Zhao S

References (77)

Title : Biodegradation of Typical Plastics: From Microbial Diversity to Metabolic Mechanisms - Lv_2024_Int.J.Mol.Sci_25_
Author(s) : Lv S , Li Y , Zhao S , Shao Z
Ref : Int J Mol Sci , 25 : , 2024
Abstract : Plastic production has increased dramatically, leading to accumulated plastic waste in the ocean. Marine plastics can be broken down into microplastics (<5 mm) by sunlight, machinery, and pressure. The accumulation of microplastics in organisms and the release of plastic additives can adversely affect the health of marine organisms. Biodegradation is one way to address plastic pollution in an environmentally friendly manner. Marine microorganisms can be more adapted to fluctuating environmental conditions such as salinity, temperature, pH, and pressure compared with terrestrial microorganisms, providing new opportunities to address plastic pollution. Pseudomonadota (Proteobacteria), Bacteroidota (Bacteroidetes), Bacillota (Firmicutes), and Cyanobacteria were frequently found on plastic biofilms and may degrade plastics. Currently, diverse plastic-degrading bacteria are being isolated from marine environments such as offshore and deep oceanic waters, especially Pseudomonas spp. Bacillus spp. Alcanivoras spp. and Actinomycetes. Some marine fungi and algae have also been revealed as plastic degraders. In this review, we focused on the advances in plastic biodegradation by marine microorganisms and their enzymes (esterase, cutinase, laccase, etc.) involved in the process of biodegradation of polyethylene terephthalate (PET), polystyrene (PS), polyethylene (PE), polyvinyl chloride (PVC), and polypropylene (PP) and highlighted the need to study plastic biodegradation in the deep sea.
ESTHER : Lv_2024_Int.J.Mol.Sci_25_
PubMedSearch : Lv_2024_Int.J.Mol.Sci_25_
PubMedID: 38203764

Title : Mix-and-Read Nanobody-Based Sandwich Homogeneous Split-Luciferase Assay for the Rapid Detection of Human Soluble Epoxide Hydrolase - He_2023_Anal.Chem__
Author(s) : He Q , McCoy MR , Yang H , Lin M , Cui X , Zhao S , Morisseau C , Li D , Hammock BD
Ref : Analytical Chemistry , : , 2023
Abstract : The soluble epoxide hydrolase (sEH) is possibly both a marker for and target of numerous diseases. Herein, we describe a homogeneous mix-and-read assay for the detection of human sEH based on using split-luciferase detection coupled with anti-sEH nanobodies. Selective anti-sEH nanobodies were individually fused with NanoLuc Binary Technology (NanoBiT), which consists of a large and small portion of NanoLuc (LgBiT and SmBiT, respectively). Different orientations of the LgBiT and SmBiT-nanobody fusions were expressed and investigated for their ability to reform the active NanoLuc in the presence of the sEH. After optimization, the linear range of the assay could reach 3 orders of magnitude with a limit of detection (LOD) of 1.4 ng/mL. The assay has a high sensitivity to human sEH and reached a similar detection limit to our previously reported conventional nanobody-based ELISA. The procedure of the assay was faster (30 min total) and easy to operate, providing a more flexible and simple way to monitor human sEH levels in biological samples. In general, the immunoassay proposed here offers a more efficient detection and quantification approach that can be easily adapted to numerous macromolecules.
ESTHER : He_2023_Anal.Chem__
PubMedSearch : He_2023_Anal.Chem__
PubMedID: 36972550

Title : Design, synthesis and biological evaluation of new multi-target scutellarein hybrids for treatment of Alzheimer's disease - Luo_2023_Bioorg.Chem_138_106596
Author(s) : Luo K , Chen J , Li H , Wu D , Du Y , Zhao S , Liu T , Li L , Dai Z , Li Y , Zhao Y , Tang L , Fu X
Ref : Bioorg Chem , 138 :106596 , 2023
Abstract : Scutellarein hybrids were designed, synthesized and evaluated as multifunctional therapeutic agents for the treatment of Alzheimer's disease (AD). Compounds 11a-i, containing a 2-hydroxymethyl-3,5,6-trimethylpyrazine fragment at the 7-position of scutellarein, were found to have balanced and effective multi-target potencies against AD. Among them, compound 11e exhibited the most potent inhibition of electric eel and human acetylcholinesterase enzymes with IC(50) values of 6.72 +/- 0.09 and 8.91 +/- 0.08 microM, respectively. In addition, compound 11e displayed not only excellent inhibition of self- and Cu(2+)-induced Abeta(1-42) aggregation (91.85% and 85.62%, respectively) but also induced disassembly of self- and Cu(2+)-induced Abeta fibrils (84.54% and 83.49% disaggregation, respectively). Moreover, 11e significantly reduced tau protein hyperphosphorylation induced by Abeta(25-35), and also exhibited good inhibition of platelet aggregation. A neuroprotective assay demonstrated that pre-treatment of PC12 cells with 11e significantly decreased lactate dehydrogenase levels, increased cell viability, enhanced expression of relevant apoptotic proteins (Bcl-2, Bax and caspase-3) and inhibited RSL3-induced PC12 cell ferroptosis. Furthermore, hCMEC/D3 and hPepT1-MDCK cell line permeability assays indicated that 11e would have optimal blood-brain barrier and intestinal absorption characteristics. In addition, in vivo studies revealed that compound 11e significantly attenuated learning and memory impairment in an AD mice model. Toxicity experiments with the compound did not reveal any safety concerns. Notably, 11e significantly reduced beta-amyloid precursor protein (APP) and beta-site APP cleaving enzyme-1 (BACE-1) protein expression in brain tissue of scopolamine-treated mice. Taken together, these outstanding properties qualified compound 11e as a promising multi-target candidate for AD therapy, worthy of further studies.
ESTHER : Luo_2023_Bioorg.Chem_138_106596
PubMedSearch : Luo_2023_Bioorg.Chem_138_106596
PubMedID: 37186997

Title : The Generation of a Nanobody-Based ELISA for Human Microsomal Epoxide Hydrolase - He_2023_Int.J.Mol.Sci_24_
Author(s) : He Q , McCoy MR , Qi M , Morisseau C , Yang H , Xu C , Shey R , Goodman MC , Zhao S , Hammock BD
Ref : Int J Mol Sci , 24 : , 2023
Abstract : A microsomal epoxide hydrolase (mEH) metabolizes in vivo in both xenobiotic and endogenous epoxides associated with signaling function. Findings in patients suggest that mEH might be a biomarker for several diseases, including metastatic cancer and viral hepatitis. To easily quantify mEH, nanobodies specific to the human mEH were isolated from a phage library of llama VHHs. Four unique clones were obtained and used for developing ELISAs. Three formats of double antibody sandwich assays were investigated using different detection strategies. Using PolyHRP, the signal was strongly amplified, yielding a 22-fold lower LOD (12 pg mL(-1)) than the 'conventional'. To further validate the performance of the immunoassays, human tissue samples were analyzed by nanobody-based ELISAs and compared to the enzyme activities (R(2) > 0.95). The results demonstrate that these nanobodies are powerful tools for the quantification of human mEH and could eventually result in a bedside assay.
ESTHER : He_2023_Int.J.Mol.Sci_24_
PubMedSearch : He_2023_Int.J.Mol.Sci_24_
PubMedID: 37834144

Title : Acetylcholinesterase Inhibition in Rats and Humans Following Acute Fenitrothion Exposure Predicted by Physiologically Based Kinetic Modeling-Facilitated Quantitative In Vitro to In Vivo Extrapolation - Chen_2023_Environ.Sci.Technol__
Author(s) : Chen J , Zhao S , Wesseling S , Kramer NI , Rietjens I , Bouwmeester H
Ref : Environ Sci Technol , : , 2023
Abstract : Worldwide use of organophosphate pesticides as agricultural chemicals aims to maintain a stable food supply, while their toxicity remains a major public health concern. A common mechanism of acute neurotoxicity following organophosphate pesticide exposure is the inhibition of acetylcholinesterase (AChE). To support Next Generation Risk Assessment for public health upon acute neurotoxicity induced by organophosphate pesticides, physiologically based kinetic (PBK) modeling-facilitated quantitative in vitro to in vivo extrapolation (QIVIVE) approach was employed in this study, with fenitrothion (FNT) as an exemplary organophosphate pesticide. Rat and human PBK models were parametrized with data derived from in silico predictions and in vitro incubations. Then, PBK model-based QIVIVE was performed to convert species-specific concentration-dependent AChE inhibition obtained from in vitro blood assays to corresponding in vivo dose-response curves, from which points of departure (PODs) were derived. The obtained values for rats and humans were comparable with reported no-observed-adverse-effect levels (NOAELs). Humans were found to be more susceptible than rats toward erythrocyte AChE inhibition induced by acute FNT exposure due to interspecies differences in toxicokinetics and toxicodynamics. The described approach adequately predicts toxicokinetics and acute toxicity of FNT, providing a proof-of-principle for applying this approach in a 3R-based chemical risk assessment paradigm.
ESTHER : Chen_2023_Environ.Sci.Technol__
PubMedSearch : Chen_2023_Environ.Sci.Technol__
PubMedID: 38008925

Title : A S-substituted Nile Blue-derived bifunctional near-infrared fluorescent probe for in vivo carboxylesterase imaging-guided photodynamic therapy of hepatocellular carcinoma - Wang_2023_J.Mater.Chem.B__
Author(s) : Wang B , Huang Y , Yang D , Xu J , Zhong X , Zhao S , Liang H
Ref : J Mater Chem B , : , 2023
Abstract : The development of theranostic probes that integrate both diagnostic and therapeutic functions still remains an intractable challenge in precise cancer treatment. Herein, a novel bifunctional near-infrared (NIR) fluorescent probe (CEP1) for carboxylesterase (CE) imaging and photodynamic therapy (PDT) of hepatocellular carcinoma (HCC) has been firstly developed and successfully applied in vitro and in vivo. The probe was constructed by introducing carbamate as both the recognition unit and the fluorescence quenching unit into the fluorophore S-substituted Nile Blue (ENBS) via a self-eliminating spacer with substituted chloride. It can be activated by CE and hydrolyzed into fluorescent ENBS, which recover fluorescence at about 700 nm, and can generate superoxide radical anions under NIR irradiation. Additionally, the probe could effectively distinguish tumor cells from normal cells by CE imaging of live cells. Furthermore, it could achieve CE imaging in vivo and significantly inhibits tumor growth by imaging-guided PDT. Therefore, this study offers a promising and attractive platform for activatable imaging-guided PDT of HCC.
ESTHER : Wang_2023_J.Mater.Chem.B__
PubMedSearch : Wang_2023_J.Mater.Chem.B__
PubMedID: 37427685

Title : Biosynthesis of trans-AT PKS-Derived Shuangdaolides Featuring a trans-acting Enzyme for Online Epoxidation - Liu_2023_ACS.Chem.Biol__
Author(s) : Liu Y , Zhou H , Zhao S , Hao X , Dai G , Zhong L , Ren X , Sui H , Zhang Y , Yan F , Bian X
Ref : ACS Chemical Biology , : , 2023
Abstract : Bacterial trans-acyltransferase polyketide synthases (trans-AT PKSs) synthesize natural products with intricate structures and potent biological activities. They generally contain various unusual modules or trans-acting enzymes. Herein, we report the trans-AT PKS-derived biosynthetic pathway of the shuangdaolide with a rare internal 2-hydroxycyclopentenone moiety. The multidomain protein SdlR catalyzes the synthesis of 16,17-epoxide during polyketide chain elongation. The SdlR contains a ketoreductase, an acyl carrier protein, a flavoprotein monooxygenase, and a serine hydrolase domain. This online epoxidation occurs at unusual positions away from the thioester. Then, two tailoring enzymes, SdlB and SdlQ, convert a methylene to a carbonyl group and oxidize a hydroxyl group to a carbonyl group, respectively. The following spontaneous opening of 16,17-epoxide induces the formation of a new C-C bond to generate the 2-hydroxycyclopentenone moiety. The characterization of the shuangdaolide pathway extends the understanding of the trans-AT PKSs, facilitating the mining and identification of this class of natural products.
ESTHER : Liu_2023_ACS.Chem.Biol__
PubMedSearch : Liu_2023_ACS.Chem.Biol__
PubMedID: 37992317

Title : Quantification of soluble epoxide hydrolase inhibitors in experimental and clinical samples using the nanobody-based ELISA - Yang_2023_J.Pharm.Anal_13_1013
Author(s) : Yang H , Qi M , He Q , Hwang SH , Yang J , McCoy M , Morisseau C , Zhao S , Hammock BD
Ref : J Pharm Anal , 13 :1013 , 2023
Abstract : To ensure proper dosage of a drug, analytical quantification of it in biofluid is necessary. Liquid chromatography mass spectrometry (LC-MS) is the conventional method of choice as it permits accurate identification and quantification. However, it requires expensive instrumentation and is not appropriate for bedside use. Using soluble epoxide hydrolase (sEH) inhibitors (EC5026 and TPPU) as examples, we report development of a nanobody-based enzyme-linked immunosorbent assay (ELISA) for such small molecules and its use to accurately quantify the drug chemicals in human samples. Under optimized conditions, two nanobody-based ELISAs were successfully established for EC5026 and TPPU with low limits of detection of 0.085 ng/mL and 0.31 ng/mL, respectively, and two order of magnitude linear ranges with high precision and accuracy. The assay was designed to detect parent and two biologically active metabolites in the investigation of a new drug candidate EC5026. In addition, the ELISAs displayed excellent correlation with LC-MS analysis and evaluation of inhibitory potency. The results indicate that nanobody-based ELISA methods can efficiently analyze drug like compounds. These methods could be easily implemented by the bedside, in the field in remote areas or in veterinary practice. This work illustrates that nanobody based assays offer alternative and supplementary analytical tools to mass spectrometry for monitoring small molecule medicines during clinical development and therapy. Attributes of nanobody based pharmaceutical assays are discussed.
ESTHER : Yang_2023_J.Pharm.Anal_13_1013
PubMedSearch : Yang_2023_J.Pharm.Anal_13_1013
PubMedID: 37842656

Title : Acidic pH and thiol-driven homogeneous cathodic electrochemiluminescence strategy for determining the residue of organophosphorus pesticide in Chinese cabbage - Yang_2022_Food.Chem_393_133349
Author(s) : Yang Q , Zhao S , Li H , Li F
Ref : Food Chem , 393 :133349 , 2022
Abstract : Electrochemiluminescent (ECL) sensors for organophosphorus pesticides (OPs) have received considerable attention, whereas complicated electrode's immobilization, response to single hydrolysate and anodic emission correlated with ECL assays restrict their potential utilization. Herein, we developed a homogeneous dual-response cathodic ECL system for highly sensitive and reliable analysis of OP using CdTe QDs as emitters. CdTe QDs, emitting red light, were fabricated through a hydrothermal reaction and generated anodic and cathodic ECL emission upon stimulation of tripropyl amine and K(2)S(2)O(8), respectively. Notably, CdTe QDs-K(2)S(2)O(8) showed a simultaneous response to thiol and acidic pH, and were regarded as a ECL sensor for methidathion with limit of detection of 0.016 ng/mL based on hydrolysis of acetylthiocholine into thiocholine and CH(3)COOH by acetylcholinesterase (AChE) and OPs' inhibition on AChE activity. This sensor also exhibited good practicability to detect methidathion in Chinese cabbage. Overall, the sensor will supply more useful information for ensuring OPs-related food safety.
ESTHER : Yang_2022_Food.Chem_393_133349
PubMedSearch : Yang_2022_Food.Chem_393_133349
PubMedID: 35691064

Title : Inter-individual variation in chlorpyrifos toxicokinetics characterized by physiologically based kinetic (PBK) and Monte Carlo simulation comparing human liver microsome and Supersome() cytochromes P450 (CYP)-specific kinetic data as model input - Zhao_2022_Arch.Toxicol__
Author(s) : Zhao S , Wesseling S , Rietjens I , Strikwold M
Ref : Archives of Toxicology , : , 2022
Abstract : The present study compares two approaches to evaluate the effects of inter-individual differences in the biotransformation of chlorpyrifos (CPF) on the sensitivity towards in vivo red blood cell (RBC) acetylcholinesterase (AChE) inhibition and to calculate a chemical-specific adjustment factor (CSAF) to account for inter-individual differences in kinetics (HK(AF)). These approaches included use of a Supersome() cytochromes P450 (CYP)-based and a human liver microsome (HLM)-based physiologically based kinetic (PBK) model, both combined with Monte Carlo simulations. The results revealed that bioactivation of CPF exhibits biphasic kinetics caused by distinct differences in the Km of CYPs involved, which was elucidated by Supersome() CYP rather than by HLM. Use of Supersome() CYP-derived kinetic data was influenced by the accuracy of the intersystem extrapolation factors (ISEFs) required to scale CYP isoform activity of Supersome() to HLMs. The predicted dose-response curves for average, 99th percentile and 1st percentile sensitive individuals were found to be similar in the two approaches when biphasic kinetics was included in the HLM-based approach, resulting in similar benchmark dose lower confidence limits for 10% inhibition (BMDL(10)) and HK(AF) values. The variation in metabolism-related kinetic parameters resulted in HK(AF) values at the 99th percentile that were slightly higher than the default uncertainty factor of 3.16. While HK(AF) values up to 6.9 were obtained when including also the variability in other influential PBK model parameters. It is concluded that the Supersome() CYP-based approach appeared most adequate for identifying inter-individual variation in biotransformation of CPF and its resulting RBC AChE inhibition.
ESTHER : Zhao_2022_Arch.Toxicol__
PubMedSearch : Zhao_2022_Arch.Toxicol__
PubMedID: 35294598

Title : Salivary Abeta(1-42) may be a quick-tested biomarker for clinical use in Alzheimer's disease: a meta-analysis - Fan_2022_J.Neurol__
Author(s) : Fan Z , Li Z , Zhao S , Chen Y , Su Y , Peng G , Luo B
Ref : Journal of Neurology , : , 2022
Abstract : OBJECTIVE: Alzheimer's disease (AD) is the most prevalent form of dementia among the aging population. Cumulative studies aim to find non-invasive biomarkers in the early stages of AD. Saliva can be obtained easily, and salivary biomarkers have been proven effective in detecting neurodegenerative diseases. To find effective biomarkers in saliva and to help the diagnosis of AD, we performed a meta-analysis focusing on the salivary biomarkers (beta-amyloid 1-42 (Abeta(1-42)), total tau (t-tau), phosphorylated tau (p-tau) and acetylcholinesterase (AChE)) in AD. METHODS: We conducted a systematic online search for eligible studies reporting data on salivary biomarkers reflecting Abeta(1-42), t-tau, p-tau, and AChE in AD cohorts versus controls. Biomarkers' performance was assessed in a random-effects meta-analysis with the ratio of mean (RoM). RESULTS: A total of thirteen studies were included in the meta-analysis, of them seven involved salivary Abeta(1-42) (271 AD and 489 controls), five involved salivary t-tau (324 AD and 252 controls), four involved salivary p-tau (130 AD and 161 controls), and three involved salivary AChE (81 AD and 54 controls). AD showed significantly higher salivary Abeta(1-42) levels than control (ROM = 1.90 (95% CI 1.28-2.81, P = 0.001), while AD and control did not differ significantly on salivary t-tau, p-tau and AChE (ROM = 0.94, 95% CI 0.67-1.31, P = 0.72; ROM = 0.91, 95% CI 0.56-1.45, P = 0.68; ROM = 0.83, 95% CI 0.24-2.88, P = 0.77; respectively). CONCLUSION: The pooled results provide evidence that salivary Abeta(1-42) may serve as a sensitive biomarker for AD; nevertheless, larger AD cohorts are required to further confirm the sensitivity and specificity of salivary Abeta(1-42) for AD diagnosis.
ESTHER : Fan_2022_J.Neurol__
PubMedSearch : Fan_2022_J.Neurol__
PubMedID: 36562850

Title : Substrate-dependent inhibition of hypericin on human carboxylesterase 2: implications for herb-drug combination - Wang_2022_Curr.Drug.Metab__
Author(s) : Wang D , Zhao T , Zhao S , Chen J , Dou T , Ge G , Wang C , Sun H , Liu K , Meng Q , Wu J
Ref : Curr Drug Metab , : , 2022
Abstract : BACKGROUND: Hypericin is the main active ingredient of St. John's wort, a Chinese herb commonly used in treating depression. Previous studies have shown that hypericin can strongly inhibit human cytochrome P450 (CYP) enzyme activities; however, its potential interactions that inhibit human carboxylesterases 2 (hCE2) were unclear. PURPOSE: The study aimed to investigate the inhibition of hypericin on hCE2. METHODS: The inhibition of hypericin on hCE2 was studied by using N-(2-butyl-1,3-dioxo-2,3-dihydro-1H-phenalen-6-yl)-2-chloroacetamide (NCEN). The type of inhibition of hypericin on hCE2 and the corresponding inhibition constant (Ki) value were determined. The inhibition of hypericin on hCE2 in living cells was discussed. The herb-drug interactions (HDI) risk of hypericin and hCE2 in vivo was predicted by estimating the drug concentration-time curve (AUC) ratio of hypericin and hypericin free. To understand the inhibition mechanism of hypericin on the activity of hCE2 in-depth, molecular docking was performed. RESULTS: The half-maximal inhibitory concentration (IC50) values of hypericin against the hydrolysis of NCEN and irinotecan (CPT-11) were calculated to be 26.59 microM and 112.8 microM, respectively. Hypericin inhibited the hydrolysis of NCEN and CPT-11. Their Ki values were 10.53 microM and 81.77 microM, respectively. Moreover, hypericin distinctly suppressed hCE2 activity in living cells. In addition, the AUC of hCE2 metabolic drugs with metabolic sites similar to NCEN was estimated to increase by up to 5%, in the presence of hypericin. More importantly, the exposure of CPT-11 in the intestinal epithelium was predicted to increase by 2%-69% following the oral co-administration of hypericin. Further, molecular simulations indicated that hypericin could strongly interact with ASP98, PHE307, and ARG355 to form four hydrogen bonds within hCE2. CONCLUSION: These findings are of considerable clinical significance to the combination of hypericin-containing herbs and drugs metabolized by hCE2.
ESTHER : Wang_2022_Curr.Drug.Metab__
PubMedSearch : Wang_2022_Curr.Drug.Metab__
PubMedID: 35114918

Title : Neurotoxicity of tetrabromobisphenol A and SiO2 nanoparticle co-exposure in zebrafish and barrier function of the embryonic chorion - Zhu_2022_Sci.Total.Environ_845_157364
Author(s) : Zhu B , Lei L , Fu K , Zhao S , Hua J , Yang L , Han J , Li R , Zhou B
Ref : Sci Total Environ , 845 :157364 , 2022
Abstract : Silicon dioxide nanoparticles (n-SiO(2)) absorb tetrabromobisphenol A (TBBPA) and modify its bioavailability and toxicity in the aquatic phase; embryonic chorion is an efficient barrier against nanoparticles (e.g., SiO(2)) and influences their toxicity. However, few studies have investigated developmental neurotoxicity in fish after co-exposure to TBBPA and n-SiO(2), especially considering the barrier function of the chorion. In the present study, zebrafish embryos were exposed to TBBPA (50, 100, and 200 microg/L) alone or in combination with n-SiO(2) (25 mg/L) until 24 or 120 h post fertilization (hpf), in the presence and absence of the chorion. The results confirmed that TBBPA exposure alone significantly downregulated the expression of neurodevelopment marker genes (mbp, alpha-tubulin, shha, and gfap), altered acetylcholinesterase activity and acetylcholine content, and affected locomotor behavior at different developmental stages. Moreover, the results indicated that n-SiO(2) promoted TBBPA-induced neurotoxic effects in zebrafish larvae at 120 hpf, including further repression of the transcription of CNS-related genes, disruption of the cholinergic system, and decrease in the average swimming speed under dark/light stimulation. However, scanning electron microscopy/energy dispersive spectroscopy analysis revealed that at 24 hpf, the embryonic chorion efficiently blocked n-SiO(2) and consequently decreased the bioaccumulation of TBBPA and TBBPA-induced neurotoxicity in dechorionated zebrafish embryos. Taken together, the results demonstrate that n-SiO(2) affected the bioavailability and neurodevelopmental toxicity of TBBPA, and their combined toxicity to zebrafish embryos was mitigated by embryonic chorion, which will facilitate risk assessment on n-SiO(2) and TBBPA and improve understanding the function of the fish embryonic chorion.
ESTHER : Zhu_2022_Sci.Total.Environ_845_157364
PubMedSearch : Zhu_2022_Sci.Total.Environ_845_157364
PubMedID: 35843329

Title : Hemoperfusion in combination with hemofiltration for acute severe organophosphorus pesticide poisoning: A systematic review and meta-analysis - Zhang_2022_J.Res.Med.Sci_27_33
Author(s) : Zhang M , Zhang W , Zhao S , Tian X , Fu G , Wang B
Ref : J Res Med Sci , 27 :33 , 2022
Abstract : BACKGROUND: Acute severe organophosphorus pesticide poisoning (ASOPP) is one of the major diseases that endanger human life and health. However, the effects of conventional therapy including gastric lavages, mechanical ventilation, muscarinic antagonist drugs, and cholinesterase reactivators were uncertain. This meta-analysis aims to investigate the safety and efficacy of hemoperfusion combined with hemofiltration besides routine therapy for ASOPP. MATERIALS AND METHODS: A comprehensive search for candidate publications was performed through PubMed, Medline, Cochrane Library, WanFang, Chinese Biomedical Literature, and China National Knowledge Infrastructure from database inception to May 12, 2020. The retrieved studies were screened by the predefined inclusion and exclusion criteria. The data of important end points were extracted. The risk ratio (RR) and weighted mean difference (WMD) were pooled for categorical variables and continuous variables, respectively. Meta-analyses and publication bias were conducted by using STATA software version 15.1. RESULTS: A total of 11 randomized controlled trials with 811 patients were included. Compared to conventional therapy group, patients in the hemoperfusion plus hemofiltration group were significantly superior with regard to mortality (RR 0.38, 95% confidence interval [CI] [0.25, 0.57], P < 0.001), total atropine dosing (WMD -147.34 mg, 95% CI [-199.49, -95.18], P < 0.001), duration of mechanical ventilation (WMD -2.34 days, 95% CI [-3.77, -0.92], P < 0.001), cholinesterase recovery time (WMD -2.49 days, 95% CI [-3.14, -1.83], P < 0.001), and length of stay (WMD -4.52 days, 95% CI [-5.31, -3.73], P < 0.001). CONCLUSION: Combined hemoperfusion and hemofiltration was a very safe and effective treatment protocol for ASOPP, not only resulting in significantly decreased mortality but also resulting in reduced total atropine dosing, duration of mechanical ventilation, cholinesterase recovery time, and length of stay.
ESTHER : Zhang_2022_J.Res.Med.Sci_27_33
PubMedSearch : Zhang_2022_J.Res.Med.Sci_27_33
PubMedID: 35548179

Title : Prediction of dose-dependent in vivo acetylcholinesterase inhibition by profenofos in rats and humans using physiologically based kinetic (PBK) modeling-facilitated reverse dosimetry - Omwenga_2021_Arch.Toxicol__
Author(s) : Omwenga I , Zhao S , Kanja L , Mol H , Rietjens I , Louisse J
Ref : Archives of Toxicology , : , 2021
Abstract : Organophosphate pesticides (OPs) are known to inhibit acetylcholine esterase (AChE), a critical effect used to establish health-based guidance values. This study developed a combined in vitro-in silico approach to predict AChE inhibition by the OP profenofos in rats and humans. A physiologically based kinetic (PBK) model was developed for both species. Parameter values for profenofos conversion to 4-bromo-2-chlorophenol (BCP) were derived from in vitro incubations with liver microsomes, liver cytosol, and plasma from rats (catalytic efficiencies of 1.1, 2.8, and 0.19 ml/min/mg protein, respectively) and humans (catalytic efficiencies of 0.17, 0.79, and 0.063 ml/min/mg protein, respectively), whereas other chemical-related parameter values were derived using in silico calculations. The rat PBK model was evaluated against literature data on urinary excretion of conjugated BCP. Concentration-dependent inhibition of rat and human AChE was determined in vitro and these data were translated with the PBK models to predicted dose-dependent AChE inhibition in rats and humans in vivo. Comparing predicted dose-dependent AChE inhibition in rats to literature data on profenofos-induced AChE inhibition revealed an accurate prediction of in vivo effect levels. Comparison of rat predictions (BMDL10 of predicted dose-response data of 0.45 mg/kg bw) and human predictions (BMDL10 of predicted dose-response data of 0.01 mg/kg bw) suggests that humans are more sensitive than rats, being mainly due to differences in kinetics. Altogether, the results demonstrate that in vivo AChE inhibition upon acute exposure to profenofos was closely predicted in rats, indicating the potential of this novel approach method in chemical hazard assessment.
ESTHER : Omwenga_2021_Arch.Toxicol__
PubMedSearch : Omwenga_2021_Arch.Toxicol__
PubMedID: 33651127

Title : Physiologically based kinetic modelling based prediction of in vivo rat and human acetylcholinesterase (AChE) inhibition upon exposure to diazinon - Zhao_2021_Arch.Toxicol__
Author(s) : Zhao S , Wesseling S , Spenkelink B , Rietjens I
Ref : Archives of Toxicology , : , 2021
Abstract : The present study predicts in vivo human and rat red blood cell (RBC) acetylcholinesterase (AChE) inhibition upon diazinon (DZN) exposure using physiological based kinetic (PBK) modelling-facilitated reverse dosimetry. Due to the fact that both DZN and its oxon metabolite diazoxon (DZO) can inhibit AChE, a toxic equivalency factor (TEF) was included in the PBK model to combine the effect of DZN and DZO when predicting in vivo AChE inhibition. The PBK models were defined based on kinetic constants derived from in vitro incubations with liver fractions or plasma of rat and human, and were used to translate in vitro concentration-response curves for AChE inhibition obtained in the current study to predicted in vivo dose-response curves. The predicted dose-response curves for rat matched available in vivo data on AChE inhibition, and the benchmark dose lower confidence limits for 10% inhibition (BMDL(10) values) were in line with the reported BMDL(10) values. Humans were predicted to be 6-fold more sensitive than rats in terms of AChE inhibition, mainly because of inter-species differences in toxicokinetics. It is concluded that the TEF-coded DZN PBK model combined with quantitative in vitro to in vivo extrapolation (QIVIVE) provides an adequate approach to predict RBC AChE inhibition upon acute oral DZN exposure, and can provide an alternative testing strategy for derivation of a point of departure (POD) in risk assessment.
ESTHER : Zhao_2021_Arch.Toxicol__
PubMedSearch : Zhao_2021_Arch.Toxicol__
PubMedID: 33715020

Title : Multivalent butyrylcholinesterase inhibitor discovered by exploiting dynamic combinatorial chemistry - Zhao_2021_Bioorg.Chem_108_104656
Author(s) : Zhao S , Xu J , Zhang S , Han M , Wu Y , Li Y , Hu L
Ref : Bioorg Chem , 108 :104656 , 2021
Abstract : In this study, we report the generation of a polymer-based dynamic combinatorial library (DCL) incorporating exchangeable side chains using acylhydrazone formation reaction. In combination with tetrameric butyrylcholinesterase (BChE), the most potent binding side chain was identified, and the information obtained was further used for the synthesis of a multivalent BChE inhibitor. In the in vitro biological evaluation, this multivalent inhibitor exhibited not only better inhibitory effect than the commercial reference but also high selectivity on BChE over acetylcholinesterase (AChE).
ESTHER : Zhao_2021_Bioorg.Chem_108_104656
PubMedSearch : Zhao_2021_Bioorg.Chem_108_104656
PubMedID: 33548731

Title : Use of data-independent acquisition mass spectrometry for comparative proteomics analyses of sera from pregnant women with intrahepatic cholestasis of pregnancy - Zou_2021_J.Proteomics__104124
Author(s) : Zou S , Dong R , Wang J , Liang B , Zhu T , Zhao S , Zhang Y , Wang T , Zou P , Li N , Wang Y , Chen M , Zhou C , Zhang T , Luo L
Ref : J Proteomics , :104124 , 2021
Abstract : We used data-independent acquisition (DIA) proteomics technology followed by ELISAs and automated biochemical analyses to identify and validate protein expression levels in Intrahepatic Cholestasis of Pregnancy (ICP) and healthy pregnant controls. We employed bioinformatics to identify metabolic processes associated with differentially expressed proteins.The expression levels of two proteins (S100-A9 and the L-lactate dehydrogenase A chain) were significantly higher in ICP patients than in controls; the areas under the receiver operating characteristic (ROC) curves (AUCs) were 0.774 and 0.828, respectively. The expression levels of two other proteins (apolipoprotein A-I and cholinesterase) were significantly lower in patients, with values of 0.900 and 0.842, respectively. Multiple logistic regression showed that a combination of the levels of the four proteins optimized the AUC (0.962), thus more reliably diagnosing ICP. The levels of all four proteins were positively associated with that of total bile acids. Bioinformatics analyses indicated that the four proteins principally affected neutrophil activation involved in the immune response, cell adhesion, lipoprotein metabolism, and the PPAR signaling pathway. SIGNIFICANCE: This preliminary work improves our understanding of changes in serum levels of protein in pregnant women with ICP. The four proteins may serve as novel noninvasive biomarkers for ICP.
ESTHER : Zou_2021_J.Proteomics__104124
PubMedSearch : Zou_2021_J.Proteomics__104124
PubMedID: 33545297

Title : Identification of Candidate Carboxylesterases Associated With Odorant Degradation in Holotrichia parallela Antennae Based on Transcriptome Analysis - Yi_2021_Front.Physiol_12_674023
Author(s) : Yi J , Wang S , Wang Z , Wang X , Li G , Zhang X , Pan Y , Zhao S , Zhang J , Zhou JJ , Wang J , Xi J
Ref : Front Physiol , 12 :674023 , 2021
Abstract : Insects rely on their olfactory systems in antennae to recognize sex pheromones and plant volatiles in surrounding environments. Some carboxylesterases (CXEs) are odorant-degrading enzymes (ODEs), degrading odorant signals to protect the olfactory neurons against continuous excitation. However, there is no report about CXEs in Holotrichia parallela, one of the most major agricultural underground pests in China. In the present study, 20 candidate CXEs were identified based on transcriptome analysis of female and male antennae. Sequence alignments and phylogenetic analysis were performed to investigate the characterization of these candidate CXEs. The expression profiles of CXEs were compared by RT-qPCR analysis between olfactory and non-olfactory tissues of both genders. HparCXE4, 11, 16, 17, 18, 19, and 20 were antenna-biased expressed genes, suggesting their possible roles as ODEs. HparCXE6, 10, 11, 13, and 16 showed significantly higher expression profiles in male antennae, whereas HparCXE18 was expressed more in female antennae. This study highlighted candidate CXE genes linked to odorant degradation in antennae, and provided a useful resource for further work on the H. parallela olfactory mechanism and selection of target genes for integrative control of H. parallela.
ESTHER : Yi_2021_Front.Physiol_12_674023
PubMedSearch : Yi_2021_Front.Physiol_12_674023
PubMedID: 34566671

Title : Identification and synthesis of selective cholesterol esterase inhibitor using dynamic combinatorial chemistry - Zhao_2021_Bioorg.Chem_119_105520
Author(s) : Zhao S , Wu Y , Hu L
Ref : Bioorg Chem , 119 :105520 , 2021
Abstract : In this study, the concept of dynamic combinatorial chemistry (DCC) was applied to explore novel cholesterol esterase (CEase) inhibitors. In the presence of enzyme, two substrates (A1H3 and A2H3) were amplified from the dynamic combinatorial library (DCL), which was generated through reversible acylhydrazone formation reaction. In the in vitro biological evaluation, compound A1H3 exhibited not only potent (IC(50) in nanomolar range) but also selective inhibition (>120 folds of selectivity for CEase over AChE). Furthermore, the binding pattern and possible binding mechanism were investigated in the kinetic experiment and molecular docking study, respectively.
ESTHER : Zhao_2021_Bioorg.Chem_119_105520
PubMedSearch : Zhao_2021_Bioorg.Chem_119_105520
PubMedID: 34864280

Title : Enantioselective disposition and metabolic products of isofenphos-methyl in rats and the hepatotoxic effects - Gao_2020_Environ.Int_143_105940
Author(s) : Gao B , Zhao S , Shi H , Zhang Z , Li L , He Z , Wen Y , Covaci A , Wang M
Ref : Environ Int , 143 :105940 , 2020
Abstract : Isofenphos-methyl (IFP), a chiral organophosphorus pesticide, is one of the main chemicals used to control underground insects and nematodes. Recently, the use of IFP on vegetables and fruits has been prohibited due to its high toxicity. In this study, we investigated the enantioselective distribution and metabolism of IFP and its metabolites, namely, isofenphos-methyl oxon (IFPO) and isocarbophos oxon (ICPO), in male Sprague Dawley (SD) rats. Forty eight hours (48 h) after exposure, ICPO was the main detectable compound in blood (up to 75%) and urine (up to 77%), and we found that (S)-ICPO was significantly more stable than (R)-ICPO (p < 0.05). Therefore, (S)-ICPO was proposed as a suitable candidate biomarker for the biomonitoring of IFP in human urine and blood. After 48 h exposure, 21.2-41.0%, 4.1-15.1%, and 8.6-18.7% of dosed IFP was detected in the liver of racemic, R and S enantiomer-exposed rats, respectively, and R-IFP and R-IFPO showed a faster degradation (p < 0.05). Our results showed that after one week of consecutive exposure to IFP, ICPO was accumulated in the liver of rats in both racemic and enantiopure groups (no difference between the groups, p > 0.05). We found that cytochrome P450 (CYP) (i.e. CYP2C11, CYP2D2 and CYP3A2 enzymes and carboxylesterases) is responsible for the enantioselective metabolism of IFP in liver. In addition, rats exposed to (S)-IFP exhibited hepatic lipid peroxidation, liver inflammation and hepatic fibrosis. This study provides useful information and a reference for the biomonitoring and risk assessment of IFP and organophosphorus pesticide exposure.
ESTHER : Gao_2020_Environ.Int_143_105940
PubMedSearch : Gao_2020_Environ.Int_143_105940
PubMedID: 32663714

Title : Development of a multivalent acetylcholinesterase inhibitor via dynamic combinatorial chemistry - Xu_2020_Int.J.Biol.Macromol_150_1184
Author(s) : Xu J , Zhao S , Zhang S , Pei J , Li Y , Zhang Y , He X , Hu L
Ref : Int J Biol Macromol , 150 :1184 , 2020
Abstract : In this study, we report the generation of a polymer based dynamic combinatorial library (DCL) using aldehyde-functionalized linear poly(glycidol) and hydrazide derivatives as initial building blocks. In combination with tetrameric acetylcholinesterase (AChE), a certain type of amplified acylhydrazone side chain is identified and further used for the synthesis of a multivalent AChE inhibitor. The cytotoxicity and inhibition properties of the multivalent inhibitor are evaluated, and the results indicate superior bioactivity compared to the commercial reference Edrophonium chloride.
ESTHER : Xu_2020_Int.J.Biol.Macromol_150_1184
PubMedSearch : Xu_2020_Int.J.Biol.Macromol_150_1184
PubMedID: 31758986

Title : The genome sequence of the grape phylloxera provides insights into the evolution, adaptation, and invasion routes of an iconic pest - Rispe_2020_BMC.Biol_18_90
Author(s) : Rispe C , Legeai F , Nabity PD , Fernandez R , Arora AK , Baa-Puyoulet P , Banfill CR , Bao L , Barbera M , Bouallegue M , Bretaudeau A , Brisson JA , Calevro F , Capy P , Catrice O , Chertemps T , Couture C , Deliere L , Douglas AE , Dufault-Thompson K , Escuer P , Feng H , Forneck A , Gabaldon T , Guigo R , Hilliou F , Hinojosa-Alvarez S , Hsiao YM , Hudaverdian S , Jacquin-Joly E , James EB , Johnston S , Joubard B , Le Goff G , Le Trionnaire G , Librado P , Liu S , Lombaert E , Lu HL , Maibeche M , Makni M , Marcet-Houben M , Martinez-Torres D , Meslin C , Montagne N , Moran NA , Papura D , Parisot N , Rahbe Y , Lopes MR , Ripoll-Cladellas A , Robin S , Roques C , Roux P , Rozas J , Sanchez-Gracia A , Sanchez-Herrero JF , Santesmasses D , Scatoni I , Serre RF , Tang M , Tian W , Umina PA , van Munster M , Vincent-Monegat C , Wemmer J , Wilson ACC , Zhang Y , Zhao C , Zhao J , Zhao S , Zhou X , Delmotte F , Tagu D
Ref : BMC Biol , 18 :90 , 2020
Abstract : BACKGROUND: Although native to North America, the invasion of the aphid-like grape phylloxera Daktulosphaira vitifoliae across the globe altered the course of grape cultivation. For the past 150 years, viticulture relied on grafting-resistant North American Vitis species as rootstocks, thereby limiting genetic stocks tolerant to other stressors such as pathogens and climate change. Limited understanding of the insect genetics resulted in successive outbreaks across the globe when rootstocks failed. Here we report the 294-Mb genome of D. vitifoliae as a basic tool to understand host plant manipulation, nutritional endosymbiosis, and enhance global viticulture. RESULTS: Using a combination of genome, RNA, and population resequencing, we found grape phylloxera showed high duplication rates since its common ancestor with aphids, but similarity in most metabolic genes, despite lacking obligate nutritional symbioses and feeding from parenchyma. Similarly, no enrichment occurred in development genes in relation to viviparity. However, phylloxera evolved > 2700 unique genes that resemble putative effectors and are active during feeding. Population sequencing revealed the global invasion began from the upper Mississippi River in North America, spread to Europe and from there to the rest of the world. CONCLUSIONS: The grape phylloxera genome reveals genetic architecture relative to the evolution of nutritional endosymbiosis, viviparity, and herbivory. The extraordinary expansion in effector genes also suggests novel adaptations to plant feeding and how insects induce complex plant phenotypes, for instance galls. Finally, our understanding of the origin of this invasive species and its genome provide genetics resources to alleviate rootstock bottlenecks restricting the advancement of viticulture.
ESTHER : Rispe_2020_BMC.Biol_18_90
PubMedSearch : Rispe_2020_BMC.Biol_18_90
PubMedID: 32698880

Title : Adipose ABHD6 regulates tolerance to cold and thermogenic programs - Poursharifi_2020_JCI.Insight_5_
Author(s) : Poursharifi P , Attane C , Mugabo Y , Al-Mass A , Ghosh A , Schmitt C , Zhao S , Guida J , Lussier R , Erb H , Chenier I , Peyot ML , Joly E , Noll C , Carpentier AC , Madiraju SRM , Prentki M
Ref : JCI Insight , 5 : , 2020
Abstract : Enhanced energy expenditure in brown (BAT) and white adipose tissues (WAT) can be therapeutic against metabolic diseases. We examined the thermogenic role of adipose alpha/beta-hydrolase domain 6 (ABHD6), which hydrolyzes monoacylglycerol (MAG), by employing adipose-specific ABHD6-KO mice. Control and KO mice showed similar phenotypes at room temperature and thermoneutral conditions. However, KO mice were resistant to hypothermia, which can be accounted for by the simultaneously increased lipolysis and lipogenesis of the thermogenic glycerolipid/free fatty acid (GL/FFA) cycle in visceral fat, despite unaltered uncoupling protein 1 expression. Upon cold stress, nuclear 2-MAG levels increased in visceral WAT of the KO mice. Evidence is provided that 2-MAG causes activation of PPARalpha in white adipocytes, leading to elevated expression and activity of GL/FFA cycle enzymes. In the ABHD6-ablated BAT, glucose and oxidative metabolism were elevated upon cold induction, without changes in GL/FFA cycle and lipid turnover. Moreover, response to in vivo beta3-adrenergic stimulation was comparable between KO and control mice. Our data reveal a MAG/PPARalpha/GL/FFA cycling metabolic signaling network in visceral adipose tissue, which contributes to cold tolerance, and that adipose ABHD6 is a negative modulator of adaptive thermogenesis.
ESTHER : Poursharifi_2020_JCI.Insight_5_
PubMedSearch : Poursharifi_2020_JCI.Insight_5_
PubMedID: 33201859
Gene_locus related to this paper: human-ABHD6

Title : Association of alpha\/beta-Hydrolase D16B with Bovine Conception Rate and Sperm Plasma Membrane Lipid Composition - Shan_2020_Int.J.Mol.Sci_21_
Author(s) : Shan S , Xu F , Bleyer M , Becker S , Melbaum T , Wemheuer W , Hirschfeld M , Wacker C , Zhao S , Schutz E , Brenig B
Ref : Int J Mol Sci , 21 : , 2020
Abstract : We have identified a Holstein sire named Tarantino who had been approved for artificial insemination that is based on normal semen characteristics (i.e., morphology, thermoresistance, motility, sperm concentration), but had no progeny after 412 first inseminations, resulting in a non-return rate (NRdev) of -29. Using whole genome association analysis and next generation sequencing, an associated nonsense variant in the alpha/beta-hydrolase domain-containing 16B gene (ABHD16B) on bovine chromosome 13 was identified. The frequency of the mutant allele in the German Holstein population was determined to be 0.0018 in 222,645 investigated cattle specimens. The mutant allele was traced back to Whirlhill Kingpin (bornFeb. 13th, 1959) as potential founder. The expression of ABHD16B was detected by Western blotting and immunohistochemistry in testis and epididymis of control bulls. A lipidome comparison of the plasma membrane of fresh semen from carriers and controls showed significant differences in the concentration of phosphatidylcholine (PC), diacylglycerol (DAG), ceramide (Cer), sphingomyelin (SM), and phosphatidylcholine (-ether) (PC O-), indicating that ABHD16B plays a role in lipid biosynthesis. The altered lipid contents may explain the reduced fertilization ability of mutated sperms.
ESTHER : Shan_2020_Int.J.Mol.Sci_21_
PubMedSearch : Shan_2020_Int.J.Mol.Sci_21_
PubMedID: 31963602
Gene_locus related to this paper: bovin-ABHD16B , human-ABHD16B , mouse-Abhd16b

Title : Effect of salt promote the muscle triglyceride hydrolysis during dry-salting by inducing the phosphorylation of adipose tissue triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL) and lipid droplets splitting - Zhao_2020_Food.Chem_327_127061
Author(s) : Zhao S , He L , Zhang M , Liu X , Jin G
Ref : Food Chem , 327 :127061 , 2020
Abstract : This study mainly investigated the effect of different salt concentrations (1, 3, or 5%) on triglycerides (TG) hydrolysis in muscle during salting by analyzing moisture distribution, TG hydrolysis, TG hydrolase activity, native and phosphorylated adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL) protein content, lipid droplets morphology, and muscle microstructure. The results showed that increasing salt concentration could significantly decrease T21 moisture proportion and relaxation time (p < 0.05), which was more beneficial to the lipase activity. The TG hydrolase activity increased first and then decreased with the salt concentration increasing during dry-salting process, and 3% salt concentration was the point of inflection. Western blot (WB) analysis detected both ATGL, HSL and their phosphorylated proteins, which were increased with the salt content increase. The microstructure analysis showed that the lipid droplets were split into small lipid droplets with the increase of salt content, which was more conducive to the triglycerides hydrolysis.
ESTHER : Zhao_2020_Food.Chem_327_127061
PubMedSearch : Zhao_2020_Food.Chem_327_127061
PubMedID: 32454271

Title : A potential biomarker of isofenphos-methyl in humans: A chiral view - Gao_2019_Environ.Int_127_694
Author(s) : Gao B , Zhao S , Zhang Z , Li L , Hu K , Kaziem AE , He Z , Hua X , Shi H , Wang M
Ref : Environ Int , 127 :694 , 2019
Abstract : Isofenphos-methyl (IFP) is a very active and persistent chiral insecticide. However, IFP has lower activity against acetylcholinesterases (AChEs). Previously, it was confirmed that phosphorothioate organophosphorus pesticides with N-alkyl (POPN) require activation by oxidative desulfuration and N-dealkylation. In this work, we demonstrated that IFP could be metabolized in human liver microsomes to isofenphos-methyl oxon (IFPO, 52.7%), isocarbophos (ICP, 14.2%) and isocarbophos oxon (ICPO, 11.2%). It was found that (R)-IFP was preferentially degraded compared to the (S)-enantiomer, and the enantiomeric fraction (EF) value reached 0.61 at 60min. However, (S)-enantiomers of the three metabolites, were degraded preferentially, and the EF values ranged from 0.34 to 0.45. Cytochrome P450 (CYP) isoforms CYP3A4, CYP2E1, and CYP1A2 and carboxylesterase enzyme have an essential role in the enantioselective metabolism of IFP; but, the enzymes that participate in the degradation of IFP metabolites are different. The AChE inhibition bioassay indicated that ICPO is the only effective inhibitor of AChE. The covalent molecular docking has proposed that the metabolites of IFP and its analogs after N-dealkylation and oxidative desulfuration will possess the highest inhibitory activity against AChE. This study is the first to demonstrate that ICPO can be regarded as a potential biomarker for the biomonitoring of IFP and ICP exposure in humans.
ESTHER : Gao_2019_Environ.Int_127_694
PubMedSearch : Gao_2019_Environ.Int_127_694
PubMedID: 30991225

Title : Physiologically based kinetic modelling-facilitated reverse dosimetry to predict in vivo red blood cell acetylcholinesterase inhibition following exposure to chlorpyrifos in the Caucasian and Chinese population - Zhao_2019_Toxicol.Sci_171_69
Author(s) : Zhao S , Kamelia L , Boonpawa R , Wesseling S , Spenkelink B , Rietjens I
Ref : Toxicol Sci , 171 :69 , 2019
Abstract : Organophosphates (OPs) have a long history of use as insecticides over the world. The aim of the present study was to investigate the interethnic differences in kinetics, biomarker formation and in vivo red blood cell (RBC) acetylcholinesterase (AChE) inhibition of chlorpyrifos (CPF) in the Chinese and the Caucasian population. To this purpose, PBK models for CPF in both the Chinese and Caucasian population were developed, and used to study time- and dose-dependent interethnic variation in urinary biomarkers and to convert concentration-response curves for RBC AChE inhibition to in vivo dose-response curves in these two populations by reverse dosimetry. The results obtained revealed a marked interethnic difference in toxicokinetics of CPF, with lower urinary biomarker levels at similar dose levels and slower CPF bioactivation and faster CPO detoxification in the Chinese compared with the Caucasian population, resulting in 5- to 6-fold higher CPF sensitivity of the Caucasian than the Chinese population. These differences might be related to variation in the frequency of single-nucleotide polymorphisms (SNPs) for the major biotransformation enzymes involved. To conclude, the interethnic variation in kinetics of CPF may affect both its biomarker-based exposure assessment as well as its toxicity and risk assessment and that PBK modelling facilitates the characterisation and quantification of these interethnic variations.
ESTHER : Zhao_2019_Toxicol.Sci_171_69
PubMedSearch : Zhao_2019_Toxicol.Sci_171_69
PubMedID: 31214721

Title : Accumulation, biodegradation and toxicological effects of N-ethyl perfluorooctane sulfonamidoethanol on the earthworms Eisenia fetida exposed to quartz sands - Zhao_2019_Ecotoxicol.Environ.Saf_181_138
Author(s) : Zhao S , Liu T , Wang B , Fu J , Liang T , Zhong Z , Zhan J , Liu L
Ref : Ecotoxicology & Environmental Safety , 181 :138 , 2019
Abstract : While N-ethyl perfluorooctane sulfonamidoethanol (EtFOSE) is a precursor of perfluorooctane sulfonate (PFOS), its bioaccumulation, transformation and toxicological effects in earthworms (Eisenia fetida) exposed to quartz sands are poorly understood. The present study showed that except for parent EtFOSE, N-ethylperfluorooctane sulfonamide acetate (EtFOSAA), N-ethyl perfluorooctane sulfonamide (EtFOSA), perfluorooctane sulfonamide acetate (FOSAA), perfluorooctane sulfonamide (FOSA) and PFOS were detected in earthworms, with EtFOSAA as the primary biotransformation product. The biota-to-sand accumulation factor (BSAF) and uptake rate coefficient (ku) of EtFOSE were 5.7 and 0.542/d, respectively. The elimination rate constants (ke) decreased in the order EtFOSA (0.167/d) approximately FOSAA (0.147/d)>FOSA (0.119/d) approximately EtFOSAA (0.117/d)>EtFOSE (0.095/d)>PFOS (0.069/d). No significant effects were observed in malondialdehyde (MDA) contents and acetylcholinesterase (AChE) activities between EtFOSE treatments and controls. EtFOSE could cause significant accumulation of reactive oxygen species (ROS) in earthworms. Peroxidase (POD), superoxide dismutase (SOD) and catalase (CAT) were significantly activated by 41.4-74.3%, 37.2-44.4% and 32.4-52.3% from day 4-10, respectively, while 8-Hydroxy-2-deoxyguanosine (8-OHdG) levels were elevated by 47.7-70.3% from day 8-10, demonstrating that EtFOSE induced oxidative stress and oxidative DNA damage in earthworms. Significant increase of glutathione-S-transferase (GST) with 41.6-62.8% activation (8-10d) gave indirect evidence on the conjugation of EtFOSE or its corresponding metabolites during phase II of detoxication. This study provides important information on the fate and potential risks of EtFOSE to terrestrial invertebrates.
ESTHER : Zhao_2019_Ecotoxicol.Environ.Saf_181_138
PubMedSearch : Zhao_2019_Ecotoxicol.Environ.Saf_181_138
PubMedID: 31176248

Title : Musa balbisiana genome reveals subgenome evolution and functional divergence - Wang_2019_Nat.Plants_5_810
Author(s) : Wang Z , Miao H , Liu J , Xu B , Yao X , Xu C , Zhao S , Fang X , Jia C , Wang J , Zhang J , Li J , Xu Y , Ma W , Wu Z , Yu L , Yang Y , Liu C , Guo Y , Sun S , Baurens FC , Martin G , Salmon F , Garsmeur O , Yahiaoui N , Hervouet C , Rouard M , Laboureau N , Habas R , Ricci S , Peng M , Guo A , Xie J , Li Y , Ding Z , Yan Y , Tie W , D'Hont A , Hu W , Jin Z
Ref : Nat Plants , 5 :810 , 2019
Abstract : Banana cultivars (Musa ssp.) are diploid, triploid and tetraploid hybrids derived from Musa acuminata and Musa balbisiana. We presented a high-quality draft genome assembly of M. balbisiana with 430 Mb (87%) assembled into 11 chromosomes. We identified that the recent divergence of M. acuminata (A-genome) and M. balbisiana (B-genome) occurred after lineage-specific whole-genome duplication, and that the B-genome may be more sensitive to the fractionation process compared to the A-genome. Homoeologous exchanges occurred frequently between A- and B-subgenomes in allopolyploids. Genomic variation within progenitors resulted in functional divergence of subgenomes. Global homoeologue expression dominance occurred between subgenomes of the allotriploid. Gene families related to ethylene biosynthesis and starch metabolism exhibited significant expansion at the pathway level and wide homoeologue expression dominance in the B-subgenome of the allotriploid. The independent origin of 1-aminocyclopropane-1-carboxylic acid oxidase (ACO) homoeologue gene pairs and tandem duplication-driven expansion of ACO genes in the B-subgenome contributed to rapid and major ethylene production post-harvest in allotriploid banana fruits. The findings of this study provide greater context for understanding fruit biology, and aid the development of tools for breeding optimal banana cultivars.
ESTHER : Wang_2019_Nat.Plants_5_810
PubMedSearch : Wang_2019_Nat.Plants_5_810
PubMedID: 31308504
Gene_locus related to this paper: musam-m0tuu7 , musam-a0a804kav5

Title : Draft genome sequence of Camellia sinensis var. sinensis provides insights into the evolution of the tea genome and tea quality - Wei_2018_Proc.Natl.Acad.Sci.U.S.A_115_E4151
Author(s) : Wei C , Yang H , Wang S , Zhao J , Liu C , Gao L , Xia E , Lu Y , Tai Y , She G , Sun J , Cao H , Tong W , Gao Q , Li Y , Deng W , Jiang X , Wang W , Chen Q , Zhang S , Li H , Wu J , Wang P , Li P , Shi C , Zheng F , Jian J , Huang B , Shan D , Shi M , Fang C , Yue Y , Li F , Li D , Wei S , Han B , Jiang C , Yin Y , Xia T , Zhang Z , Bennetzen JL , Zhao S , Wan X
Ref : Proc Natl Acad Sci U S A , 115 :E4151 , 2018
Abstract : Tea, one of the world's most important beverage crops, provides numerous secondary metabolites that account for its rich taste and health benefits. Here we present a high-quality sequence of the genome of tea, Camellia sinensis var. sinensis (CSS), using both Illumina and PacBio sequencing technologies. At least 64% of the 3.1-Gb genome assembly consists of repetitive sequences, and the rest yields 33,932 high-confidence predictions of encoded proteins. Divergence between two major lineages, CSS and Camellia sinensis var. assamica (CSA), is calculated to approximately 0.38 to 1.54 million years ago (Mya). Analysis of genic collinearity reveals that the tea genome is the product of two rounds of whole-genome duplications (WGDs) that occurred approximately 30 to 40 and approximately 90 to 100 Mya. We provide evidence that these WGD events, and subsequent paralogous duplications, had major impacts on the copy numbers of secondary metabolite genes, particularly genes critical to producing three key quality compounds: catechins, theanine, and caffeine. Analyses of transcriptome and phytochemistry data show that amplification and transcriptional divergence of genes encoding a large acyltransferase family and leucoanthocyanidin reductases are associated with the characteristic young leaf accumulation of monomeric galloylated catechins in tea, while functional divergence of a single member of the glutamine synthetase gene family yielded theanine synthetase. This genome sequence will facilitate understanding of tea genome evolution and tea metabolite pathways, and will promote germplasm utilization for breeding improved tea varieties.
ESTHER : Wei_2018_Proc.Natl.Acad.Sci.U.S.A_115_E4151
PubMedSearch : Wei_2018_Proc.Natl.Acad.Sci.U.S.A_115_E4151
PubMedID: 29678829
Gene_locus related to this paper: camsi-a0a4s4dr18 , camsi-a0a4s4etg9 , camsi-a0a4s4e3j5 , camsi-a0a4s4d2s5 , camsi-a0a4s4duc4 , camsi-a0a4v3wr80 , camsi-a0a4v3wpu4

Title : Toxicological analysis of roast duck flavor components - Zhou_2018_Food.Chem.Toxicol_119_438
Author(s) : Zhou Y , Yan B , Zhao S , Zhou X , Xiao Y
Ref : Food & Chemical Toxicology , 119 :438 , 2018
Abstract : The aim of the study was to investigate toxicity of the synthesized roast duck flavor through animal experiment (mice feeding with the flavor for 35 days), and the major toxic compounds (acrylamide and 3,4-benzopyrene) were detected by high performance liquid chromatography. Compared with the control group, the blood biochemical indexes including protein content, bilirubin content, activity of alkaline phosphatase, activity of aspartate transaminase (AST) and alanine transaminase (ALT), cholesterol content, high density lipoprotein (HDL) and low density lipoprotein (LDL) content, triglycerides content, activity of creatine kinase (CK) and CK-MB, activity of cholinesterase (CHE) and lactate dehydrogenase (LDH), total bile acid (TBA) in high dose feeding group were significantly different. And body weight of mice fed by the flavor was decreased distinctly, and the heart weight was also decreased, while the liver weight was increased obviously. Superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities in liver and heart were significantly decreased, while methane dicarboxylic aldehyde (MDA) contents were increased evidently. Acrylamide was detected by high performance liquid-mass spectrum (HPLC-MS), and the content was 5.21 mg/kg 3,4-benzoapryene was calculated by HPLC with fluorescence detector, and the content was 21.13 mug/kg. Thus, the roast duck flavor was considered to be potential toxicity to human being.
ESTHER : Zhou_2018_Food.Chem.Toxicol_119_438
PubMedSearch : Zhou_2018_Food.Chem.Toxicol_119_438
PubMedID: 29208505

Title : Identification and characterization of a novel carboxylesterase from Phaseolus vulgaris for detection of organophosphate and carbamates pesticides - Yang_2018_J.Sci.Food.Agric_98_5095
Author(s) : Yang X , Dai J , Zhao S , Li R , Goulette T , Chen X , Xiao H
Ref : J Sci Food Agric , 98 :5095 , 2018
Abstract : BACKGROUND: Organophosphate and carbamate pesticide residues in food and the environment pose a great threat to human health and have made the easy and rapid detection of these pesticide residues an important task. Discovering new enzyme sources from plants can help reduce the cost of large-scale applications of rapid pesticide detection via enzyme inhibition. RESULTS: Plant esterase from kidney beans was purified. Kidney bean esterase is identified as a carboxylesterase by substrate and inhibitor specificity tests and mass spectrometry identification. The kidney bean esterase demonstrates optimal catalytic activity at 40 degrees C, pH 6.5 and an enzyme concentration of 0.30 microg mL(-1) . The kidney bean esterase can be inhibited by organophosphate and carbamate pesticides, which can be substituted for acetylcholinesterase. The limit of detection of the purified kidney bean esterase was two- to 20-fold higher than that of the crude one. The method detection limit meets the detection requirement for the maximum residue limits (MRL) in actual samples. CONCLUSION: The findings of the present study provide a new source of enzymes for pesticides detection by enzyme inhibition. (c) 2018 Society of Chemical Industry.
ESTHER : Yang_2018_J.Sci.Food.Agric_98_5095
PubMedSearch : Yang_2018_J.Sci.Food.Agric_98_5095
PubMedID: 29604085
Gene_locus related to this paper: phavu-PvCarE1

Title : Cholinesterase inhibitors for the treatment of delirium in non-ICU settings - Yu_2018_Cochrane.Database.Syst.Rev_6_CD012494
Author(s) : Yu A , Wu S , Zhang Z , Dening T , Zhao S , Pinner G , Xia J , Yang D
Ref : Cochrane Database Syst Rev , 6 :CD012494 , 2018
Abstract : BACKGROUND: Delirium is a common clinical syndrome defined as alterations in attention with an additional disturbance in cognition or perception, which develop over a short period of time and tend to fluctuate during the course of the episode. Delirium is commonly treated in hospitals or community settings and is often associated with multiple adverse outcomes such as increased cost, morbidity, and even mortality. The first-line intervention involves a multicomponent non-pharmacological approach that includes ensuring effective communication and reorientation in addition to providing reassurance or a suitable care environment. There are currently no drugs approved specifically for the treatment of delirium. Clinically, however, various medications are employed to provide symptomatic relief, such as antipsychotic medications and cholinesterase inhibitors, among others. OBJECTIVES: To evaluate the effectiveness and safety of cholinesterase inhibitors for treating people with established delirium in a non-intensive care unit (ICU) setting. SEARCH METHODS: We searched ALOIS, which is the Cochrane Dementia and Cognitive Improvement Group's Specialised Register, on 26 October 2017. We also cross-checked the reference lists of included studies to identify any potentially eligible trials. SELECTION CRITERIA: We included randomised controlled trials, published or unpublished, reported in English or Chinese, which compared cholinesterase inhibitors to placebo or other drugs intended to treat people with established delirium in a non-ICU setting. DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures expected by Cochrane. The primary outcomes were duration of delirium, severity of delirium, and adverse events. The secondary outcomes were use of rescue medications, persistent cognitive impairment, length of hospitalisation, institutionalisation, mortality, cost of intervention, leaving the study early, and quality of life. For dichotomous outcomes, we calculated the risk ratio (RR) with 95% confidence intervals (CIs); for continuous outcomes we calculated the mean difference (MD) with 95% CIs. We assessed the quality of evidence using GRADE to generate a 'Summary of findings' table. MAIN RESULTS: We included one study involving 15 participants from the UK. The included participants were diagnosed with delirium based on the Confusion Assessment Method (CAM) criteria. Eight males and seven females were included, with a mean age of 82.5 years. Seven of the 15 participants had comorbid dementia at baseline. The risk of bias was low in all domains.The study compared rivastigmine with placebo. We did not find any clear differences between the two groups in terms of duration of delirium (MD -3.6, 95% CI -15.6 to 8.4), adverse events (nausea, RR 0.30, 95% CI 0.01 to 6.29), use of rescue medications (RR 0.13, 95% CI 0.01 to 2.1), mortality (RR 0.10, 95% CI 0.01 to 1.56), and leaving the study early (RR 0.88, 95% CI 0.07 to 11.54). Evidence was not available regarding the severity of delirium, persistent cognitive impairment, length of hospitalisation, cost of intervention, or other predefined secondary outcomes.The quality of evidence is low due to the very small sample size. AUTHORS' CONCLUSIONS: There is insufficient evidence to support or refute the use of cholinesterase inhibitors for the treatment of delirium in non-ICU settings. No clear benefits or harms associated with cholinesterase inhibitors were observed when compared with placebo due to the lack of data. More trials are required.
ESTHER : Yu_2018_Cochrane.Database.Syst.Rev_6_CD012494
PubMedSearch : Yu_2018_Cochrane.Database.Syst.Rev_6_CD012494
PubMedID: 29952000

Title : Application of Chitosan, Chitooligosaccharide, and Their Derivatives in the Treatment of Alzheimer's Disease - Ouyang_2017_Mar.Drugs_15_
Author(s) : Ouyang QQ , Zhao S , Li SD , Song C
Ref : Mar Drugs , 15 : , 2017
Abstract : Classic hypotheses of Alzheimer's disease (AD) include cholinergic neuron death, acetylcholine (ACh) deficiency, metal ion dynamic equilibrium disorder, and deposition of amyloid and tau. Increased evidence suggests neuroinflammation and oxidative stress may cause AD. However, none of these factors induces AD independently, but they are all associated with the formation of Abeta and tau proteins. Current clinical treatments based on ACh deficiency can only temporarily relieve symptoms, accompanied with many side-effects. Hence, searching for natural neuroprotective agents, which can significantly improve the major symptoms and reverse disease progress, have received great attention. Currently, several bioactive marine products have shown neuroprotective activities, immunomodulatory and anti-inflammatory effects with low toxicity and mild side effects in laboratory studies. Recently, chitosan (CTS), chitooligosaccharide (COS) and their derivatives from exoskeletons of crustaceans and cell walls of fungi have shown neuroprotective and antioxidative effects, matrix metalloproteinase inhibition, anti-HIV and anti-inflammatory properties. With regards to the hypotheses of AD, the neuroprotective effect of CTS, COS, and their derivatives on AD-like changes in several models have been reported. CTS and COS exert beneficial effects on cognitive impairments via inhibiting oxidative stress and neuroinflammation. They are also a new type of non-toxic beta-secretase and AChE inhibitor. As neuroprotective agents, they could reduce the cell membrane damage caused by copper ions and decrease the content of reactive oxygen species. This review will focus on their anti-neuroinflammation, antioxidants and their inhibition of beta-amyloid, acetylcholinesterase and copper ions adsorption. Finally, the limitations and future work will be discussed.
ESTHER : Ouyang_2017_Mar.Drugs_15_
PubMedSearch : Ouyang_2017_Mar.Drugs_15_
PubMedID: 29112116

Title : alpha\/beta-Hydrolase Domain 6 Deletion Induces Adipose Browning and Prevents Obesity and Type 2 Diabetes - Zhao_2016_Cell.Rep_14_2872
Author(s) : Zhao S , Mugabo Y , Ballentine G , Attane C , Iglesias J , Poursharifi P , Zhang D , Nguyen TA , Erb H , Prentki R , Peyot ML , Joly E , Tobin S , Fulton S , Brown JM , Madiraju SR , Prentki M
Ref : Cell Rep , 14 :2872 , 2016
Abstract : Suppression of alpha/beta-domain hydrolase-6 (ABHD6), a monoacylglycerol (MAG) hydrolase, promotes glucose-stimulated insulin secretion by pancreatic beta cells. We report here that high-fat-diet-fed ABHD6-KO mice show modestly reduced food intake, decreased body weight gain and glycemia, improved glucose tolerance and insulin sensitivity, and enhanced locomotor activity. ABHD6-KO mice also show increased energy expenditure, cold-induced thermogenesis, brown adipose UCP1 expression, fatty acid oxidation, and white adipose browning. Adipose browning and cold-induced thermogenesis are replicated by the ABHD6 inhibitor WWL70 and by antisense oligonucleotides targeting ABHD6. Our evidence suggests that one mechanism by which the lipolysis derived 1-MAG signals intrinsic and cell-autonomous adipose browning is via PPARalpha and PPARgamma activation, and that ABHD6 regulates adipose browning by controlling signal competent 1-MAG levels. Thus, ABHD6 regulates energy homeostasis, brown adipose function, and white adipose browning and is a potential therapeutic target for obesity and type 2 diabetes.
ESTHER : Zhao_2016_Cell.Rep_14_2872
PubMedSearch : Zhao_2016_Cell.Rep_14_2872
PubMedID: 26997277
Gene_locus related to this paper: human-ABHD6 , mouse-ABHD6

Title : Simplified assays of lipolysis enzymes for drug discovery and specificity assessment of known inhibitors - Iglesias_2016_J.Lipid.Res_57_131
Author(s) : Iglesias J , Lamontagne J , Erb H , Gezzar S , Zhao S , Joly E , Truong VL , Skorey K , Crane S , Madiraju SR , Prentki M
Ref : J Lipid Res , 57 :131 , 2016
Abstract : Lipids are used as cellular building blocks and condensed energy stores and also act as signaling molecules. The glycerolipid/ fatty acid cycle, encompassing lipolysis and lipogenesis, generates many lipid signals. Reliable procedures are not available for measuring activities of several lipolytic enzymes for the purposes of drug screening, and this resulted in questionable selectivity of various known lipase inhibitors. We now describe simple assays for lipolytic enzymes, including adipose triglyceride lipase (ATGL), hormone sensitive lipase (HSL), sn-1-diacylglycerol lipase (DAGL), monoacylglycerol lipase, alpha/beta-hydrolase domain 6, and carboxylesterase 1 (CES1) using recombinant human and mouse enzymes either in cell extracts or using purified enzymes. We observed that many of the reported inhibitors lack specificity. Thus, Cay10499 (HSL inhibitor) and RHC20867 (DAGL inhibitor) also inhibit other lipases. Marked differences in the inhibitor sensitivities of human ATGL and HSL compared with the corresponding mouse enzymes was noticed. Thus, ATGListatin inhibited mouse ATGL but not human ATGL, and the HSL inhibitors WWL11 and Compound 13f were effective against mouse enzyme but much less potent against human enzyme. Many of these lipase inhibitors also inhibited human CES1. Results describe reliable assays for measuring lipase activities that are amenable for drug screening and also caution about the specificity of the many earlier described lipase inhibitors.
ESTHER : Iglesias_2016_J.Lipid.Res_57_131
PubMedSearch : Iglesias_2016_J.Lipid.Res_57_131
PubMedID: 26423520

Title : Microcystin-LR exposure induces developmental neurotoxicity in zebrafish embryo - Wu_2016_Environ.Pollut_213_793
Author(s) : Wu Q , Yan W , Liu C , Li L , Yu L , Zhao S , Li G
Ref : Environ Pollut , 213 :793 , 2016
Abstract : Microcystin-LR (MCLR) is a commonly acting potent hepatotoxin and has been pointed out of potentially causing developmental neurotoxicity, but the exact mechanism is little known. In this study, zebrafish embryos were exposed to 0, 0.8, 1.6 or 3.2 mg/L MCLR for 120 h. MCLR exposure through submersion caused serious hatching delay and body length decrease. The content of MCLR in zebrafish larvae was analyzed and the results demonstrated that MCLR can accumulate in zebrafish larvae. The locomotor speed of zebrafish larvae was decreased. Furthermore, the dopamine and acetylcholine (ACh) content were detected to be significantly decreased in MCLR exposure groups. And the acetylcholinesterase (AChE) activity was significantly increased after exposure to 1.6 and 3.2 mg/L MCLR. The transcription pattern of manf, chrnalpha7 and ache gene was consistent with the change of the dopamine content, ACh content and AChE activity. Gene expression involved in the development of neurons was also measured. a1-tubulin and shha gene expression were down-regulated, whereas mbp and gap43 gene expression were observed to be significantly up-regulated upon exposure to MCLR. The above results indicated that MCLR-induced developmental toxicity might attribute to the disorder of cholinergic system, dopaminergic signaling, and the development of neurons.
ESTHER : Wu_2016_Environ.Pollut_213_793
PubMedSearch : Wu_2016_Environ.Pollut_213_793
PubMedID: 27038211

Title : [Effect of Bacillus thuringiensis var. israelensis (Bti) on detoxification en- zyme activity of larvae of Culex pipiens pallens and Aedes aegypti] - Han_2015_Zhongguo.Xue.Xi.Chong.Bing.Fang.Zhi.Za.Zhi_27_385
Author(s) : Han GJ , Li CM , Sun J , Liu Q , Zhao S , Qi JH , Xu J
Ref : Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi , 27 :385 , 2015
Abstract : OBJECTIVE: To investigate the effect of Bacillus thuringiensis var. israelensis (Bti) on the activities of three detoxification enzymes of Culex pipiens pallens and Aedes aegypti larvae.
METHODS: The activities of glutathione transferase, acetyl cholinesterase and carboxyl esterase, were detected after two kinds of mosquito larvae were treated by Bti at different time and concentrations.
RESULTS: The activities of three detoxification enzymes of the two kinds of mosquito larvae were influenced by Bti treatment. The activity of glutathione transferase was increased after the Bti treatment, but declined significantly and inhibited at a low level sustainably. The activity of carboxyl esterase was increased after the Bti treatment, but recovered to normal level quickly. Acetyl cholinesterase was affected slightly by the Bti treatment, shortly inhibited in the first time and then recovered. The active effects of the three detoxification enzymes were positively related to the concentration of Bti. CONCLUSION: The enzyme activities of glutathione transferase, acetyl cholinesterase and carboxyl esterase could be affected by Bti significantly.
ESTHER : Han_2015_Zhongguo.Xue.Xi.Chong.Bing.Fang.Zhi.Za.Zhi_27_385
PubMedSearch : Han_2015_Zhongguo.Xue.Xi.Chong.Bing.Fang.Zhi.Za.Zhi_27_385
PubMedID: 26767261

Title : The resurrection genome of Boea hygrometrica: A blueprint for survival of dehydration - Xiao_2015_Proc.Natl.Acad.Sci.U.S.A_112_5833
Author(s) : Xiao L , Yang G , Zhang L , Yang X , Zhao S , Ji Z , Zhou Q , Hu M , Wang Y , Chen M , Xu Y , Jin H , Xiao X , Hu G , Bao F , Hu Y , Wan P , Li L , Deng X , Kuang T , Xiang C , Zhu JK , Oliver MJ , He Y
Ref : Proc Natl Acad Sci U S A , 112 :5833 , 2015
Abstract : "Drying without dying" is an essential trait in land plant evolution. Unraveling how a unique group of angiosperms, the Resurrection Plants, survive desiccation of their leaves and roots has been hampered by the lack of a foundational genome perspective. Here we report the approximately 1,691-Mb sequenced genome of Boea hygrometrica, an important resurrection plant model. The sequence revealed evidence for two historical genome-wide duplication events, a compliment of 49,374 protein-coding genes, 29.15% of which are unique (orphan) to Boea and 20% of which (9,888) significantly respond to desiccation at the transcript level. Expansion of early light-inducible protein (ELIP) and 5S rRNA genes highlights the importance of the protection of the photosynthetic apparatus during drying and the rapid resumption of protein synthesis in the resurrection capability of Boea. Transcriptome analysis reveals extensive alternative splicing of transcripts and a focus on cellular protection strategies. The lack of desiccation tolerance-specific genome organizational features suggests the resurrection phenotype evolved mainly by an alteration in the control of dehydration response genes.
ESTHER : Xiao_2015_Proc.Natl.Acad.Sci.U.S.A_112_5833
PubMedSearch : Xiao_2015_Proc.Natl.Acad.Sci.U.S.A_112_5833
PubMedID: 25902549
Gene_locus related to this paper: 9lami-a0a2z7c6k4 , 9lami-a0a2z7bgj4

Title : Inhibition of soluble epoxide hydrolase in mice promotes reverse cholesterol transport and regression of atherosclerosis - Shen_2015_Atherosclerosis_239_557
Author(s) : Shen L , Peng H , Peng R , Fan Q , Zhao S , Xu D , Morisseau C , Chiamvimonvat N , Hammock BD
Ref : Atherosclerosis , 239 :557 , 2015
Abstract : Adipose tissue is the body largest free cholesterol reservoir and abundantly expresses ATP binding cassette transporter A1 (ABCA1), which maintains plasma high-density lipoprotein (HDL) levels. HDLs have a protective role in atherosclerosis by mediating reverse cholesterol transport (RCT). Soluble epoxide hydrolase (sEH) is a cytosolic enzyme whose inhibition has various beneficial effects on cardiovascular disease. The sEH is highly expressed in adipocytes, and it converts epoxyeicosatrienoic acids (EETs) into less bioactive dihydroxyeicosatrienoic acids. We previously showed that increasing EETs levels with a sEH inhibitor (sEHI) (t-AUCB) resulted in elevated ABCA1 expression and promoted ABCA1-mediated cholesterol efflux from 3T3-L1 adipocytes. The present study investigates the impacts of t-AUCB in mice deficient for the low density lipoprotein (LDL) receptor (Ldlr(-/-) mice) with established atherosclerotic plaques. The sEH inhibitor delivered in vivo for 4 weeks decreased the activity of sEH in adipose tissue, enhanced ABCA1 expression and cholesterol efflux from adipose depots, and consequently increased HDL levels. Furthermore, t-AUCB enhanced RCT to the plasma, liver, bile and feces. It also showed the reduction of plasma LDL-C levels. Consistently, t-AUCB-treated mice showed reductions in the size of atherosclerotic plaques. These studies establish that raising adipose ABCA1 expression, cholesterol efflux, and plasma HDL levels with t-AUCB treatment promotes RCT, decreasing LDL-C and atherosclerosis regression, suggesting that sEH inhibition may be a promising strategy to treat atherosclerotic vascular disease.
ESTHER : Shen_2015_Atherosclerosis_239_557
PubMedSearch : Shen_2015_Atherosclerosis_239_557
PubMedID: 25733327

Title : alpha\/beta-Hydrolase domain-6 and saturated long chain monoacylglycerol regulate insulin secretion promoted by both fuel and non-fuel stimuli - Zhao_2015_Mol.Metab_4_940
Author(s) : Zhao S , Poursharifi P , Mugabo Y , Levens EJ , Vivot K , Attane C , Iglesias J , Peyot ML , Joly E , Madiraju SR , Prentki M
Ref : Mol Metab , 4 :940 , 2015
Abstract : OBJECTIVE: alpha/beta-Hydrolase domain-6 (ABHD6) is a newly identified monoacylglycerol (MAG) lipase. We recently reported that it negatively regulates glucose stimulated insulin secretion (GSIS) in the beta cells by hydrolyzing lipolysis-derived MAG that acts as a metabolic coupling factor and signaling molecule via exocytotic regulator Munc13-1. Whether ABHD6 and MAG play a role in response to all classes of insulin secretagogues, in particular various fuel and non-fuel stimuli, is unknown.
METHODS: Insulin secretion in response to various classes of secretagogues, exogenous MAG and pharmacological agents was measured in islets of mice deficient in ABHD6 specifically in the beta cell (BKO). Islet perifusion experiments and determinations of glucose and fatty acid metabolism, cytosolic Ca(2+) and MAG species levels were carried out.
RESULTS: Deletion of ABHD6 potentiated insulin secretion in response to the fuels glutamine plus leucine and alpha-ketoisocaproate and to the non-fuel stimuli glucagon-like peptide 1, carbamylcholine and elevated KCl. Fatty acids amplified GSIS in control and BKO mice to the same extent. Exogenous 1-MAG amplified insulin secretion in response to fuel and non-fuel stimuli. MAG hydrolysis activity was greatly reduced in BKO islets without changes in total diacylglycerol and triacylglycerol lipase activity. ABHD6 deletion induced insulin secretion independently from KATP channels and did not alter the glucose induced rise in intracellular Ca(2+). Perifusion studies showed elevated insulin secretion during second phase of GSIS in BKO islets that was not due to altered cytosolic Ca(2+) signaling or because of changes in glucose and fatty acid metabolism. Glucose increased islet saturated long chain 1-MAG species and ABHD6 deletion caused accumulation of these 1-MAG species at both low and elevated glucose. CONCLUSION: ABHD6 regulates insulin secretion in response to fuel stimuli at large and some non-fuel stimuli by controlling long chain saturated 1-MAG levels that synergize with other signaling pathways for secretion.
ESTHER : Zhao_2015_Mol.Metab_4_940
PubMedSearch : Zhao_2015_Mol.Metab_4_940
PubMedID: 26909310
Gene_locus related to this paper: human-ABHD6 , mouse-ABHD6

Title : Nanostructured photoelectrochemical biosensor for highly sensitive detection of organophosphorous pesticides - Li_2014_Biosens.Bioelectron_64C_1
Author(s) : Li X , Zheng Z , Liu X , Zhao S , Liu S
Ref : Biosensors & Bioelectronics , 64C :1 , 2014
Abstract : A sensitive photoelectrochemical (PEC) biosensor for detection of organophosphorus pesticides (OPs) using the nanocomposite of CdSe@ZnS quantum dots (QDs) and graphene deposited on the ITO coated glass electrode as a photoactive electrode is presented. The integration of CdSe@ZnS/graphene nanocomposite with biomolecules acetylcholinesterase (AChE) as a biorecognition element yields a novel biosensing platform. Under visible light irradiation, the AChE-CdSe@ZnS/graphene nanocomposite can generate a stable photocurrent and the photocurrent is found to be inversely dependent on the concentration of OPs. Under the optimal experimental conditions, the photocurrents were proportional to the logarithm of paraoxon and dichlorvos within the concentration range of 10-12-10-6M. The detection limits (LOD) of the proposed biosensor for paraoxon and dichlorvos are as low as 10-14M and 10-12M. The photoelectrochemical biosensor shows good sensitivity, reproducibility, stability, and could be successfully applied to detection of OPs in real fruit samples.
ESTHER : Li_2014_Biosens.Bioelectron_64C_1
PubMedSearch : Li_2014_Biosens.Bioelectron_64C_1
PubMedID: 25173731

Title : alpha\/beta-Hydrolase domain-6-accessible monoacylglycerol controls glucose-stimulated insulin secretion - Zhao_2014_Cell.Metab_19_993
Author(s) : Zhao S , Mugabo Y , Iglesias J , Xie L , Delghingaro-Augusto V , Lussier R , Peyot ML , Joly E , Taib B , Davis MA , Brown JM , Abousalham A , Gaisano H , Madiraju SR , Prentki M
Ref : Cell Metab , 19 :993 , 2014
Abstract : Glucose metabolism in pancreatic beta cells stimulates insulin granule exocytosis, and this process requires generation of a lipid signal. However, the signals involved in lipid amplification of glucose-stimulated insulin secretion (GSIS) are unknown. Here we show that in beta cells, glucose stimulates production of lipolysis-derived long-chain saturated monoacylglycerols, which further increase upon inhibition of the membrane-bound monoacylglycerol lipase alpha/beta-Hydrolase Domain-6 (ABHD6). ABHD6 expression in beta cells is inversely proportional to GSIS. Exogenous monoacylglycerols stimulate beta cell insulin secretion and restore GSIS suppressed by the pan-lipase inhibitor orlistat. Whole-body and beta-cell-specific ABHD6-KO mice exhibit enhanced GSIS, and their islets show elevated monoacylglycerol production and insulin secretion in response to glucose. Inhibition of ABHD6 in diabetic mice restores GSIS and improves glucose tolerance. Monoacylglycerol binds and activates the vesicle priming protein Munc13-1, thereby inducing insulin exocytosis. We propose saturated monoacylglycerol as a signal for GSIS and ABHD6 as a negative modulator of insulin secretion.
ESTHER : Zhao_2014_Cell.Metab_19_993
PubMedSearch : Zhao_2014_Cell.Metab_19_993
PubMedID: 24814481

Title : GW1929 inhibits alpha7 nAChR expression through PPARgamma-independent activation of p38 MAPK and inactivation of PI3-K\/mTOR: The role of Egr-1 - Hahn_2014_Cell.Signal_26_730
Author(s) : Hahn SS , Tang Q , Zheng F , Zhao S , Wu J
Ref : Cell Signal , 26 :730 , 2014
Abstract : Studies demonstrated that peroxisome proliferator-activated receptor gamma (PPARgamma) ligands reduce nicotine-induced non small cell lung carcinoma (NSCLC) cell growth through inhibition of nicotinic acetylcholine receptor (nAChR) mediated signaling pathways. However, the mechanisms by which PPARgamma ligands inhibited nAChR expression remain elucidated. Here, we show that GW1929, a synthetic PPARgamma ligand, not only inhibited but also antagonized the stimulatory effect of acetylcholine on NSCLC cell proliferation. Interestingly, GW1929 inhibited alpha7 nAChR expression, which was not blocked by GW9662, an antagonist of PPARgamma, or by PPARgamma siRNA, but was abrogated by the p38 MPAK inhibitor SB239063. GW1929 reduced the promoter activity of alpha7 nAChR and induced early growth response-1 (Egr-1) protein expression, which was overcame by SB239063, but enhanced by inhibitors of PI3-K and mTOR. Silencing of Egr-1 blocked, while overexpression of Egr-1 enhanced, the effect of GW1929 on alpha7 nAChR expression and promoter activity. Finally, GW1929 induced Egr-1 bound to specific DNA areas in the alpha7 nAChR gene promoter. Collectively, these results demonstrate that GW1929 not only inhibits but also antagonizes Ach-induced NSCLC cell growth by inhibition of alpha7 nAChR expression through PPARgamma-independent signals that are associated with activation of p38 MPAK and inactivation of PI3-K/mTOR, followed by inducing Egr-1 protein and Egr-1 binding activity in the alpha7 nAChR gene promoter. By downregulation of the alpha7 nAchR, GW1929 blocks cholinergic signaling and inhibits NSCLC cell growth.
ESTHER : Hahn_2014_Cell.Signal_26_730
PubMedSearch : Hahn_2014_Cell.Signal_26_730
PubMedID: 24412748

Title : Genomic characterization of three unique Dehalococcoides that respire on persistent polychlorinated biphenyls - Wang_2014_Proc.Natl.Acad.Sci.U.S.A_111_12103
Author(s) : Wang S , Chng KR , Wilm A , Zhao S , Yang KL , Nagarajan N , He J
Ref : Proc Natl Acad Sci U S A , 111 :12103 , 2014
Abstract : Fastidious anaerobic bacteria play critical roles in environmental bioremediation of halogenated compounds. However, their characterization and application have been largely impeded by difficulties in growing them in pure culture. Thus far, no pure culture has been reported to respire on the notorious polychlorinated biphenyls (PCBs), and functional genes responsible for PCB detoxification remain unknown due to the extremely slow growth of PCB-respiring bacteria. Here we report the successful isolation and characterization of three Dehalococcoides mccartyi strains that respire on commercial PCBs. Using high-throughput metagenomic analysis, combined with traditional culture techniques, tetrachloroethene (PCE) was identified as a feasible alternative to PCBs to isolate PCB-respiring Dehalococcoides from PCB-enriched cultures. With PCE as an alternative electron acceptor, the PCB-respiring Dehalococcoides were boosted to a higher cell density (1.2 x 10(8) to 1.3 x 10(8) cells per mL on PCE vs. 5.9 x 10(6) to 10.4 x 10(6) cells per mL on PCBs) with a shorter culturing time (30 d on PCE vs. 150 d on PCBs). The transcriptomic profiles illustrated that the distinct PCB dechlorination profile of each strain was predominantly mediated by a single, novel reductive dehalogenase (RDase) catalyzing chlorine removal from both PCBs and PCE. The transcription levels of PCB-RDase genes are 5-60 times higher than the genome-wide average. The cultivation of PCB-respiring Dehalococcoides in pure culture and the identification of PCB-RDase genes deepen our understanding of organohalide respiration of PCBs and shed light on in situ PCB bioremediation.
ESTHER : Wang_2014_Proc.Natl.Acad.Sci.U.S.A_111_12103
PubMedSearch : Wang_2014_Proc.Natl.Acad.Sci.U.S.A_111_12103
PubMedID: 25028492
Gene_locus related to this paper: dehm1-q3z6q3 , dehmv-d2bg80

Title : Complete Genome Sequences of Salmonella enterica Serovar Heidelberg Strains Associated with a Multistate Food-Borne Illness Investigation - Evans_2014_Genome.Announc_2_e01154
Author(s) : Evans PS , Luo Y , Muruvanda T , Ayers S , Hiatt B , Hoffman M , Zhao S , Allard MW , Brown EW
Ref : Genome Announc , 2 :e01154 , 2014
Abstract : Next-generation sequencing is being evaluated for use with food-borne illness investigations, especially when the outbreak strains produce patterns that cannot be discriminated from non-outbreak strains using conventional procedures. Here we report complete genome assemblies of two Salmonella enterica serovar Heidelberg strains with a common pulsed-field gel electrophoresis pattern isolated during an outbreak investigation.
ESTHER : Evans_2014_Genome.Announc_2_e01154
PubMedSearch : Evans_2014_Genome.Announc_2_e01154
PubMedID: 24903882

Title : Comparative genomic analysis and virulence differences in closely related salmonella enterica serotype heidelberg isolates from humans, retail meats, and animals - Hoffmann_2014_Genome.Biol.Evol_6_1046
Author(s) : Hoffmann M , Zhao S , Pettengill J , Luo Y , Monday SR , Abbott J , Ayers SL , Cinar HN , Muruvanda T , Li C , Allard MW , Whichard J , Meng J , Brown EW , McDermott PF
Ref : Genome Biol Evol , 6 :1046 , 2014
Abstract : Salmonella enterica subsp. enterica serovar Heidelberg (S. Heidelberg) is one of the top serovars causing human salmonellosis. Recently, an antibiotic-resistant strain of this serovar was implicated in a large 2011 multistate outbreak resulting from consumption of contaminated ground turkey that involved 136 confirmed cases, with one death. In this study, we assessed the evolutionary diversity of 44 S. Heidelberg isolates using whole-genome sequencing (WGS) generated by the 454 GS FLX (Roche) platform. The isolates, including 30 with nearly indistinguishable (one band difference) Xbal pulsed-field gel electrophoresis patterns (JF6X01.0032, JF6X01.0058), were collected from various sources between 1982 and 2011 and included nine isolates associated with the 2011 outbreak. Additionally, we determined the complete sequence for the chromosome and three plasmids from a clinical isolate associated with the 2011 outbreak using the Pacific Biosciences (PacBio) system. Using single-nucleotide polymorphism (SNP) analyses, we were able to distinguish highly clonal isolates, including strains isolated at different times in the same year. The isolates from the recent 2011 outbreak clustered together with a mean SNP variation of only 17 SNPs. The S. Heidelberg isolates carried a variety of phages, such as prophage P22, P4, lambda-like prophage Gifsy-2, and the P2-like phage which carries the sopE1 gene, virulence genes including 62 pathogenicity, and 13 fimbrial markers and resistance plasmids of the incompatibility (Inc)I1, IncA/C, and IncHI2 groups. Twenty-one strains contained an IncX plasmid carrying a type IV secretion system. On the basis of the recent and historical isolates used in this study, our results demonstrated that, in addition to providing detailed genetic information for the isolates, WGS can identify SNP targets that can be utilized for differentiating highly clonal S. Heidelberg isolates.
ESTHER : Hoffmann_2014_Genome.Biol.Evol_6_1046
PubMedSearch : Hoffmann_2014_Genome.Biol.Evol_6_1046
PubMedID: 24732280

Title : Resistance selection and biochemical mechanism of resistance against cyflumetofen in Tetranychus cinnabarinus (Boisduval) - Wang_2014_Pestic.Biochem.Physiol_111_24
Author(s) : Wang Y , Zhao S , Shi L , Xu Z , He L
Ref : Pestic Biochem Physiol , 111 :24 , 2014
Abstract : The carmine spider mite, Tetranychus cinnabarinus is an important crop and vegetable plants pest mite. As a novel acaricide, cyflumetofen is effective against Tetranychus and Panonychus mites, but its risk and biochemical mechanism of resistance in mites is not clear. In this study, the resistance against cyflumetofen was selected and its biochemical mechanisms were studied in T. cinnabarinus. After selection the susceptibility and resistance against cyflumetofen in T. cinnabarinus, the final resistance ratio reached 21.33 at LC50 (CyR-43/CyS). All the collected field populations showed low resistance against cyflumetofen, although it had never been used in China. The activity of detoxifying enzymes CarE, MFO and GSTs were significantly increased in the final selected resistance strain (CyR-43), especially that for GSTs increased more than 7-folds after selection. The resistance against cyflumetofen developed slowly when selected from the susceptible strain in laboratory, but the resistant genes already existed in field populations, and the GSTs was the most important detoxifying enzyme conferring resistance against cyflumetofen in T. cinnabarinus. These results would provide the valuable information for designing appropriate strategies for the practical application of cyflumetofen in the field and delaying resistance development.
ESTHER : Wang_2014_Pestic.Biochem.Physiol_111_24
PubMedSearch : Wang_2014_Pestic.Biochem.Physiol_111_24
PubMedID: 24861930

Title : Whole-genome sequencing of cultivated and wild peppers provides insights into Capsicum domestication and specialization - Qin_2014_Proc.Natl.Acad.Sci.U.S.A_111_5135
Author(s) : Qin C , Yu C , Shen Y , Fang X , Chen L , Min J , Cheng J , Zhao S , Xu M , Luo Y , Yang Y , Wu Z , Mao L , Wu H , Ling-Hu C , Zhou H , Lin H , Gonzalez-Morales S , Trejo-Saavedra DL , Tian H , Tang X , Zhao M , Huang Z , Zhou A , Yao X , Cui J , Li W , Chen Z , Feng Y , Niu Y , Bi S , Yang X , Cai H , Luo X , Montes-Hernandez S , Leyva-Gonzalez MA , Xiong Z , He X , Bai L , Tan S , Liu D , Liu J , Zhang S , Chen M , Zhang L , Zhang Y , Liao W , Wang M , Lv X , Wen B , Liu H , Luan H , Yang S , Wang X , Xu J , Li X , Li S , Wang J , Palloix A , Bosland PW , Li Y , Krogh A , Rivera-Bustamante RF , Herrera-Estrella L , Yin Y , Yu J , Hu K , Zhang Z
Ref : Proc Natl Acad Sci U S A , 111 :5135 , 2014
Abstract : As an economic crop, pepper satisfies people's spicy taste and has medicinal uses worldwide. To gain a better understanding of Capsicum evolution, domestication, and specialization, we present here the genome sequence of the cultivated pepper Zunla-1 (C. annuum L.) and its wild progenitor Chiltepin (C. annuum var. glabriusculum). We estimate that the pepper genome expanded approximately 0.3 Mya (with respect to the genome of other Solanaceae) by a rapid amplification of retrotransposons elements, resulting in a genome comprised of approximately 81% repetitive sequences. Approximately 79% of 3.48-Gb scaffolds containing 34,476 protein-coding genes were anchored to chromosomes by a high-density genetic map. Comparison of cultivated and wild pepper genomes with 20 resequencing accessions revealed molecular footprints of artificial selection, providing us with a list of candidate domestication genes. We also found that dosage compensation effect of tandem duplication genes probably contributed to the pungent diversification in pepper. The Capsicum reference genome provides crucial information for the study of not only the evolution of the pepper genome but also, the Solanaceae family, and it will facilitate the establishment of more effective pepper breeding programs.
ESTHER : Qin_2014_Proc.Natl.Acad.Sci.U.S.A_111_5135
PubMedSearch : Qin_2014_Proc.Natl.Acad.Sci.U.S.A_111_5135
PubMedID: 24591624
Gene_locus related to this paper: capch-q75qh4 , capan-a0a1u8fuf5 , capan-a0a1u8gmz3 , capan-a0a1u8f879 , capan-a0a1u8ftr2 , capan-a0a1u8g8s6

Title : Draft genome of the wheat A-genome progenitor Triticum urartu - Ling_2013_Nature_496_87
Author(s) : Ling HQ , Zhao S , Liu D , Wang J , Sun H , Zhang C , Fan H , Li D , Dong L , Tao Y , Gao C , Wu H , Li Y , Cui Y , Guo X , Zheng S , Wang B , Yu K , Liang Q , Yang W , Lou X , Chen J , Feng M , Jian J , Zhang X , Luo G , Jiang Y , Liu J , Wang Z , Sha Y , Zhang B , Tang D , Shen Q , Xue P , Zou S , Wang X , Liu X , Wang F , Yang Y , An X , Dong Z , Zhang K , Luo MC , Dvorak J , Tong Y , Yang H , Li Z , Wang D , Zhang A
Ref : Nature , 496 :87 , 2013
Abstract : Bread wheat (Triticum aestivum, AABBDD) is one of the most widely cultivated and consumed food crops in the world. However, the complex polyploid nature of its genome makes genetic and functional analyses extremely challenging. The A genome, as a basic genome of bread wheat and other polyploid wheats, for example, T. turgidum (AABB), T. timopheevii (AAGG) and T. zhukovskyi (AAGGA(m)A(m)), is central to wheat evolution, domestication and genetic improvement. The progenitor species of the A genome is the diploid wild einkorn wheat T. urartu, which resembles cultivated wheat more extensively than do Aegilops speltoides (the ancestor of the B genome) and Ae. tauschii (the donor of the D genome), especially in the morphology and development of spike and seed. Here we present the generation, assembly and analysis of a whole-genome shotgun draft sequence of the T. urartu genome. We identified protein-coding gene models, performed genome structure analyses and assessed its utility for analysing agronomically important genes and for developing molecular markers. Our T. urartu genome assembly provides a diploid reference for analysis of polyploid wheat genomes and is a valuable resource for the genetic improvement of wheat.
ESTHER : Ling_2013_Nature_496_87
PubMedSearch : Ling_2013_Nature_496_87
PubMedID: 23535596
Gene_locus related to this paper: triua-m8a764 , triua-m8ag96 , triua-m7zp69 , wheat-w5d1z6 , wheat-w5d232 , wheat-w5bnf5 , triua-t1nm05 , wheat-w5cae4 , triua-m7ytf7 , wheat-w5f1j8 , triua-m8ad49 , wheat-a0a077s1q2 , wheat-a0a3b6c2m6 , triua-m7zi26 , wheat-a0a3b6at77 , wheat-a0a3b6atp7

Title : Genome Sequences of Salmonella enterica Serovar Heidelberg Isolates Isolated in the United States from a Multistate Outbreak of Human Salmonella Infections - Hoffmann_2013_Genome.Announc_1_e00004
Author(s) : Hoffmann M , Luo Y , Lafon PC , Timme R , Allard MW , McDermott PF , Brown EW , Zhao S
Ref : Genome Announc , 1 : , 2013
Abstract : Salmonella enterica is recognized as one of the most common bacterial agents of foodborne illness. We report draft genomes of four Salmonella serovar Heidelberg isolates associated with the recent multistate outbreak of human Salmonella Heidelberg infections linked to kosher broiled chicken livers in the United States in 2011. Isolates 2011K-1259 and 2011K-1232 were recovered from humans, whereas 2011K-1724 and 2011K-1726 were isolated from chicken liver. Whole genome sequence analysis of these isolates provides a tool for studying the short-term evolution of these epidemic clones and can be used for characterizing potentially new virulence factors.
ESTHER : Hoffmann_2013_Genome.Announc_1_e00004
PubMedSearch : Hoffmann_2013_Genome.Announc_1_e00004
PubMedID: 23405335
Gene_locus related to this paper: salty-STY1441

Title : Soluble epoxide hydrolase inhibition does not prevent cardiac remodeling and dysfunction after aortic constriction in rats and mice - Morgan_2013_J.Cardiovasc.Pharmacol_61_291
Author(s) : Morgan LA , Olzinski AR , Upson JJ , Zhao S , Wang T , Eisennagel SH , Hoang B , Tunstead JR , Marino JP, Jr. , Willette RN , Jucker BM , Behm DJ
Ref : J Cardiovasc Pharmacol , 61 :291 , 2013
Abstract : Epoxyeicosatrienoic acids, substrates for soluble epoxide hydrolase (sEH), exhibit vasodilatory and antihypertrophic activities. Inhibitors of sEH might therefore hold promise as heart failure therapeutics. We examined the ability of sEH inhibitors GSK2188931 and GSK2256294 to modulate cardiac hypertrophy, fibrosis, and function after transverse aortic constriction (TAC) in rats and mice. GSK2188931 administration was initiated in rats 1 day before TAC, whereas GSK2256294 treatment was initiated in mice 2 weeks after TAC. Four weeks later, cardiovascular function was assessed, plasma was collected for drug and sEH biomarker concentrations, and left ventricle was isolated for messenger RNA and histological analyses. In rats, although GSK2188931 prevented TAC-mediated increases in certain genes associated with hypertrophy and fibrosis (alpha-skeletal actin and connective tissue growth factor), the compound failed to attenuate TAC-induced increases in left ventricle mass, posterior wall thickness, end-diastolic volume and pressure, and perivascular fibrosis. Similarly, in mice, GSK2256294 did not reverse cardiac remodeling or systolic dysfunction induced by TAC. Both compounds increased the sEH substrate/product (leukotoxin/leukotoxin diol) ratio, indicating sEH inhibition. In summary, sEH inhibition does not prevent cardiac remodeling or dysfunction after TAC. Thus, targeting sEH seems to be insufficient for reducing pressure overload hypertrophy.
ESTHER : Morgan_2013_J.Cardiovasc.Pharmacol_61_291
PubMedSearch : Morgan_2013_J.Cardiovasc.Pharmacol_61_291
PubMedID: 23232840

Title : Genome Sequences of Two Emerging Non-O157 Shiga Toxin-Producing Escherichia coli Strains - Cao_2013_Genome.Announc_1_E00200
Author(s) : Cao G , Ju W , Rump L , Zhao S , Zou L , Wang C , Strain E , Luo Y , Timme R , Allard M , Brown E , Meng J
Ref : Genome Announc , 1 :E00200 , 2013
Abstract : Shiga toxin-producing Escherichia coli (STEC) causes severe illness in humans, including hemorrhagic colitis and hemolytic uremic syndrome. A parallel evolutionary model was proposed in which E. coli strains of distinct phylogenies independently integrate Shiga toxin-encoding genes and evolve into STEC. We report the draft genomes of two emerging non-O157 STEC strains.
ESTHER : Cao_2013_Genome.Announc_1_E00200
PubMedSearch : Cao_2013_Genome.Announc_1_E00200
PubMedID: 23682138
Gene_locus related to this paper: ecoli-d7xp23 , ecoli-ybff , ecoli-ycfp , ecoli-yiel , ecoli-yqia , ecoli-Z1930 , ecoli-YfhR

Title : Complete Genome Sequence of a Multidrug-Resistant Salmonella enterica Serovar Typhimurium var. 5- Strain Isolated from Chicken Breast - Hoffmann_2013_Genome.Announc_1_e01068
Author(s) : Hoffmann M , Muruvanda T , Allard MW , Korlach J , Roberts RJ , Timme R , Payne J , McDermott PF , Evans P , Meng J , Brown EW , Zhao S
Ref : Genome Announc , 1 : , 2013
Abstract : Salmonella enterica subsp. enterica serovar Typhimurium is a leading cause of salmonellosis. Here, we report a closed genome sequence, including sequences of 3 plasmids, of Salmonella serovar Typhimurium var. 5- CFSAN001921 (National Antimicrobial Resistance Monitoring System [NARMS] strain ID N30688), which was isolated from chicken breast meat and shows resistance to 10 different antimicrobials. Whole-genome and plasmid sequence analyses of this isolate will help enhance our understanding of this pathogenic multidrug-resistant serovar.
ESTHER : Hoffmann_2013_Genome.Announc_1_e01068
PubMedSearch : Hoffmann_2013_Genome.Announc_1_e01068
PubMedID: 24356834

Title : Genome sequences of five Salmonella enterica serovar Heidelberg isolates associated with a 2011 multistate outbreak in the United States - Hoffmann_2012_J.Bacteriol_194_3274
Author(s) : Hoffmann M , Zhao S , Luo Y , Li C , Folster JP , Whichard J , Allard MW , Brown EW , McDermott PF
Ref : Journal of Bacteriology , 194 :3274 , 2012
Abstract : Salmonella enterica serovar Heidelberg has caused numerous outbreaks in humans. Here, we report draft genomes of five isolates of serovar Heidelberg associated with the recent (2011) multistate outbreak linked to ground turkey in the United States. Isolates 2011K-1110 and 2011K-1132 were recovered from humans, while isolates 2011K-1138, 2011K-1224, and 2011K-1225 were recovered from ground turkey. Whole-genome sequence analysis of these isolates provides a tool for studying the short-term evolution of these epidemic clones.
ESTHER : Hoffmann_2012_J.Bacteriol_194_3274
PubMedSearch : Hoffmann_2012_J.Bacteriol_194_3274
PubMedID: 22628505
Gene_locus related to this paper: salty-STY1441 , salty-YFBB

Title : Draft genome sequences of eight Salmonella enterica serotype newport strains from diverse hosts and locations - Cao_2012_J.Bacteriol_194_5146
Author(s) : Cao G , Zhao S , Strain E , Luo Y , Timme R , Wang C , Brown E , Meng J , Allard M
Ref : Journal of Bacteriology , 194 :5146 , 2012
Abstract : Salmonellosis is a major contributor to the global public health burden. Salmonella enterica serotype Newport has ranked among three Salmonella serotypes most commonly associated with food-borne outbreaks in the United States. It was thought to be polyphyletic and composed of independent lineages. Here we report draft genomes of eight strains of S. Newport from diverse hosts and locations.
ESTHER : Cao_2012_J.Bacteriol_194_5146
PubMedSearch : Cao_2012_J.Bacteriol_194_5146
PubMedID: 22933769
Gene_locus related to this paper: salty-STY1441

Title : Lhx8 promote differentiation of hippocampal neural stem\/progenitor cells into cholinergic neurons in vitro - Shi_2012_In.Vitro.Cell.Dev.Biol.Anim_48_603
Author(s) : Shi J , Li H , Jin G , Zhu P , Tian M , Qin J , Tan X , Zhao S , Wang F , Hua Y , Xiao Y
Ref : In Vitro Cell Developmental Biology Anim , 48 :603 , 2012
Abstract : Lhx8, also named L3, is a recently identified member of the LIM homeobox gene family. Previously, we found acetylcholinesterase (AChE)-positive cells in fimbria-fornix (FF) transected rat hippocampal subgranular zone (SGZ). In the present study, we detected choline acetyltransferase (ChAT)-positive cholinergic cells in hippocampal SGZ after FF transaction, and these ChAT-positive cells were double labeled by Lhx8. Then we overexpressed Lhx8 during neural differentiation of hippocampal neural stem/progenitor cells on adherent conditions using lentivirus Lenti6.3-Lhx8. The result indicated that overexpression of Lhx8 did not affect the proportion of MAP2-positive neurons, but increased the proportion of ChAT-positive cells in vitro. These results suggested that FF-transected hippocampal niche promoted the ChAT/Lhx8-positive cholinergic neurons generation in rodent hippocampus, and Lhx8 was not associated with the MAP2-positive neurons differentiation on adherent conditions, but played a role in the specification of cholinergic neurons derived from hippocampal neural stem/progenitor cells in vitro.
ESTHER : Shi_2012_In.Vitro.Cell.Dev.Biol.Anim_48_603
PubMedSearch : Shi_2012_In.Vitro.Cell.Dev.Biol.Anim_48_603
PubMedID: 23150137

Title : Exceptional thermal stability and organic solvent tolerance of an esterase expressed from a thermophilic host - Mei_2012_Appl.Microbiol.Biotechnol_93_1965
Author(s) : Mei Y , Peng N , Zhao S , Hu Y , Wang H , Liang Y , She Q
Ref : Applied Microbiology & Biotechnology , 93 :1965 , 2012
Abstract : A protein expression system recently developed for the thermophilic crenarchaeon Sulfolobus islandicus was employed to produce recombinant protein for EstA, a thermophilic esterase encoded in the same organism. Large amounts of protein were readily obtained by an affinity protein purification, giving SisEstA. Upon Escherichia coli expression, only the thioredoxin-tagged EstA recombinant protein was soluble. The fusion protein was then purified, and removing the protein tag yielded EcSisEstA. Both forms of the thermophilic EstA enzyme were characterized. We found that SisEstA formed dimer exclusively in solution, whereas EcSisEstA appeared solely as monomer. The former exhibited a stronger resistance to organic solvents than the latter in general, having a much higher temperature optimum (90 degrees C vs. 65 degrees C). More strikingly, SisEstA exhibited a half-life that was more than 32-fold longer than that of EcSisEstA at 90 degrees C. This indicated that thermophilic enzymes yielded from homologous expression should be better biocatalysts than those obtained from mesophilic expression.
ESTHER : Mei_2012_Appl.Microbiol.Biotechnol_93_1965
PubMedSearch : Mei_2012_Appl.Microbiol.Biotechnol_93_1965
PubMedID: 21847512
Gene_locus related to this paper: sulir-f0ndq1

Title : Phylogenetic analysis of non-O157 Shiga toxin-producing Escherichia coli strains by whole-genome sequencing - Ju_2012_J.Clin.Microbiol_50_4123
Author(s) : Ju W , Cao G , Rump L , Strain E , Luo Y , Timme R , Allard M , Zhao S , Brown E , Meng J
Ref : J Clin Microbiol , 50 :4123 , 2012
Abstract : Non-O157 Shiga toxin-producing Escherichia coli (STEC) strains are emerging food-borne pathogens causing life-threatening diseases and food-borne outbreaks. A better understanding of their evolution provides a framework for developing tools to control food safety. We obtained 15 genomes of non-O157 STEC strains, including O26, O111, and O103 strains. Phylogenetic trees revealed a close relationship between O26:H11 and O111:H11 and a scattered distribution of O111. We hypothesize that STEC serotypes with the same H antigens might share common ancestors.
ESTHER : Ju_2012_J.Clin.Microbiol_50_4123
PubMedSearch : Ju_2012_J.Clin.Microbiol_50_4123
PubMedID: 23052305
Gene_locus related to this paper: ecoli-d7xp23 , ecoli-MCMK , ecoli-yaim , ecoli-ybff , ecoli-ycfp , ecoli-yhet , ecoli-yiel , ecoli-ypt1 , ecoli-yqia , ecoli-Z1341 , ecoli-Z1930 , ecoli-YfhR

Title : Cell type-specific channelrhodopsin-2 transgenic mice for optogenetic dissection of neural circuitry function - Zhao_2011_Nat.Methods_8_745
Author(s) : Zhao S , Ting JT , Atallah HE , Qiu L , Tan J , Gloss B , Augustine GJ , Deisseroth K , Luo M , Graybiel AM , Feng G
Ref : Nat Methods , 8 :745 , 2011
Abstract : Optogenetic methods have emerged as powerful tools for dissecting neural circuit connectivity, function and dysfunction. We used a bacterial artificial chromosome (BAC) transgenic strategy to express the H134R variant of channelrhodopsin-2, ChR2(H134R), under the control of cell type-specific promoter elements. We performed an extensive functional characterization of the newly established VGAT-ChR2(H134R)-EYFP, ChAT-ChR2(H134R)-EYFP, Tph2-ChR2(H134R)-EYFP and Pvalb(H134R)-ChR2-EYFP BAC transgenic mouse lines and demonstrate the utility of these lines for precisely controlling action-potential firing of GABAergic, cholinergic, serotonergic and parvalbumin-expressing neuron subsets using blue light. This resource of cell type-specific ChR2(H134R) mouse lines will facilitate the precise mapping of neuronal connectivity and the dissection of the neural basis of behavior.
ESTHER : Zhao_2011_Nat.Methods_8_745
PubMedSearch : Zhao_2011_Nat.Methods_8_745
PubMedID: 21985008

Title : Transcription and induction profiles of two esterase genes in susceptible and acaricide-resistant Tetranychus cinnabarinus - Feng_2011_Pestic.Biochem.Physiol_100_70
Author(s) : Feng Y-n , Yan J , Sun W , Zhao S , Lu W-C , Li M , He L
Ref : Pesticide Biochemistry and Physiology , 100 :70 , 2011
Abstract : The carmine spider mite Tetranychus cinnabarinus is the most serious of crop mite pests in China. Their ability to rapidly develop resistance to acaricides has caused difficulty in controlling this mite. In this study, the molecular mechanism of acaricide resistance associated with esterase genes TCE1 and TCE2 was investigated in susceptible and acaricide-resistant strains of T. cinnabarinus. The quantitative real-time PCR (qrtPCR) method was adopted to compare the expression level of two esterase genes TCE1 and TCE2 among four different strains (abamectin-resistant, AbR; fenpropathrin-resistant, FeR; omethoate-resistant, OmR and susceptible strains, S) of T. cinnabarinus. The relative expression level of TCE2 was 1.39-2.47 fold in the three resistant strains compared with the S strain. And after inducing with abamectin, fenpropathrin, and omethoate the highest expression level of TCE2 in the S was 1.64-, 2.92- and 2.24-fold compared with the control, respectively, and this difference was found to be significant. However, there was no obvious difference of the mRNA relative expression levels of TCE1 genes among the four strains, and those of TCE1 were not higher than the control throughout the study. Furthermore, the expression modes of TCE1 and TCE2 in AbR and FeR were similar with that in the S after being treated with abamectin and fenpropathrin, respectively. These results indicated that the enhanced expression of esterase gene TCE2 was associated with acaricide-resistance in T. cinnabarinus.
ESTHER : Feng_2011_Pestic.Biochem.Physiol_100_70
PubMedSearch : Feng_2011_Pestic.Biochem.Physiol_100_70
PubMedID:

Title : Hepatic lipolysis in broiler chickens with different fat deposition during embryonic development - Zhao_2010_Res.Vet.Sci_88_321
Author(s) : Zhao S , Ma H , Huang G , Zou S
Ref : Res Vet Sci , 88 :321 , 2010
Abstract : The aim of this study was to explore the hepatic lipolysis in broiler chickens with different fat deposition during embryonic development. The mRNA expression of CPT-1 (carmitine palmtoyltransferase-1), PPARalpha (peroxisome proliferator-activated receptor alpha) and LPL (lipoprotein lipase) genes were determined using Real time RT-PCR. The start of incubation was called day 1 (E1) and after hatching called day 1 (H1). On incubation days 9 (E9), 14 (E14) and 19 (E19) as well as at hatching (H1), samples of liver were collected. Blood samples were obtained during days 14 (E14) and 19 (E19) of embryonic development and at hatching. This study showed that serum TG (triglycerol) decreased and TC (total cholesterol) and NEFA (non-estered fatty acid) increased during embryonic development. The expression of CPT-1, PPARalpha and LPL genes exhibited different developmental changes. For example, little LPL gene was expressed at hatching and PPARalpha gene expression peaked before hatching. However, CPT-1 gene exhibited no significance during the embryonic development. Our results showed that expression of these genes in Arbor Acres (AA) broilers was significantly higher than that in San Huang (SH) broilers. Therefore, this study suggested that hepatic lipolysis in broiler chickens exhibited developmental changes during embryogenesis and breed difference which may be one of the factors in the fat deposition difference between fat line and lean line broilers during embryonic development.
ESTHER : Zhao_2010_Res.Vet.Sci_88_321
PubMedSearch : Zhao_2010_Res.Vet.Sci_88_321
PubMedID: 19709700

Title : The sequence and de novo assembly of the giant panda genome - Li_2010_Nature_463_311
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
Ref : Nature , 463 :311 , 2010
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.
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

Title : Effects of low-intensity microwave radiation on Tribolium castaneum physiological and biochemical characteristics and survival - Lu_2010_J.Insect.Physiol_56_1356
Author(s) : Lu H , Zhou J , Xiong S , Zhao S
Ref : J Insect Physiol , 56 :1356 , 2010
Abstract : The red flour beetle, Tribolium castaneum (Coleoptera: Tenebrionidae) is a widespread pest that lives in, and feeds on, wheat flour. Here, we studied the effects of low-intensity microwave radiation (LIMR;
ESTHER : Lu_2010_J.Insect.Physiol_56_1356
PubMedSearch : Lu_2010_J.Insect.Physiol_56_1356
PubMedID: 20438733

Title : Identification of a new functional domain in angiopoietin-like 3 (ANGPTL3) and angiopoietin-like 4 (ANGPTL4) involved in binding and inhibition of lipoprotein lipase (LPL) - Lee_2009_J.Biol.Chem_284_13735
Author(s) : Lee EC , Desai U , Gololobov G , Hong S , Feng X , Yu XC , Gay J , Wilganowski N , Gao C , Du LL , Chen J , Hu Y , Zhao S , Kirkpatrick L , Schneider M , Zambrowicz BP , Landes G , Powell DR , Sonnenburg WK
Ref : Journal of Biological Chemistry , 284 :13735 , 2009
Abstract : Angiopoietin-like 3 (ANGPTL3) and angiopoietin-like 4 (ANGPTL4) are secreted proteins that regulate triglyceride (TG) metabolism in part by inhibiting lipoprotein lipase (LPL). Recently, we showed that treatment of wild-type mice with monoclonal antibody (mAb) 14D12, specific for ANGPTL4, recapitulated the Angptl4 knock-out (-/-) mouse phenotype of reduced serum TG levels. In the present study, we mapped the region of mouse ANGPTL4 recognized by mAb 14D12 to amino acids Gln(29)-His(53), which we designate as specific epitope 1 (SE1). The 14D12 mAb prevented binding of ANGPTL4 with LPL, consistent with its ability to neutralize the LPL-inhibitory activity of ANGPTL4. Alignment of all angiopoietin family members revealed that a sequence similar to ANGPTL4 SE1 was present only in ANGPTL3, corresponding to amino acids Glu(32)-His(55). We produced a mouse mAb against this SE1-like region in ANGPTL3. This mAb, designated 5.50.3, inhibited the binding of ANGPTL3 to LPL and neutralized ANGPTL3-mediated inhibition of LPL activity in vitro. Treatment of wild-type as well as hyperlipidemic mice with mAb 5.50.3 resulted in reduced serum TG levels, recapitulating the lipid phenotype found in Angptl3(-/-) mice. These results show that the SE1 region of ANGPTL3 and ANGPTL4 functions as a domain important for binding LPL and inhibiting its activity in vitro and in vivo. Moreover, these results demonstrate that therapeutic antibodies that neutralize ANGPTL4 and ANGPTL3 may be useful for treatment of some forms of hyperlipidemia.
ESTHER : Lee_2009_J.Biol.Chem_284_13735
PubMedSearch : Lee_2009_J.Biol.Chem_284_13735
PubMedID: 19318355
Gene_locus related to this paper: human-LPL

Title : Isolation and biochemical characterization of two lipases from a metagenomic library of China Holstein cow rumen - Liu_2009_Biochem.Biophys.Res.Commun_385_605
Author(s) : Liu K , Wang J , Bu D , Zhao S , McSweeney C , Yu P , Li D
Ref : Biochemical & Biophysical Research Communications , 385 :605 , 2009
Abstract : Two novel lipase genes RlipE1 and RlipE2 which encoded 361- and 265-amino acid peptides, respectively, were recovered from a metagenomic library of the rumen microbiota of Chinese Holstein cows. A BLAST search revealed a high similarity (90%) between RlipE2 and a carboxylesterase from Thermosinus carboxydivorans Nor1, while there was a low similarity (below 50%) between RlipE1 and other lipases. Phylogenetic analysis indicated that RlipE2 clustered with the lipolytic enzymes from family V while RlipE1 clustered with six other putative bacterial lipases which might constitute a new subfamily. The recombinant lipases were thermally unstable and retained 60% activity over a pH range of 6.5-8.5. Substrate specificity assay indicated that both enzymes had higher hydrolytic activity toward laurate (C(12)), palmitate (C(16)) and stearate (C(18)). The novel phylogenetic affiliation and high specificity of both enzymes for long-chain fatty acid make them interesting targets for manipulation of rumen lipid metabolism.
ESTHER : Liu_2009_Biochem.Biophys.Res.Commun_385_605
PubMedSearch : Liu_2009_Biochem.Biophys.Res.Commun_385_605
PubMedID: 19486892
Gene_locus related to this paper: 9bact-c0k075 , 9bact-c0k085

Title : Antimicrobial resistance-conferring plasmids with similarity to virulence plasmids from avian pathogenic Escherichia coli strains in Salmonella enterica serovar Kentucky isolates from poultry - Fricke_2009_Appl.Environ.Microbiol_75_5963
Author(s) : Fricke WF , McDermott PF , Mammel MK , Zhao S , Johnson TJ , Rasko DA , Fedorka-Cray PJ , Pedroso A , Whichard JM , Leclerc JE , White DG , Cebula TA , Ravel J
Ref : Applied Environmental Microbiology , 75 :5963 , 2009
Abstract : Salmonella enterica, a leading cause of food-borne gastroenteritis worldwide, may be found in any raw food of animal, vegetable, or fruit origin. Salmonella serovars differ in distribution, virulence, and host specificity. Salmonella enterica serovar Kentucky, though often found in the food supply, is less commonly isolated from ill humans. The multidrug-resistant isolate S. Kentucky CVM29188, isolated from a chicken breast sample in 2003, contains three plasmids (146,811 bp, 101,461 bp, and 46,121 bp), two of which carry resistance determinants (pCVM29188_146 [strAB and tetRA] and pCVM29188_101 [bla(CMY-2) and sugE]). Both resistance plasmids were transferable by conjugation, alone or in combination, to S. Kentucky, Salmonella enterica serovar Newport, and Escherichia coli recipients. pCVM29188_146 shares a highly conserved plasmid backbone of 106 kb (>90% nucleotide identity) with two virulence plasmids from avian pathogenic Escherichia coli strains (pAPEC-O1-ColBM and pAPEC-O2-ColV). Shared avian pathogenic E. coli (APEC) virulence factors include iutA iucABCD, sitABCD, etsABC, iss, and iroBCDEN. PCR analyses of recent (1997 to 2005) S. Kentucky isolates from food animal, retail meat, and human sources revealed that 172 (60%) contained similar APEC-like plasmid backbones. Notably, though rare in human- and cattle-derived isolates, this plasmid backbone was found at a high frequency (50 to 100%) among S. Kentucky isolates from chickens within the same time span. Ninety-four percent of the APEC-positive isolates showed resistance to tetracycline and streptomycin. Together, our findings of a resistance-conferring APEC virulence plasmid in a poultry-derived S. Kentucky isolate and of similar resistance/virulence plasmids in most recent S. Kentucky isolates from chickens and, to lesser degree, from humans and cattle highlight the need for additional research in order to examine the prevalence and spread of combined virulence and resistance plasmids in bacteria in agricultural, environmental, and clinical settings.
ESTHER : Fricke_2009_Appl.Environ.Microbiol_75_5963
PubMedSearch : Fricke_2009_Appl.Environ.Microbiol_75_5963
PubMedID: 19648374
Gene_locus related to this paper: ecoli-IROD , shidy-q67dv1

Title : Imprinting analysis of the porcine MEST gene in 75 and 90 day placentas and prenatal tissues - Xu_2007_Acta.Biochim.Biophys.Sin.(Shanghai)_39_633
Author(s) : Xu C , Su L , Zhou Q , Li C , Zhao S
Ref : Acta Biochim Biophys Sin (Shanghai) , 39 :633 , 2007
Abstract : Imprinted genes play important roles in mammalian growth, development and behavior. Mouse mesoderm-specific transcript (MEST) has been identified as an imprinted gene and mapped to an imprinted region of mouse chromosome 6 (MMU6). It plays essential roles in embryonic and placental growth, and it is required for maternal behavior in adult female mouse. Here, we isolated the porcine MEST gene and detected a single nucleotide polymorphism in the 3 -untranslated region. The RsaI polymorphism was used to investigate the allele frequencies in different pig breeds and the imprinting status in prenatal porcine tissues. Allele frequencies were significantly different between the native Chinese and Landrace breeds, except that most of the native Yushan pigs (21/26) are heterozygous at this locus. The results indicate that MEST was imprinted in placentas on days 75 and 90 of gestation as well as in the 75 d fetal heart, muscle, kidney, lung and liver.
ESTHER : Xu_2007_Acta.Biochim.Biophys.Sin.(Shanghai)_39_633
PubMedSearch : Xu_2007_Acta.Biochim.Biophys.Sin.(Shanghai)_39_633
PubMedID: 17687499

Title : The -250G-->A polymorphism in the human hepatic lipase gene promoter affects blood lipids in Chinese - Zhao_2006_Clin.Chim.Acta_365_149
Author(s) : Zhao S , Xie X , Nie S
Ref : Clinica Chimica Acta , 365 :149 , 2006
Abstract : BACKGROUND: Human hepatic lipase (HL) is a glycoprotein that catalyzes the hydrolysis of triglycerides and phospholipids in all major classes of lipoproteins. We studied whether the hepatic lipase gene -250G(guanine)-->A(adenine) polymorphism affect blood lipids level and the coronary heart disease.
METHODS: Two hundred and thirty subjects were included. Among them there were 122 patients with coronary heart disease and 108 subjects without coronary heart disease. Polymerase chain reaction-restricted fragments length polymorphism was used to determine HL genotype.
RESULTS: The serum HDL-C level of HL-250A heterozygote (carriers of GA genotype) and homozygote (carriers of AA genotype) [(1.32+/-0.35) mmol/l] was significantly higher than wild type [carriers of GG genotype, (1.19+/-0.30) mmol/l, P<0.005]. This effect to blood lipids appears more evident in women (P<0.005). But the distribution of the 3 genotypes of HL-250 among the patients with coronary heart disease (GG54.1%, GA37.7%, AA8.2%) were similar with those of the control (GG54.6%, GA37.0%, AA8.4%, P>0.05). Both the male and the female had similar ratio for 3 HL genotypes.
CONCLUSIONS: HL-250G-->A variation affects blood lipids profile and results in the increasing of the serum HDL-C level. This beneficial effect to blood lipids profile is more obviously seen in the female.
ESTHER : Zhao_2006_Clin.Chim.Acta_365_149
PubMedSearch : Zhao_2006_Clin.Chim.Acta_365_149
PubMedID: 16153627

Title : A molecular neuroethological approach for identifying and characterizing a cascade of behaviorally regulated genes - Wada_2006_Proc.Natl.Acad.Sci.U.S.A_103_15212
Author(s) : Wada K , Howard JT , McConnell P , Whitney O , Lints T , Rivas MV , Horita H , Patterson MA , White SA , Scharff C , Haesler S , Zhao S , Sakaguchi H , Hagiwara M , Shiraki T , Hirozane-Kishikawa T , Skene P , Hayashizaki Y , Carninci P , Jarvis ED
Ref : Proc Natl Acad Sci U S A , 103 :15212 , 2006
Abstract : Songbirds have one of the most accessible neural systems for the study of brain mechanisms of behavior. However, neuroethological studies in songbirds have been limited by the lack of high-throughput molecular resources and gene-manipulation tools. To overcome these limitations, we constructed 21 regular, normalized, and subtracted full-length cDNA libraries from brains of zebra finches in 57 developmental and behavioral conditions in an attempt to clone as much of the brain transcriptome as possible. From these libraries, approximately 14,000 transcripts were isolated, representing an estimated 4,738 genes. With the cDNAs, we created a hierarchically organized transcriptome database and a large-scale songbird brain cDNA microarray. We used the arrays to reveal a set of 33 genes that are regulated in forebrain vocal nuclei by singing behavior. These genes clustered into four anatomical and six temporal expression patterns. Their functions spanned a large range of cellular and molecular categories, from signal transduction, trafficking, and structural, to synaptically released molecules. With the full-length cDNAs and a lentiviral vector system, we were able to overexpress, in vocal nuclei, proteins of representative singing-regulated genes in the absence of singing. This publicly accessible resource http:\/\/songbirdtranscriptome.net can now be used to study molecular neuroethological mechanisms of behavior.
ESTHER : Wada_2006_Proc.Natl.Acad.Sci.U.S.A_103_15212
PubMedSearch : Wada_2006_Proc.Natl.Acad.Sci.U.S.A_103_15212
PubMedID: 17018643
Gene_locus related to this paper: taegu-b5fyu7

Title : Genome sequence of the Brown Norway rat yields insights into mammalian evolution - Gibbs_2004_Nature_428_493
Author(s) : Gibbs RA , Weinstock GM , Metzker ML , Muzny DM , Sodergren EJ , Scherer S , Scott G , Steffen D , Worley KC , Burch PE , Okwuonu G , Hines S , Lewis L , DeRamo C , Delgado O , Dugan-Rocha S , Miner G , Morgan M , Hawes A , Gill R , Celera , Holt RA , Adams MD , Amanatides PG , Baden-Tillson H , Barnstead M , Chin S , Evans CA , Ferriera S , Fosler C , Glodek A , Gu Z , Jennings D , Kraft CL , Nguyen T , Pfannkoch CM , Sitter C , Sutton GG , Venter JC , Woodage T , Smith D , Lee HM , Gustafson E , Cahill P , Kana A , Doucette-Stamm L , Weinstock K , Fechtel K , Weiss RB , Dunn DM , Green ED , Blakesley RW , Bouffard GG , de Jong PJ , Osoegawa K , Zhu B , Marra M , Schein J , Bosdet I , Fjell C , Jones S , Krzywinski M , Mathewson C , Siddiqui A , Wye N , McPherson J , Zhao S , Fraser CM , Shetty J , Shatsman S , Geer K , Chen Y , Abramzon S , Nierman WC , Havlak PH , Chen R , Durbin KJ , Egan A , Ren Y , Song XZ , Li B , Liu Y , Qin X , Cawley S , Cooney AJ , D'Souza LM , Martin K , Wu JQ , Gonzalez-Garay ML , Jackson AR , Kalafus KJ , McLeod MP , Milosavljevic A , Virk D , Volkov A , Wheeler DA , Zhang Z , Bailey JA , Eichler EE , Tuzun E , Birney E , Mongin E , Ureta-Vidal A , Woodwark C , Zdobnov E , Bork P , Suyama M , Torrents D , Alexandersson M , Trask BJ , Young JM , Huang H , Wang H , Xing H , Daniels S , Gietzen D , Schmidt J , Stevens K , Vitt U , Wingrove J , Camara F , Mar Alba M , Abril JF , Guigo R , Smit A , Dubchak I , Rubin EM , Couronne O , Poliakov A , Hubner N , Ganten D , Goesele C , Hummel O , Kreitler T , Lee YA , Monti J , Schulz H , Zimdahl H , Himmelbauer H , Lehrach H , Jacob HJ , Bromberg S , Gullings-Handley J , Jensen-Seaman MI , Kwitek AE , Lazar J , Pasko D , Tonellato PJ , Twigger S , Ponting CP , Duarte JM , Rice S , Goodstadt L , Beatson SA , Emes RD , Winter EE , Webber C , Brandt P , Nyakatura G , Adetobi M , Chiaromonte F , Elnitski L , Eswara P , Hardison RC , Hou M , Kolbe D , Makova K , Miller W , Nekrutenko A , Riemer C , Schwartz S , Taylor J , Yang S , Zhang Y , Lindpaintner K , Andrews TD , Caccamo M , Clamp M , Clarke L , Curwen V , Durbin R , Eyras E , Searle SM , Cooper GM , Batzoglou S , Brudno M , Sidow A , Stone EA , Payseur BA , Bourque G , Lopez-Otin C , Puente XS , Chakrabarti K , Chatterji S , Dewey C , Pachter L , Bray N , Yap VB , Caspi A , Tesler G , Pevzner PA , Haussler D , Roskin KM , Baertsch R , Clawson H , Furey TS , Hinrichs AS , Karolchik D , Kent WJ , Rosenbloom KR , Trumbower H , Weirauch M , Cooper DN , Stenson PD , Ma B , Brent M , Arumugam M , Shteynberg D , Copley RR , Taylor MS , Riethman H , Mudunuri U , Peterson J , Guyer M , Felsenfeld A , Old S , Mockrin S , Collins F
Ref : Nature , 428 :493 , 2004
Abstract : The laboratory rat (Rattus norvegicus) is an indispensable tool in experimental medicine and drug development, having made inestimable contributions to human health. We report here the genome sequence of the Brown Norway (BN) rat strain. The sequence represents a high-quality 'draft' covering over 90% of the genome. The BN rat sequence is the third complete mammalian genome to be deciphered, and three-way comparisons with the human and mouse genomes resolve details of mammalian evolution. This first comprehensive analysis includes genes and proteins and their relation to human disease, repeated sequences, comparative genome-wide studies of mammalian orthologous chromosomal regions and rearrangement breakpoints, reconstruction of ancestral karyotypes and the events leading to existing species, rates of variation, and lineage-specific and lineage-independent evolutionary events such as expansion of gene families, orthology relations and protein evolution.
ESTHER : Gibbs_2004_Nature_428_493
PubMedSearch : Gibbs_2004_Nature_428_493
PubMedID: 15057822
Gene_locus related to this paper: rat-abhea , rat-abheb , rat-cd029 , rat-d3zaw4 , rat-dpp9 , rat-d3zhq1 , rat-d3zkp8 , rat-d3zuq1 , rat-d3zxw8 , rat-d4a4w4 , rat-d4a7w1 , rat-d4a9l7 , rat-d4a071 , rat-d4aa31 , rat-d4aa33 , rat-d4aa61 , rat-dglb , rat-f1lz91 , rat-Kansl3 , rat-nceh1 , rat-Tex30 , ratno-1hlip , ratno-1neur , ratno-1plip , ratno-2neur , ratno-3neur , ratno-3plip , ratno-ABH15 , ratno-ACHE , ratno-balip , ratno-BCHE , ratno-cauxin , ratno-Ces1d , ratno-Ces1e , ratno-Ces2f , ratno-d3ze31 , ratno-d3zp14 , ratno-d3zxi3 , ratno-d3zxq0 , ratno-d3zxq1 , ratno-d4a3d4 , ratno-d4aa05 , ratno-dpp4 , ratno-dpp6 , ratno-est8 , ratno-FAP , ratno-hyep , ratno-hyes , ratno-kmcxe , ratno-lmcxe , ratno-LOC246252 , ratno-MGLL , ratno-pbcxe , ratno-phebest , ratno-Ppgb , ratno-q4qr68 , ratno-q6ayr2 , ratno-q6q629 , ratno-SPG21 , ratno-thyro , rat-m0rc77 , rat-a0a0g2k9y7 , rat-a0a0g2kb83 , rat-d3zba8 , rat-d3zbj1 , rat-d3zcr8 , rat-d3zxw5 , rat-d4a340 , rat-f1lvg7 , rat-m0r509 , rat-m0r5d4 , rat-b5den3 , rat-d3zxk4 , rat-d4a1b6 , rat-d3zmg4 , rat-ab17c

Title : The genome sequence of the malaria mosquito Anopheles gambiae - Holt_2002_Science_298_129
Author(s) : Holt RA , Subramanian GM , Halpern A , Sutton GG , Charlab R , Nusskern DR , Wincker P , Clark AG , Ribeiro JM , Wides R , Salzberg SL , Loftus B , Yandell M , Majoros WH , Rusch DB , Lai Z , Kraft CL , Abril JF , Anthouard V , Arensburger P , Atkinson PW , Baden H , de Berardinis V , Baldwin D , Benes V , Biedler J , Blass C , Bolanos R , Boscus D , Barnstead M , Cai S , Center A , Chaturverdi K , Christophides GK , Chrystal MA , Clamp M , Cravchik A , Curwen V , Dana A , Delcher A , Dew I , Evans CA , Flanigan M , Grundschober-Freimoser A , Friedli L , Gu Z , Guan P , Guigo R , Hillenmeyer ME , Hladun SL , Hogan JR , Hong YS , Hoover J , Jaillon O , Ke Z , Kodira C , Kokoza E , Koutsos A , Letunic I , Levitsky A , Liang Y , Lin JJ , Lobo NF , Lopez JR , Malek JA , McIntosh TC , Meister S , Miller J , Mobarry C , Mongin E , Murphy SD , O'Brochta DA , Pfannkoch C , Qi R , Regier MA , Remington K , Shao H , Sharakhova MV , Sitter CD , Shetty J , Smith TJ , Strong R , Sun J , Thomasova D , Ton LQ , Topalis P , Tu Z , Unger MF , Walenz B , Wang A , Wang J , Wang M , Wang X , Woodford KJ , Wortman JR , Wu M , Yao A , Zdobnov EM , Zhang H , Zhao Q , Zhao S , Zhu SC , Zhimulev I , Coluzzi M , della Torre A , Roth CW , Louis C , Kalush F , Mural RJ , Myers EW , Adams MD , Smith HO , Broder S , Gardner MJ , Fraser CM , Birney E , Bork P , Brey PT , Venter JC , Weissenbach J , Kafatos FC , Collins FH , Hoffman SL
Ref : Science , 298 :129 , 2002
Abstract : Anopheles gambiae is the principal vector of malaria, a disease that afflicts more than 500 million people and causes more than 1 million deaths each year. Tenfold shotgun sequence coverage was obtained from the PEST strain of A. gambiae and assembled into scaffolds that span 278 million base pairs. A total of 91% of the genome was organized in 303 scaffolds; the largest scaffold was 23.1 million base pairs. There was substantial genetic variation within this strain, and the apparent existence of two haplotypes of approximately equal frequency ("dual haplotypes") in a substantial fraction of the genome likely reflects the outbred nature of the PEST strain. The sequence produced a conservative inference of more than 400,000 single-nucleotide polymorphisms that showed a markedly bimodal density distribution. Analysis of the genome sequence revealed strong evidence for about 14,000 protein-encoding transcripts. Prominent expansions in specific families of proteins likely involved in cell adhesion and immunity were noted. An expressed sequence tag analysis of genes regulated by blood feeding provided insights into the physiological adaptations of a hematophagous insect.
ESTHER : Holt_2002_Science_298_129
PubMedSearch : Holt_2002_Science_298_129
PubMedID: 12364791
Gene_locus related to this paper: anoga-a0nb77 , anoga-a0nbp6 , anoga-a0neb7 , anoga-a0nei9 , anoga-a0nej0 , anoga-a0ngj1 , anoga-a7ut12 , anoga-a7uuz9 , anoga-ACHE1 , anoga-ACHE2 , anoga-agCG44620 , anoga-agCG44666 , anoga-agCG45273 , anoga-agCG45279 , anoga-agCG45511 , anoga-agCG46741 , anoga-agCG47651 , anoga-agCG47655 , anoga-agCG47661 , anoga-agCG47690 , anoga-agCG48797 , anoga-AGCG49362 , anoga-agCG49462 , anoga-agCG49870 , anoga-agCG49872 , anoga-agCG49876 , anoga-agCG50851 , anoga-agCG51879 , anoga-agCG52383 , anoga-agCG54954 , anoga-AGCG55021 , anoga-agCG55401 , anoga-agCG55408 , anoga-agCG56978 , anoga-ebiG239 , anoga-ebiG2660 , anoga-ebiG5718 , anoga-ebiG5974 , anoga-ebiG8504 , anoga-ebiG8742 , anoga-glita , anoga-nrtac , anoga-q5tpv0 , anoga-Q5TVS6 , anoga-q7pm39 , anoga-q7ppw9 , anoga-q7pq17 , anoga-Q7PQT0 , anoga-q7q8m4 , anoga-q7q626 , anoga-q7qa14 , anoga-q7qa52 , anoga-q7qal7 , anoga-q7qbj0 , anoga-f5hl20 , anoga-q7qkh2 , anoga-a0a1s4h1y7 , anoga-q7q887

Title : The sequence of the human genome - Venter_2001_Science_291_1304
Author(s) : Venter JC , Adams MD , Myers EW , Li PW , Mural RJ , Sutton GG , Smith HO , Yandell M , Evans CA , Holt RA , Gocayne JD , Amanatides P , Ballew RM , Huson DH , Wortman JR , Zhang Q , Kodira CD , Zheng XH , Chen L , Skupski M , Subramanian G , Thomas PD , Zhang J , Gabor Miklos GL , Nelson C , Broder S , Clark AG , Nadeau J , McKusick VA , Zinder N , Levine AJ , Roberts RJ , Simon M , Slayman C , Hunkapiller M , Bolanos R , Delcher A , Dew I , Fasulo D , Flanigan M , Florea L , Halpern A , Hannenhalli S , Kravitz S , Levy S , Mobarry C , Reinert K , Remington K , Abu-Threideh J , Beasley E , Biddick K , Bonazzi V , Brandon R , Cargill M , Chandramouliswaran I , Charlab R , Chaturvedi K , Deng Z , Di Francesco V , Dunn P , Eilbeck K , Evangelista C , Gabrielian AE , Gan W , Ge W , Gong F , Gu Z , Guan P , Heiman TJ , Higgins ME , Ji RR , Ke Z , Ketchum KA , Lai Z , Lei Y , Li Z , Li J , Liang Y , Lin X , Lu F , Merkulov GV , Milshina N , Moore HM , Naik AK , Narayan VA , Neelam B , Nusskern D , Rusch DB , Salzberg S , Shao W , Shue B , Sun J , Wang Z , Wang A , Wang X , Wang J , Wei M , Wides R , Xiao C , Yan C , Yao A , Ye J , Zhan M , Zhang W , Zhang H , Zhao Q , Zheng L , Zhong F , Zhong W , Zhu S , Zhao S , Gilbert D , Baumhueter S , Spier G , Carter C , Cravchik A , Woodage T , Ali F , An H , Awe A , Baldwin D , Baden H , Barnstead M , Barrow I , Beeson K , Busam D , Carver A , Center A , Cheng ML , Curry L , Danaher S , Davenport L , Desilets R , Dietz S , Dodson K , Doup L , Ferriera S , Garg N , Gluecksmann A , Hart B , Haynes J , Haynes C , Heiner C , Hladun S , Hostin D , Houck J , Howland T , Ibegwam C , Johnson J , Kalush F , Kline L , Koduru S , Love A , Mann F , May D , McCawley S , McIntosh T , McMullen I , Moy M , Moy L , Murphy B , Nelson K , Pfannkoch C , Pratts E , Puri V , Qureshi H , Reardon M , Rodriguez R , Rogers YH , Romblad D , Ruhfel B , Scott R , Sitter C , Smallwood M , Stewart E , Strong R , Suh E , Thomas R , Tint NN , Tse S , Vech C , Wang G , Wetter J , Williams S , Williams M , Windsor S , Winn-Deen E , Wolfe K , Zaveri J , Zaveri K , Abril JF , Guigo R , Campbell MJ , Sjolander KV , Karlak B , Kejariwal A , Mi H , Lazareva B , Hatton T , Narechania A , Diemer K , Muruganujan A , Guo N , Sato S , Bafna V , Istrail S , Lippert R , Schwartz R , Walenz B , Yooseph S , Allen D , Basu A , Baxendale J , Blick L , Caminha M , Carnes-Stine J , Caulk P , Chiang YH , Coyne M , Dahlke C , Mays A , Dombroski M , Donnelly M , Ely D , Esparham S , Fosler C , Gire H , Glanowski S , Glasser K , Glodek A , Gorokhov M , Graham K , Gropman B , Harris M , Heil J , Henderson S , Hoover J , Jennings D , Jordan C , Jordan J , Kasha J , Kagan L , Kraft C , Levitsky A , Lewis M , Liu X , Lopez J , Ma D , Majoros W , McDaniel J , Murphy S , Newman M , Nguyen T , Nguyen N , Nodell M , Pan S , Peck J , Peterson M , Rowe W , Sanders R , Scott J , Simpson M , Smith T , Sprague A , Stockwell T , Turner R , Venter E , Wang M , Wen M , Wu D , Wu M , Xia A , Zandieh A , Zhu X
Ref : Science , 291 :1304 , 2001
Abstract : A 2.91-billion base pair (bp) consensus sequence of the euchromatic portion of the human genome was generated by the whole-genome shotgun sequencing method. The 14.8-billion bp DNA sequence was generated over 9 months from 27,271,853 high-quality sequence reads (5.11-fold coverage of the genome) from both ends of plasmid clones made from the DNA of five individuals. Two assembly strategies-a whole-genome assembly and a regional chromosome assembly-were used, each combining sequence data from Celera and the publicly funded genome effort. The public data were shredded into 550-bp segments to create a 2.9-fold coverage of those genome regions that had been sequenced, without including biases inherent in the cloning and assembly procedure used by the publicly funded group. This brought the effective coverage in the assemblies to eightfold, reducing the number and size of gaps in the final assembly over what would be obtained with 5.11-fold coverage. The two assembly strategies yielded very similar results that largely agree with independent mapping data. The assemblies effectively cover the euchromatic regions of the human chromosomes. More than 90% of the genome is in scaffold assemblies of 100,000 bp or more, and 25% of the genome is in scaffolds of 10 million bp or larger. Analysis of the genome sequence revealed 26,588 protein-encoding transcripts for which there was strong corroborating evidence and an additional approximately 12,000 computationally derived genes with mouse matches or other weak supporting evidence. Although gene-dense clusters are obvious, almost half the genes are dispersed in low G+C sequence separated by large tracts of apparently noncoding sequence. Only 1.1% of the genome is spanned by exons, whereas 24% is in introns, with 75% of the genome being intergenic DNA. Duplications of segmental blocks, ranging in size up to chromosomal lengths, are abundant throughout the genome and reveal a complex evolutionary history. Comparative genomic analysis indicates vertebrate expansions of genes associated with neuronal function, with tissue-specific developmental regulation, and with the hemostasis and immune systems. DNA sequence comparisons between the consensus sequence and publicly funded genome data provided locations of 2.1 million single-nucleotide polymorphisms (SNPs). A random pair of human haploid genomes differed at a rate of 1 bp per 1250 on average, but there was marked heterogeneity in the level of polymorphism across the genome. Less than 1% of all SNPs resulted in variation in proteins, but the task of determining which SNPs have functional consequences remains an open challenge.
ESTHER : Venter_2001_Science_291_1304
PubMedSearch : Venter_2001_Science_291_1304
PubMedID: 11181995
Gene_locus related to this paper: human-AADAC , human-ABHD1 , human-ABHD10 , human-ABHD11 , human-ACHE , human-BCHE , human-LDAH , human-ABHD18 , human-CMBL , human-ABHD17A , human-KANSL3 , human-LIPA , human-LYPLAL1 , human-NDRG2 , human-NLGN3 , human-NLGN4X , human-NLGN4Y , human-PAFAH2 , human-PREPL , human-RBBP9 , human-SPG21

Title : Syntheses of benzoquinolizidine and benzoindolizidine derivatives as anti-amnesic agents - Zhao_1999_Bioorg.Med.Chem_7_1637
Author(s) : Zhao S , Totleben MJ , Freeman JP , Bacon CL , Fox GB , O'Driscoll E , Foley AG , Kelly J , Farrell U , Regan C , Mizsak SA , Szmuszkovicz J
Ref : Bioorganic & Medicinal Chemistry , 7 :1637 , 1999
Abstract : Tacrine, one of the drugs available for Alzheimer's disease based on the cholinergic approach, suffers from considerable toxicity. Many analogues of tacrine have been prepared which retain the pharmacologically rich aminopyridine or aminoquinoline motifs. The current research was undertaken to produce an acetylcholinesterase inhibitor by employing 11-aminobenzoquinolizidines (4) and 10-aminobenzoindolizidines (5) as templates. Thus, we aimed to achieve three goals relative to tacrine: eliminate the pyridine and quinoline moieties and render the molecule less flat. Overall, the compounds we prepared were poorer inhibitors of acetylcholinesterase compared to tacrine. The single exception was compound 6f which exhibited an effect comparable to that of tacrine, but only at a dose of the order of 10(-3) M. However, despite the poor acetylcholinesterase inhibition by 6b, this compound proved to be an effective anti-amnesic agent at 45 mg/kg dose.
ESTHER : Zhao_1999_Bioorg.Med.Chem_7_1637
PubMedSearch : Zhao_1999_Bioorg.Med.Chem_7_1637
PubMedID: 10482456

Title : Syntheses of 1,2-diamino and 1,2-aminoalcohol derivatives in the piperidine and pyrrolidine series as anti-amnesic agents - Zhao_1999_Bioorg.Med.Chem_7_1647
Author(s) : Zhao S , Freeman JP , Bacon CL , Fox GB , O'Driscoll E , Foley AG , Kelly J , Farrell U , Regan C , Mizsak SA , Szmuszkovicz J
Ref : Bioorganic & Medicinal Chemistry , 7 :1647 , 1999
Abstract : Tacrine, one of the drugs available for Alzheimer's disease based on the cholinergic approach, suffers from considerable toxicity. Many analogues of tacrine has been prepared which retain the pharmacologically rich aminopyridine or aminoquinoline motifs. The current research is a continuation of our efforts in the area of 11-aminobenzoquinolizidines (4) and 10-aminobenzoindolizidines (5) (cf. ref9). A serendipitous discovery led us to the biologically active open chain analogue 9, and we proceeded to elaborate on this molecule. Overall, the compounds we prepared were poor inhibitors of acetylcholinesterase as compared to tacrine. The single exception was compound 20 which exhibited an effect comparable to that of tacrine, but only at a dose in the order of 10(-3) M. However, despite the poor acetylcholinesterase inhibition by 9, this compound was found to be an effective antiamnesic agent.
ESTHER : Zhao_1999_Bioorg.Med.Chem_7_1647
PubMedSearch : Zhao_1999_Bioorg.Med.Chem_7_1647
PubMedID: 10482457

Title : Histochemical and immunohistochemical studies of distribution of acetylcholinesterase-positive fibers and peptidergic terminals in the nasal mucosa of rats - Zhao_1998_Chin.Med.J.(Engl)_111_644
Author(s) : Zhao C , Tao Z , Xiao J , Zhao S , Qiao J
Ref : Chinese Medical Journal (Engl) , 111 :644 , 1998
Abstract : OBJECTIVE: To further investigate the mechanism of nasal secretion closely related to the innervation patterns in nasal mucosa with emphasis on the acetylcholinesterase (AChE)-positive fibers and peptidergic terminals in nasal mucosa as well as trigeminal ganglion (TG) cells.
METHODS: Histochemical demonstration of AChE-positive fibers, immunohistochemical study of the distribution patterns of multiple peptidergic terminals, double labelling of AChE and substance P (SP) and somatostatin (SOM) mRNA in situ hybridization were carried out in nasal mucosa and trigeminal ganglion (TG) in rats.
RESULTS: AChE-positive terminals were mainly distributed in the mid to posterior one third of septal nasal mucosa, with greater staining density on the walls of small vessels and glands. There were fewer such terminals in turbinate mucosa. Tachykinins-ergic terminals, including substance P (SP)-, neurokinin A (NKA)-, neurokinin B (NKB)- and calcitonin gene-related peptide (CGRP)-ergic terminals, had an extensive localizations in nasal mucosa, involving the following areas: between epithelial cells, submucosa, the walls of small vessels, glands and venous sinusoids in both septal and turbinate nasal mucosa. Septal mucosa had the greater density. There were overlaps in the distribution of these peptidergic terminals. There were also vasoactive intestinal peptide (VIP)-, neuropeptide Y (NPY)- and galanin (GAL)-ergic terminals in nasal mucosa. But no neurotensin (NT)- and somatostatin (SOM)-ergic terminals were found. In situ hybridization revealed SOMmRNA expression in TG cells. AChE and nine neuropeptides existed in the cytoplasms of TG cells. Besides, AChE and SP could exist simultaneously in cytoplasms of TG cells.
CONCLUSIONS: AChE-positive (corresponding to parasympathetic nerves) and peptidergic terminals have different distribution patterns in the nasal mucosa of rats, although an overlap does exist, indicative of their different physiological effects on the regulation of nasal secretion and other functions; AChE and multiple neuropeptides in the cytoplasm of TG cells might play a role in modulating the nasal secretion in response to stimuli in the nasal mucosa.
ESTHER : Zhao_1998_Chin.Med.J.(Engl)_111_644
PubMedSearch : Zhao_1998_Chin.Med.J.(Engl)_111_644
PubMedID: 11245055