrially important microorganisms.



        

Title: The genome of black cottonwood, Populus trichocarpa (Torr. & Gray)
Tuskan GA, Difazio S, Jansson S, Bohlmann J, Grigoriev I, Hellsten U, Putnam N, Ralph S, Rombauts S and Rokhsar D <100 more author(s)> Tuskan GA, Difazio S, Jansson S, Bohlmann J, Grigoriev I, Hellsten U, Putnam N, Ralph S, Rombauts S, Salamov A, Schein J, Sterck L, Aerts A, Bhalerao RR, Bhalerao RP, Blaudez D, Boerjan W, Brun A, Brunner A, Busov V, Campbell M, Carlson J, Chalot M, Chapman J, Chen GL, Cooper D, Coutinho PM, Couturier J, Covert S, Cronk Q, Cunningham R, Davis J, Degroeve S, Dejardin A, dePamphilis C, Detter J, Dirks B, Dubchak I, Duplessis S, Ehlting J, Ellis B, Gendler K, Goodstein D, Gribskov M, Grimwood J, Groover A, Gunter L, Hamberger B, Heinze B, Helariutta Y, Henrissat B, Holligan D, Holt R, Huang W, Islam-Faridi N, Jones S, Jones-Rhoades M, Jorgensen R, Joshi C, Kangasjarvi J, Karlsson J, Kelleher C, Kirkpatrick R, Kirst M, Kohler A, Kalluri U, Larimer F, Leebens-Mack J, Leple JC, Locascio P, Lou Y, Lucas S, Martin F, Montanini B, Napoli C, Nelson DR, Nelson C, Nieminen K, Nilsson O, Pereda V, Peter G, Philippe R, Pilate G, Poliakov A, Razumovskaya J, Richardson P, Rinaldi C, Ritland K, Rouze P, Ryaboy D, Schmutz J, Schrader J, Segerman B, Shin H, Siddiqui A, Sterky F, Terry A, Tsai CJ, Uberbacher E, Unneberg P, Vahala J, Wall K, Wessler S, Yang G, Yin T, Douglas C, Marra M, Sandberg G, Van de Peer Y, Rokhsar D (- 100)
Ref: Science, 313:1596, 2006 : PubMed
Abstract


ESTHER: Tuskan_2006_Science_313_1596
PubMedSearch: Tuskan 2006 Science 313 1596
PubMedID: 16973872
Gene_locus related to this paper: burvg-a4jw31, delas-a9c1v9, poptr-a9pfp5, poptr-a9ph43, poptr-a9ph71, poptr-a9pha7, poptr-b9giq0, poptr-b9gjs0, poptr-b9gl72, poptr-b9gmx8, poptr-b9gnp9, poptr-b9gny4, poptr-b9grg2, poptr-b9gsc2, poptr-b9gvp3, poptr-b9gvs3, poptr-b9gwn9, poptr-b9gy32, poptr-b9gyq1, poptr-b9gys8, poptr-b9h0h0, poptr-b9h4j2, poptr-b9h6c2, poptr-b9h6c5, poptr-b9h6l8, poptr-b9h8c9, poptr-b9h301, poptr-b9h579, poptr-b9hbl2, poptr-b9hbw5, poptr-b9hcn9, poptr-b9hee0, poptr-b9hee2, poptr-b9hee5, poptr-b9hee6, poptr-b9hef3, poptr-b9hfa7, poptr-b9hfd3, poptr-b9hfi6, poptr-b9hft8, poptr-b9hg83, poptr-b9hif5, poptr-b9hll5, poptr-b9hmd0, poptr-b9hnv3, poptr-b9hqr6, poptr-b9hqr7, poptr-b9hrv7, poptr-b9hs66, poptr-b9huf0, poptr-b9hur3, poptr-b9hux1, poptr-b9hwp2, poptr-b9hxr7, poptr-b9hyk8, poptr-b9hyx2, poptr-b9i2q8, poptr-b9i5b8, poptr-b9i5j8, poptr-b9i5j9, poptr-b9i5k0, poptr-b9i6b6, poptr-b9i7b7, poptr-b9i9p8, poptr-b9i484, poptr-b9i994, poptr-b9ial3, poptr-b9ial4, poptr-b9ib28, poptr-b9ibr8, poptr-b9id97, poptr-b9idr4, poptr-b9iid9, poptr-b9iip0, poptr-b9ik80, poptr-b9ik90, poptr-b9il63, poptr-b9ink7, poptr-b9iqa0, poptr-b9iqd5, poptr-b9mwf1, poptr-b9mwi8, poptr-b9n0c6, poptr-b9n0n1, poptr-b9n0n4, poptr-b9n0z5, poptr-b9n1t8, poptr-b9n1z3, poptr-b9n3m7, poptr-b9n233, poptr-b9n236, poptr-b9n395, poptr-b9nd33, poptr-b9nd34, poptr-b9ndi6, poptr-b9ndj5, poptr-b9p9i8, poptr-a9pfa7, poptr-b9hdp2, poptr-b9inj0, poptr-b9n5g7, poptr-b9i8q4, poptr-u5g0r4, poptr-u5gf59, poptr-u7e1l9, poptr-b9hj61, poptr-b9hwd0, poptr-u5fz17, poptr-a0a2k2brq1, poptr-a0a2k2b9i6, poptr-a0a2k1x9y8, poptr-a9pch4, poptr-a0a2k1wwt1, poptr-a0a2k1wv10, poptr-a0a2k2a850, poptr-a0a2k2asj6, poptr-a0a2k1x6k1, poptr-u5fv96, poptr-a0a2k2blg2, poptr-a0a2k1xpi3, poptr-a0a2k1xpj0, poptr-a0a2k2b331, poptr-a0a2k2byl7, poptr-b9iek5, poptr-a9pfg4

Abstract

We report the draft genome of the black cottonwood tree, Populus trichocarpa. Integration of shotgun sequence assembly with genetic mapping enabled chromosome-scale reconstruction of the genome. More than 45,000 putative protein-coding genes were identified. Analysis of the assembled genome revealed a whole-genome duplication event; about 8000 pairs of duplicated genes from that event survived in the Populus genome. A second, older duplication event is indistinguishably coincident with the divergence of the Populus and Arabidopsis lineages. Nucleotide substitution, tandem gene duplication, and gross chromosomal rearrangement appear to proceed substantially more slowly in Populus than in Arabidopsis. Populus has more protein-coding genes than Arabidopsis, ranging on average from 1.4 to 1.6 putative Populus homologs for each Arabidopsis gene. However, the relative frequency of protein domains in the two genomes is similar. Overrepresented exceptions in Populus include genes associated with lignocellulosic wall biosynthesis, meristem development, disease resistance, and metabolite transport.



        

Title: Tyrosine phosphorylated Par3 regulates epithelial tight junction assembly promoted by EGFR signaling
Wang Y, Du D, Fang L, Yang G, Zhang C, Zeng R, Ullrich A, Lottspeich F, Chen Z
Ref: EMBO Journal, 25:5058, 2006 : PubMed
Abstract


ESTHER: Wang_2006_EMBO.J_25_5058
PubMedSearch: Wang 2006 EMBO.J 25 5058
PubMedID: 17053785

Abstract

The conserved polarity complex, comprising the partitioning-defective (Par) proteins Par3 and Par6, and the atypical protein kinase C, functions in various cell-polarization events and asymmetric cell divisions. However, little is known about whether and how external stimuli-induced signals may regulate Par3 function in epithelial cell polarity. Here, we found that Par3 was tyrosine phosphorylated through phosphoproteomic profiling of pervanadate-induced phosphotyrosine proteins. We also demonstrated that the tyrosine phosphorylation event induced by multiple growth factors including epidermal growth factor (EGF) was dependent on activation of Src family kinase (SFK) members c-Src and c-Yes. The tyrosine residue 1127 (Y1127) of Par3 was identified as the major EGF-induced phosphorylation site. Moreover, we found that Y1127 phosphorylation reduced the association of Par3 with LIM kinase 2 (LIMK2), thus enabling LIMK2 to regulate cofilin phosphorylation dynamics. Substitution of Y1127 for phenylalanine impaired the EGF-induced Par3 and LIMK2 dissociation and delayed epithelial tight junction (TJ) assembly considerably. Collectively, these data suggest a novel, phosphotyrosine-dependent fine-tuning mechanism of Par3 in epithelial TJ assembly controlled by the EGF receptor-SFK signaling pathway.



        

Title: Discrimination of esterase and peptidase activities of acylaminoacyl peptidase from hyperthermophilic Aeropyrum pernix K1 by a single mutation
Wang Q, Yang G, Liu Y, Feng Y
Ref: Journal of Biological Chemistry, 281:18618, 2006 : PubMed
Abstract


ESTHER: Wang_2006_J.Biol.Chem_281_18618
PubMedSearch: Wang 2006 J.Biol.Chem 281 18618
PubMedID: 16670095
Gene_locus related to this paper: aerpe-APE1547

Abstract

It has been shown that highly conserved residues that form crucial structural elements of the catalytic apparatus may be used to account for the evolutionary history of enzymes. Using saturation mutagenesis, we investigated the role of a conserved residue (Arg(526)) at the active site of acylaminoacyl peptidase from hyperthermophilic Aeropyrum pernix K1 in substrate discrimination and catalytic mechanism. This enzyme has both peptidase and esterase activities. The esterase activity of the wild-type enzyme with p-nitrophenyl caprylate as substrate is approximately 7 times higher than the peptidase activity with Ac-Leu-p-nitroanilide as substrate. However, with the same substrates, this difference was increased to approximately 150-fold for mutant R526V. A more dramatic effect occurred with mutant R526E, which essentially completely abolished the peptidase activity but decreased the esterase activity only by a factor of 2, leading to a 785-fold difference in the enzyme activities. These results provide rare examples that illustrate how enzymes can be evolved to discriminate their substrates by a single mutation. The possible structural and energetic effects of the mutations on k(cat) and K(m) of the enzyme were discussed based on molecular dynamics simulation studies.



        

Title: Computational redesign of human butyrylcholinesterase for anticocaine medication
Pan Y, Gao D, Yang W, Cho H, Yang G, Tai HH, Zhan CG
Ref: Proc Natl Acad Sci U S A, 102:16656, 2005 : PubMed
Abstract


ESTHER: Pan_2005_Proc.Natl.Acad.Sci.U.S.A_102_16656
PubMedSearch: Pan 2005 Proc.Natl.Acad.Sci.U.S.A 102 16656
PubMedID: 16275916

Abstract

Molecular dynamics was used to simulate the transition state for the first chemical reaction step (TS1) of cocaine hydrolysis catalyzed by human butyrylcholinesterase (BChE) and its mutants. The simulated results demonstrate that the overall hydrogen bonding between the carbonyl oxygen of (-)-cocaine benzoyl ester and the oxyanion hole of BChE in the TS1 structure for (-)-cocaine hydrolysis catalyzed by A199S/S287G/A328W/Y332G BChE should be significantly stronger than that in the TS1 structure for (-)-cocaine hydrolysis catalyzed by the WT BChE and other simulated BChE mutants. Thus, the transition-state simulations predict that A199S/S287G/A328W/Y332G mutant of BChE should have a significantly lower energy barrier for the reaction process and, therefore, a significantly higher catalytic efficiency for (-)-cocaine hydrolysis. The theoretical prediction has been confirmed by wet experimental tests showing an approximately (456 +/- 41)-fold improved catalytic efficiency of A199S/S287G/A328W/Y332G BChE against (-)-cocaine. This is a unique study to design an enzyme mutant based on transitionstate simulation. The designed BChE mutant has the highest catalytic efficiency against cocaine of all of the reported BChE mutants, demonstrating that the unique design approach based on transition-state simulation is promising for rational enzyme redesign and drug discovery.



        

Title: Genome sequence of Shigella flexneri 2a: insights into pathogenicity through comparison with genomes of Escherichia coli K12 and O157
Jin Q, Yuan Z, Xu J, Wang Y, Shen Y, Lu W, Wang J, Liu H, Yang J and Yu J <23 more author(s)> Jin Q, Yuan Z, Xu J, Wang Y, Shen Y, Lu W, Wang J, Liu H, Yang J, Yang F, Zhang X, Zhang J, Yang G, Wu H, Qu D, Dong J, Sun L, Xue Y, Zhao A, Gao Y, Zhu J, Kan B, Ding K, Chen S, Cheng H, Yao Z, He B, Chen R, Ma D, Qiang B, Wen Y, Hou Y, Yu J (- 23)
Ref: Nucleic Acids Research, 30:4432, 2002 : PubMed
Abstract


ESTHER: Jin_2002_Nucleic.Acids.Res_30_4432
PubMedSearch: Jin 2002 Nucleic.Acids.Res 30 4432
PubMedID: 12384590
Gene_locus related to this paper: ecoli-Aes, ecoli-yafa, ecoli-ycfp, ecoli-yqia, ecoli-YfhR, shifl-AES, shifl-BIOH, shifl-entf, shifl-FES, shifl-PLDB, shifl-PTRB, shifl-SF1334, shifl-SF1808, shifl-SF3046, shifl-SF3908, shifl-yafa, shifl-YBFF, shifl-YCDJ, shifl-YCJY, shifl-YFBB, shifl-YHET, shifl-YIEL, shifl-YJFP, shifl-YPFH

Abstract

We have sequenced the genome of Shigella flexneri serotype 2a, the most prevalent species and serotype that causes bacillary dysentery or shigellosis in man. The whole genome is composed of a 4 607 203 bp chromosome and a 221 618 bp virulence plasmid, designated pCP301. While the plasmid shows minor divergence from that sequenced in serotype 5a, striking characteristics of the chromosome have been revealed. The S.flexneri chromosome has, astonishingly, 314 IS elements, more than 7-fold over those possessed by its close relatives, the non-pathogenic K12 strain and enterohemorrhagic O157:H7 strain of Escherichia coli. There are 13 translocations and inversions compared with the E.coli sequences, all involve a segment larger than 5 kb, and most are associated with deletions or acquired DNA sequences, of which several are likely to be bacteriophage-transmitted pathogenicity islands. Furthermore, S.flexneri, resembling another human-restricted enteric pathogen, Salmonella typhi, also has hundreds of pseudogenes compared with the E.coli strains. All of these could be subjected to investigations towards novel preventative and treatment strategies against shigellosis.



        

Title: A polyketide synthase is required for fungal virulence and production of the polyketide T-toxin
Yang G, Rose MS, Turgeon BG, Yoder OC
Ref: Plant Cell, 8:2139, 1996 : PubMed
Abstract


ESTHER: Yang_1996_Plant.Cell_8_2139
PubMedSearch: Yang 1996 Plant.Cell 8 2139
PubMedID: 8953776
Gene_locus related to this paper: coch4-tox9

Abstract

Race T of the fungal pathogen Cochliobolus heterostrophus is highly virulent toward Texas male sterile (T) maize and differs from its relative, race O, at a locus (Tox1) that is responsible for the production of T-toxin, a family of linear long-chain (C35 to E41) polyketides. In a previous study, the restriction enzyme-mediated integration procedure was used to mutagenize and tag Tox1. Here, we report that the DNA recovered from the insertion site of one mutant encodes a 7.6-kb open reading frame (2530 amino acids) that identifies a multifunctional polyketide synthase (PKS)-encoding gene (PKS1) with six catalytic domains arranged in the following order, starting at the N terminus: beta-ketoacyl synthase, acyltransferase, dehydratase, enoyl reductase, beta-ketoacyl reductase, and acyl carrier protein. PKS1 is interrupted by four apparent introns (74, 57, 49, and 41 bp) and exists in the genome as a single copy surrounded by highly repetitive, A + T-rich DNA. When PKS1 in race T was inactivated by targeted gene disruption, T-toxin production and high virulence were eliminated, indicating that this PKS is required for fungal virulence. Race O strains, which do not produce T-toxin, lack a detectable homolog of PKS1, suggesting that race T may have acquired PKS1 by horizontal transfer of DNA rather than by vertical inheritance from an ancestral strain.



        

Title: Identification of active site residues essential to 4-chlorobenzoyl- coenzyme A dehalogenase catalysis by chemical modification and site directed mutagenesis
Yang G, Liu RQ, Taylor KL, Xiang H, Price J, Dunaway-Mariano D
Ref: Biochemistry, 35:10879, 1996 : PubMed
Abstract


ESTHER: Yang_1996_Biochemistry_35_10879
PubMedSearch: Yang 1996 Biochemistry 35 10879
PubMedID: 8718880

Abstract

4-Chlorobenzoyl-coenzyme A (4-CBA-CoA) dehalogenase catalyzes the hydrolysis of 4-CBA-CoA to 4-hydroxybenzoyl-coenzyme A (4-HBA-CoA) via a nucleophilic aromatic substitution pathway involving the participation of an active site carboxylate side chain in covalent catalysis. In this paper we report on the identification of conserved aspartate, histidine, and tryptophan residues essential to 4-CBA-CoA catalysis using chemical modification and site-directed mutagenesis techniques. Treatment of the dehalogenase with diethyl pyrocarbonate resulted in complete loss of catalytic activity (Kinact = 0.17 mM-1 min-1 at pH 6.5, 25 degrees C) that was fully regained by subsequent treatment with hydroxylamine. The protection from inactivation afforded by enzyme bound 4-HBA-CoA indicated that the essential histidine residues are located at the active site. Replacement of conserved histidine residues 81, 90, 94, and 208 with glutamine residues resulted in a significant loss of catalytic activity only in the cases of the histidine 81 and 90 mutants. Substrate and product ligand binding studies showed that binding is not significantly inhibited in these mutants. Site directed mutagenesis of a selection of conserved aspartate and glutamate residues, identified aspartate 145 as being essential to dehalogenase catalysis. Ligand binding studies showed that this residue is not required for tight substrate/product binding. Chemical modification of the dehalogenase with N-bromosuccinimide resulted in full loss of catalytic activity that was prevented by saturation of the active site with product ligand, providing evidence favoring an essential active site tryptophan. Phenylalanine replacement of conserved tryptophan residues 179 and 137 reduced catalytic activity only in the latter (Kcat = 0.03% of wild-type dehalogenase). On the basis of these results and the recently determined X-ray crystal structure of the complex of 4-CBA-CoA dehalogenase and 4-HBA-CoA [Benning, M. M., Taylor, K.L., Liu, R.-Q., Yang, G., Xiang, H., Wesenberg, G., Dunaway-Mariano, D., Holden, H.M. (1996) Biochemistry 35,8103-8109] we propose that aspartate 145 functions as the active site nucleophile, that tryptophan 137 serves as a hydrogen bond donor to the aspartate 145 C = O, and that histidine 90 serves to deprotonate the bound H2O molecule.