Author Report for: Zhu HNo contact information in database for Zhu H
Hu R, Niu Z, Lu Y, Zhu H, Mao Z, Yan K, Hu X, Chen H Ref: Appl Biochem Biotechnol, :, 2022 : PubMed ESTHER: Hu_2022_Appl.Biochem.Biotechnol__ PubMedSearch: Hu 2022 Appl.Biochem.Biotechnol PubMedID: 35852759 Abstract In this study, an enhanced activity and stability method for immobilizing porcine pancreatic lipase (PPL) was developed based on ZIF-8 encapsulated supramolecular-modified gold nanoparticle complexes (pSC(4)-AuNPs@ZIF-8). Supramolecular calix[4]arene (pSC(4)) can recognize the amino group of PPL through non-covalent force, and this flexible binding method protected the structure of PPL during the immobilization process. Due to the hydrophilic of pSC(4)-AuNPs and hydrophobic of ZIF-8, PPL can maintain a "lid open" conformation, which can enhance the stability of PPL structure and reduce PPL activity loss. ZIF-8 was used to immobilize PPL to avoid the difficult recovery of free PPL. Compared with the native form of PPL, it exhibited 70.6% maintained activity with terrific pH and temperature stability, and had good performance in thermal stability, time stability, and reusability. In addition, three immobilized PPL methods were designed to further clarify the influence of synthetic methods and additives on the activity and stability of PPL. Importantly, the loading rate of pSC(4)-AuNPs@ZIF-8@PPL was up to 51.2% among these immobilized PPL systems. Therefore, pSC(4)-AuNPs@ZIF-8 may serve as a versatile and promising immobilization system for enzymes. Title: The dark side of synaptic proteins in tumours Li J, Xu Y, Zhu H, Wang Y, Li P, Wang D Ref: Br J Cancer, :, 2022 : PubMed ESTHER: Li_2022_Br.J.Cancer__ PubMedSearch: Li 2022 Br.J.Cancer PubMedID: 35624299 Abstract Research in the past decade has uncovered the essential role of the nervous system in the tumour microenvironment. The recent advances in cancer neuroscience, especially the discovery of neuron-tumour synaptic/perisynaptic structures, have revealed the dark side of synaptic proteins in the progression of brain tumours. Here, we provide an overview of the synaptic proteins expressed by tumour cells and analyse their molecular functions and organisation by comparing them with neuronal synaptic proteins. We focus on the studies of neuroligin-3, the glutamate receptors AMPAR and NMDAR and the synaptic scaffold protein DLGAP1, for their newly discovered regulatory role in the proliferation and progression of tumours. Progress in cancer neuroscience has brought novel insights into the treatment of cancers. In the last part of this review, we discuss the therapeutical strategies targeting synaptic proteins and the current challenges and possible toolkits regarding their clinical application in cancer treatment. Our understanding of cancer neuroscience is still in its infancy; deeper investigation of how tumour cells co-opt synaptic signaling will help fulfil the therapeutical potential of the synaptic proteins as promising anti-tumour targets. Title: Safety, tolerability, and pharmacokinetics of fluoropezil (DC20), a novel AChE inhibitor: a singlecenter, phase I study in healthy young and elderly Chinese subjects Qian H, Yu C, Zhu H, Ding Q, Cai Y, Jing J, Xu X, Guo R, Zhang H and Liu Y <2 more author(s)> Qian H, Yu C, Zhu H, Ding Q, Cai Y, Jing J, Xu X, Guo R, Zhang H, Liu H, Chen X, Liu Y (- 2) Ref: ResearchSquare, :, 2022 : PubMed ESTHER: Qian_2022_ResearchSquare__ PubMedSearch: Qian 2022 ResearchSquare Inhibitor(s) related to this paper: Fluoropezil Abstract https://www.researchsquare.com/article/rs-1744060/latest.pdf Background Acetylcholinesterase (AChE) inhibitors attempt to reduce the breakdown of acetylcholine levels in the brain of patients with Alzheimers disease (AD) by inhibiting the responsible enzyme AChE in the synaptic cleft. This study evaluated the safety, tolerability, and pharmacokinetics of fluoropezil (DC20), a novel AChE inhibitor under development for the treatment of AD in healthy young and elderly Chinese subjects. Methods The study on young subjects were divided into two arms: the multiple ascending-dose (MAD) arm (double-blind, randomized, placebo-controlled, multiple ascending-dose, 2 and 6 mg, N = 24), and the food effect arm (three-period, self-crossover, open-labeled, fasting/standard diet/high-fat diet administration, 4 mg, N = 12). A two-period, self-crossover, open-labeled, single ascending-dose study was designed for elderly subjects (2 and 4 mg, N = 11). Results For young subjects study: In the MAD arm, the accumulation ratios of DC20 in vivo were 2.29 and 2.15, respectively. In the food effect arm, compared with fasting administration, area under the concentrationtime curve from zero to t (AUC0-t) orally after a standard diet and high-fat diet slightly increased by about 19% and 29% and the Tmax were delayed by around 1 hour. For elderly subjects study, Tmax were 1.5 and 1.25 hour, t1/2 were 77.1 and 74.2 hour, respectively. After oral administration of DC20 in healthy young and elderly subjects, no serious adverse events occurred, the most common adverse events associated with the study drug were gastrointestinal reactions. Conclusion We predicted the safety risks of DC20 in the clinical treatment of AD, which were well tolerated by the healthy young and elderly subjects. The elimination of DC20 from the body was slower in elderly subjects than in young subjects. Title: Pisa syndrome in dementia with Lewy bodies: A Chinese multicenter study Su Z, Liu S, Chen G, Gan J, Bao X, Zhu H, Wang X, Wu H, Ji Y Ref: Parkinsonism Relat Disord, 103:50, 2022 : PubMed ESTHER: Su_2022_Parkinsonism.Relat.Disord_103_50 PubMedSearch: Su 2022 Parkinsonism.Relat.Disord 103 50 PubMedID: 36041278 Abstract BACKGROUND: Pisa syndrome (PS) is rarely reported in Dementia with Lewy bodies (DLB). The aim of this article is to investigate the prevalence rate of PS and the correlation with clinical features evaluated in patients with DLB. METHODS: A total of 209 DLB patients were consecutively recruited and underwent standardized clinical evaluation in our multicenter study. The associations between PS and clinical factors were evaluated. RESULTS: The prevalence rate of PS in patients with DLB was 15.3%, which was higher in the moderate and severe stages than mild cognitive impairment and mild stages (81.2% vs. 18.8%). Patients with PS had a longer duration of disease (P = 0.020) and parkinsonism (P = 0.003), higher scores of NPI (P = 0.028), ADL (P = 0.002) and UPDRS part III (P < 0.001), lower scores of clock drawing test (P = 0.009), visuospatial/executive abilities (P = 0.018), attention (P = 0.020), language and praxis (P = 0.020), registration (P = 0.012), greater H&Y stage (P < 0.001), and higher proportion of cholinesterase inhibitors used (P = 0.044) than those without PS. Longer disease duration (OR = 1.166, P = 0.023), presence of parkinsonism (OR = 7.971, P = 0.007), moderate and severe dementia (OR = 3.215, P = 0.021) were associated with the presence of PS. Patients had a longer duration of PS (P = 0.014) and lower mean age of onset (P = 0.040) in the group with severe lateral trunk flexion. CONCLUSION: The development of PS may be associated with longer disease duration, the presence of parkinsonism and severe stages of dementia in DLB. Cholinesterase inhibitors may have a correlation with PS. The severity of lateral flexion is related to the duration of PS and mean age of onset. Title: Distinct AMPK-Mediated FAS/HSL Pathway Is Implicated in the Alleviating Effect of Nuciferine on Obesity and Hepatic Steatosis in HFD-Fed Mice Xu H, Lyu X, Guo X, Yang H, Duan L, Zhu H, Pan H, Gong F, Wang L Ref: Nutrients, 14:, 2022 : PubMed ESTHER: Xu_2022_Nutrients_14_ PubMedSearch: Xu 2022 Nutrients 14 PubMedID: 35565866 Abstract Nuciferine (Nuci), the main aporphine alkaloid component in lotus leaf, was reported to reduce lipid accumulation in vitro. Herein we investigated whether Nuci prevents obesity in high fat diet (HFD)-fed mice and the underlying mechanism in liver/HepG2 hepatocytes and epididymal white adipose tissue (eWAT) /adipocytes. Male C57BL/6J mice were fed with HFD supplemented with Nuci (0.10%) for 12 weeks. We found that Nuci significantly reduced body weight and fat mass, improved glycolipid profiles, and enhanced energy expenditure in HFD-fed mice. Nuci also ameliorated hepatic steatosis and decreased the size of adipocytes. Furthermore, Nuci remarkably promoted the phosphorylation of AMPK, suppressed lipogenesis (SREBP1, FAS, ACC), promoted lipolysis (HSL, ATGL), and increased the expressions of adipokines (FGF21, ZAG) in liver and eWAT. Besides, fatty acid oxidation in liver and thermogenesis in eWAT were also activated by Nuci. Similar results were further observed at cellular level, and these beneficial effects of Nuci in cells were abolished by an effective AMPK inhibitor compound C. In conclusion, Nuci supplementation prevented HFD-induced obesity, attenuated hepatic steatosis, and reduced lipid accumulation in liver/hepatocytes and eWAT/adipocytes through regulating AMPK-mediated FAS/HSL pathway. Our findings provide novel insight into the clinical application of Nuci in treating obesity and related complications. Title: Functional and Transcriptome Analysis of Streptococcus pyogenes Virulence on Loss of Its Secreted Esterase Zhang X, Wang Y, Zhu H, Zhong Z Ref: Int J Mol Sci, 23:7954, 2022 : PubMed ESTHER: Zhang_2022_Int.J.Mol.Sci_23_7954 PubMedSearch: Zhang 2022 Int.J.Mol.Sci 23 7954 PubMedID: 35887300 Abstract Esterases are broadly expressed in bacteria, but much remains unknown about their pathogenic effect. In previous studies, we focused on an esterase secreted by Streptococcus pyogenes (group A Streptococcus, GAS). Streptococcal secreted esterase (Sse) can hydrolyze the sn-2 ester bonds of platelet-activating factor (PAF), converting it to an inactive form that inhibits neutrophil chemotaxis to the infection sites. However, as a virulent protein, Sse probably participates in GAS pathogenesis far beyond chemotaxis inhibition. In this study, we generated the sse gene knockout strain (deltasse) from the parent strain MGAS5005 (hypervirulent M1T1 serotype) and compared the difference in phenotypes. Absence of Sse was related to weakened skin invasion in a murine infection model, and significantly reduced GAS epithelial adherence, invasion, and intracellular survival. Reduced virulence of the deltasse mutant strain was explored through transcriptome analysis, revealing a striking reduction in the abundance of invasive virulence factors including M protein, SIC, ScpA, and SclA. Besides the influence on the virulence, Sse also affected carbohydrate, amino acid, pyrimidine, and purine metabolism pathways. By elucidating Sse-mediated pathogenic process, the study will contribute to the development of new therapeutic agents that target bacterial esterases to control clinical GAS infections. Title: Capsulation of AuNCs with AIE Effect into Metal-Organic Framework for the Marriage of a Fluorescence and Colorimetric Biosensor to Detect Organophosphorus Pesticides Cai Y, Zhu H, Zhou W, Qiu Z, Chen C, Qileng A, Li K, Liu Y Ref: Analytical Chemistry, :, 2021 : PubMed ESTHER: Cai_2021_Anal.Chem__ PubMedSearch: Cai 2021 Anal.Chem PubMedID: 33957044 Abstract Organophosphorus pesticides (OPs) can inhibit the activity of acetylcholinesterase (AChE) to induce neurological diseases. It is significant to exploit a rapid and sensitive strategy to monitor OPs. Here, a metal-organic framework (MOF) acted as a carrier to encapsulate AuNCs, which can limit the molecular motion of AuNCs, trigger the aggregation-induced emission (AIE) effect, and exhibit a strong fluorescence with a fluorescence lifetime and quantum yield of 6.83 micros and 4.63%, respectively. Then, the marriage of fluorescence and colorimetric signals was realized on the basis of the dual function of the enzymolysis product from AChE and choline oxidase (CHO) on AuNCs@ZIF-8. First, it can decompose ZIF-8 to weaken the restraint on AuNCs, and thus the fluorescence receded. Second, it can be used as a substrate for the peroxidase mimics of the released AuNCs to oxidize 3,3',5,5'-tetramethylbenzidine (TMB) and a visible blue appeared. Thus, on the basis of the inhibition of AChE activity by OPs, a fluorescence-colorimetric dual-signal biosensor was established. In addition, colorimetric paper strips were exploited to realize a visual semiquantitative detection, and a smartphone APP was developed to make the visualization results more precise and realize real-time supervision of pesticide contamination. Title: The Impact of ABCB1 and CES1 Polymorphisms on Dabigatran Pharmacokinetics in Healthy Chinese Subjects Liu Y, Yang C, Qi W, Pei Z, Xue W, Zhu H, Dong M, Guo Y, Cong D, Wang F Ref: Pharmgenomics Pers Med, 14:477, 2021 : PubMed ESTHER: Liu_2021_Pharmgenomics.Pers.Med_14_477 PubMedSearch: Liu 2021 Pharmgenomics.Pers.Med 14 477 PubMedID: 33935512 Abstract Dabigatran is a novel direct oral anticoagulant agent, whose plasma concentration is closely related to bleeding risk. Genetic polymorphisms can affect the level of plasma dabigatran. The purpose of this study was to understand the relationship between dabigatran-related genes and the plasma level of dabigatran in healthy Chinese subjects after taking a single oral dose. This study was performed with a single-center, single-dose, randomized, open-label, and four-period crossover trial design under both fasting and fed conditions. A total of 106 eligible healthy subjects were enrolled in the study and 104 were genotyped. One-way analysis of variance (ANOVA) was used to compare pharmacokinetic parameters among different genotypes and linear regression was applied to explore the multiplicative interaction between variables. In this study, we found that the genotype frequencies of CES1 rs2244613 and CES1 rs8192935 were significantly different between Chinese and Caucasians, but the genotype frequencies of ABCB1 rs1045642 and ABCB1 rs4148738 were similar in both populations. CES1 rs8192935 were associated with the peak concentration of dabigatran. There was no significant gender difference in the exposure level of dabigatran. Furthermore, food significantly delayed the absorption of dabigatran but had little effect on C(max) and AUC(0-). Title: Preparation and properties of a dual-function cellulose nanofiber-based bionic biosensor for detecting silver ions and acetylcholinesterase Wang L, Guo W, Zhu H, He H, Wang S Ref: J Hazard Mater, 403:123921, 2021 : PubMed ESTHER: Wang_2021_J.Hazard.Mater_403_123921 PubMedSearch: Wang 2021 J.Hazard.Mater 403 123921 PubMedID: 33264972 Abstract A dual-function cellulose nanofiber (CNF)-based bionic biosensor with good biocompatibility was developed for detecting Ag(+) and acetylcholinesterase (AChE) by grafting deoxyribonucleic acid (DNA) onto CNF. The Ag(+) ions captured by the biosensor acted as recognition sites for the detection of AChE. The CNF-based bionic biosensor (CNF-DNA) could detect Ag(+) concentrations as low as 10(-6) nM in the presence of interference metal ions (Hg(2+), Ba(2+), Cd(2+), Mg(2+), Mn(2+), Pb(2+), and Zn(2+)). DNA-template silver nanoclusters (DNA-AgNCs) were formed on the surface of CNF-DNA during the detection of Ag(+) (CNF-DNA-AgNCs). This new strategy yielded CNF-DNA-AgNCs through the adsorption of Ag(+) ions onto the cytosine base of the single-stranded DNA in CNF-DNA without the use of any additional reducer. Meanwhile, the CNF-DNA-AgNCs exhibited excellent sensitivity and selectivity for trace levels (0.053 mU/mL) of AChE in the presence of interference reagents. The novel strategy proposed in this paper may establish a foundation for further research on DNA-template AgNCs for developing biosensors and biomarkers for in vivo and in vitro detection. Title: Comprehensive Interrogation on Acetylcholinesterase Inhibition by Ionic Liquids Using Machine Learning and Molecular Modeling Yan J, Yan X, Hu S, Zhu H, Yan B Ref: Environ Sci Technol, :, 2021 : PubMed ESTHER: Yan_2021_Environ.Sci.Technol__ PubMedSearch: Yan 2021 Environ.Sci.Technol PubMedID: 34636548 Abstract Quantitative structure-activity relationship (QSAR) modeling can be used to predict the toxicity of ionic liquids (ILs), but most QSAR models have been constructed by arbitrarily selecting one machine learning method and ignored the overall interactions between ILs and biological systems, such as proteins. In order to obtain more reliable and interpretable QSAR models and reveal the related molecular mechanism, we performed a systematic analysis of acetylcholinesterase (AChE) inhibition by 153 ILs using machine learning and molecular modeling. Our results showed that more reliable and stable QSAR models (R(2) > 0.85 for both cross-validation and external validation) were obtained by combining the results from multiple machine learning approaches. In addition, molecular docking results revealed that the cations and organic anions of ILs bound to specific amino acid residues of AChE through noncovalent interactions such as Pi interactions and hydrogen bonds. The calculation results of binding free energy showed that an electrostatic interaction (deltaE(ele) < -285 kJ/mol) was the main driving force for the binding of ILs to AChE. The overall findings from this investigation demonstrate that a systematic approach is much more convincing. Future research in this direction will help design the next generation of biosafe ILs. Title: Thirteen cyathane diterpenoids with acetylcholinesterase inhibitory effects from the fungus Cyathus africanus Yu M, Kang X, Li Q, Liang Y, Zhang M, Gong Y, Chen C, Zhu H, Zhang Y Ref: Phytochemistry, 193:112982, 2021 : PubMed ESTHER: Yu_2021_Phytochemistry_193_112982 PubMedSearch: Yu 2021 Phytochemistry 193 112982 PubMedID: 34700067 Abstract Eight undescribed cyathane diterpenoids, representative specialised metabolites of the genus Cyathus, named cyathins Q-X, along with five known congeners, were isolated from the liquid fermentation of Cyathus africanus. Their structures and absolute configurations were elucidated by integrating NMR spectroscopic analyses, electronic circular dichroism (ECD) calculations, and X-ray diffraction. Reasonable correction to the C-12 configuration of cyathin I was corroborated by the crystal data. The structural identification in this research expanded the number of candidates to allow for more bioactivity-screening options. Among them, (12S)-11alpha,14alpha-epoxy-13alpha,14beta,15-trihydroxycyath-3-ene displayed significant acetylcholinesterase (AChE) inhibitory effect with an IC(50) value of 4.60 +/- 0.85 microM. Molecular docking studies were also performed to unravel the underlying modes of interactions with the active sites of AChE for active compounds. Title: Attenuation of virulence in multiple serotypes (M1, M3, and M28) of Group A Streptococcus after the loss of secreted esterase Zhang X, Zhao Y, Wang Y, Cai M, Song Y, Zhu H Ref: J Microbiol Immunol Infect, :, 2021 : PubMed ESTHER: Zhang_2021_J.Microbiol.Immunol.Infect__ PubMedSearch: Zhang 2021 J.Microbiol.Immunol.Infect PubMedID: 34674958 Abstract INTRODUCTION: Group A Streptococcus (GAS) can produce streptococcal secreted esterase (Sse), which inhibits neutrophil recruitment to the site of infection and is crucial for GAS pathogenesis. As an effective esterase, Sse hydrolyzes the sn-2 ester bond of human platelet-activating factor, inactivating it and abolishing its ability to recruit neutrophils. OBJECTIVES: The purpose of this study was to investigate the effects of sse deletion on the virulence of multiple serotypes of GAS. METHODS: Isogenic strains that lack the sse gene (deltasse) were derived from the parent strains MGAS5005 (serotype M1, CovRS mutant), MGAS2221 (serotype M1, wild-type CovRS), MGAS315 (serotype M3, CovRS mutant) and MGAS6180 (serotype M28, wild-type CovRS) and were used to study the differences in virulence and pathogenicity of GAS serotypes. RESULTS: In a subcutaneous infection model, mice infected with MGAS5005(deltasse) exhibited higher survival rates but decreased dissemination to the organs compared with mice infected with MGAS5005. When mice were infected with the four deltasse mutants, the MPO activity and IFN-gamma, TNF-alpha, IL-2 and IL-6 levels increased, but the skin lesion sizes decreased. In an intraperitoneal infection model, the absence of Sse significantly reduced the virulence of GAS, leading to increased mouse survival rates and decreased GAS burdens in the organs in most of the challenge experiments. In addition, the numbers of the four deltasse mutants were greatly reduced 60 min after incubation with isolated rat neutrophils. CONCLUSION: Our results suggest that Sse participates in the pathogenesis of multiple GAS serotypes (MGAS5005, MGAS2221, MGAS315 and MGAS6180), particularly the hypervirulent CovS mutant strains MGAS5005 and MGAS315. These strain differences were positively correlated with the virulence of the serotype. Title: Efficiency of donepezil in elderly patients undergoing orthopaedic surgery due to underlying post-operative cognitive dysfunction: study protocol for a multicentre randomised controlled trial Zhu H, Cong L, Chen Y, Chen S, Chen L, Huang Z, Zhou J, Xiao J, Huang Y, Su D Ref: Trials, 22:688, 2021 : PubMed ESTHER: Zhu_2021_Trials_22_688 PubMedSearch: Zhu 2021 Trials 22 688 PubMedID: 34627332 Abstract BACKGROUND: Post-operative cognitive dysfunction (POCD) is an overarching term used to describe cognitive impairment identified in the preoperative or post-operative period. After surgical operations, older patients are particularly vulnerable to memory disturbances and other types of cognitive impairment. However, the pathogenesis of POCD remains unclear with no confirmed preventable or treatable strategy available. Our previous study demonstrated that the concentration of choline acetyl transferase in the cerebral spinal fluid was a predictive factor of POCD and that donepezil, which is an acetylcholinesterase inhibitor used in clinical settings for the treatment of Alzheimer's disease, can prevent learning and memory impairment after anaesthesia/surgery in aged mice. This study aimed to determine the critical role of donepezil in preventing cognitive impairment in elderly patients undergoing orthopaedic surgery. METHODS: A multicentre, double-blind, placebo-controlled, crossover clinical trial will be performed to assess the efficacy of donepezil in elderly patients undergoing orthopaedic surgery. Participants (n = 360) will receive donepezil (5 mg once daily) or placebo from 1 day prior to surgery until 5 days after surgery. Neuropsychological tests will be measured at 1 day before the operation and 1 week, 1 month, 6 months and 1 year after the operation. DISCUSSION: This research project mainly aimed to study the effects of donepezil in elderly patients undergoing orthopaedic surgery due to underlying POCD and to investigate the underlying physiological and neurobiological mechanisms of these effects. The results may provide important implications for the development of effective interfering strategies, specifically regarding cognitive dysfunction therapy using drugs. TRIAL REGISTRATION: ClinicalTrials.gov NCT04423276 . Registered on 14 June 2020. Title: Nanozyme-Participated Biosensing of Pesticides and Cholinesterases: A Critical Review Zhu H, Liu P, Xu L, Li X, Hu P, Liu B, Pan J, Yang F, Niu X Ref: Biosensors (Basel), 11:, 2021 : PubMed ESTHER: Zhu_2021_Biosensors.(Basel)_11_ PubMedSearch: Zhu 2021 Biosensors.(Basel) 11 PubMedID: 34677338 Abstract To improve the output and quality of agricultural products, pesticides are globally utilized as an efficient tool to protect crops from insects. However, given that most pesticides used are difficult to decompose, they inevitably remain in agricultural products and are further enriched into food chains and ecosystems, posing great threats to human health and the environment. Thus, developing efficient methods and tools to monitor pesticide residues and related biomarkers (acetylcholinesterase and butylcholinesterase) became quite significant. With the advantages of excellent stability, tailorable catalytic performance, low cost, and easy mass production, nanomaterials with enzyme-like properties (nanozymes) are extensively utilized in fields ranging from biomedicine to environmental remediation. Especially, with the catalytic nature to offer amplified signals for highly sensitive detection, nanozymes were finding potential applications in the sensing of various analytes, including pesticides and their biomarkers. To highlight the progress in this field, here the sensing principles of pesticides and cholinesterases based on nanozyme catalysis are definitively summarized, and emerging detection methods and technologies with the participation of nanozymes are critically discussed. Importantly, typical examples are introduced to reveal the promising use of nanozymes. Also, some challenges in the field and future trends are proposed, with the hope of inspiring more efforts to advance nanozyme-involved sensors for pesticides and cholinesterases. Title: Characterization of EstZY: A new acetylesterase with 7-aminocephalosporanic acid deacetylase activity from Alicyclobacillus tengchongensis Ding J, Zhou Y, Zhu H, Deng M, Gao Y, Yang Y, Huang Z Ref: Int J Biol Macromol, 148:333, 2020 : PubMed ESTHER: Ding_2020_Int.J.Biol.Macromol_148_333 PubMedSearch: Ding 2020 Int.J.Biol.Macromol 148 333 PubMedID: 31954783 Gene_locus related to this paper: 9bacl-a0a6g6c491 Abstract Deacetyl-7-aminocephalosporanic acid (D-7-ACA) is required for producing of many semisynthetic beta-lactam antibiotics; therefore, enzymes capable of converting 7-aminocephalosporanic acid (7-ACA) to D-7-ACA present a valuable resource to the pharmaceutical industry. In the present study, a putative acetylesterase, EstZY, was identified and characterized from a thermophilic bacterium Alicyclobacillus tengchongensis. Sequence alignment showed that EstZY was an acetylesterase which belonged to carbohydrate esterase family 7 (CE7), with substrate preference for short-chain acyl esters p-NPC(2) to p-NPC(8). Maximum enzyme activity was recorded at pH 9.0 and 50 degreesC, where K(m) and V(max) were calculated as 1.9 +/- 0.23 mM and 258 +/- 18.5 microM min(-)(1), respectively. The residues Ser185, Asp274, and His303 were identified as the putative catalytic triad by homology modelling, site-directed mutagenesis and molecular docking. Moreover, EstZY can remove the acetyl group at C3' position of 7-ACA to form D-7-ACA; this is the first report of a 7-ACA deacetylase from CE7 family in A. tengchongensis and may represent a new enzyme with industrial values. Title: Investigation of the transformation and toxicity of trichlorfon at the molecular level during enzymic hydrolysis of apple juice Li C, Zhu H, Guo Y, Xie Y, Cheng Y, Yu H, Qian H, Yao W Ref: Food Chem, :128653, 2020 : PubMed ESTHER: Li_2020_Food.Chem__128653 PubMedSearch: Li 2020 Food.Chem 128653 PubMedID: 33229164 Abstract Trichlorfon is one of the most widely used organophosphorus pesticides in agriculture. In this study, the extent of transformation of trichlorfon to dichlorvos (DDVP), during the polygalacturonase (PG) treatment of apple pulp was monitored. A transformation pathway is proposed for trichlorfon molecules, based on density functional theory (DFT) calculations. The transformation of trichlorfon involves hydroxyl substitution and cleavage, which was confirmed by molecular electrostatic potential (MEP) and frontier molecular orbital (FMO) theory. In addition, the toxicity of trichlorfon and its transformed products was analyzed using Ecological Structure Activity Relationships (ECOSAR) software. The binding sites of the two pesticides are located in the hydrophobic grooves of the acetylcholinesterase (AChE) active site region and both pesticides form hydrophobic interactions and hydrogen bonds with a large number of surrounding amino acid residues. DDVP binds more strongly with AChE, so it is a better AChE inhibitor and more toxic than trichlorfon. Title: Identification and characterization of an acetyl esterase from Paenibacillus sp. XW-6-66 and its novel function in 7-aminocephalosporanic acid deacetylation Ding J, Zhou Y, Zhu H, Deng M, Long L, Yang Y, Wu Q, Huang Z Ref: Biotechnol Lett, 41:1059, 2019 : PubMed ESTHER: Ding_2019_Biotechnol.Lett_41_1059 PubMedSearch: Ding 2019 Biotechnol.Lett 41 1059 PubMedID: 31302814 Gene_locus related to this paper: 9bacl-7ACAaes Abstract OBJECTIVES: To obtain a new acetyl esterase from Paenibacillus sp. XW-6-66 and apply the enzyme to 7-aminocephalosporanic acid (7-ACA) deacetylation. RESULTS: The acetyl esterase AesZY was identified from Paenibacillus sp. XW-6-66, and its enzymatic properties were investigated. With the putative catalytic triad Ser114-Asp203-His235, AesZY belongs to the Acetyl esterase (Aes) family which is included in the alpha/beta hydrolase superfamily and contains the consensus Gly-X-Ser-X-Gly motif. The maximum activity of AesZY was detected at pH 8.0 and 40 degrees C. AesZY was stable at different pH values ranging from 5.0 to 12.0, and was tolerant to several metal ions. Furthermore, the deacetylation activity of AesZY toward 7-ACA was approximately 7.5 U/mg, and the Kcat/Km value was 2.04 s(-1) mM(-1). CONCLUSIONS: Our results demonstrate the characterization of a new acetyl esterase belonging to the Aes family with potential biotechnological applications. Title: Effects of Picrasma quassioides and its active constituents on Alzheimer's disease in vitro and in vivo Guo E, Hu Y, Du T, Zhu H, Chen L, Qu W, Zhang J, Xie N, Liu W and Xu J <1 more author(s)> Guo E, Hu Y, Du T, Zhu H, Chen L, Qu W, Zhang J, Xie N, Liu W, Feng F, Xu J (- 1) Ref: Bioorg Chem, 92:103258, 2019 : PubMed ESTHER: Guo_2019_Bioorg.Chem_92_103258 PubMedSearch: Guo 2019 Bioorg.Chem 92 103258 PubMedID: 31520892 Abstract Alzheimer disease (AD), a prevalent neurodegenerative disorder, is one of the leading causes of dementia. However, there is no effective drug for this disease to date. Picrasma quassioides (D.Don) Benn, a Chinese traditional medicine, was used mainly for the treatment of inflammation, fever, microbial infection and dysentery. In this paper, we reported that the EtOAc extract of Picrasma quassioides stems showed potential neuroprotective activities in l-glutamate-stimulated PC12 and Abeta25-35-stimulated SH-SY5Y cell models, as well as improved memory and cognitive abilities in AD mice induced by amyloid-beta peptide. Moreover, it was revealed that the anti-AD mechanism was related to suppressing neuroinflammatory and reducing Abeta1-42 deposition using ELISA assay kits. To clarify the active components of the EtOAc extract of Picrasma quassioides stems, a systematic phytochemistry study led to isolate and identify six beta-carboline alkaloids (1-6), seven canthin-6-one alkaloids (7-13), and five quassinoids (14-18). Among them, four beta-carbolines (1-3, and 6) and six canthin-6-ones (7-11, and 13) exhibited potential neuroprotective activities in vitro. Based on these date, the structure-activity relationships of alkaloids were discussed. Furthermore, molecular docking experiments showed that compounds 2 and 3 have high affinity for both of dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYPKIA) and butyrylcholinesterase (BuChE). Title: Catalpol prevents denervated muscular atrophy related to the inhibition of autophagy and reduces BAX/BCL2 ratio via mTOR pathway Wang Y, Shao Y, Gao Y, Wan G, Wan D, Zhu H, Qiu Y, Ye X Ref: Drug Des Devel Ther, 13:243, 2019 : PubMed ESTHER: Wang_2019_Drug.Des.Devel.Ther_13_243 PubMedSearch: Wang 2019 Drug.Des.Devel.Ther 13 243 PubMedID: 30643390 Abstract Aim: To investigate the effects of catalpol on muscular atrophy induced by sciatic nerve crush injury (SNCI). Methods: Seventy male Kunming mice were randomized into five groups (n=10): model, sham, catalpol (Cat), rapamycin (Rapa), and catalpol+rapamycin (Rapa+Cat). The ratio of gastrocnemius muscle wet weight (right/left, R/L) between the operated leg (right) and the normal leg (left) was calculated, and acetylcholinesterase (AChE) immunohistochemistry assays were performed to observe the change of motor end plate (MEP), along with the sizes of denervated and innervated muscle fibers. The expression levels of LC3II, TUNEL, BAX/BCL-2, LC3II/LC3I and P62, Beclin1, mTOR, and p-mTOR (ser2448) proteins in muscle were examined by fluorescence immunohistochemistry or Western blotting. Results: Results show that catalpol improved the results of the grid walking tests by reducing the percentage of foot slips, which increased the gastrocnemius muscle wet weight (R/L), enhanced AChE expression at the MEP, and enlarged the section area of the muscle. The expression of LC3II and TUNEL was significantly inhibited by catalpol. The BAX/BCL-2 ratio was significantly increased in muscles of denervated and control groups. Lower LC3II/LC3I and BAX/BCL-2 ratios in denervated muscles were also detected after catalpol treatment. Conclusion: These results indicated that apoptosis and autophagy play a role in the regulation of denervation-induced muscle atrophy after SNCI, and catalpol alleviates muscle atrophy through the regulation of muscle apoptosis and autophagy via the mTOR signaling pathway. Title: Galantamine reversed early postoperative cognitive deficit via alleviating inflammation and enhancing synaptic transmission in mouse hippocampus Wang T, Zhu H, Hou Y, Gu W, Wu H, Luan Y, Xiao C, Zhou C Ref: European Journal of Pharmacology, 846:63, 2019 : PubMed ESTHER: Wang_2019_Eur.J.Pharmacol_846_63 PubMedSearch: Wang 2019 Eur.J.Pharmacol 846 63 PubMedID: 30586550 Abstract Postoperative cognitive dysfunction (POCD) is commonly seen in patients undergoing major surgeries and may persist. Although neuroinflammation is one of the important contributors to the development of POCD, the mechanisms underlying POCD remain unclear. We performed stabilized tibial fracture operation in male mice. In comparison with sham mice (anesthesia only), the surgery mice exhibited cognitive deficits in a fear conditioning paradigm at postsurgery day 3-7, and increased numbers of microglia and elevated levels of pro-inflammatory cytokines (IL-1beta, IL-6 and TNF-alpha) without change of anti-inflammatory cytokines (IL-4 and IL-10) in the hippocampus. Electrophysiological recordings from CA1 hippocampal neurons revealed that POCD mice exhibited impairment in AMPA receptor-mediated evoked excitatory postsynaptic currents (eEPSCs) without alteration in the rectification property of AMPA receptors. Interestingly, daily intraperitoneal administration of galantamine, an inhibitor of acetylcholinesterase, reversed cognitive dysfunction in surgery mice and attenuated accumulation of microglia and protein levels of IL-1beta, IL-6 and TNF-alpha in the hippocampus. Additionally, galantamine potentiated AMPA receptor-mediated eEPSCs in the hippocampus more prominent in surgery mice than in sham mice. Therefore, enhancement of cholinergic tone in the hippocampus might be a therapeutic strategy for early POCD in terms of suppression of inflammation and normalization of excitatory synaptic transmission. Title: Efficacy and outcomes of lipid resuscitation on organophosphate poisoning patients: A systematic review and meta-analysis Yu S, Zhang L, Gao Y, Walline J, Lu X, Ma Y, Zhu H, Yu X, Li Y Ref: Am J Emerg Med, 37:1611, 2019 : PubMed ESTHER: Yu_2019_Am.J.Emerg.Med_37_1611 PubMedSearch: Yu 2019 Am.J.Emerg.Med 37 1611 PubMedID: 30527914 Abstract OBJECTIVE: Organophosphate (OP) pesticides are still widely available in developing countries, leading to numerous accidental or suicidal poisonings every year. Lipid emulsion treatments are commonly used in resuscitating OP poisoning patients but few studies regarding their use have been reported. Our meta-analysis aimed to analyze the efficacy and outcomes of lipid resuscitation on OP poisoning patients. METHODS: A systematic search for associated studies was conducted in Pubmed, EMBASE, MEDLINE, the Cochrane Library and the Chinese National Knowledge Infrastructure. Collected data was pooled using Revman v5.3. Outcomes included prognosis (cured vs. mortality rates), hepatic function (serum ALT, AST, Total Bilirubin (TBIL) level), serum acetylcholinesterase (AchE) level and respiratory function (rate of respiratory muscular paralysis). RESULTS: Seven randomized controlled studies consisting of 630 patients meeting inclusion criteria were identified. Lipid emulsion helped to improve the cure rate [OR=2.54, 95% CI (1.33, 4.86), p=0.005] and lower the mortality rate [OR=0.31, 95% CI (0.13, 0.74), p=0.009]. Serum ALT, AST and TBIL in patients undergoing lipid resuscitation were lower than those in the control groups [ALT, SMD=-1.52, 95% CI (-2.64, 0.40), p=0.008; AST, SMD=-1.66, 95% CI (-3.15, 0.16), p=0.03; TBIL, SMD=-1.26, 95% CI (-2.32, 0.20), p=0.02]. Serum AchE level were increased in patients treated with lipid emulsion [SMD=2.15, 95% CI (1.60, 2.71), p<0.00001]. Rate of respiratory muscular paralysis was lower in patients undergoing lipid resuscitation than those in the control groups [OR=0.19, 95% CI (0.05, 0.71), p=0.01]. CONCLUSION: Based on our meta-analysis of included RCT reports, lipid resuscitation seems likely to help improve prognosis and liver function of OP poisoning patients. However, larger multi-center RCTs are still recommended. Title: Surrogating and redirection of pyrazolo[1,5-a]pyrimidin-7(4H)-one core, a novel class of potent and selective DPP-4 inhibitors Deng X, Shen J, Zhu H, Xiao J, Sun R, Xie F, Lam C, Wang J, Qiao Y and Jiang F <5 more author(s)> Deng X, Shen J, Zhu H, Xiao J, Sun R, Xie F, Lam C, Wang J, Qiao Y, Tavallaie MS, Hu Y, Du Y, Li J, Fu L, Jiang F (- 5) Ref: Bioorganic & Medicinal Chemistry, 26:903, 2018 : PubMed ESTHER: Deng_2018_Bioorg.Med.Chem_26_903 PubMedSearch: Deng 2018 Bioorg.Med.Chem 26 903 PubMedID: 29373269 Abstract The initial focus on characterizing novel pyrazolo[1,5-a]pyrimidin-7(4H)-one derivatives as DPP-4 inhibitors, led to a potent and selective inhibitor compound b2. This ligand exhibits potent in vitro DPP-4 inhibitory activity (IC(50): 80 nM), while maintaining other key cellular parameters such as high selectivity, low cytotoxicity and good cell viability. Subsequent optimization of b2 based on docking analysis and structure-based drug design knowledge resulted in d1. Compound d1 has nearly 2-fold increase of inhibitory activity (IC(50): 49 nM) and over 1000-fold selectivity against DPP-8 and DPP-9. Further in vivo IPGTT assays showed that compound b2 effectively reduce glucose excursion by 34% at the dose of 10 mg/kg in diabetic mice. Herein we report the optimization and design of a potent and highly selective series of pyrazolo[1,5-a]pyrimidin-7(4H)-one DPP-4 inhibitors. Title: Bioactive polycyclic polyprenylated acylphloroglucinols from Hypericum perforatum Guo Y, Zhang N, Sun W, Duan X, Zhang Q, Zhou Q, Chen C, Zhu H, Luo Z and Zhang Y <3 more author(s)> Guo Y, Zhang N, Sun W, Duan X, Zhang Q, Zhou Q, Chen C, Zhu H, Luo Z, Liu J, Li XN, Xue Y, Zhang Y (- 3) Ref: Org Biomol Chem, 16:8130, 2018 : PubMed ESTHER: Guo_2018_Org.Biomol.Chem_16_8130 PubMedSearch: Guo 2018 Org.Biomol.Chem 16 8130 PubMedID: 30334059 Abstract Fifteen new polycyclic polyprenylated acylphloroglucinols (PPAPs), hyperforatones A-O (1-15), along with 3 structurally related analogues (16-18), were isolated from the stems and leaves of Hypericum perforatum. Their structures and absolute configurations were established by a combination of NMR spectroscopic analyses, experimental and calculated electronic circular dichroism (ECD), modified Mosher's methods, Rh2(OCOCF3)4- and [Mo2(OAc)4]-induced ECD, X-ray crystallography, and the assistance of quantum chemical predictions (QCP) of 13C NMR chemical shifts. Compound 5 was found to be the first PPAP decorated by a rare 2,2,4,4,5-(pentamethyltetrahydrofuran-3-yl)methanol moiety and an oxepane ring. Furthermore, the isolates were screened for their acetylcholinesterase (AChE) and beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) inhibitory activities. Compounds 5, 10, 11, and 15 showed desirable AChE inhibitory activities (IC50 6.9-9.2 muM) and simultaneously inhibited BACE1 (at a concentration of 5 muM) with inhibition rates of 50.3%, 34.3%, 47.2%, and 34.6%, respectively. Interestingly, compound 5 showed the most balanced inhibitory activities against both AChE and BACE1 of all the tested compounds, which means that 5 could serve as the first valuable dual-targeted PPAP for the treatment of Alzheimer's disease. Preliminary molecular docking studies of 5 with BACE1 and AChE were also performed. Title: Asperversins A and B, Two Novel Meroterpenoids with an Unusual 5/6/6/6 Ring from the Marine-Derived Fungus Aspergillus versicolor Li H, Sun W, Deng M, Qi C, Chen C, Zhu H, Luo Z, Wang J, Xue Y, Zhang Y Ref: Mar Drugs, 16:, 2018 : PubMed ESTHER: Li_2018_Mar.Drugs_16_ PubMedSearch: Li 2018 Mar.Drugs 16 PubMedID: 29882867 Abstract Asperversins A (1) and B (2), two novel meroterpenoids featuring an uncommon 5/6/6/6 ring system, along with five new analogues (3(-)7) and a known compound asperdemin (8), were obtained from the marine-derived fungus Aspergillus versicolor. Their structures and absolute configurations were confirmed by extensive spectroscopic analyses, single-crystal X-ray diffraction studies, and electronic circular dichroism (ECD) calculation. All new compounds were tested for their acetylcholinesterase enzyme (AChE) inhibitory activities and cytotoxic activities, of which compound 7 displayed moderate inhibitory activity against the AChE with an IC50 value of 13.6 μM. Title: New 3,5-dimethylorsellinic acid-based meroterpenoids with BACE1 and AchE inhibitory activities from Aspergillus terreus Qi C, Qiao Y, Gao W, Liu M, Zhou Q, Chen C, Lai Y, Xue Y, Zhang J and Zhang Y <5 more author(s)> Qi C, Qiao Y, Gao W, Liu M, Zhou Q, Chen C, Lai Y, Xue Y, Zhang J, Li D, Wang J, Zhu H, Hu Z, Zhou Y, Zhang Y (- 5) Ref: Org Biomol Chem, 16:9046, 2018 : PubMed ESTHER: Qi_2018_Org.Biomol.Chem_16_9046 PubMedSearch: Qi 2018 Org.Biomol.Chem 16 9046 PubMedID: 30430177 Abstract Chemical investigation of the extracts of Aspergillus terreus resulted in the identification of terreusterpenes A-D (1-4), four new 3,5-dimethylorsellinic acid-based meroterpenoids. The structures and absolute configurations of 1-4 were elucidated by spectroscopic analyses including HRESIMS and 1D- and 2D-NMR, chemical conversion, and single crystal X-ray diffraction. Terreusterpenes A (1) and B (2) featured 2,3,5-trimethyl-4-oxo-5-carboxy tetrahydrofuran moieties. Terreusterpene D (4) was characterized by a 4-hydroxy-3-methyl gamma lactone fragment that was generated by accident from the rearrangement of 3 in a mixed tetrahydrofuran-H2O-MeOH solvent. All these compounds were evaluated for the beta-site amyloid precursor protein-cleaving enzyme 1 (BACE1) and acetylcholinesterase (AchE) inhibitory activities. Among them, compounds 1 and 2 showed potentially significant BACE1 inhibitory activity, with IC50 values of 5.98 and 11.42 muM, respectively. Interestingly, compound 4 exhibited promising BACE1 and AchE inhibitory activities, with IC50 values of 1.91 and 8.86 muM, respectively, while 3 showed no such activity. Taken together, terreusterpenes A and B could be of great importance for the development of new BACE1 inhibitors, while terreusterpene D could serve as the first dual-targeted 3,5-dimethylorsellinic acid-based meroterpenoid for the treatment of Alzheimer's disease. Title: Sequence analysis and structure prediction of ABHD16A and the roles of the ABHD family members in human disease Xu J, Gu W, Ji K, Xu Z, Zhu H, Zheng W Ref: Open Biol, 8:, 2018 : PubMed ESTHER: Xu_2018_Open.Biol_8_ PubMedSearch: Xu 2018 Open.Biol 8 PubMedID: 29794032 Gene_locus related to this paper: human-ABHD16A, human-ABHD16B Abstract Abhydrolase domain containing 16A (ABHD16A) is a member of the alpha/beta hydrolase domain-containing (ABHD) protein family and is expressed in a variety of animal cells. Studies have shown that ABHD16A has acylglycerol lipase and phosphatidylserine lipase activities. Its gene location in the main histocompatibility complex (MHC) III gene cluster suggests that this protein may participate in the immunomodulation of the body. The results of studies investigating nearly 20 species of ABHDs reveal that the ABHD proteins are key factors in metabolic regulation and disease occurrence and development. In this paper, we summarize the related progress regarding the function of ABHD16A and other ABHD proteins. A prediction of the active sites and structural domains of ABHD16A and an analysis of the amino acid sites are included. Moreover, we analysed the amino acid sequences of the ABHD16A molecules in different species and provide an overview of the related functions and diseases associated with these proteins. The functions and diseases related to ABHD are systematically summarized and highlighted. Future research directions for studies investigating the functions and mechanisms of these proteins are also suggested. Further studies investigating the function of ABHD proteins may further confirm their positions as important determinants of lipid metabolism and related diseases. Title: Tricyclic Polyprenylated Acylphloroglucinols from St John's Wort, Hypericum perforatum Guo Y, Zhang N, Chen C, Huang J, Li XN, Liu J, Zhu H, Tong Q, Zhang J and Zhang Y <2 more author(s)> Guo Y, Zhang N, Chen C, Huang J, Li XN, Liu J, Zhu H, Tong Q, Zhang J, Luo Z, Xue Y, Zhang Y (- 2) Ref: Journal of Natural Products, 80:1493, 2017 : PubMed ESTHER: Guo_2017_J.Nat.Prod_80_1493 PubMedSearch: Guo 2017 J.Nat.Prod 80 1493 PubMedID: 28445039 Abstract The new polyprenylated acylphloroglucinol derivatives 1-15 and the known furohyperforin (16) were isolated from the stems and leaves of Hypericum perforatum. Their structures were determined by analyses of NMR and HRESIMS data. Their absolute configurations were elucidated by a combination of electronic circular dichroism (ECD) and Rh2(OCOCF3)4-induced ECD, as well as X-ray diffraction crystallography. The new hyperforatin F (9) contains a unique acetyl functionality at C-1 of the bicyclo[3.3.1]nonane core. Hyperforatins G (10) and H (11) are similarly the first examples of naturally occurring [3.3.1]-type polycyclic prenylated acylphloroglucinols possessing a carbonyl functionality at C-32. The compounds were tested for their acetylcholinesterase (AChE) inhibitory activities and cytotoxic activities against a panel of human tumor cell lines. Compounds 3, 5, 6, 8, and 9 exerted moderate inhibitory activities (IC50 3.98-9.13 muM) against AChE. Title: Identification of lysophospholipase protein from Spiroplasma eriocheiris and verification of its function Zhu H, Liu P, Du J, Wang J, Jing Y, Zhang J, Gu W, Wang W, Meng Q Ref: Microbiology, 163:175, 2017 : PubMed ESTHER: Zhu_2017_Microbiology_163_175 PubMedSearch: Zhu 2017 Microbiology 163 175 PubMedID: 27926815 Gene_locus related to this paper: 9molu-a0a0h3xm88 Abstract Spiroplasma eriocheiris is known to cause tremor disease in the Chinese mitten crab Eriocheir sinensis; however, the molecular characterization of this pathogen is still unclear. S. eriocheiris has the ability to invade and survive within mouse 3T6 cells. The invasion process may require causing damage to the host cell membrane by chemical, physical or enzymatic means. In this study, we systematically characterized a novel lysophospholipase (lysoPL) of S. eriocheiris TDA-040725-5T. The gene that encodes lysoPL in S. eriocheiris (SE-LysoPL) was cloned, sequenced and expressed in Escherichia coli BL21 (DE3). Enzymatic assays revealed that the purified recombinant SE-LysoPL hydrolysed long-chain acyl esterases at pH 7 and 30 degrees C. SE-LysoPL was detected in the membrane and cytoplasmic protein fractions using the SE-LysoPL antibody in Western blot. The virulence ability of S. eriocheiris was effectively reduced at the early stage of infection (m.o.i.=100) by the SE-LysoPL antibody neutralization test. To the best of our knowledge, this is the first study to identify and characterize a gene from S. eriocheiris encoding a protein exhibiting lysoPL and esterase activities. Our findings indicate that SE-LysoPL plays important roles in the pathogenicity of S. eriocheiris. Title: Clinical Outcomes of Thymectomy in Myasthenia Gravis Patients with a History of Crisis Liu Z, Lai Y, Yao S, Feng H, Zou J, Liu W, Lei Y, Zhu H, Cheng C Ref: World J Surg, 40:2681, 2016 : PubMed ESTHER: Liu_2016_World.J.Surg_40_2681 PubMedSearch: Liu 2016 World.J.Surg 40 2681 PubMedID: 27312319 Abstract BACKGROUND: The use of thymectomy in myasthenia gravis (MG) patients with a history of myasthenic crisis (MC) has not been well established. Here, we determined the efficacy of thymectomy by assessing the long-term clinical outcomes and reviewed thymectomy reports on MC patients. Title: Deciphering the venomic transcriptome of killer-wasp Vespa velutina Liu Z, Chen S, Zhou Y, Xie C, Zhu B, Zhu H, Liu S, Wang W, Chen H, Ji Y Ref: Sci Rep, 5:9454, 2015 : PubMed ESTHER: Liu_2015_Sci.Rep_5_9454 PubMedSearch: Liu 2015 Sci.Rep 5 9454 PubMedID: 25896434 Gene_locus related to this paper: vesve-pa1 Abstract Wasp stings have been arising to be a severe public health problem in China in recent years. However, molecular information about lethal or toxic factors in wasp venom is extremely lacking. In this study, we used two pyrosequencing platforms to analyze the transcriptome of Vespa velutina, the most common wasp species native in China. Besides the substantial amount of transcripts encoding for allergens usually regarded as the major lethal factor of wasp sting, a greater abundance of hemostasis-impairing toxins and neurotoxins in the venom of V. velutina were identified, implying that toxic reactions and allergic effects are envenoming strategy for the dangerous outcomes. The pattern of differentially expressed genes before and after venom extraction clearly indicates that the manifestation of V. velutina stings depends on subtle regulations in the metabolic pathway required for toxin recruitment. This comparative analysis offers timely clues for developing clinical treatments for wasp envenoming in China and around the world. Title: Whole Genome Sequence of the Probiotic Strain Lactobacillus paracasei N1115, Isolated from Traditional Chinese Fermented Milk Wang S, Zhu H, He F, Luo Y, Kang Z, Lu C, Feng L, Lu X, Xue Y, Wang H Ref: Genome Announc, 2:, 2014 : PubMed ESTHER: Wang_2014_Genome.Announc_2_e00059 PubMedSearch: Wang 2014 Genome.Announc 2 e00059 PubMedID: 24625864 Gene_locus related to this paper: lacc3-q03b36, lacrh-pepr, lacca-b5qt93, lacca-k0n1x0, lacpa-s2ter8, lacpa-s2rz88 Abstract Lactobacillus paracasei N1115 is a new strain with probiotic properties isolated from traditional homemade dairy products in Inner Mongolia, China. Here, we report the complete genome sequence of L. paracasei N1115, which shows high similarity to the well-studied probiotic Lactobacillus rhamnosus GG, and 3 structures turned out to be inversions, according to the colinearity analysis of the BLAST alignment. Title: Intestinal Cgi-58 deficiency reduces postprandial lipid absorption Xie P, Guo F, Ma Y, Zhu H, Wang F, Xue B, Shi H, Yang J, Yu L Ref: PLoS ONE, 9:e91652, 2014 : PubMed ESTHER: Xie_2014_PLoS.One_9_e91652 PubMedSearch: Xie 2014 PLoS.One 9 e91652 PubMedID: 24618586 Abstract Comparative Gene Identification-58 (CGI-58), a lipid droplet (LD)-associated protein, promotes intracellular triglyceride (TG) hydrolysis in vitro. Mutations in human CGI-58 cause TG accumulation in numerous tissues including intestine. Enterocytes are thought not to store TG-rich LDs, but a fatty meal does induce temporary cytosolic accumulation of LDs. Accumulated LDs are eventually cleared out, implying existence of TG hydrolytic machinery in enterocytes. However, identities of proteins responsible for LD-TG hydrolysis remain unknown. Here we report that intestine-specific inactivation of CGI-58 in mice significantly reduces postprandial plasma TG concentrations and intestinal TG hydrolase activity, which is associated with a 4-fold increase in intestinal TG content and large cytosolic LD accumulation in absorptive enterocytes during the fasting state. Intestine-specific CGI-58 knockout mice also display mild yet significant decreases in intestinal fatty acid absorption and oxidation. Surprisingly, inactivation of CGI-58 in intestine significantly raises plasma and intestinal cholesterol, and reduces hepatic cholesterol, without altering intestinal cholesterol absorption and fecal neutral sterol excretion. In conclusion, intestinal CGI-58 is required for efficient postprandial lipoprotein-TG secretion and for maintaining hepatic and plasma lipid homeostasis. Our animal model will serve as a valuable tool to further define how intestinal fat metabolism influences the pathogenesis of metabolic disorders, such as obesity and type 2 diabetes. Title: Eliciting antibiotics active against the ESKAPE pathogens in a collection of actinomycetes isolated from mountain soils Zhu H, Swierstra J, Wu C, Girard G, Choi YH, van Wamel W, Sandiford SK, van Wezel GP Ref: Microbiology, 160:1714, 2014 : PubMed ESTHER: Zhu_2014_Microbiology_160_1714 PubMedSearch: Zhu 2014 Microbiology 160 1714 PubMedID: 24794971 Gene_locus related to this paper: 9actn-a0a2s6pnd1 Abstract The rapid emergence of multidrug-resistant (MDR) bacterial pathogens poses a major threat for human health. In recent years, genome sequencing has unveiled many poorly expressed antibiotic clusters in actinomycetes. Here, we report a well-defined ecological collection of >800 actinomycetes obtained from sites in the Himalaya and Qinling mountains, and we used these in a concept study to see how efficiently antibiotics can be elicited against MDR pathogens isolated recently from the clinic. Using 40 different growth conditions, 96 actinomycetes were identified - predominantly Streptomyces - that produced antibiotics with efficacy against the MDR clinical isolates referred to as ESKAPE pathogens: Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and/or Enterobacter cloacae. Antimicrobial activities that fluctuated strongly with growth conditions were correlated with specific compounds, including borrelidin, resistomycin, carbomethoxy-phenazine, and 6,7,8- and 5,6,8-trimethoxy-3-methylisocoumarin, of which the latter was not described previously. Our work provided insights into the potential of actinomycetes as producers of drugs with efficacy against clinical isolates that have emerged recently and also underlined the importance of targeting a specific pathogen. Title: Galantamine attenuates the heroin seeking behaviors induced by cues after prolonged withdrawal in rats Liu H, Lai M, Zhou X, Zhu H, Liu Y, Sun A, Ma B, Zhang F, Zhou W Ref: Neuropharmacology, 62:2515, 2012 : PubMed ESTHER: Liu_2012_Neuropharmacol_62_2515 PubMedSearch: Liu 2012 Neuropharmacol 62 2515 PubMedID: 22342742 Abstract BACKGROUND AND OBJECTIVE: Evidence shows that acetylcholinergic transmission in the ventral tegmental area (VTA) or nucleus accumbens (NAc) plays an important role in heroin-seeking induced by cues. Cholinergic modulation of VTA neurons arises from the lateral dorsal tegmental nucleus (LDT). The present studies investigated the effect of systemic or intra- LDT administration of galantamine, an inhibitor of acetylcholinesterase, on heroin-seeking induced by cues. METHODS: Rats were trained to self-administer heroin for 12 days, underwent extinction training for 12 days followed by two weeks in their home cages. Then the conditioned cues were introduced for the reinstatement of heroin-seeking. RESULTS: The reinstatement of heroin-seeking induced by cues was attenuated by the administration of galantamine (0, 0.3, 1 or 3mg/kg, i.p.) in a dose-dependent manner. In contrast, galantamine only at the dose of 3mg/kg could inhibit the reinstatement of sucrose-seeking. Galantamine at those doses failed to alter the locomotor activity in heroin-withdrawn rats. The inhibition of drug-seeking by galantamine was reversed by pretreatment with scopolamine (0.5mg/kg) but not with mecamylamine (3mg/kg) or scopolamine methobromide (1mg/kg). Moreover, the microinjection of galantamine into the LDT blocked cue-induced heroin-seeking, while the microinjection of scopolamine into the LDT reversed the inhibitory effect of galantamine on drug-seeking behavior. CONCLUSION: The results suggest that cholinergic transmission in the LDT may play a critical role in heroin-seeking behavior induced by cues and that galantamine may have the beneficial effect of blocking heroin-seeking behavior, which is mediated through its actions on the muscarinic receptors. Title: Draft genome sequence of CBS 2479, the standard type strain of Trichosporon asahii Yang RY, Li HT, Zhu H, Zhou GP, Wang M, Wang L Ref: Eukaryot Cell, 11:1415, 2012 : PubMed ESTHER: Yang_2012_Eukaryot.Cell_11_1415 PubMedSearch: Yang 2012 Eukaryot.Cell 11 1415 PubMedID: 23104369 Abstract Trichosporon asahii is one of the important opportunistic pathogenic fungi. Here, we first report the draft nuclear chromosome genome sequence and mitochondrial genome sequence of T. asahii CBS 2479, which is a standard strain of T. asahii that was isolated from a progressive psoriatic lesion. COG analysis predicted that 3,131 genes were assigned to 23 functional categories and that 628 genes were predicted to have a general function. Title: Genome sequence of the Trichosporon asahii environmental strain CBS 8904 Yang RY, Li HT, Zhu H, Zhou GP, Wang M, Wang L Ref: Eukaryot Cell, 11:1586, 2012 : PubMed ESTHER: Yang_2012_Eukaryot.Cell_11_1586 PubMedSearch: Yang 2012 Eukaryot.Cell 11 1586 PubMedID: 23193141 Abstract This is the first report of the genome sequence of Trichosporon asahii environmental strain CBS 8904, which was isolated from maize cobs. Comparison of the genome sequence with that of clinical strain CBS 2479 revealed that they have >99% chromosomal and mitochondrial sequence identity, yet CBS 8904 has 368 specific genes. Analysis of clusters of orthologous groups predicted that 3,307 genes belong to 23 functional categories and 703 genes were predicted to have a general function. Title: In vitro stability and metabolism of O2', O3', O5'-tri-acetyl-N6-(3-hydroxylaniline) adenosine in rat, dog and human plasma: chemical hydrolysis and role of plasma esterases Liu Y, He J, Abliz Z, Zhu H Ref: Xenobiotica, 41:549, 2011 : PubMed ESTHER: Liu_2011_Xenobiotica_41_549 PubMedSearch: Liu 2011 Xenobiotica 41 549 PubMedID: 21486191 Abstract O2', O3', O5'-tri-acetyl-N(6)-(3-hydroxylaniline)adenosine (WS070117), a new structure-type lipid regulator, is being developed in pre-clinical study. In order to monitor drug kinetics it is essential to understand pre-analytical factors that may affect drug assay. In vitro stability and metabolism were investigated using high-performance liquid chromatography (HPLC) method in this study. The hydrolysis products were identified by HPLC-mass spectrometry (MS)/MS method. The esterases involved in WS070117 hydrolysis was assigned via inhibition rate assay. It was found that WS070117 was chemically unstable in alkaline solutions compared to acidic and near neutral solutions. Enzymatic hydrolysis was even more rapid. Hydrolytic rate constants differ between species, being 4.24, 5.96 x 10(-3) and 6.85 x 10(-2) min(-1) in rat, dog and human plasma at 37 degrees C, respectively. The hydrolysis was catalyzed by plasma esterase because NaF (sodium fluoride: a general esterase inhibitor) inhibited WS070117 hydrolysis and metabolite production. Hydrolysis was fast in rat plasma and was catalysed by carboxylesterase and butyrylcholinesterase. In dog plasma, carboxylesterase, butyrylcholinesterase and paraoxonase were mainly responsible. Butyrylcholinesterase was the major esterase involved in WS070117 hydrolysis in human plasma. The WS070117 hydrolysis in plasma proceeded by gradual loss of acetyl groups. The knowledge of in vitro drug stability and metabolic pathways identified in this study will be essential for future pre-clinical and clinical pharmacokinetics studies. Title: Enhanced pesticide sensitivity of novel housefly acetylcholinesterases: a new tool for the detection of residual pesticide contamination Tan F, Wang L, Wang J, Wu X, Zhu H, Jiang L, Tao S, Zhao K, Yang Y, Tang X Ref: Bioprocess Biosyst Eng, 34:305, 2011 : PubMed ESTHER: Tan_2011_Bioprocess.Biosyst.Eng_34_305 PubMedSearch: Tan 2011 Bioprocess.Biosyst.Eng 34 305 PubMedID: 20963445 Abstract The full-length cDNA encoding an acetylcholinesterase (AChE) was cloned and sequenced from the housefly, Musca domestica, by reverse transcriptase-polymerase chain reaction (RT-PCR). Sequence analysis revealed that this 2,076 bp sequence encodes a mature protein of 612 amino acids (67 kDa) and a 79 residue signal peptide. The amino acid sequence shared 52.8-81.4% identity with the AChE proteins of other insects. The cDNA sequence, which lacked the signal peptide was inserted into the vector pPIC9K and then introduced into strain GS115 of the yeast Pichia pastoris. The recombinant AChE protein was then expressed in P. pastoris strain GS115 by methanol induction. Site-directed mutagenesis of the A262G, Y327F, Y327D and I374D residues, either singly or in combination, was performed by reverse PCR. These mutants improved the catalytic activity and sensitivity to the organophosphate and carbamate insecticides. Although the sensitivity of other mutants was slightly increased, the results still showed that the sensitivity of triple mutant, GDD (A262G/Y327D/I374D), enhanced remarkably as much as 16 times for methomyl, 14 times for both carbofuran and chlorpyrifos, and ten times for parathion-methyl, compared to that of the wild-type. The results strongly suggested that these residues are the key structural elements controlling AChE enzyme catalytic activity and sensitivity to inhibition by insecticides. The AChE enzyme obtained by this method could be used to detect the organophosphate and carbamate insecticide residues in fruits and vegetables, a characteristic of great potential research and industrial application. Title: Skeletal muscle IP3R1 receptors amplify physiological and pathological synaptic calcium signals Zhu H, Bhattacharyya BJ, Lin H, Gomez CM Ref: Journal of Neuroscience, 31:15269, 2011 : PubMed ESTHER: Zhu_2011_J.Neurosci_31_15269 PubMedSearch: Zhu 2011 J.Neurosci 31 15269 PubMedID: 22031873 Abstract Ca(2+) release from internal stores is critical for mediating both normal and pathological intracellular Ca(2+) signaling. Recent studies suggest that the inositol 1,4,5-triphosphate (IP(3)) receptor mediates Ca(2+) release from internal stores upon cholinergic activation of the neuromuscular junction (NMJ) in both physiological and pathological conditions. Here, we report that the type I IP(3) receptor (IP(3)R(1))-mediated Ca(2+) release plays a crucial role in synaptic gene expression, development, and neuromuscular transmission, as well as mediating degeneration during excessive cholinergic activation. We found that IP(3)R(1)-mediated Ca(2+) release plays a key role in early development of the NMJ, homeostatic regulation of neuromuscular transmission, and synaptic gene expression. Reducing IP(3)R(1)-mediated Ca(2+) release via siRNA knockdown or IP(3)R blockers in C2C12 cells decreased calpain activity and prevented agonist-induced acetylcholine receptor (AChR) cluster dispersal. In fully developed NMJ in adult muscle, IP(3)R(1) knockdown or blockade effectively increased synaptic strength at presynaptic and postsynaptic sites by increasing both quantal release and expression of AChR subunits and other NMJ-specific genes in a pattern resembling muscle denervation. Moreover, in two mouse models of cholinergic overactivity and NMJ Ca(2+) overload, anti-cholinesterase toxicity and the slow-channel myasthenic syndrome (SCS), IP(3)R(1) knockdown eliminated NMJ Ca(2+) overload, pathological activation of calpain and caspase proteases, and markers of DNA damage at subsynaptic nuclei, and improved both neuromuscular transmission and clinical measures of motor function. Thus, blockade or genetic silencing of muscle IP(3)R(1) may be an effective and well tolerated therapeutic strategy in SCS and other conditions of excitotoxicity or Ca(2+) overload. Title: Enhanced cholinergic transmission promotes recall in honeybees Guez D, Zhu H, Zhang SW, Srinivasan MV Ref: J Insect Physiol, 56:1341, 2010 : PubMed ESTHER: Guez_2010_J.Insect.Physiol_56_1341 PubMedSearch: Guez 2010 J.Insect.Physiol 56 1341 PubMedID: 20438731 Abstract The involvement of the cholinergic system in learning and memory in honeybees has been well established using olfactory conditioning. We examined the effect of Methyl Parathion (MeP), an acetylcholinesterase inhibitor of the organo-phosphate family, on the learning and recall of visual and olfactory discrimination tasks in honeybees. One of our expectations was to observe the effects induced by both the nicotinic and muscarinic systems, as the blocking of acetylcholinesterase should induce an increase in the activity of both systems. We were also interested in knowing whether the type of tasks could influence the results. The visual tasks involved learning to discriminate the orientation of gratings in a Y-maze; the olfactory task involved learning to discriminate odours in a proboscis extension reflex (PER) paradigm. The results indicate that MeP treatment enhances recall of learned tasks in the visual and olfactory domains, but it does not affect the acquisition phase in either domain. Surprisingly, MeP treatment led to muscarinic-like effects but failed to mimic the nicotinic-like effects already described in relation to learning phases in honeybees. Implications for the role of cholinergic pathways in learning and memory and the nature of their involvement are discussed, and a hypothesis relating to the organisation of the cholinergic system and the relationship between the nicotinic and muscarinic systems in honeybees is proposed. The results are also discussed in terms of their ecotoxicological consequences. Title: The sequence and de novo assembly of the giant panda genome Li R, Fan W, Tian G, Zhu H, He L, Cai J, Huang Q, Cai Q, Li B and Yang H <103 more author(s)> Li R, Fan W, Tian G, Zhu H, He L, Cai J, Huang Q, Cai Q, Li B, Bai Y, Zhang Z, Zhang Y, Wang W, Li J, Wei F, Li H, Jian M, Nielsen R, Li D, Gu W, Yang Z, Xuan Z, Ryder OA, Leung FC, Zhou Y, Cao J, Sun X, Fu Y, Fang X, Guo X, Wang B, Hou R, Shen F, Mu B, Ni P, Lin R, Qian W, Wang G, Yu C, Nie W, Wang J, Wu Z, Liang H, Min J, Wu Q, Cheng S, Ruan J, Wang M, Shi Z, Wen M, Liu B, Ren X, Zheng H, Dong D, Cook K, Shan G, Zhang H, Kosiol C, Xie X, Lu Z, Li Y, Steiner CC, Lam TT, Lin S, Zhang Q, Li G, Tian J, Gong T, Liu H, Zhang D, Fang L, Ye C, Zhang J, Hu W, Xu A, Ren Y, Zhang G, Bruford MW, Li Q, Ma L, Guo Y, An N, Hu Y, Zheng Y, Shi Y, Li Z, Liu Q, Chen Y, Zhao J, Qu N, Zhao S, Tian F, Wang X, Wang H, Xu L, Liu X, Vinar T, Wang Y, Lam TW, Yiu SM, Liu S, Huang Y, Yang G, Jiang Z, Qin N, Li L, Bolund L, Kristiansen K, Wong GK, Olson M, Zhang X, Li S, Yang H (- 103) Ref: Nature, 463:311, 2010 : PubMed ESTHER: Li_2010_Nature_463_311 PubMedSearch: Li 2010 Nature 463 311 PubMedID: 20010809 Gene_locus related to this paper: ailme-ABH15, ailme-ACHE, ailme-BCHE, ailme-d2gtv3, ailme-d2gty9, ailme-d2gu87, ailme-d2gu97, ailme-d2gve7, ailme-d2gwu1, ailme-d2gx08, ailme-d2gyt0, ailme-d2gz36, ailme-d2gz37, ailme-d2gz38, ailme-d2gz39, ailme-d2gz40, ailme-d2h5r9, ailme-d2h7b7, ailme-d2h9c9, ailme-d2h794, ailme-d2hau7, ailme-d2hau8, ailme-d2hcd9, ailme-d2hdi6, ailme-d2heu6, ailme-d2hga4, ailme-d2hqw5, ailme-d2hs98, ailme-d2hsx4, ailme-d2hti6, ailme-d2htv3, ailme-d2htz6, ailme-d2huc7, ailme-d2hwj8, ailme-d2hwy7, ailme-d2hxm1, ailme-d2hyc8, ailme-d2hyv2, ailme-d2hz11, ailme-d2hza3, ailme-d2hzr4, ailme-d2i1l4, ailme-d2i2g8, ailme-g1l7m3, ailme-g1lu36, ailme-g1m769, ailme-g1mc29, ailme-g1mdj8, ailme-g1mdr5, ailme-g1mfp4, ailme-g1mfx5, ailme-g1lj41, ailme-g1lm28, ailme-g1l3u1, ailme-g1l7l1, ailme-g1m5i3, ailme-g1l2f6, ailme-g1lji5, ailme-g1lqk3, ailme-g1l8s9, ailme-d2h717, ailme-d2h718, ailme-d2h719, ailme-d2h720, ailme-g1m5v0, ailme-g1m5y7, ailme-g1lkt7, ailme-g1l2a1, ailme-g1lsc8, ailme-g1lrp4, ailme-d2gv02, ailme-g1mik5, ailme-g1ljr1, ailme-g1lxw7, ailme-d2h8b5, ailme-d2h2r2, ailme-d2h9w7, ailme-g1meh3, ailme-g1m719 Abstract Using next-generation sequencing technology alone, we have successfully generated and assembled a draft sequence of the giant panda genome. The assembled contigs (2.25 gigabases (Gb)) cover approximately 94% of the whole genome, and the remaining gaps (0.05 Gb) seem to contain carnivore-specific repeats and tandem repeats. Comparisons with the dog and human showed that the panda genome has a lower divergence rate. The assessment of panda genes potentially underlying some of its unique traits indicated that its bamboo diet might be more dependent on its gut microbiome than its own genetic composition. We also identified more than 2.7 million heterozygous single nucleotide polymorphisms in the diploid genome. Our data and analyses provide a foundation for promoting mammalian genetic research, and demonstrate the feasibility for using next-generation sequencing technologies for accurate, cost-effective and rapid de novo assembly of large eukaryotic genomes. Title: Discovery of novel alpha7 nicotinic receptor antagonists Peng Y, Zhang Q, Snyder GL, Zhu H, Yao W, Tomesch J, Papke RL, O'Callaghan JP, Welsh WJ, Wennogle LP Ref: Bioorganic & Medicinal Chemistry Lett, 20:4825, 2010 : PubMed ESTHER: Peng_2010_Bioorg.Med.Chem.Lett_20_4825 PubMedSearch: Peng 2010 Bioorg.Med.Chem.Lett 20 4825 PubMedID: 20638843 Abstract Two distinct families of small molecules were discovered as novel alpha7 nicotinic acetylcholine receptor (nAChR) antagonists by pharmacophore-based virtual screening. These novel antagonists exhibited selectivity for the neuronal alpha7 subtype over other nAChRs and good brain penetration. Neuroprotection was demonstrated by representative compounds 7i and 8 in a mouse seizure-like behavior model induced by the nerve agent diisopropylfluorophosphate (DFP). These novel nAChR antagonists have potential use as antidote for organophosphorus nerve agent intoxication. Title: Nerve agent exposure elicits site-specific changes in protein phosphorylation in mouse brain Zhu H, O'Brien JJ, O'Callaghan JP, Miller DB, Zhang Q, Rana M, Tsui T, Peng Y, Tomesch J and Snyder GL <2 more author(s)> Zhu H, O'Brien JJ, O'Callaghan JP, Miller DB, Zhang Q, Rana M, Tsui T, Peng Y, Tomesch J, Hendrick JP, Wennogle LP, Snyder GL (- 2) Ref: Brain Research, 1342:11, 2010 : PubMed ESTHER: Zhu_2010_Brain.Res_1342_11 PubMedSearch: Zhu 2010 Brain.Res 1342 11 PubMedID: 20423708 Abstract Organophosphorus (OP) compounds cause toxic symptoms, including convulsions, coma, and death, as the result of irreversible inhibition of acetylcholinesterase (AChE). The development of effective treatments to block these effects and attenuate long-term cognitive and motor disabilities that result from OP intoxication is hampered by a limited understanding of the CNS pathways responsible for these actions. We employed a candidate method (called CNSProfile) to identify changes in the phosphorylation state of key neuronal phosphoproteins evoked by the OP compound, diisopropyl fluorophosphate (DFP). Focused microwave fixation was used to preserve the phosphorylation state of phosphoproteins in brains of DFP-treated mice; hippocampus and striatum were analyzed by immunoblotting with a panel of phospho-specific antibodies. DFP exposure elicited comparable effects on phosphorylation of brain phosphoproteins in both C57BL/6 and FVB mice. DFP treatment significantly altered phosphorylation at regulatory residues on glutamate receptors, including Serine897 (S897) of the NR1 NMDA receptor. NR1 phosphorylation was bi-directionally regulated after DFP in striatum versus hippocampus. NR1 phosphorylation was reduced in striatum, but elevated in hippocampus, compared with controls. DARPP-32 phosphorylation in striatum was selectively increased at the Cdk5 kinase substrate, Threonine75 (T75). Phencynonate hydrochloride, a muscarinic cholinergic antagonist, prevented seizure-like behaviors and the observed changes in phosphorylation induced by DFP. The data reveal region-specific effects of nerve agent exposure on intracellular signaling pathways that correlate with seizure-like behavior and which are reversed by the muscarinic receptor blockade. This approach identifies specific targets for nerve agents, including substrates for Cdk5 kinase, which may be the basis for new anti-convulsant therapies. Title: Calcium signaling-induced Smad3 nuclear accumulation induces acetylcholinesterase transcription in apoptotic HeLa cells Gao W, Zhu H, Zhang JY, Zhang XJ Ref: Cell Mol Life Sciences, 66:2181, 2009 : PubMed ESTHER: Gao_2009_Cell.Mol.Life.Sci_66_2181 PubMedSearch: Gao 2009 Cell.Mol.Life.Sci 66 2181 PubMedID: 19468687 Abstract Recently, acetylcholinesterase (AChE) has been studied as an important apoptosis regulator. We previously showed that cellular calcium mobilization upregulated AChE expression by modulating promoter activity and mRNA stability. In this study, we have identified a potential Smad3/4 binding element, TGCCAGACA, located within the -601 to -571 bp fragment of the AChE promoter, as an important calcium response motif. Smad2/3 and Smad4 were shown to bind this element. Overexpression of human Smad3 increased AChE transcription activity in a dose-dependent manner in HeLa cells, whereas dominant-negative Smad3 blocked this activation. Upon A23187 and thapsigargin treatment, nuclear Smad3 accumulation was observed, an effect that was blocked by the intracellular Ca(2+) chelator BAPTA-AM. Calcium-induced AChE transcriptional activation was significantly blocked when the nuclear localization signal of Smad3 was destroyed. Taken together, our data suggest Smad3 can regulate AChE transcriptional activation following calcium-induced nuclear accumulation. Title: The genome of the cucumber, Cucumis sativus L Huang S, Li R, Zhang Z, Li L, Gu X, Fan W, Lucas WJ, Wang X, Xie B and Du Y <77 more author(s)> Huang S, Li R, Zhang Z, Li L, Gu X, Fan W, Lucas WJ, Wang X, Xie B, Ni P, Ren Y, Zhu H, Li J, Lin K, Jin W, Fei Z, Li G, Staub J, Kilian A, van der Vossen EA, Wu Y, Guo J, He J, Jia Z, Tian G, Lu Y, Ruan J, Qian W, Wang M, Huang Q, Li B, Xuan Z, Cao J, Asan, Wu Z, Zhang J, Cai Q, Bai Y, Zhao B, Han Y, Li Y, Li X, Wang S, Shi Q, Liu S, Cho WK, Kim JY, Xu Y, Heller-Uszynska K, Miao H, Cheng Z, Zhang S, Wu J, Yang Y, Kang H, Li M, Liang H, Ren X, Shi Z, Wen M, Jian M, Yang H, Zhang G, Yang Z, Chen R, Ma L, Liu H, Zhou Y, Zhao J, Fang X, Fang L, Liu D, Zheng H, Zhang Y, Qin N, Li Z, Yang G, Yang S, Bolund L, Kristiansen K, Li S, Zhang X, Wang J, Sun R, Zhang B, Jiang S, Du Y (- 77) Ref: Nat Genet, 41:1275, 2009 : PubMed ESTHER: Huang_2009_Nat.Genet_41_1275 PubMedSearch: Huang 2009 Nat.Genet 41 1275 PubMedID: 19881527 Gene_locus related to this paper: cucsa-a0a0a0ktw5, cucsa-a0a0a0lnt6, cucsa-a0a0a0kpn7, cucsa-a0a0a0lvt9, cucsa-a0a0a0kdx8, cucsa-a0a0a0m228, cucsa-a0a0a0kz31, cucsa-a0a0a0k5t5, cucsa-a0a0a0kfs7, cucsa-a0a0a0kjj7, cucsa-a0a0a0kzs7, cucsa-a0a0a0l0a6, cucsa-a0a0a0l4w4, cucsa-a0a0a0lpz0, cucsa-a0a0a0ls66 Abstract Cucumber is an economically important crop as well as a model system for sex determination studies and plant vascular biology. Here we report the draft genome sequence of Cucumis sativus var. sativus L., assembled using a novel combination of traditional Sanger and next-generation Illumina GA sequencing technologies to obtain 72.2-fold genome coverage. The absence of recent whole-genome duplication, along with the presence of few tandem duplications, explains the small number of genes in the cucumber. Our study establishes that five of the cucumber's seven chromosomes arose from fusions of ten ancestral chromosomes after divergence from Cucumis melo. The sequenced cucumber genome affords insight into traits such as its sex expression, disease resistance, biosynthesis of cucurbitacin and 'fresh green' odor. We also identify 686 gene clusters related to phloem function. The cucumber genome provides a valuable resource for developing elite cultivars and for studying the evolution and function of the plant vascular system. Title: Genome sequence of Azotobacter vinelandii, an obligate aerobe specialized to support diverse anaerobic metabolic processes Setubal JC, dos Santos P, Goldman BS, Ertesvag H, Espin G, Rubio LM, Valla S, Almeida NF, Balasubramanian D and Wood D <34 more author(s)> Setubal JC, dos Santos P, Goldman BS, Ertesvag H, Espin G, Rubio LM, Valla S, Almeida NF, Balasubramanian D, Cromes L, Curatti L, Du Z, Godsy E, Goodner B, Hellner-Burris K, Hernandez JA, Houmiel K, Imperial J, Kennedy C, Larson TJ, Latreille P, Ligon LS, Lu J, Maerk M, Miller NM, Norton S, O'Carroll IP, Paulsen I, Raulfs EC, Roemer R, Rosser J, Segura D, Slater S, Stricklin SL, Studholme DJ, Sun J, Viana CJ, Wallin E, Wang B, Wheeler C, Zhu H, Dean DR, Dixon R, Wood D (- 34) Ref: Journal of Bacteriology, 191:4534, 2009 : PubMed ESTHER: Setubal_2009_J.Bacteriol_191_4534 PubMedSearch: Setubal 2009 J.Bacteriol 191 4534 PubMedID: 19429624 Gene_locus related to this paper: azovd-c1dex6, azovd-c1df21, azovd-c1dfb5, azovd-c1dg75, azovd-c1dgm6, azovd-c1dh91, azovd-c1di03, azovd-c1dib3, azovd-c1dif2, azovd-c1dIq5, azovd-c1dir1, azovd-c1dis2, azovd-c1djq5, azovd-c1djw3, azovd-c1dk37, azovd-c1dkb2, azovd-c1dkj0, azovd-c1dli6, azovd-c1dng8, azovd-c1dni5, azovd-c1dpr0, azovd-c1dqu3, azovd-c1dri5, azovd-c1drx0, azovd-c1dsl7, azovd-c1dsq7, azovd-c1dss1, azovd-metx, azovi-PHBC, azovd-c1dem4 Abstract Azotobacter vinelandii is a soil bacterium related to the Pseudomonas genus that fixes nitrogen under aerobic conditions while simultaneously protecting nitrogenase from oxygen damage. In response to carbon availability, this organism undergoes a simple differentiation process to form cysts that are resistant to drought and other physical and chemical agents. Here we report the complete genome sequence of A. vinelandii DJ, which has a single circular genome of 5,365,318 bp. In order to reconcile an obligate aerobic lifestyle with exquisitely oxygen-sensitive processes, A. vinelandii is specialized in terms of its complement of respiratory proteins. It is able to produce alginate, a polymer that further protects the organism from excess exogenous oxygen, and it has multiple duplications of alginate modification genes, which may alter alginate composition in response to oxygen availability. The genome analysis identified the chromosomal locations of the genes coding for the three known oxygen-sensitive nitrogenases, as well as genes coding for other oxygen-sensitive enzymes, such as carbon monoxide dehydrogenase and formate dehydrogenase. These findings offer new prospects for the wider application of A. vinelandii as a host for the production and characterization of oxygen-sensitive proteins. Title: Genome sequences of three agrobacterium biovars help elucidate the evolution of multichromosome genomes in bacteria Slater SC, Goldman BS, Goodner B, Setubal JC, Farrand SK, Nester EW, Burr TJ, Banta L, Dickerman AW and Wood DW <26 more author(s)> Slater SC, Goldman BS, Goodner B, Setubal JC, Farrand SK, Nester EW, Burr TJ, Banta L, Dickerman AW, Paulsen I, Otten L, Suen G, Welch R, Almeida NF, Arnold F, Burton OT, Du Z, Ewing A, Godsy E, Heisel S, Houmiel KL, Jhaveri J, Lu J, Miller NM, Norton S, Chen Q, Phoolcharoen W, Ohlin V, Ondrusek D, Pride N, Stricklin SL, Sun J, Wheeler C, Wilson L, Zhu H, Wood DW (- 26) Ref: J. Bacteriol, 191:2501, 2009 : PubMed ESTHER: Slater_2009_J.Bacteriol_191_2501 PubMedSearch: Slater 2009 J.Bacteriol 191 2501 PubMedID: 19251847 Gene_locus related to this paper: agrrk-b9j7k2, agrrk-b9j8e4, agrrk-b9j8g5, agrrk-b9j9n4, agrrk-b9j9p4, agrrk-b9ja88, agrrk-b9jbs5, agrrk-b9jd67, agrrk-b9jd85, agrrk-b9jfh5, agrrk-b9jfj6, agrrk-b9jfu6, agrrk-b9jfy6, agrrk-b9jh78, agrrk-b9ji04, agrrk-b9jih5, agrrk-b9jih7, agrrk-b9jj14, agrrk-b9jjt5, agrrk-b9jjt6, agrrk-b9jk42, agrrk-b9jki6, agrrk-b9jkt4, agrrk-b9jla0, agrrk-b9jlc3, agrrk-b9jlj1, agrrk-b9jlj2, agrrk-b9jlr1, agrrk-b9jmj9, agrrk-b9jml0, agrrk-b9jmn1, agrrk-b9jnw6, agrrk-b9jq01, agrrk-b9jq11, agrrk-b9jq35, agrtu-DHAA, agrvs-b9jqv2, agrvs-b9jr09, agrvs-b9js24, agrvs-b9js61, agrvs-b9ju03, agrvs-b9jw40, agrvs-b9jx20, agrvs-b9jy84, agrvs-b9k1h8, agrvs-b9k2m9, agrvs-b9k3r6, agrvs-b9k5p9, agrvs-b9k093, agrvs-b9k188, agrvs-b9k312, agrrk-b9jls9, agrrk-b9jca1, agrvs-b9jur1, agrrk-rutd Abstract The family Rhizobiaceae contains plant-associated bacteria with critical roles in ecology and agriculture. Within this family, many Rhizobium and Sinorhizobium strains are nitrogen-fixing plant mutualists, while many strains designated as Agrobacterium are plant pathogens. These contrasting lifestyles are primarily dependent on the transmissible plasmids each strain harbors. Members of the Rhizobiaceae also have diverse genome architectures that include single chromosomes, multiple chromosomes, and plasmids of various sizes. Agrobacterium strains have been divided into three biovars, based on physiological and biochemical properties. The genome of a biovar I strain, A. tumefaciens C58, has been previously sequenced. In this study, the genomes of the biovar II strain A. radiobacter K84, a commercially available biological control strain that inhibits certain pathogenic agrobacteria, and the biovar III strain A. vitis S4, a narrow-host-range strain that infects grapes and invokes a hypersensitive response on nonhost plants, were fully sequenced and annotated. Comparison with other sequenced members of the Alphaproteobacteria provides new data on the evolution of multipartite bacterial genomes. Primary chromosomes show extensive conservation of both gene content and order. In contrast, secondary chromosomes share smaller percentages of genes, and conserved gene order is restricted to short blocks. We propose that secondary chromosomes originated from an ancestral plasmid to which genes have been transferred from a progenitor primary chromosome. Similar patterns are observed in select Beta- and Gammaproteobacteria species. Together, these results define the evolution of chromosome architecture and gene content among the Rhizobiaceae and support a generalized mechanism for second-chromosome formation among bacteria. Title: Sustained CPEB-dependent local protein synthesis is required to stabilize synaptic growth for persistence of long-term facilitation in Aplysia Miniaci MC, Kim JH, Puthanveettil SV, Si K, Zhu H, Kandel ER, Bailey CH Ref: Neuron, 59:1024, 2008 : PubMed ESTHER: Miniaci_2008_Neuron_59_1024 PubMedSearch: Miniaci 2008 Neuron 59 1024 PubMedID: 18817739 Abstract The time course of the requirement for local protein synthesis in the stabilization of learning-related synaptic growth and the persistence of long-term memory was examined using Aplysia bifurcated sensory neuron-motor neuron cultures. We find that, following repeated pulses of serotonin (5-HT), the local perfusion of emetine, an inhibitor of protein synthesis, or a TAT-AS oligonucleotide directed against ApCPEB blocks long-term facilitation (LTF) at either 24 or 48 hr and leads to a selective retraction of newly formed sensory neuron varicosities induced by 5-HT. By contrast, later inhibition of local protein synthesis, at 72 hr after 5-HT, has no effect on either synaptic growth or LTF. These results define a specific stabilization phase for the storage of long-term memory during which newly formed varicosities are labile and require sustained CPEB-dependent local protein synthesis to acquire the more stable properties of mature varicosities required for the persistence of LTF. Title: Esterase SeE of Streptococcus equi ssp. equi is a novel nonspecific carboxylic ester hydrolase Xie G, Liu M, Zhu H, Lei B Ref: FEMS Microbiology Letters, 289:181, 2008 : PubMed ESTHER: Xie_2008_FEMS.Microbiol.Lett_289_181 PubMedSearch: Xie 2008 FEMS.Microbiol.Lett 289 181 PubMedID: 19054107 Abstract Extracellular carboxylic ester hydrolases are produced by many bacterial pathogens and have been shown recently to be important for virulence of some pathogens. However, these hydrolases are poorly characterized in enzymatic activity. This study prepared and characterized the secreted ester hydrolase of Streptococcus equi ssp. equi (designated SeE for S. equi esterase). SeE hydrolyzes ethyl acetate, acetylsalicylic acid, and tributyrin but not ethyl butyrate. This substrate specificity pattern does not match those of the three conventional types of nonspecific carboxylic ester hydrolases (carboxylesterases, arylesterases, and acetylesterases). To determine whether SeE has lipase activity, a number of triglycerides and vinyl esters were tested in SeE-catalyzed hydrolysis. SeE does not hydrolyze triglycerides and vinyl esters of long-chain carboxylic acids nor display interfacial activation, indicating that SeE is not a lipase. Like the conventional carboxylesterases, SeE is inhibited by di-isopropylfluorophosphate. These findings indicate that SeE is a novel carboxylesterase with optimal activity for acetyl esters. Title: Nerve growth factor prevents the apoptosis-associated increase in acetylcholinesterase activity after hydrogen peroxide treatment by activating Akt Jiang H, Zhang J, Zhu H, Li H, Zhang X Ref: Acta Biochim Biophys Sin (Shanghai), 39:46, 2007 : PubMed ESTHER: Jiang_2007_Acta.Biochim.Biophys.Sin.(Shanghai)_39_46 PubMedSearch: Jiang 2007 Acta.Biochim.Biophys.Sin.(Shanghai) 39 46 PubMedID: 17213958 Abstract Acetylcholinesterase (AChE) is thought to play an important role during apoptosis. Our results showed that H2O2 induced AChE activity, a functional marker in apoptosis, increases in neuronal-like PC12 cells. Glutathione, which is involved in cellular redox homeostasis, inhibited the increase of AChE activity, suggesting that reactive oxygen species (ROS) play a key role in this process. Further investigation showed that the elevation of AChE was observed after the degradation of Akt, release of cytochrome c from mitochondria into the cytosol, and activation of caspase family members. When nerve growth factor (NGF) was present, with the maintenance of Akt level, the elevation of AChE, the cytochrome c diffusion, as well as apoptosis were markedly attenuated in H2O2-treated PC12 cells. However, wortmannin, an inhibitor of the PI3K/Akt pathway, accelerated the apoptosis and increased the AChE activity. The overexpression of constitutively activated Akt, which is a downstream signalling element of the NGF receptor TrkA, delayed mitochondrial collapse and inhibited elevation of AChE activity. Thus, NGF prevented apoptosis and elevation of AChE activity by activating the Akt pathway and stabilizing the function of mitochondria. Title: Role of acetylcholine transmission in nucleus accumbens and ventral tegmental area in heroin-seeking induced by conditioned cues Zhou W, Liu H, Zhang F, Tang S, Zhu H, Lai M, Kalivas PW Ref: Neuroscience, 144:1209, 2007 : PubMed ESTHER: Zhou_2007_Neurosci_144_1209 PubMedSearch: Zhou 2007 Neurosci 144 1209 PubMedID: 17184925 Abstract The involvement of cholinergic transmission in heroin self-administration and the reinstatement of heroin-seeking was examined in rats trained to nose-poke for i.v. heroin. Systemic treatment with physostigmine, an inhibitor of acetylcholinesterase, modestly reduced the acquisition and rate of heroin self-administration, and this suppression of heroin intake was reversed by pretreatment with scopolamine but not by mecamylamine. Following 10-14 days of self-administration, rats were left in the home environment for 14 days. Subsequently, rats were evaluated for extinction of nose-pokes during the first hour after being returned to the self-administration apparatus. One hour later a conditioned stimulus (house light, light in the nose-poke hole, sound of the infusion pump) was presented to initiate cue-induced reinstatement. Physostigmine produced a dose-dependent inhibition of cue-induced reinstatement, but only the dose of 0.5 mg/kg significantly decreased nose-poke responding in the extinction test. Chronic treatment with physostigmine (0.1 mg/kg) did not impair performance during acquisition of heroin self-administration. However, during a subsequent reinstatement test conducted in the absence of physostigmine pretreatment, heroin seeking was significantly below that of rats chronically pretreated with saline. To evaluate brain regions mediating the effects of systemic drug treatment on reinstatement, physostigmine was microinjected into the nucleus accumbens (NAc) or ventral tegmental area (VTA). Microinjection of physostigmine into the NAc prior to presenting conditioned cues inhibited the reinstatement of heroin-seeking, without affecting extinction responding. In contrast, microinjection of physostigmine into the VTA augmented the reinstatement induced by conditioned cues and extinction responding. Inactivation of either NAc or VTA by microinjecting tetrodotoxin blocked both extinction responding and cue-induced reinstatement. These data demonstrate that cholinergic transmission influences heroin self-administration and reinstatement. Moreover, cue-induced reinstatement was inhibited by physostigmine in the NAc and potentiated by cholinergic stimulation in the VTA. Title: Regulation of acetylcholinesterase expression by calcium signaling during calcium ionophore A23187- and thapsigargin-induced apoptosis Zhu H, Gao W, Jiang H, Jin QH, Shi YF, Tsim KWK, Zhang XJ Ref: International Journal of Biochemistryistry & Cell Biology, 39:93, 2007 : PubMed ESTHER: Zhu_2007_Int.J.Biochem.Cell.Biol_39_93 PubMedSearch: Zhu 2007 Int.J.Biochem.Cell.Biol 39 93 PubMedID: 17000130 Abstract We have recently reported that acetylcholinesterase expression was induced during apoptosis in various cell types. In the current study we provide evidence to suggest that the induction of acetylcholinesterase expression during apoptosis is regulated by the mobilization of intracellular Ca(2+). During apoptosis, treatment of HeLa and MDA-MB-435s cells with the calcium ionophore A23187 resulted in a significant increase in acetylcholinesterase mRNA and protein levels. Chelation of intracellular Ca(2+) by BAPTA-AM (1,2-bis-(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-acetoxymethyl ester), an intracellular Ca(2+) chelator, inhibited acetylcholinesterase expression. A23187 also enhanced the stability of acetylcholinesterase mRNA and increased the activity of acetylcholinesterase promoter, effects that were blocked by BAPTA-AM. Perturbations of cellular Ca(2+) homeostasis by thapsigargin resulted in the increase of acetylcholinesterase expression as well as acetylcholinesterase promoter activity during thapsigargin induced apoptosis in HeLa and MDA-MB-435s cells, effects that were also inhibited by BAPTA-AM. We further demonstrated that the transactivation of the human acetylcholinesterase promoter by A23187 and thapsigargin was partially mediated by a CCAAT motif within the -1270 to -1248 fragment of the human acetylcholinesterase promoter. This motif was able to bind to CCAAT binding factor (CBF/NF-Y). These results strongly suggest that cytosolic Ca(2+) plays a key role in acetylcholinesterase regulation during apoptosis induced by A23187 and thapsigargin. Title: The CCAAT-binding factor CBF/NF-Y regulates the human acetylcholinesterase promoter activity during calcium ionophore A23187-induced cell apoptosis Zhu H, Gao W, Shi YF, Zhang XJ Ref: Biochimica & Biophysica Acta, 1770:1475, 2007 : PubMed ESTHER: Zhu_2007_Biochim.Biophys.Acta_1770_1475 PubMedSearch: Zhu 2007 Biochim.Biophys.Acta 1770 1475 PubMedID: 17728068 Abstract We previously reported that the expression of acetylcholinesterase during A23187-induced apoptosis of HeLa cells is regulated by Ca(2+) mobilization through the modulation of mRNA stability and acetylcholinesterase promoter activity. Transactivation of the human acetylcholinesterase promoter by A23187 was partially mediated by the distal CCAAT motif within the -1270 to -1248 fragment of the human acetylcholinesterase promoter, which was bound by the CCAAT binding factor (CBF/NF-Y). In the present study, we investigated the molecular mechanisms by which CBF/NF-Y regulates A23187-induced activation of the human acetylcholinesterase promoter. The results indicate that CBF/NF-Y binding to the distal CCAAT motif suppresses the promoter activity. Electrophoretic mobility shift assays (EMSAs) demonstrated that binding of CBF/NF-Y to the distal CCAAT motif decreased after A23187 treatment. Our results suggest that acetylcholinesterase promoter activation during A23187-induced HeLa cell apoptosis may result partly from the dissociation of CBF/NF-Y from the distal CCAAT motif in the acetylcholinesterase promoter, reversing this suppression. Title: Calcineurin mediates acetylcholinesterase expression during calcium ionophore A23187-induced HeLa cell apoptosis Zhu H, Gao W, Jiang H, Wu J, Shi YF, Zhang XJ Ref: Biochimica & Biophysica Acta, 1773:593, 2007 : PubMed ESTHER: Zhu_2007_Biochim.Biophys.Acta_1773_593 PubMedSearch: Zhu 2007 Biochim.Biophys.Acta 1773 593 PubMedID: 17320203 Abstract We previously reported that acetylcholinesterase plays a critical role in apoptosis and its expression is regulated by Ca(2+) mobilization. In the present study, we show that activated calpain, a cytosolic calcium-activated cysteine protease, and calcineurin, a calcium-dependent protein phosphatase, regulate acetylcholinesterase expression during A23187-induced apoptosis. The calpain inhibitor, calpeptin, and the calcineurin inhibitors, FK506 and cyclosporine A, inhibited acetylcholinesterase expression at both mRNA and protein levels and suppressed the activity of the human acetylcholinesterase promoter. In contrast, overexpression of constitutively active calcineurin significantly activated the acetylcholinesterase promoter. Furthermore, we identify a role for the transcription factor NFAT (nuclear factor of activated T cells), a calcineurin target, in regulating the acetylcholinesterase promoter during ionophore-induced apoptosis. Overexpression of human NFATc3 and NFATc4 greatly increased the acetylcholinesterase promoter activity in HeLa cells treated with A23187. Overexpression of constitutive nuclear NFATc4 activated the acetylcholinesterase promoter independent of A23187, whereas overexpression of dominant-negative NFAT blocked A23187-induced acetylcholinesterase promoter activation. These results indicate that calcineurin mediates acetylcholinesterase expression during apoptosis. Title: Expression of a novel dipeptidyl peptidase 8 (DPP8) transcript variant, DPP8-v3, in human testis Zhu H, Zhou ZM, Lu L, Xu M, Wang H, Li JM, Sha JH Ref: Asian J Androl, 7:245, 2005 : PubMed ESTHER: Zhu_2005_Asian.J.Androl_7_245 PubMedSearch: Zhu 2005 Asian.J.Androl 7 245 PubMedID: 16110352 Abstract AIM: To investigate the role of a novel dipeptidyl peptidase 8 transcript variant (DPP8-v3) gene in testis development and/or spermatogenesis. Title: Methyl parathion increases neuronal activities in the rat locus coeruleus Zhu H, Zhou W, Li XR, Ma T, Ho IK, Rockhold RW Ref: J Biomed Sci, 11:732, 2004 : PubMed ESTHER: Zhu_2004_J.Biomed.Sci_11_732 PubMedSearch: Zhu 2004 J.Biomed.Sci 11 732 PubMedID: 15591769 Abstract Exposure to organophosphate insecticides induces undesirable behavioral changes in humans, including anxiety and irritability, depression, cognitive disturbances and sleep disorders. Little information currently exists concerning the neural mechanisms underlying such behavioral changes. The brain stem locus coeruleus (LC) could be a mediator of organophosphate insecticide-induced behavioral toxicities since it contains high levels of acetylcholinesterase and is involved in the regulation of the sleep-wake cycle, attention, arousal, memory, and pathological processes, including anxiety and depression. In the present study, using a multi-wire recording technique, we examined the effects of methyl parathion, a commonly used organophosphate insecticide, on the firing patterns of LC neurons in rats. Systemic administration of a single dose of methyl parathion (1 mg/kg, i.v.) increased the spontaneous firing rates of LC neurons by 240% but did not change the temporal relationships among the activities of multiple LC neurons. This dose of methyl parathion induced a 50% decrease in blood acetylcholinesterase activity and a 48% decrease in LC acetylcholinesterase activity. The methyl parathion-induced excitation of LC neurons was reversed by administration of atropine sulfate, a muscarinic receptor antagonist, indicating an involvement of muscarinic receptors. The methyl parathion-induced increase in LC neuronal activity returned to normal within 30 min while the blood acetylcholinesterase activity remained inhibited for over 1 h. These data indicate that methyl parathion treatment can elicit excitation of LC neurons. Such excitation could contribute to the neuronal basis of organophosphate insecticide-induced behavioral changes in human. Title: A neuronal isoform of CPEB regulates local protein synthesis and stabilizes synapse-specific long-term facilitation in aplysia Si K, Giustetto M, Etkin A, Hsu R, Janisiewicz AM, Miniaci MC, Kim JH, Zhu H, Kandel ER Ref: Cell, 115:893, 2003 : PubMed ESTHER: Si_2003_Cell_115_893 PubMedSearch: Si 2003 Cell 115 893 PubMedID: 14697206 Abstract Synapse-specific facilitation requires rapamycin-dependent local protein synthesis at the activated synapse. In Aplysia, rapamycin-dependent local protein synthesis serves two functions: (1) it provides a component of the mark at the activated synapse and thereby confers synapse specificity and (2) it stabilizes the synaptic growth associated with long-term facilitation. Here we report that a neuron-specific isoform of cytoplasmic polyadenylation element binding protein (CPEB) regulates this synaptic protein synthesis in an activity-dependent manner. Aplysia CPEB protein is upregulated locally at activated synapses, and it is needed not for the initiation but for the stable maintenance of long-term facilitation. We suggest that Aplysia CPEB is one of the stabilizing components of the synaptic mark. Title: Genome sequence of Streptococcus mutans UA159, a cariogenic dental pathogen Ajdic D, McShan WM, McLaughlin RE, Savic G, Chang J, Carson MB, Primeaux C, Tian R, Kenton S and Ferretti JJ <9 more author(s)> Ajdic D, McShan WM, McLaughlin RE, Savic G, Chang J, Carson MB, Primeaux C, Tian R, Kenton S, Jia H, Lin S, Qian Y, Li S, Zhu H, Najar F, Lai H, White J, Roe BA, Ferretti JJ (- 9) Ref: Proceedings of the National Academy of Sciences of the United States of America, 99:14434, 2002 : PubMed ESTHER: Ajdic_2002_Proc.Natl.Acad.Sci.U.S.A_99_14434 PubMedSearch: Ajdic 2002 Proc.Natl.Acad.Sci.U.S.A 99 14434 PubMedID: 12397186 Gene_locus related to this paper: strmu-BACT, strmu-BGLB, strmu-GBPD, strmu-pepx, strmu-SMU.118C, strmu-SMU.178, strmu-SMU.633, strmu-SMU.643, strmu-SMU.737, strmu-SMU.1028, strmu-SMU.1071C, strmu-SMU.1280C, strmu-SMU.1314, strmu-SMU.1319C, strmu-SMU.1337C, strmu-SMU.1393C, strmu-SMU.1443C, strmu-SMU.1482C, strmu-SMU.1678 Abstract Streptococcus mutans is the leading cause of dental caries (tooth decay) worldwide and is considered to be the most cariogenic of all of the oral streptococci. The genome of S. mutans UA159, a serotype c strain, has been completely sequenced and is composed of 2,030,936 base pairs. It contains 1,963 ORFs, 63% of which have been assigned putative functions. The genome analysis provides further insight into how S. mutans has adapted to surviving the oral environment through resource acquisition, defense against host factors, and use of gene products that maintain its niche against microbial competitors. S. mutans metabolizes a wide variety of carbohydrates via nonoxidative pathways, and all of these pathways have been identified, along with the associated transport systems whose genes account for almost 15% of the genome. Virulence genes associated with extracellular adherent glucan production, adhesins, acid tolerance, proteases, and putative hemolysins have been identified. Strain UA159 is naturally competent and contains all of the genes essential for competence and quorum sensing. Mobile genetic elements in the form of IS elements and transposons are prominent in the genome and include a previously uncharacterized conjugative transposon and a composite transposon containing genes for the synthesis of antibiotics of the gramicidin/bacitracin family; however, no bacteriophage genomes are present. Title: Discovery of aminothiazole inhibitors of cyclin-dependent kinase 2: synthesis, X-ray crystallographic analysis, and biological activities Kim KS, Kimball SD, Misra RN, Rawlins DB, Hunt JT, Xiao HY, Lu S, Qian L, Han WC and Webster KR <20 more author(s)> Kim KS, Kimball SD, Misra RN, Rawlins DB, Hunt JT, Xiao HY, Lu S, Qian L, Han WC, Shan W, Mitt T, Cai ZW, Poss MA, Zhu H, Sack JS, Tokarski JS, Chang CY, Pavletich N, Kamath A, Humphreys WG, Marathe P, Bursuker I, Kellar KA, Roongta U, Batorsky R, Mulheron JG, Bol D, Fairchild CR, Lee FY, Webster KR (- 20) Ref: Journal of Medicinal Chemistry, 45:3905, 2002 : PubMed ESTHER: Kim_2002_J.Med.Chem_45_3905 PubMedSearch: Kim 2002 J.Med.Chem 45 3905 PubMedID: 12190313 Abstract High throughput screening identified 2-acetamido-thiazolylthio acetic ester 1 as an inhibitor of cyclin-dependent kinase 2 (CDK2). Because this compound is inactive in cells and unstable in plasma, we have stabilized it to metabolic hydrolysis by replacing the ester moiety with a 5-ethyl-substituted oxazole as in compound 14. Combinatorial and parallel synthesis provided a rapid analysis of the structure-activity relationship (SAR) for these inhibitors of CDK2, and over 100 analogues with IC(50) values in the 1-10 nM range were rapidly prepared. The X-ray crystallographic data of the inhibitors bound to the active site of CDK2 protein provided insight into the binding modes of these inhibitors, and the SAR of this series of analogues was rationalized. Many of these analogues displayed potent and broad spectrum antiproliferative activity across a panel of tumor cell lines in vitro. In addition, A2780 ovarian carcinoma cells undergo rapid apoptosis following exposure to CDK2 inhibitors of this class. Mechanism of action studies have confirmed that the phosphorylation of CDK2 substrates such as RB, histone H1, and DNA polymerase alpha (p70 subunit) is reduced in the presence of compound 14. Further optimization led to compounds such as water soluble 45, which possesses a favorable pharmacokinetic profile in mice and demonstrates significant antitumor activity in vivo in several murine and human models, including an engineered murine mammary tumor that overexpresses cyclin E, the coactivator of CDK2. Title: A comparison of cholinesterase activity after intravenous, oral or dermal administration of methyl parathion Kramer RE, Wellman SE, Zhu H, Rockhold RW, Baker RC Ref: J Biomed Sci, 9:140, 2002 : PubMed ESTHER: Kramer_2002_J.Biomed.Sci_9_140 PubMedSearch: Kramer 2002 J.Biomed.Sci 9 140 PubMedID: 11914581 Abstract Time-dependent changes in blood cholinesterase activity caused by single intravenous, oral or dermal administration of methyl parathion to adult female rats were defined. Intravenous and oral administration of 2.5 mg/kg methyl parathion resulted in rapid (<60 min) decreases in cholinesterase activity which recovered fully in vivo within 30-48 h. In contrast, spontaneous reactivation of cholinesterase in vitro was complete within 6 h at 37 degrees C. Dermal administration of methyl parathion caused dose-dependent inhibition of cholinesterase activity which developed slowly (> or =6 h) and was prolonged (> or =48 h). Time- and route-dependent effects of methyl parathion on cholinesterase activity in brain and other tissues generally paralleled its effects on activity in blood. In conclusion, pharmacodynamics of methyl parathion differ substantially with route of exposure. Recovery of cholinesterase in vivo after intravenous or oral exposure may partially reflect spontaneous reactivation and suggests a rapid clearance of methyl parathion or its active metabolite methyl paraoxon. The more gradual and prolonged inhibition of cholinesterase caused by dermal administration is consistent with disposition of methyl parathion at a site from which it or methyl paraoxon is only slowly distributed. Thus, dermal exposure to methyl parathion may pose the greatest risk for long-term adverse effects. Title: Complete genome sequence of an M1 strain of Streptococcus pyogenes Ferretti JJ, McShan WM, Ajdic D, Savic DJ, Savic G, Lyon K, Primeaux C, Sezate S, Suvorov AN and McLaughlin R <13 more author(s)> Ferretti JJ, McShan WM, Ajdic D, Savic DJ, Savic G, Lyon K, Primeaux C, Sezate S, Suvorov AN, Kenton S, Lai HS, Lin SP, Qian Y, Jia HG, Najar FZ, Ren Q, Zhu H, Song L, White J, Yuan X, Clifton SW, Roe BA, McLaughlin R (- 13) Ref: Proc Natl Acad Sci U S A, 98:4658, 2001 : PubMed ESTHER: Ferretti_2001_Proc.Natl.Acad.Sci.U.S.A_98_4658 PubMedSearch: Ferretti 2001 Proc.Natl.Acad.Sci.U.S.A 98 4658 PubMedID: 11296296 Gene_locus related to this paper: strpy-ESTA, strpy-PEPXP, strpy-Q8K5W4, strpy-SPY1308, strpy-SPYM18.1727 Abstract The 1,852,442-bp sequence of an M1 strain of Streptococcus pyogenes, a Gram-positive pathogen, has been determined and contains 1,752 predicted protein-encoding genes. Approximately one-third of these genes have no identifiable function, with the remainder falling into previously characterized categories of known microbial function. Consistent with the observation that S. pyogenes is responsible for a wider variety of human disease than any other bacterial species, more than 40 putative virulence-associated genes have been identified. Additional genes have been identified that encode proteins likely associated with microbial "molecular mimicry" of host characteristics and involved in rheumatic fever or acute glomerulonephritis. The complete or partial sequence of four different bacteriophage genomes is also present, with each containing genes for one or more previously undiscovered superantigen-like proteins. These prophage-associated genes encode at least six potential virulence factors, emphasizing the importance of bacteriophages in horizontal gene transfer and a possible mechanism for generating new strains with increased pathogenic potential. Title: Effects of single or repeated dermal exposure to methyl parathion on behavior and blood cholinesterase activity in rats Zhu H, Rockhold RW, Baker RC, Kramer RE, Ho IK Ref: J Biomed Sci, 8:467, 2001 : PubMed ESTHER: Zhu_2001_J.Biomed.Sci_8_467 PubMedSearch: Zhu 2001 J.Biomed.Sci 8 467 PubMedID: 11702010 Abstract The effects of a single or repeated dermal administration of methyl parathion on motor function, learning and memory were investigated in adult female rats and correlated with blood cholinesterase activity. Exposure to a single dose of 50 mg/kg methyl parathion (75% of the dermal LD(50)) resulted in an 88% inhibition of blood cholinesterase activity and was associated with severe acute toxicity. Spontaneous locomotor activity and neuromuscular coordination were also depressed. Rats treated with a lower dose of methyl parathion, i.e. 6.25 or 12.5 mg/kg, displayed minimal signs of acute toxicity. Blood cholinesterase activity and motor function, however, were depressed initially but recovered fully within 1-3 weeks. There were no delayed effects of a single dose of methyl parathion on learning acquisition or memory as assessed by a step-down inhibitory avoidance learning task. Repeated treatment with 1 mg/kg/day methyl parathion resulted in a 50% inhibition of blood cholinesterase activity. A decrease in locomotor activity and impairment of memory were also observed after 28 days of repeated treatment. Thus, a single dermal exposure of rats to doses of methyl parathion which are lower than those that elicit acute toxicity can cause decrements in both cholinesterase activity and motor function which are reversible. In contrast, repeated low-dose dermal treatment results in a sustained inhibition of cholinesterase activity and impairment of both motor function and memory. Title: Analysis of point mutants in the Caenorhabditis elegans vesicular acetylcholine transporter reveals domains involved in substrate translocation Zhu H, Duerr JS, Varoqui H, McManus JR, Rand JB, Erickson JD Ref: Journal of Biological Chemistry, 276:41580, 2001 : PubMed ESTHER: Zhu_2001_J.Biol.Chem_276_41580 PubMedSearch: Zhu 2001 J.Biol.Chem 276 41580 PubMedID: 11551909 Abstract Cholinergic neurotransmission depends upon the regulated release of acetylcholine. This requires the loading of acetylcholine into synaptic vesicles by the vesicular acetylcholine transporter (VAChT). Here, we identify point mutants in Caenorhabditis elegans that map to highly conserved regions of the VAChT gene of Caenorhabditis elegans (CeVAChT) (unc-17) and exhibit behavioral phenotypes consistent with a reduction in vesicular transport activity and neurosecretion. Several of these mutants express normal amounts of VAChT protein and exhibit appropriate targeting of VAChT to synaptic vesicles. By site-directed mutagenesis, we have replaced the conserved amino acid residues found in human VAChT with the mutated residue in CeVAChT and stably expressed these cDNAs in PC-12 cells. These mutants display selective defects in initial acetylcholine transport velocity (K(m)), with values ranging from 2- to 8-fold lower than that of the wild-type. One of these mutants has lost its specific interaction with vesamicol, a selective inhibitor of VAChT, and displays vesamicol-insensitive uptake of acetylcholine. The relative order of behavioral severity of the CeVAChT point mutants is identical to the order of reduced affinity of VAChT for acetylcholine in vitro. This indicates that specific structural changes in VAChT translate into specific alterations in the intrinsic parameters of transport and in the storage and synaptic release of acetylcholine in vivo. Title: A novel function for serotonin-mediated short-term facilitation in aplysia: conversion of a transient, cell-wide homosynaptic hebbian plasticity into a persistent, protein synthesis-independent synapse-specific enhancement Bailey CH, Giustetto M, Zhu H, Chen M, Kandel ER Ref: Proc Natl Acad Sci U S A, 97:11581, 2000 : PubMed ESTHER: Bailey_2000_Proc.Natl.Acad.Sci.U.S.A_97_11581 PubMedSearch: Bailey 2000 Proc.Natl.Acad.Sci.U.S.A 97 11581 PubMedID: 11027355 Abstract Studies of sensitization and classical conditioning of the gill-withdrawal reflex in Aplysia have shown that the synaptic connections between identified glutamatergic sensory neurons and motor neurons can be enhanced in one of two ways: by a heterosynaptic (modulatory input-dependent) mechanism that gives rise with repetition to long-term facilitation and by a homosynaptic (activity-dependent) mechanism that gives rise with repetition to a facilitation that is partially blocked by 2-amino-5-phosphonovaleric acid and by injection of 1,2-bis(2-aminophenoxy)ethane-N,N,N', N'-tetraacetate (BAPTA) into the postsynaptic cell and is similar to long-term potentiation in the hippocampus. We here have examined how these two forms of facilitation interact at the level of an individual synaptic connection by using a culture preparation consisting of a single bifurcated sensory neuron that forms independent synaptic contacts with each of two spatially separated motor neurons. We find that the homosynaptic facilitation produced by a train of action potentials is cell wide and is evident at all of the terminals of the sensory neuron. By contrast, the heterosynaptic facilitation mediated by the modulatory transmitter serotonin (5-HT) can operate at the level of a single synapse. Homosynaptic activation gives rise to only a transient facilitation lasting a few hours, even when repeated in a spaced manner. The heterosynaptic facilitation produced by a single pulse of 5-HT, applied to one terminal of the sensory neuron, also lasts only minutes. However, when one or more homosynaptic trains of spike activity are paired with even a single pulse of 5-HT applied to one of the two branches of the sensory neuron, the combined actions lead to a selective enhancement in synaptic strength only at the 5-HT-treated branch that now lasts more than a day, and thus amplifies, by more than 20-fold, the duration of the individually produced homo- and heterosynaptic facilitation. This form of synapse-specific facilitation has unusual long-term properties. It does not require protein synthesis, nor is it accompanied by synaptic growth. Title: A transient, neuron-wide form of CREB-mediated long-term facilitation can be stabilized at specific synapses by local protein synthesis Casadio A, Martin KC, Giustetto M, Zhu H, Chen M, Bartsch D, Bailey CH, Kandel ER Ref: Cell, 99:221, 1999 : PubMed ESTHER: Casadio_1999_Cell_99_221 PubMedSearch: Casadio 1999 Cell 99 221 PubMedID: 10535740 Abstract In a culture system where a bifurcated Aplysia sensory neuron makes synapses with two motor neurons, repeated application of serotonin (5-HT) to one synapse produces a CREB-mediated, synapse-specific, long-term facilitation, which can be captured at the opposite synapse by a single pulse of 5-HT. Repeated pulses of 5-HT applied to the cell body of the sensory neuron produce a CREB-dependent, cell-wide facilitation, which, unlike synapse-specific facilitation, is not associated with growth and does not persist beyond 48 hr. Persistent facilitation and synapse-specific growth can be induced by a single pulse of 5-HT applied to a peripheral synapse. Thus, the short-term process initiated by a single pulse of 5-HT serves not only to produce transient facilitation, but also to mark and stabilize any synapse of the neuron for long-term facilitation by means of a covalent mark and rapamycin-sensitive local protein synthesis. Title: Synapse-specific, long-term facilitation of aplysia sensory to motor synapses: a function for local protein synthesis in memory storage Martin KC, Casadio A, Zhu H, Yaping E, Rose JC, Chen M, Bailey CH, Kandel ER Ref: Cell, 91:927, 1997 : PubMed ESTHER: Martin_1997_Cell_91_927 PubMedSearch: Martin 1997 Cell 91 927 PubMedID: 9428516 Abstract The requirement for transcription during long-lasting synaptic plasticity has raised the question of whether the cellular unit of synaptic plasticity is the soma and its nucleus or the synapse. To address this question, we cultured a single bifurcated Aplysia sensory neuron making synapses with two spatially separated motor neurons. By perfusing serotonin onto the synapses made onto one motor neuron, we found that a single axonal branch can undergo long-term branch-specific facilitation. This branch-specific facilitation depends on CREB-mediated transcription and involves the growth of new synaptic connections exclusively at the treated branch. Branch-specific long-term facilitation requires local protein synthesis in the presynaptic but not the postsynaptic cell. In fact, presynaptic sensory neuron axons deprived of their cell bodies are capable of protein synthesis, and this protein synthesis is stimulated 3-fold by exposure to serotonin. Title: MAP kinase translocates into the nucleus of the presynaptic cell and is required for long-term facilitation in Aplysia Martin KC, Michael D, Rose JC, Barad M, Casadio A, Zhu H, Kandel ER Ref: Neuron, 18:899, 1997 : PubMed ESTHER: Martin_1997_Neuron_18_899 PubMedSearch: Martin 1997 Neuron 18 899 PubMedID: 9208858 Abstract Long-term facilitation of the sensory to motor synapse in Aplysia requires gene expression. While some transcription factors involved in long-term facilitation are phosphorylated by PKA, others lack PKA sites but contain MAP Kinase (MAPK) phosphorylation sites. We now show that MAPK translocates into the nucleus of the presynaptic but not the postsynaptic cell during 5-HT-induced long-term facilitation. The presynaptic nuclear translocation of MAPK is also triggered by elevations in intracellular cAMP. Injection of anti-MAPK antibodies or of MAPK Kinase inhibitors into the presynaptic cell blocks long-term facilitation, without affecting basal synaptic transmission or short-term facilitation. Thus, MAPK appears to be specifically recruited and necessary for the long-term form of facilitation. This mechanism for long-term plasticity may be quite general: cAMP also activated MAPK in mouse hippocampal neurons, suggesting that MAPK may play a role in hippocampal long-term potentiation. | |||||||
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