Cheng S

References (26)

Title : Design, synthesis, and activity evaluation of novel multitargeted l-tryptophan derivatives with powerful antioxidant activity against Alzheimer's disease - Zeng_2024_Arch.Pharm.(Weinheim)__e2300603
Author(s) : Zeng X , Cheng S , Li H , Yu H , Cui Y , Fang Y , Yang S , Feng Y
Ref : Arch Pharm (Weinheim) , :e2300603 , 2024
Abstract : Alzheimer's disease (AD) is a multifactorial neurological disease, and the multitarget directed ligand (MTDL) strategy may be an effective approach to delay its progression. Based on this strategy, 27 derivatives of l-tryptophan, 3a-1-3d-1, were designed, synthesized, and evaluated for their biological activity. Among them, IC(50) (inhibitor concentration resulting in 50% inhibitory activity) values of compounds 3a-18 and 3b-1 were 0.58 and 0.44 microM for human serum butyrylcholinesterase (hBuChE), respectively, and both of them exhibited more than 30-fold selectivity for human serum acetylcholinesterase. Enzyme kinetics studies showed that these two compounds were mixed inhibitors of hBuChE. In addition, these two derivatives possessed extraordinary antioxidant activity in OH radical scavenging and oxygen radical absorption capacity fluorescein assays. Meanwhile, these compounds could also prevent beta-amyloid (Abeta) self-aggregation and possessed low toxicity on PC12 and AML12 cells. Molecular modeling studies revealed that these two compounds could interact with the choline binding site, acetyl binding site, and peripheral anionic site to exert submicromolar BuChE inhibitory activity. In the vitro blood-brain barrier permeation assay, compounds 3a-18 and 3b-1 showed enough blood-brain barrier permeability. In drug-likeness prediction, compounds 3a-18 and 3b-1 showed good gastrointestinal absorption and a low risk of human ether-a-go-go-related gene toxicity. Therefore, compounds 3a-18 and 3b-1 are potential multitarget anti-AD lead compounds, which could work as powerful antioxidants with submicromolar selective inhibitory activity for hBuChE as well as prevent Abeta self-aggregation.
ESTHER : Zeng_2024_Arch.Pharm.(Weinheim)__e2300603
PubMedSearch : Zeng_2024_Arch.Pharm.(Weinheim)__e2300603
PubMedID: 38290060

Title : OsLDDT1, encoding a transmembrane structural DUF726 family protein, is essential for tapetum degradation and pollen formation in rice - Sun_2023_Plant.Sci__111596
Author(s) : Sun Z , Liu K , Chen C , Chen D , Peng Z , Zhou R , Liu L , He D , Duan W , Chen H , Huang C , Ruan Z , Zhang Y , Cao L , Zhan X , Cheng S , Sun L
Ref : Plant Sci , :111596 , 2023
Abstract : Formation of the pollen wall, which is mainly composed of lipid substances secreted by tapetal cells, is important to ensure pollen development in rice. Although several regulatory factors related to lipid biosynthesis during pollen wall formation have been identified in rice, the molecular mechanisms controlling lipid biosynthesis are unclear. We isolated the male-sterile rice mutant oslddt1 (leaked and delayed degraded tapetum 1). oslddt1 plants show complete pollen abortion resulting from delayed degradation of the tapetum and blocked formation of Ubisch bodies and pollen walls. OsLDDT1 (LOC_Os03g02170) encodes a DUF726 containing protein of unknown functionwith highly conserved transmembrane and alpha/beta Hydrolase domains. OsLDDT1 localizes to the endoplasmic reticulum and the gene is highly expressed in rice panicles. Genes involved in regulating fatty acid synthesis and formation of sporopollenin and pollen exine during anther developmentshowed significantly different expression patterns in oslddt1 plants. Interestingly, the wax and cutin contents in mature oslddt1-1 anthers were decreased by 74.07% and 72.22% compared to WT, indicating that OsLDDT1 is involved in fatty acid synthesis and affects formation of the anther epidermis. Our results provide as deeper understanding of the role of OsLDDT1 in regulating male sterility and also provide materials for hybrid rice breeding.
ESTHER : Sun_2023_Plant.Sci__111596
PubMedSearch : Sun_2023_Plant.Sci__111596
PubMedID: 36657664
Gene_locus related to this paper: orysj-q10ss2

Title : Variants within the LPL gene confer susceptility to diabetic kidney disease and rapid decline in kidney function in Chinese patients with type 2 diabetes - Wu_2023_Diabetes.Obes.Metab__
Author(s) : Wu Y , Cheng S , Gu H , Yang K , Xu Z , Meng X , Wang Y , Jiang Y , Li H , Zhou Y
Ref : Diabetes Obes Metab , : , 2023
Abstract : AIM: To examine the association between lipoprotein lipase (LPL) polymorphisms and susceptibility to diabetic kidney disease (DKD) and early renal function decline in Chinese patients with type 2 diabetes (T2D). METHODS: The association of eight LPL single nucleotide polymorphisms (SNPs) with DKD was analysed in 2793 patients with T2D from the third China National Stroke Registry. DKD was defined as either an urine albumin-to-creatinine ratio (UACR) of 30 mg/g or higher at baseline and 3 months, or an estimated glomerular filtration rate (eGFR) of less than 60 mL/min/1.73 m(2) at baseline and 3 months. Rapid decline in kidney function (RDKF) was defined as a reduction in the eGFR of 3 mL/min/1.73 m(2) or greater per year. Logistic regression models were used to evaluate the association of LPL SNP and DKD with an additive model. RESULTS: The SNPs rs285 C>T (OR = 1.40, P = .0154), rs328 C>G (OR = 2.24, P = .0104) and rs3208305 A>T (OR = 1.85, P = .0015) were identified to be significantly associated with DKD defined by eGFR. Among 1241 participants with follow-up data, 441 (35.5%) showed RDKF over a mean follow-up period of 1 year, and the rs285 C allele was associated with higher odds of RDKF (OR = 1.31, 95% CI 1.04-1.66; P = .025) after adjustment for multiple variables. CONCLUSIONS: These results suggest that LPL-related SNPs are new candidate factors for conferring susceptibility to DKD and may promote rapid loss of renal function in Chinese patients with T2D.
ESTHER : Wu_2023_Diabetes.Obes.Metab__
PubMedSearch : Wu_2023_Diabetes.Obes.Metab__
PubMedID: 37427758

Title : Remodeling the polymer-binding cavity to improve the efficacy of PBAT-degrading enzyme - Yang_2023_J.Hazard.Mater_464_132965
Author(s) : Yang Y , Cheng S , Zheng Y , Xue T , Huang JW , Zhang L , Guo RT , Chen CC
Ref : J Hazard Mater , 464 :132965 , 2023
Abstract : Poly(butylene adipate-co-terephthalate) (PBAT) is among the most widely applied synthetic polyesters that are utilized in the packaging and agricultural industries, but the accumulation of PBAT wastes has posed a great burden to ecosystems. Using renewable enzymes to decompose PBAT is an eco-friendly solution to tackle this problem. Recently, we demonstrated that cutinase is the most effective PBAT-degrading enzyme and that an engineered cutinase termed TfCut-DM could completely decompose PBAT film to terephthalate (TPA). Here, we report crystal structures of a variant of leaf compost cutinase in complex with soluble fragments of PBAT, including BTa and TaBTa. In the TaBTa complex, one TPA moiety was located at a polymer-binding site distal to the catalytic center that has never been experimentally validated. Intriguingly, the composition of the distal TPA-binding site shows higher diversity relative to the one proximal to the catalytic center in various cutinases. We thus modified the distal TPA-binding site of TfCut-DM and obtained variants that exhibit higher activity. Notably, the time needed to completely degrade the PBAT film to TPA was shortened to within 24 h by TfCut-DM Q132Y (5813 mol per mol protein). Taken together, the structural information regarding the substrate-binding behavior of PBAT-degrading enzymes could be useful guidance for direct enzyme engineering.
ESTHER : Yang_2023_J.Hazard.Mater_464_132965
PubMedSearch : Yang_2023_J.Hazard.Mater_464_132965
PubMedID: 37979420
Gene_locus related to this paper: 9bact-g9by57

Title : Lonicera japonica polysaccharides alleviate D-galactose-induced oxidative stress and restore gut microbiota in ICR mice - Sun_2023_Int.J.Biol.Macromol__125517
Author(s) : Sun W , Zhu J , Qin G , Huang Y , Cheng S , Chen Z , Zhang Y , Shu Y , Zeng X , Guo R
Ref : Int J Biol Macromol , :125517 , 2023
Abstract : Lonicera japonica polysaccharides (LJPs) exhibit anti-aging effect in nematodes. Here, we further studied the function of LJPs on aging-related disorders in D-galactose (D-gal)-induced ICR mice. Four groups of mice including the control group, the D-gal-treated group, the intervening groups with low and high dose of LJPs (50 and 100 mg/kg/day) were raised for 8 weeks. The results showed that intragastric administration with LJPs improved the organ indexes of D-gal-treated mice. Moreover, LJPs improved the activity of superoxide dismutase (SOD), catalase (CAT) as well as glutathione peroxidase (GSH-Px) and decreasing the malondialdehyde (MDA) level in serum, liver and brain. Meanwhile, LJPs restored the content of acetylcholinesterase (AChE) in the brain. Further, LJPs reversed the liver tissue damages in aging mice. Mechanistically, LJPs alleviate oxidative stress at least partially through regulating Nrf2 signaling. Additionally, LJPs restored the gut microbiota composition of D-gal-treated mice by adjusting the Firmicutes/Bacteroidetes ratio at the phylum level and upregulating the relative abundances of Lactobacillaceae and Bifidobacteriacesa. Notably, the KEGG pathways involved in hazardous substances degradation and flavone and flavonol biosynthesis were significantly enhanced by LJPs treatment. Overall, our study uncovers the role of LJPs in modulating oxidative stress and gut microbiota in the D-gal-induced aging mice.
ESTHER : Sun_2023_Int.J.Biol.Macromol__125517
PubMedSearch : Sun_2023_Int.J.Biol.Macromol__125517
PubMedID: 37353132

Title : Identification of novel immune-related targets mediating disease progression in acute pancreatitis - Liu_2022_Front.Cell.Infect.Microbiol_12_1052466
Author(s) : Liu Q , Li L , Xu D , Zhu J , Huang Z , Yang J , Cheng S , Gu Y , Zheng L , Zhang X , Shen H
Ref : Front Cell Infect Microbiol , 12 :1052466 , 2022
Abstract : INTRODUCTION: Acute pancreatitis (AP) is an inflammatory disease with very poor outcomes. However, the order of induction and coordinated interactions of systemic inflammatory response syndrome (SIRS) and compensatory anti-inflammatory response syndrome (CARS) and the potential mechanisms in AP are still unclear. METHODS: An integrative analysis was performed based on transcripts of blood from patients with different severity levels of AP (GSE194331), as well as impaired lung (GSE151572), liver (GSE151927) and pancreas (GSE65146) samples from an AP experimental model to identify inflammatory signals and immune response-associated susceptibility genes. An AP animal model was established in wild-type (WT) mice and Tlr2-deficient mice by repeated intraperitoneal injection of cerulein. Serum lipase and amylase, pancreas impairment and neutrophil infiltration were evaluated to assess the effects of Tlr2 in vivo. RESULTS: The numbers of anti-inflammatory response-related cells, such as M2 macrophages (P = 3.2 x 10(-3)), were increased with worsening AP progression, while the numbers of pro-inflammatory response-related cells, such as neutrophils (P = 3.0 x 10(-8)), also increased. Then, 10 immune-related AP susceptibility genes (SOSC3, ITGAM, CAMP, FPR1, IL1R1, TLR2, S100A8/9, HK3 and MMP9) were identified. Finally, compared with WT mice, Tlr2-deficient mice exhibited not only significantly reduced serum lipase and amylase levels after cerulein induction but also alleviated pancreatic inflammation and neutrophil accumulation. DISCUSSION: In summary, we discovered SIRS and CARS were stimulated in parallel, not activated consecutively. In addition, among the novel susceptibility genes, TLR2might be a novel therapeutic target that mediates dysregulation of inflammatory responses during AP progression.
ESTHER : Liu_2022_Front.Cell.Infect.Microbiol_12_1052466
PubMedSearch : Liu_2022_Front.Cell.Infect.Microbiol_12_1052466
PubMedID: 36590588

Title : Fluorine impairs carboxylesterase 1-mediated hydrolysis of T-2 toxin and increases its chondrocyte toxicity - Jia_2022_Front.Nutr_9_935112
Author(s) : Jia Y , Shi S , Cheng B , Cheng S , Liu L , Meng P , Yang X , Chu X , Wen Y , Zhang F , Guo X
Ref : Front Nutr , 9 :935112 , 2022
Abstract : BACKGROUND: T-2 toxin is recognized as one of the high-risk environmental factors for etiology and pathogenesis of Kashin-Beck disease (KBD). Previous evidence indicates decreased serum fluorine level in KBD patients. However, whether fluoride could regulate carboxylesterase 1 (CES1)-mediated T-2 toxin hydrolysis and alter its chondrocyte toxicity remains largely unknown. METHODS: In this study, in vitro hydrolytic kinetics were explored using recombinant human CES1. HPLC-MS/MS was used to quantitative determination of hydrolytic metabolites of T-2 toxin. HepG2 cells were treated with different concentration of sodium fluoride (NaF). qRT-PCR and western blot analysis were used to compare the mRNA and protein expression levels of CES1. C28/I2 cells were treated with T-2 toxin, HT-2 toxin, and neosolaniol (NEO), and then cell viability was determined by MTT assay, cell apoptosis was determined by Annexin V-FITC/PI, Hoechst 33258 staining, and cleaved caspase-3, and cell cycle was monitored by flow cytometry assay, CKD4 and CDK6. RESULTS: We identified that recombinant human CES1 was involved in T-2 toxin hydrolysis to generate HT-2 toxin, but not NEO, and NaF repressed the formation of HT-2 toxin. Both mRNA and protein expression of CES1 were significantly down-regulated in a dose-dependent manner after NaF treatment in HepG2 cells. Moreover, we evaluated the chondrocyte toxicity of T-2 toxin and its hydrolytic metabolites. Results showed that T-2 toxin induced strongest cell apoptosis, followed by HT-2 toxin and NEO. The decreased the proportion of cells in G0/G1 phase was observed with the descending order of T-2 toxin, HT-2 toxin, and NEO. CONCLUSIONS: This study reveals that CES1 is responsible for the hydrolysis of T-2 toxin, and that fluoride impairs CES1-mediated T-2 toxin detoxification to increase its chondrocyte toxicity. This study provides novel insight into understanding the relationship between fluoride and T-2 toxin in the etiology of KBD.
ESTHER : Jia_2022_Front.Nutr_9_935112
PubMedSearch : Jia_2022_Front.Nutr_9_935112
PubMedID: 35990316

Title : Online Monitoring of Enzymatic Reactions Using Time-Resolved Desorption Electrospray Ionization Mass Spectrometry - Cheng_2017_Anal.Chem_89_2338
Author(s) : Cheng S , Wu Q , Xiao H , Chen H
Ref : Analytical Chemistry , 89 :2338 , 2017
Abstract : Electrospray ionization mass spectrometry (ESI-MS) is powerful for determining enzymatic reaction kinetics because of its soft ionization nature. However, it is limited to use ESI-favored solvents containing volatile buffers (e.g., ammonium acetate). In addition, lack of a quenching step for online ESI-MS reaction monitoring might introduce inaccuracy, due to the possible acceleration of reaction in the sprayed microdroplets. To overcome these issues, this study presents a new approach for online measuring enzymatic reaction kinetics using desorption electrospray ionization mass spectrometry (DESI-MS). By using DESI-MS, enzymatic reaction products in a buffered aqueous media (e.g., a solution containing Tris buffer or high concentration of inorganic salts) could be directly detected. Furthermore, by adjusting the pH and solvent composition of the DESI spray, reaction can be online quenched to avoid the postionization reaction event, leading to fast and accurate measurement of kinetic constants. Reaction time control can be obtained simply by adjusting the injection flow rates of enzyme and substrate solutions. Enzymatic reactions examined in this study include hydrolysis of 2-nitrophenyl-beta-D-galactopyranoside by beta-galactosidase and hydrolysis of acetylcholine by acetylcholinesterase. Derived Michaelis-Menten constants Km for these two reactions were determined to be 214 muM and 172 muM, respectively, which are in good agreement with the values of 300 muM and 230 muM reported in literature, validating the DESI-MS approach. Furthermore, this time-resolved DESI-MS also allowed us to determine Km and turnover number kcat for trypsin digestion of angiotensin II (Km and kcat are determined to be 6.4 mM and 1.3 s-1, respectively).
ESTHER : Cheng_2017_Anal.Chem_89_2338
PubMedSearch : Cheng_2017_Anal.Chem_89_2338
PubMedID: 28192910

Title : Gorge Motions of Acetylcholinesterase Revealed by Microsecond Molecular Dynamics Simulations - Cheng_2017_Sci.Rep_7_3219
Author(s) : Cheng S , Song W , Yuan X , Xu Y
Ref : Sci Rep , 7 :3219 , 2017
Abstract : Acetylcholinesterase, with a deep, narrow active-site gorge, attracts enormous interest due to its particularly high catalytic efficiency and its inhibitors used for treatment of Alzheimer's disease. To facilitate the massive pass-through of the substrate and inhibitors, "breathing" motions to modulate the size of the gorge are an important prerequisite. However, the molecular mechanism that governs such motions is not well explored. Here, to systematically investigate intrinsic motions of the enzyme, we performed microsecond molecular dynamics simulations on the monomer and dimer of Torpedo californica acetylcholinesterase (TcAChE) as well as the complex of TcAChE bound with the drug E2020. It has been revealed that protein-ligand interactions and dimerization both keep the gorge in bulk, and opening events of the gorge increase dramatically compared to the monomer. Dynamics of three subdomains, S3, S4 and the Omega-loop, are tightly associated with variations of the gorge size while the dynamics can be changed by ligand binding or protein dimerization. Moreover, high correlations among these subdomains provide a basis for remote residues allosterically modulating the gorge motions. These observations are propitious to expand our understanding of protein structure and function as well as providing clues for performing structure-based drug design.
ESTHER : Cheng_2017_Sci.Rep_7_3219
PubMedSearch : Cheng_2017_Sci.Rep_7_3219
PubMedID: 28607438

Title : Computational Studies on Acetylcholinesterases - Xu_2017_Molecules_22_
Author(s) : Xu Y , Cheng S , Sussman JL , Silman I , Jiang H
Ref : Molecules , 22 : , 2017
Abstract : Functions of biomolecules, in particular enzymes, are usually modulated by structural fluctuations. This is especially the case in a gated diffusion-controlled reaction catalyzed by an enzyme such as acetylcholinesterase. The catalytic triad of acetylcholinesterase is located at the bottom of a long and narrow gorge, but it catalyzes the extremely rapid hydrolysis of the neurotransmitter, acetylcholine, with a reaction rate close to the diffusion-controlled limit. Computational modeling and simulation have produced considerable advances in exploring the dynamical and conformational properties of biomolecules, not only aiding in interpreting the experimental data, but also providing insights into the internal motions of the biomolecule at the atomic level. Given the remarkably high catalytic efficiency and the importance of acetylcholinesterase in drug development, great efforts have been made to understand the dynamics associated with its functions by use of various computational methods. Here, we present a comprehensive overview of recent computational studies on acetylcholinesterase, expanding our views of the enzyme from a microstate of a single structure to conformational ensembles, strengthening our understanding of the integration of structure, dynamics and function associated with the enzyme, and promoting the structure-based and/or mechanism-based design of new inhibitors for it.
ESTHER : Xu_2017_Molecules_22_
PubMedSearch : Xu_2017_Molecules_22_
PubMedID: 28796192

Title : A high-quality carrot genome assembly provides new insights into carotenoid accumulation and asterid genome evolution - Iorizzo_2016_Nat.Genet_48_657
Author(s) : Iorizzo M , Ellison S , Senalik D , Zeng P , Satapoomin P , Huang J , Bowman M , Iovene M , Sanseverino W , Cavagnaro P , Yildiz M , Macko-Podgorni A , Moranska E , Grzebelus E , Grzebelus D , Ashrafi H , Zheng Z , Cheng S , Spooner D , Van Deynze A , Simon P
Ref : Nat Genet , 48 :657 , 2016
Abstract : We report a high-quality chromosome-scale assembly and analysis of the carrot (Daucus carota) genome, the first sequenced genome to include a comparative evolutionary analysis among members of the euasterid II clade. We characterized two new polyploidization events, both occurring after the divergence of carrot from members of the Asterales order, clarifying the evolutionary scenario before and after radiation of the two main asterid clades. Large- and small-scale lineage-specific duplications have contributed to the expansion of gene families, including those with roles in flowering time, defense response, flavor, and pigment accumulation. We identified a candidate gene, DCAR_032551, that conditions carotenoid accumulation (Y) in carrot taproot and is coexpressed with several isoprenoid biosynthetic genes. The primary mechanism regulating carotenoid accumulation in carrot taproot is not at the biosynthetic level. We hypothesize that DCAR_032551 regulates upstream photosystem development and functional processes, including photomorphogenesis and root de-etiolation.
ESTHER : Iorizzo_2016_Nat.Genet_48_657
PubMedSearch : Iorizzo_2016_Nat.Genet_48_657
PubMedID: 27158781
Gene_locus related to this paper: dauca-a0a166ecg9 , dauca-a0a164t4s9 , dauca-a0a166dau6 , dauca-a0a164uvg0 , daucs-a0a162at85 , daucs-a0a166dr70 , daucs-a0a166dr78 , daucs-a0a164tjh8 , daucs-a0a175ykr1 , daucs-a0a162a5i7 , daucs-a0a175yg59 , daucs-a0a161x622 , daucs-a0a161xtm5 , daucs-a0a161wtu8 , daucs-a0a161ya61 , daucs-a0a162aju4 , daucs-a0a166az33 , daucs-a0a166az54 , daucs-a0a166gb36 , daucs-a0a164ul57 , daucs-a0a164ul46 , daucs-a0a164v6h1 , daucs-a0a165a8x0 , daucs-a0a165a8w1

Title : (-)-Meptazinol-melatonin hybrids as novel dual inhibitors of cholinesterases and amyloid-beta aggregation with high antioxidant potency for Alzheimer's therapy - Cheng_2015_Bioorg.Med.Chem_23_3110
Author(s) : Cheng S , Zheng W , Gong P , Zhou Q , Xie Q , Yu L , Zhang P , Chen L , Li J , Chen J , Chen H
Ref : Bioorganic & Medicinal Chemistry , 23 :3110 , 2015
Abstract : The multifactorial pathogenesis of Alzheimer's disease (AD) implicates that multi-target-directed ligands (MTDLs) intervention may represent a promising therapy for AD. Amyloid-beta (Abeta) aggregation and oxidative stress, two prominent neuropathological hallmarks in patients, play crucial roles in the neurotoxic cascade of this disease. In the present study, a series of novel (-)-meptazinol-melatonin hybrids were designed, synthesized and biologically characterized as potential MTDLs against AD. Among them, hybrids 7-7c displayed higher dual inhibitory potency toward cholinesterases (ChEs) and better oxygen radical absorbance capacity (ORAC) than the parental drugs. Furthermore, compound 7c could effectively inhibit Abeta self-aggregation, showed favorable safety and the blood-brain barrier (BBB) permeability. Therefore, 7c may serve as a valuable candidate that is worthy of further investigations in the treatment of AD.
ESTHER : Cheng_2015_Bioorg.Med.Chem_23_3110
PubMedSearch : Cheng_2015_Bioorg.Med.Chem_23_3110
PubMedID: 26025073

Title : Mudskipper genomes provide insights into the terrestrial adaptation of amphibious fishes - You_2014_Nat.Commun_5_5594
Author(s) : You X , Bian C , Zan Q , Xu X , Liu X , Chen J , Wang J , Qiu Y , Li W , Zhang X , Sun Y , Chen S , Hong W , Li Y , Cheng S , Fan G , Shi C , Liang J , Tom Tang Y , Yang C , Ruan Z , Bai J , Peng C , Mu Q , Lu J , Fan M , Yang S , Huang Z , Jiang X , Fang X , Zhang G , Zhang Y , Polgar G , Yu H , Li J , Liu Z , Ravi V , Coon SL , Yang H , Venkatesh B , Shi Q
Ref : Nat Commun , 5 :5594 , 2014
Abstract : Mudskippers are amphibious fishes that have developed morphological and physiological adaptations to match their unique lifestyles. Here we perform whole-genome sequencing of four representative mudskippers to elucidate the molecular mechanisms underlying these adaptations. We discover an expansion of innate immune system genes in the mudskippers that may provide defence against terrestrial pathogens. Several genes of the ammonia excretion pathway in the gills have experienced positive selection, suggesting their important roles in mudskippers' tolerance to environmental ammonia. Some vision-related genes are differentially lost or mutated, illustrating genomic changes associated with aerial vision. Transcriptomic analyses of mudskippers exposed to air highlight regulatory pathways that are up- or down-regulated in response to hypoxia. The present study provides a valuable resource for understanding the molecular mechanisms underlying water-to-land transition of vertebrates.
ESTHER : You_2014_Nat.Commun_5_5594
PubMedSearch : You_2014_Nat.Commun_5_5594
PubMedID: 25463417
Gene_locus related to this paper: 9gobi-a0a3b4bh68 , 9gobi-a0a3b4bmj6 , 9gobi-a0a3b4alj9 , 9gobi-a0a3b4biy6 , 9gobi-a0a3b4ah01 , 9gobi-a0a3b3z8m7 , 9gobi-a0a3b4aaj5 , 9gobi-a0a3b4b6y7

Title : Effects of subchronic exposure to benzo[a]pyrene (B[a]P) on learning and memory, and neurotransmitters in male Sprague-Dawley rat - Xia_2011_Neurotoxicol_32_188
Author(s) : Xia Y , Cheng S , He J , Liu X , Tang Y , Yuan H , He L , Lu T , Tu B , Wang Y
Ref : Neurotoxicology , 32 :188 , 2011
Abstract : The harmful effects of the environmental carcinogen, benzo[a]pyrene (B[a]P), on mammalian neurodevelopment and behavior as yet remain unclear. Several studies have suggested that B[a]P impairs learning and memory. In the present investigation, we investigated the effects of subchronic exposure to B[a]P on rats. Male rats received daily injection of B[a]P (0, 1.0, 2.5, and 6.25 mg/kg, i.p.) or vehicle for 13 weeks. Employing the Morris water maze (MWM) test, we observed that rats exposed to either 2.5 mg/kg or 6.25 mg/kg B[a]P had modified behavior compared to controls as indicated by the increased mean latencies, the decreased number of crossing platform and the decreased swimming time in the target area. B[a]P treatment decreased the levels of malondialdehyde (MDA), nitric oxide (NO), nitric oxide synthase (NOS), superoxide dismutase (SOD), acetylcholine (ACh), choline acetyltransferase (ChAT), and increased the activity of acetylcholinesterase (AChE). Endogenous monoamine levels, norepinephrine (NE), adrenaline (A), dopamine (DA) and 5-hydroxytryptamine (5-HT) and their selected metabolites dihydroxyphenylacetic acid (DOPAC) and 5-hydroxyindoleacetic acid (5-HIAA) in hippocampus were measured using high performance liquid chromatography (HPLC). B[a]P at both doses, 2.5 and 6.25 mg/kg, increased NE, DA, DOPAC and 5-HT content in the hippocampus. Our results suggested a close link between the modified levels of neurotransmitters in the hippocampus and the impaired behavioral performance, indicating that B[a]P is a potential neurotoxic pollutant.
ESTHER : Xia_2011_Neurotoxicol_32_188
PubMedSearch : Xia_2011_Neurotoxicol_32_188
PubMedID: 21216261

Title : Genome sequence and analysis of the tuber crop potato - Xu_2011_Nature_475_189
Author(s) : Xu X , Pan S , Cheng S , Zhang B , Mu D , Ni P , Zhang G , Yang S , Li R , Wang J , Orjeda G , Guzman F , Torres M , Lozano R , Ponce O , Martinez D , De la Cruz G , Chakrabarti SK , Patil VU , Skryabin KG , Kuznetsov BB , Ravin NV , Kolganova TV , Beletsky AV , Mardanov AV , Di Genova A , Bolser DM , Martin DM , Li G , Yang Y , Kuang H , Hu Q , Xiong X , Bishop GJ , Sagredo B , Mejia N , Zagorski W , Gromadka R , Gawor J , Szczesny P , Huang S , Zhang Z , Liang C , He J , Li Y , He Y , Xu J , Zhang Y , Xie B , Du Y , Qu D , Bonierbale M , Ghislain M , Herrera Mdel R , Giuliano G , Pietrella M , Perrotta G , Facella P , O'Brien K , Feingold SE , Barreiro LE , Massa GA , Diambra L , Whitty BR , Vaillancourt B , Lin H , Massa AN , Geoffroy M , Lundback S , DellaPenna D , Buell CR , Sharma SK , Marshall DF , Waugh R , Bryan GJ , Destefanis M , Nagy I , Milbourne D , Thomson SJ , Fiers M , Jacobs JM , Nielsen KL , Sonderkaer M , Iovene M , Torres GA , Jiang J , Veilleux RE , Bachem CW , De Boer J , Borm T , Kloosterman B , van Eck H , Datema E , Hekkert B , Goverse A , van Ham RC , Visser RG
Ref : Nature , 475 :189 , 2011
Abstract : Potato (Solanum tuberosum L.) is the world's most important non-grain food crop and is central to global food security. It is clonally propagated, highly heterozygous, autotetraploid, and suffers acute inbreeding depression. Here we use a homozygous doubled-monoploid potato clone to sequence and assemble 86% of the 844-megabase genome. We predict 39,031 protein-coding genes and present evidence for at least two genome duplication events indicative of a palaeopolyploid origin. As the first genome sequence of an asterid, the potato genome reveals 2,642 genes specific to this large angiosperm clade. We also sequenced a heterozygous diploid clone and show that gene presence/absence variants and other potentially deleterious mutations occur frequently and are a likely cause of inbreeding depression. Gene family expansion, tissue-specific expression and recruitment of genes to new pathways contributed to the evolution of tuber development. The potato genome sequence provides a platform for genetic improvement of this vital crop.
ESTHER : Xu_2011_Nature_475_189
PubMedSearch : Xu_2011_Nature_475_189
PubMedID: 21743474
Gene_locus related to this paper: soltu-q2tqv0 , soltu-q4h433 , soltu-m0zl00 , soltu-m1aw23 , soltu-m0zxh5 , soltu-m1d3q4 , soltu-m1bz14 , soltu-m1d3q6 , sollc-k4b1g3 , soltu-m0zzn8 , soltu-m1ba60 , sollc-k4bf33 , soltu-m1c8d8 , soltu-m1ced9 , soltu-m1a385 , soltu-m1bz15 , soltu-m1a7s9 , soltu-m1bc84 , soltu-m1bpd1 , sollc-k4bm34 , soltu-m1a487 , soltu-m1a5u0 , soltu-m1cjx7 , soltu-m1bvq8 , soltu-m1baq1 , soltu-m1cfh4 , soltu-m1azl4 , soltu-m0ztj0 , soltu-m1d6d0 , soltu-m1cap1 , soltu-m1a7m1 , soltu-m1d3s6

Title : The genome of the mesopolyploid crop species Brassica rapa - Wang_2011_Nat.Genet_43_1035
Author(s) : Wang X , Wang H , Wang J , Sun R , Wu J , Liu S , Bai Y , Mun JH , Bancroft I , Cheng F , Huang S , Li X , Hua W , Freeling M , Pires JC , Paterson AH , Chalhoub B , Wang B , Hayward A , Sharpe AG , Park BS , Weisshaar B , Liu B , Li B , Tong C , Song C , Duran C , Peng C , Geng C , Koh C , Lin C , Edwards D , Mu D , Shen D , Soumpourou E , Li F , Fraser F , Conant G , Lassalle G , King GJ , Bonnema G , Tang H , Belcram H , Zhou H , Hirakawa H , Abe H , Guo H , Jin H , Parkin IA , Batley J , Kim JS , Just J , Li J , Xu J , Deng J , Kim JA , Yu J , Meng J , Min J , Poulain J , Hatakeyama K , Wu K , Wang L , Fang L , Trick M , Links MG , Zhao M , Jin M , Ramchiary N , Drou N , Berkman PJ , Cai Q , Huang Q , Li R , Tabata S , Cheng S , Zhang S , Sato S , Sun S , Kwon SJ , Choi SR , Lee TH , Fan W , Zhao X , Tan X , Xu X , Wang Y , Qiu Y , Yin Y , Li Y , Du Y , Liao Y , Lim Y , Narusaka Y , Wang Z , Li Z , Xiong Z , Zhang Z
Ref : Nat Genet , 43 :1035 , 2011
Abstract : We report the annotation and analysis of the draft genome sequence of Brassica rapa accession Chiifu-401-42, a Chinese cabbage. We modeled 41,174 protein coding genes in the B. rapa genome, which has undergone genome triplication. We used Arabidopsis thaliana as an outgroup for investigating the consequences of genome triplication, such as structural and functional evolution. The extent of gene loss (fractionation) among triplicated genome segments varies, with one of the three copies consistently retaining a disproportionately large fraction of the genes expected to have been present in its ancestor. Variation in the number of members of gene families present in the genome may contribute to the remarkable morphological plasticity of Brassica species. The B. rapa genome sequence provides an important resource for studying the evolution of polyploid genomes and underpins the genetic improvement of Brassica oil and vegetable crops.
ESTHER : Wang_2011_Nat.Genet_43_1035
PubMedSearch : Wang_2011_Nat.Genet_43_1035
PubMedID: 21873998
Gene_locus related to this paper: braol-Q8GTM3 , braol-Q8GTM4 , brarp-m4ei94 , brarp-m4c988 , brana-a0a078j4a9 , brana-a0a078e1m0 , brana-a0a078cd75 , brarp-m4dwa6 , brana-a0a078j4f0 , brana-a0a078cus4 , brana-a0a078f8c2 , brana-a0a078jql1 , brana-a0a078dgj3 , brana-a0a078hw50 , brana-a0a078cuu0 , brana-a0a078dfa9 , brana-a0a078ic91 , brarp-m4ctw3 , brana-a0a078ca65 , brana-a0a078ctc8 , brana-a0a078h021 , brana-a0a078jx23 , brarp-m4da84 , brarp-m4dwr7 , brana-a0a078dh94 , brana-a0a078h612 , brana-a0a078j2t3 , braol-a0a0d3dpb2 , braol-a0a0d3dx76 , brana-a0a078jxa8 , brana-a0a078i2k3 , brarp-m4cwq4 , brarp-m4dcj8 , brarp-m4eh17 , brarp-m4eey4 , brarp-m4dnj8 , brarp-m4ey83 , brarp-m4ey84

Title : GRK5 deficiency accelerates {beta}-amyloid accumulation in Tg2576 mice via impaired cholinergic activity - Cheng_2010_J.Biol.Chem_285_41541
Author(s) : Cheng S , Li L , He S , Liu J , Sun Y , He M , Grasing K , Premont RT , Suo WZ
Ref : Journal of Biological Chemistry , 285 :41541 , 2010
Abstract : Membrane G protein-coupled receptor kinase 5 (GRK5) deficiency is linked to Alzheimer disease, yet its precise roles in the disease pathogenesis remain to be delineated. We have previously demonstrated that GRK5 deficiency selectively impairs desensitization of presynaptic M2 autoreceptors, which causes presynaptic M2 hyperactivity and inhibits acetylcholine release. Here we report that inactivation of one copy of Grk5 gene in transgenic mice overexpressing beta-amyloid precursor protein (APP) carrying Swedish mutations (Tg2576 or APPsw) resulted in significantly increased beta-amyloid (Abeta) accumulation, including increased Abeta(+) plaque burdens and soluble Abeta in brain lysates and interstitial fluid (ISF). In addition, secreted beta-APP fragment (sAPPbeta) also increased, whereas full-length APP level did not change, suggesting an alteration in favor of beta-amyloidogenic APP processing in these animals. Reversely, perfusion of methoctramine, a selective M2 antagonist, fully corrected the difference between the control and GRK5-deficient APPsw mice for ISF Abeta. In contrast, a cholinesterase inhibitor, eserine, although significantly decreasing the ISF Abeta in both control and GRK5-deficient APPsw mice, failed to correct the difference between them. However, combining eserine with methoctramine additively reduced the ISF Abeta further in both animals. Altogether, these findings indicate that GRK5 deficiency accelerates beta-amyloidogenic APP processing and Abeta accumulation in APPsw mice via impaired cholinergic activity and that presynaptic M2 hyperactivity is the specific target for eliminating the pathologic impact of GRK5 deficiency. Moreover, a combination of an M2 antagonist and a cholinesterase inhibitor may reach the maximal disease-modifying effect for both amyloid pathology and cholinergic dysfunction.
ESTHER : Cheng_2010_J.Biol.Chem_285_41541
PubMedSearch : Cheng_2010_J.Biol.Chem_285_41541
PubMedID: 21041302

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 : Polymorphism in the beta2-adrenergic receptor and lipoprotein lipase genes as risk determinants for idiopathic venous thromboembolism: a multilocus, population-based, prospective genetic analysis - Zee_2006_Circulation_113_2193
Author(s) : Zee RY , Cook NR , Cheng S , Erlich HA , Lindpaintner K , Ridker PM
Ref : Circulation , 113 :2193 , 2006
Abstract : BACKGROUND: Candidate genes in inflammation, thrombosis, coagulation, and lipid metabolism pathways have been implicated in venous thromboembolism (VTE). METHODS AND
RESULTS: Using DNA samples collected at baseline in the Physicians' Health Study cohort, we genotyped 92 polymorphisms from 56 candidate genes among 304 individuals who subsequently developed VTE (144 idiopathic, 156 secondary cases) and among 2070 individuals who remained free of reported vascular disease over a mean follow-up of 13.2 years to prospectively determine whether these gene polymorphisms contribute to the risk of VTE. For idiopathic VTE, in addition to the factor V (Leiden) mutation (odds ratio [OR], 5.13; 95% confidence interval [CI], 3.24 to 8.14; P<0.0001; false discovery rate [FDR], P<0.0001), an N291S lipoprotein lipase gene polymorphism (OR, 3.09; 95% CI, 1.56 to 6.09; P=0.001; FDR, P=0.036) and a Q27E beta2-adrenergic receptor gene polymorphism (OR, 1.40; 95% CI, 1.09 to 1.79; P=0.006; FDR, P=0.036) were found to be significantly associated with increased risk. For secondary VTE, a Q360H apolipoprotein A4 gene polymorphism (OR, 0.34; 95% CI, 0.18 to 0.65; P=0.001; FDR, P=0.07) and an I50V interleukin-4 receptor polymorphism (OR, 0.66; 95% CI, 0.52 to 0.84; P=0.0009; FDR, P=0.07) were moderately, but not statistically and significantly, associated with reduced risk after adjustment for multiple comparisons.
CONCLUSIONS: These present findings are hypothesis generating and require replication and confirmation in an independent investigation.
ESTHER : Zee_2006_Circulation_113_2193
PubMedSearch : Zee_2006_Circulation_113_2193
PubMedID: 16651467

Title : Interaction between metabolic syndrome and PON1 polymorphisms as a determinant of the risk of coronary artery disease - Martinelli_2005_Clin.Exp.Med_5_20
Author(s) : Martinelli N , Girelli D , Olivieri O , Cavallari U , Biscuola M , Trabetti E , Friso S , Pizzolo F , Tenuti I , Bozzini C , Villa G , Ceradini B , Sandri M , Cheng S , Grow MA , Pignatti PF , Corrocher R
Ref : Clin Exp Med , 5 :20 , 2005
Abstract : The enzyme serum paraoxonase plays an important role in antioxidant defences and prevention of atherosclerosis. Metabolic syndrome (MS) is a clinical condition associated with increased oxidant stress and cardiovascular mortality. Two common polymorphisms of serum paraoxonase, PON1 Leu(55)Met and Gln(192)Arg, have been postulated to modulate the cardiovascular risk. We studied 915 subjects with angiographic documentation: 642 subjects with coronary atherosclerosis and 273 with normal coronary arteries. Two hundred and twenty-four subjects met the diagnostic criteria of MS. We found a significant interaction between MS and both the PON1 polymorphisms in determining the risk of coronary artery disease (P<0.05 by likelihood-ratio test). The 55Leu and the 192Arg alleles, associated with reduced protection against lipid peroxidation, were associated with coronary artery disease only in the MS subgroup. Subjects with MS and both 55Leu and 192Arg alleles had significantly increased risk (OR=9.38 with 95% CI=3.02-29.13 after adjustment by multiple logistic regression) as compared to subjects without MS and with 55Met/Met-192Gln/Gln genotype. No increased risk was found for subjects with MS and the 55Met/Met-192Gln/Gln genotype. This study highlights a potential example of genetic (paraoxonase polymorphisms)-clinical (MS) interaction influencing cardiovascular risk.
ESTHER : Martinelli_2005_Clin.Exp.Med_5_20
PubMedSearch : Martinelli_2005_Clin.Exp.Med_5_20
PubMedID: 15928879

Title : Effect of hepatic lipase -514C->T polymorphism and its interactions with apolipoprotein C3 -482C->T and apolipoprotein E exon 4 polymorphisms on the risk of nephropathy in chinese type 2 diabetic patients - Baum_2005_Diabetes.Care_28_1704
Author(s) : Baum L , Ng MC , So WY , Lam VK , Wang Y , Poon E , Tomlinson B , Cheng S , Lindpaintner K , Chan JC
Ref : Diabetes Care , 28 :1704 , 2005
Abstract : OBJECTIVE: Triglyceride-rich lipoprotein particles may promote the progression of diabetic nephropathy. Patients with diabetic nephropathy have increased plasma triglycerides and reduced activity of hepatic lipase (HL), which hydrolyzes triglycerides. We hypothesized that the HL -514C-->T polymorphism, which reduces HL expression, and its interactions with polymorphisms in apolipoprotein (apo) E and apoC3 increase the risk of diabetic nephropathy. RESEARCH DESIGN AND
METHODS: In a case-control study involving 374 Chinese type 2 diabetic patients with and 392 without diabetic nephropathy, we genotyped the HL -514C-->T, apoE exon 4, and apoC3 -482C-->T polymorphisms.
RESULTS: HL -514T-containing genotypes (T+) were associated with diabetic nephropathy (OR = 1.7, P = 0.0009). Adjustment by multiple logistic regression for hypertension, triglycerides, sex, non-HDL cholesterol, BMI, smoking, and alcohol intake did not diminish the association (OR = 1.8, P = 0.003). The association between HL T+ genotypes and diabetic nephropathy appeared stronger in diabetic patients with apoC3 -482 non-TT genotypes (OR = 1.9, P = 0.003) or apoE epsilon2 or epsilon4 alleles (OR = 2.2, P = 0.005). Subjects with HL TT exhibited trends toward increased triglyceride and non-HDL cholesterol levels compared with CC carriers.
CONCLUSIONS: HL T+ genotypes might increase the risk of developing diabetic nephropathy by slowing clearance of triglyceride-rich remnant lipoproteins. In concert with other risk factors (e.g., hyperglycemia), lipid abnormalities may damage the kidneys and endothelium, where reduced binding sites for lipases may precipitate a vicious cycle of dyslipidemia, proteinuria, and nephropathy.
ESTHER : Baum_2005_Diabetes.Care_28_1704
PubMedSearch : Baum_2005_Diabetes.Care_28_1704
PubMedID: 15983323

Title : Interaction between smoking and PON2 Ser311Cys polymorphism as a determinant of the risk of myocardial infarction - Martinelli_2004_Eur.J.Clin.Invest_34_14
Author(s) : Martinelli N , Girelli D , Olivieri O , Stranieri C , Trabetti E , Pizzolo F , Friso S , Tenuti I , Cheng S , Grow MA , Pignatti PF , Corrocher R
Ref : European Journal of Clinical Investigation , 34 :14 , 2004
Abstract : BACKGROUND: Increased oxidative stress is thought to play a role in the pathogenesis of the atherothrombotic process. Paraoxonases (PONs) are closely related antioxidant enzymes encoded by clustered genes on chromosome 7q. We evaluated three PON polymorphisms (PON1 Leu55Met and Gln192Arg; PON2 Ser311Cys) as possible risk factors for coronary atherosclerotic disease (CAD) and/or its main thrombotic complication, myocardial infarction (MI). MATERIALS AND
METHODS: We studied 890 subjects with angiographic documentation of coronary vessels (272=CAD-free; 618=CAD). In the CAD group, 341 subjects had a previous MI.
RESULTS: Frequencies of various genotypes were not significantly different between CAD-free subjects and the entire CAD population. In the latter group, there were more carriers of the PON2 311Cys variation among those who had suffered a MI than among those who had not (P<0.01 by chi2). The adjusted OR for MI among PON2 311Cys carriers was 1.5 (95%CI, 1.03-2.19). A gene-environmental interaction was found between PON2 Ser311Cys and smoking. Smoking by itself was associated with an increased MI risk. Among smokers, however, the MI risk was related to PON2 genotype: Cys/Cys homozygotes (OR=5.3; 95%CI, 1.7-16.4) and Ser/Cys heterozygotes (OR=2.1; 95%CI, 1.3-3.6) were at greater risk than Ser/Ser subjects (OR=1.2; 95%CI, 0.8-1.8). The PON2 polymorphism did not influence the MI risk among nonsmokers.
CONCLUSIONS: In CAD subjects, a proportion of the risk of MI may be influenced by the interaction between smoking and a polymorphism in the antioxidant enzyme PON2.
ESTHER : Martinelli_2004_Eur.J.Clin.Invest_34_14
PubMedSearch : Martinelli_2004_Eur.J.Clin.Invest_34_14
PubMedID: 14984433

Title : A single residual replacement improves the folding and stability of recombinant cassava hydroxynitrile lyase in E. coil - Yan_2003_Biotechnol.Lett_25_1041
Author(s) : Yan G , Cheng S , Zhao G , Wu S , Liu Y , Sun W
Ref : Biotechnol Lett , 25 :1041 , 2003
Abstract : Substitution of Ser113 for Gly113 in the cap domain of hydroxynitrile lyase from Manihot esculenta (MeHNL) was performed by site-directed mutagenesis to improve its self-generated folding and stability under denaturation conditions. The yield of the recombinant mutant HNL1 (mut-HNL1), which had higher specific activity than the wild type HNL0 (wt-HNL0), was increased by 2 to 3-fold. Thermostability of MeHNL was also enhanced, probably due to an increase in content of the beta-strand secondary structure according to CD analysis. Our data in this report suggest that Ser113 significantly contributes to the in vivo folding and stability of MeHNL and demonstrates an economic advantage of mut-HNL1 over the wt-HNL0.
ESTHER : Yan_2003_Biotechnol.Lett_25_1041
PubMedSearch : Yan_2003_Biotechnol.Lett_25_1041
PubMedID: 12889812
Gene_locus related to this paper: manes-hnl

Title : Lipoprotein lipase gene polymorphisms in Croatian patients with coronary artery disease - Ferencak_2003_Clin.Chem.Lab.Med_41_541
Author(s) : Ferencak G , Pasalic D , Grskovic B , Cheng S , Fijal B , Sesto M , Skodlar J , Rukavina AS
Ref : Clinical Chemistry & Laboratory Medicine , 41 :541 , 2003
Abstract : Modifications in lipoprotein lipase levels lead to elevated triglycerides and reduced high density lipoprotein (HDL), both of which are risk factors for coronary artery disease (CAD). Hence, we examined the influence of the -93T/G, D9N, N291S, and S447X polymorphisms in the lipoprotein lipase (LPL) gene on CAD risk and lipid levels in Croatian patients with and without angiographically confirmed CAD. The N291S polymorphism was significantly associated with CAD (OR = 0.36; 95% CI = 0.13, 0.99; p = 0.048). This association was only moderately affected by adjusting for various lipids (OR = 0.36; 95% CI = 0.12, 1.08; p = 0.068). HDL2-cholesterol and apolipoprotein A-I levels were significantly higher in non-carriers of the -93T/G and D9N polymorphisms in the CAD group (p = 0.017 and 0.028, respectively). The N291S genetic variant did not show any significant difference between carriers and non-carriers in either group studied for any of the lipids. Lower triglyceride and higher HDL2-cholesterol levels in the control group were associated with carriers of the S447X mutation (p = 0.043 and 0.056, respectively). LPL gene polymorphisms might be involved in predisposition to CAD and determination of lipid profiles.
ESTHER : Ferencak_2003_Clin.Chem.Lab.Med_41_541
PubMedSearch : Ferencak_2003_Clin.Chem.Lab.Med_41_541
PubMedID: 12747600

Title : A common promoter polymorphism in the hepatic lipase gene (LIPC-480C>T) is associated with an increase in coronary calcification in type 1 diabetes - Hokanson_2002_Diabetes_51_1208
Author(s) : Hokanson JE , Cheng S , Snell-Bergeon JK , Fijal BA , Grow MA , Hung C , Erlich HA , Ehrlich J , Eckel RH , Rewers M
Ref : Diabetes , 51 :1208 , 2002
Abstract : Type 1 diabetes is associated with coronary heart disease (CHD) and coronary artery calcification (CAC), a measure of subclinical CHD. The hepatic lipase gene promoter polymorphism (LIPC-480C>T) is a common variant affecting lipid metabolism. This study examined the relation between the LIPC-480C>T and CAC in type 1 diabetes. In the type 1 diabetic patients studied, 56% had CAC >0 Agatston units (AU). These subjects had a longer duration of diabetes (26.2 +/- 1.3 vs. 17.8 +/- 1.4 years; P < 0.001), lower HDL cholesterol levels (55.7 +/- 2.4 vs. 61.0 +/- 2.5 mg/dl; P = 0.05), higher triglyceride levels (101 +/- 17.3 vs. 66 +/- 7.6 mg/dl; P < 0.05), and higher diastolic blood pressure (79.7 +/- 1.0 vs. 76.0 +/- 1.4 mmHg; P < 0.05). The LIPC-480 T allele was more common in subjects with CAC (frequency = 0.31 +/- 0.05 vs. 0.14 +/- 0.04; P = 0.006). The proportion with CAC was 44% in LIPC-480CC subjects, 71% in heterozygotes, and 83% in LIPC-480TT subjects (P < 0.01). LIPC-480 T allele frequency increased as the amount of CAC increased (P = 0.007). LIPC-480 genotype was independently associated with the CAC (odds ratio = 2.90, 95% CI 1.22-6.92, P < 0.05) after adjusting for duration of diabetes, age, sex, diastolic blood pressure, HDL cholesterol, and triglyceride levels. In conclusion, the LIPC-480C>T polymorphism was associated with subclinical CHD in type 1 diabetes. This genetic variant may identify subjects in which early intervention to prevent CHD may be appropriate.
ESTHER : Hokanson_2002_Diabetes_51_1208
PubMedSearch : Hokanson_2002_Diabetes_51_1208
PubMedID: 11916946

Title : [Expression of the Cholinesterase-Related Cell Division Controller Gene in Peripheral Blood Cell from Patients with Myelodysplastic Syndrome] - Liao_2000_Zhongguo.Shi.Yan.Xue.Ye.Xue.Za.Zhi_8_192
Author(s) : Liao J , Li Y , Cheng S , Ma X , Yang L , Zhao X
Ref : Zhongguo Shi Yan Xue Ye Xue Za Zhi , 8 :192 , 2000
Abstract : To investigate the expression of the cholinesterase-related cell division controller (CHED) gene in the patients with myelodysplastic syndrome (MDS), CHED gene expression was assayed by RT-PCR and its relative expression rate (RER) was determined by the semi-quantitative RT-PCR analysis in peripheral blood mononuclear cells from 21 patients with MDS, 12 normal individuals served as controls. Results showed that RER of CHED in the patients (2.69 +/- 0.76) was significantly higher than that in controls (1.12 +/- 0.51, P < 0.01), the RER out of 85.7% of the patients was higher than the mean value of the controls, in which three patients developed into acute leukemia; the RER out of 61.9% of the patients was higher than the upper limit of the mean value of the controls; three patients whose RER was lower than the mean value of the controls did not developed into leukemia. These findings suggested that the expression of CHED gene in patients with MDS was significantly higher than in controls.
ESTHER : Liao_2000_Zhongguo.Shi.Yan.Xue.Ye.Xue.Za.Zhi_8_192
PubMedSearch : Liao_2000_Zhongguo.Shi.Yan.Xue.Ye.Xue.Za.Zhi_8_192
PubMedID: 12578681