Du F

References (16)

Title : Phillyrin: an adipose triglyceride lipase inhibitor supported by molecular docking, dynamics simulation, and pharmacological validation - Zhou_2024_J.Mol.Model_30_68
Author(s) : Zhou C , Yan L , Xu J , Hamezah HS , Wang T , Du F , Tong X , Han R
Ref : J Mol Model , 30 :68 , 2024
Abstract : CONTEXT: Adipose triglyceride lipase (ATGL), a key enzyme responsible for lipolysis, catalyzes the first step of lipolysis and converts triglycerides to diacylglycerols and free fatty acids (FFA). Our previous work suggested that phillyrin treatment improves insulin resistance in HFD-fed mice, which was associated with ATGL inhibition. In this study, using docking simulation, we explored the binding pose of phillyrin and atglistatin (a mouse ATGL inhibitor) to ATGL in mouse. From the docking results, the interactions with Ser47 and Asp166 were speculated to have caused phillyrin to inhibit ATGL in mice. Further, molecular dynamics simulation of 100 ns and MM-GBSA were conducted for the protein-ligand complex, which indicated that the system was stable and that phillyrin displayed a better affinity to ATGL than did atglistatin throughout the simulation period. Moreover, the results of pharmacological validation were consistent with those of the in silico simulations. In summary, our study illustrates the potential of molecular docking to accurately predict the binding protein produced by AlphaFold and suggests that phillyrin is a potential small molecule that targets and inhibits ATGL enzymatic activity. METHODS: The ATGL-predicted protein structure, verified by PROCHECK, was determined using AlphaFold. Molecular docking, molecular dynamics simulation, and prime molecular mechanic-generalized born surface area were performed using LigPrep, Desmond, and prime MM-GBSA modules of Schrodinger software release 2021-2, respectively. For pharmacological validation, immunoblotting was performed to assess ATGL protein expression. The fluorescence intensity and glycerol concentration were quantified to evaluate the efficiency of phillyrin in inhibiting ATGL.
ESTHER : Zhou_2024_J.Mol.Model_30_68
PubMedSearch : Zhou_2024_J.Mol.Model_30_68
PubMedID: 38347278

Title : Construction of a ratiometric fluorescent sensing platform based on near-infrared carbon dots for organophosphorus pesticides detection - Xie_2023_Anal.Sci__
Author(s) : Xie W , Liu J , Qu Y , Du F
Ref : Anal Sci , : , 2023
Abstract : In this work, a convenient ratiometric fluorescent platform was designed to measure organophosphorus pesticides (OPs) based on acetylcholinesterase (AChE), acetylthiocholine (ATCh), manganese dioxide nanosheets (MnO(2)), near-infrared carbon dots (RCDs) and o-phenylenediamine (OPD). In this platform, a direct oxidation of OPD by MnO(2) generated the luminescent product 2,3-diaminophenolazine (DAP) through intrinsic oxidase activity, while RCDs served as a fluorescent reference indicator. In the presence of AChE and ATCh, the enzymatic hydrolysate thiocholine (TCh) would reduce MnO(2) nanosheets to Mn(2+), leading to the quenching of DAP fluorescence. On the other hand, OPs can inhibit the catabolism of ATCh by AChE thus acting as a recognizer of OPs. According to these reactions, OPs were quantitatively analyzed by the intensity ratio of fluorescence emitted from RCDs and DAP (F(560)/F(676)). The constructed platform can detect OPs with the range of 0.2-0.6 microM with a detection limit of 4.3 nM. Figure A ratiometric fluorescent probe based on carbon dots was obtained and using it to determine the concentration of organophosphorus pesticides.
ESTHER : Xie_2023_Anal.Sci__
PubMedSearch : Xie_2023_Anal.Sci__
PubMedID: 36944823

Title : Structure-guided discovery of potent and oral soluble epoxide hydrolase inhibitors for the treatment of neuropathic pain - Du_2022_Acta.Pharm.Sin.B_12_1377
Author(s) : Du F , Cao R , Chen L , Sun J , Shi Y , Fu Y , Hammock BD , Zheng Z , Liu Z , Chen G
Ref : Acta Pharm Sin B , 12 :1377 , 2022
Abstract : Soluble epoxide hydrolase (sEH) is related to arachidonic acid cascade and is over-expressed in a variety of diseases, making sEH an attractive target for the treatment of pain as well as inflammatory-related diseases. A new series of memantyl urea derivatives as potent sEH inhibitors was obtained using our previous reported compound 4 as lead compound. A preferential modification of piperidinyl to 3-carbamoyl piperidinyl was identified for this series via structure-based rational drug design. Compound A20 exhibited moderate percentage plasma protein binding (88.6%) and better metabolic stability in vitro. After oral administration, the bioavailability of A20 was 28.6%. Acute toxicity test showed that A20 was well tolerated and there was no adverse event encountered at dose of 6.0 g/kg. Inhibitor A20 also displayed robust analgesic effect in vivo and dose-dependently attenuated neuropathic pain in rat model induced by spared nerve injury, which was better than gabapentin and sEH inhibitor (+/-)-EC-5026. In one word, the oral administration of A20 significantly alleviated pain and improved the health status of the rats, demonstrating that A20 was a promising candidate to be further evaluated for the treatment of neuropathic pain.
ESTHER : Du_2022_Acta.Pharm.Sin.B_12_1377
PubMedSearch : Du_2022_Acta.Pharm.Sin.B_12_1377
PubMedID: 35530144

Title : Discovery of memantyl urea derivatives as potent soluble epoxide hydrolase inhibitors against lipopolysaccharide-induced sepsis - Du_2021_Eur.J.Med.Chem_223_113678
Author(s) : Du F , Sun W , Morisseau C , Hammock BD , Bao X , Liu Q , Wang C , Zhang T , Yang H , Zhou J , Xiao W , Liu Z , Chen G
Ref : Eur Journal of Medicinal Chemistry , 223 :113678 , 2021
Abstract : Sepsis, a systemic inflammatory response, caused by pathogenic factors including microorganisms, has high mortality and limited therapeutic approaches. Herein, a new soluble epoxide hydrolase (sEH) inhibitor series comprising a phenyl ring connected to a memantyl moiety via a urea or amide linkage has been designed. A preferential urea pharmacophore that improved the binding properties of the compounds was identified for those series via biochemical assay in vitro and in vivo studies. Molecular docking displayed that 3,5-dimethyl on the adamantyl group in B401 could make van der Waals interactions with residues at a hydrophobic pocket of sEH active site, which might indirectly explain the subnanomolar level activities of memantyl urea derivatives in vitro better than AR-9281. Among them, compound B401 significantly improved the inhibition potency with human and murine sEH IC(50) values as 0.4 nM and 0.5 nM, respectively. Although the median survival time of C57BL/6 mice in LPS-induced sepsis model was slightly increased, the survival rate did not reach significant efficacy. Based on safety profile, metabolic stability, pharmacokinetic and in vivo efficacy, B401 demonstrated the proof of potential for this class of memantyl urea-based sEH inhibitors as therapeutic agents in sepsis.
ESTHER : Du_2021_Eur.J.Med.Chem_223_113678
PubMedSearch : Du_2021_Eur.J.Med.Chem_223_113678
PubMedID: 34218083

Title : Soman-induced toxicity, cholinesterase inhibition and neuropathology in adult male Gttingen minipigs - Lumley_2021_Toxicol.Rep_8_896
Author(s) : Lumley L , Du F , Marrero-Rosado B , Stone M , Keith ZM , Schultz C , Whitten K , Walker K , Acon-Chen C , Wright L , Shih TM
Ref : Toxicol Rep , 8 :896 , 2021
Abstract : Animal models are essential for evaluating the toxicity of chemical warfare nerve agents (CWNAs) to extrapolate to human risk and are necessary to evaluate the efficacy of medical countermeasures. The Gottingen minipig is increasingly used for toxicological studies because it has anatomical and physiological characteristics that are similar to those of humans. Our objective was to determine whether the minipig would be a useful large animal model to evaluate the toxic effects of soman (GD). We determined the intramuscular (IM) median lethal dose (LD(50)) of GD in adult male Gottingen minipigs using an up-and-down dosing method. In addition to lethality estimates, we characterized the observable signs of toxicity, blood and tissue cholinesterase (ChE) activity and brain pathology following GD exposure. The 24 h LD(50) of GD was estimated to be 4.7 microg/kg, with 95 % confidence limits of 3.6 and 6.3 microg/kg. As anticipated, GD inhibited ChE activity in blood and several tissues. Neurohistopathological analysis showed neurodegeneration and neuroinflammation in survivors exposed to 4.7 microg/kg of GD, including in the primary visual cortex and various thalamic nuclei. These findings suggest that the minipig will be a useful large animal model for assessing drugs to mitigate neuropathological effects of exposure to CWNAs.
ESTHER : Lumley_2021_Toxicol.Rep_8_896
PubMedSearch : Lumley_2021_Toxicol.Rep_8_896
PubMedID: 33996503

Title : Soman-induced status epilepticus, epileptogenesis, and neuropathology in carboxylesterase knockout mice treated with midazolam - Marrero-Rosado_2018_Epilepsia_59_2206
Author(s) : Marrero-Rosado B , de Araujo Furtado M , Schultz CR , Stone M , Kundrick E , Walker K , O'Brien S , Du F , Lumley LA
Ref : Epilepsia , 59 :2206 , 2018
Abstract : OBJECTIVE: Exposure to chemical warfare nerve agents (CWNAs), such as soman (GD), can induce status epilepticus (SE) that becomes refractory to benzodiazepines when treatment is delayed, leading to increased risk of epileptogenesis, severe neuropathology, and long-term behavioral and cognitive deficits. Rodent models, widely used to evaluate novel medical countermeasures (MCMs) against CWNA exposure, normally express plasma carboxylesterase, an enzyme involved in the metabolism of certain organophosphorus compounds. To better predict the efficacy of novel MCMs against CWNA exposure in human casualties, it is crucial to use appropriate animal models that mirror the human condition. We present a comprehensive characterization of the seizurogenic, epileptogenic, and neuropathologic effects of GD exposure with delayed anticonvulsant treatment in the plasma carboxylesterase knockout (ES1-/-) mouse. METHODS: Electroencephalography (EEG) electrode-implanted ES1-/- and wild-type (C57BL/6) mice were exposed to various seizure-inducing doses of GD, treated with atropine sulfate and the oxime HI-6 at 1 minute after exposure, and administered midazolam at 15-30 minutes following the onset of seizure activity. The latency of acute seizure onset and spontaneous recurrent seizures (SRS) was assessed, as were changes in EEG power spectra. At 2 weeks after GD exposure, neurodegeneration and neuroinflammation were assessed. RESULTS: GD-exposed ES1-/- mice displayed a dose-dependent response in seizure severity. Only ES1-/- mice exposed to the highest tested dose of GD developed SE, subchronic alterations in EEG power spectra, and SRS. Degree of neuronal cell loss and neuroinflammation were dose-dependent; no significant neuropathology was observed in C57BL/6 mice or ES1-/- mice exposed to lower GD doses. SIGNIFICANCE: The US Food and Drug Administration (FDA) animal rule requires the use of relevant animal models for the advancement of MCMs against CWNAs. We present evidence that argues for the use of the ES1-/- mouse model to screen anticonvulsant, antiepileptic, and/or neuroprotective drugs against GD-induced toxicity, as well as to identify mechanisms of GD-induced epileptogenesis.
ESTHER : Marrero-Rosado_2018_Epilepsia_59_2206
PubMedSearch : Marrero-Rosado_2018_Epilepsia_59_2206
PubMedID: 30368799
Gene_locus related to this paper: mouse-Ces1c

Title : Feruloyl Esterase from the Edible Mushroom Panus giganteus: A Potential Dietary Supplement - Wang_2014_J.Agric.Food.Chem_62_7822
Author(s) : Wang L , Ma Z , Du F , Wang H , Ng TB
Ref : Journal of Agricultural and Food Chemistry , 62 :7822 , 2014
Abstract : A novel 61 kDa feruloyl esterase (FAE) was purified to homogeneity from freshly collected fruiting bodies of Panus giganteus. The isolation procedure involved chromatography on the ion exchangers DEAE-cellulose and Q-Sepharose, followed by size exclusion chromatography on Superdex 75, which produced a purified enzyme with a high specific activity (170.0 U/mg) which was 130-fold higher than that of crude extract. The purified FAE exhibited activity toward synthetic methyl esters and short-chain fatty acid nitrophenyl esters. The Km and Vmax for this enzyme on methyl ferulate were 0.36 mM and 18.97 U/mg proteins, respectively. FAE activity was attained at a maximum at pH 4 and 40 degrees C, respectively. The FAE activity was inhibited by metal ions to various degrees. The purified FAE could bring about the release of ferulic acid from wheat bran and corn bran under the action of the single purified FAE, and the amount released from wheat bran rose to 51.9% (of the total amount) by the synergistic action of xylanase.
ESTHER : Wang_2014_J.Agric.Food.Chem_62_7822
PubMedSearch : Wang_2014_J.Agric.Food.Chem_62_7822
PubMedID: 25065258

Title : Histopathologic characterization of the BTBR mouse model of autistic-like behavior reveals selective changes in neurodevelopmental proteins and adult hippocampal neurogenesis - Stephenson_2011_Mol.Autism_2_7
Author(s) : Stephenson DT , O'Neill SM , Narayan S , Tiwari A , Arnold E , Samaroo HD , Du F , Ring RH , Campbell B , Pletcher M , Vaidya VA , Morton D
Ref : Mol Autism , 2 :7 , 2011
Abstract : BACKGROUND: The inbred mouse strain BTBR T+ tf/J (BTBR) exhibits behavioral deficits that mimic the core deficits of autism. Neuroanatomically, the BTBR strain is also characterized by a complete absence of the corpus callosum. The goal of this study was to identify novel molecular and cellular changes in the BTBR mouse, focusing on neuronal, synaptic, glial and plasticity markers in the limbic system as a model for identifying putative molecular and cellular substrates associated with autistic behaviors. METHODS: Forebrains of 8 to 10-week-old male BTBR and age-matched C57Bl/6J control mice were evaluated by immunohistochemistry using free-floating and paraffin embedded sections. Twenty antibodies directed against antigens specific to neurons, synapses and glia were used. Nissl, Timm and acetylcholinesterase (AchE) stains were performed to assess cytoarchitecture, mossy fibers and cholinergic fiber density, respectively. In the hippocampus, quantitative stereological estimates for the mitotic marker bromodeoxyuridine (BrdU) were performed to determine hippocampal progenitor proliferation, survival and differentiation, and brain-derived neurotrophic factor (BDNF) mRNA was quantified by in situ hybridization. Quantitative image analysis was performed for NG2, doublecortin (DCX), NeuroD, GAD67 and Poly-Sialic Acid Neural Cell Adhesion Molecule (PSA-NCAM). RESULTS: In midline structures including the region of the absent corpus callosum of BTBR mice, the myelin markers 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) and myelin basic protein (MBP) were reduced, and the oligodendrocyte precursor NG2 was increased. MBP and CNPase were expressed in small ectopic white matter bundles within the cingulate cortex. Microglia and astrocytes showed no evidence of gliosis, yet orientations of glial fibers were altered in specific white-matter areas. In the hippocampus, evidence of reduced neurogenesis included significant reductions in the number of doublecortin, PSA-NCAM and NeuroD immunoreactive cells in the subgranular zone of the dentate gyrus, and a marked reduction in the number of 5-bromo-2'-deoxyuridine (BrdU) positive progenitors. Furthermore, a significant and profound reduction in BDNF mRNA was seen in the BTBR dentate gyrus. No significant differences were seen in the expression of AchE, mossy fiber synapses or immunoreactivities of microtubule-associated protein MAP2, parvalbumin and glutamate decarboxylase GAD65 or GAD67 isoforms. CONCLUSIONS: We documented modest and selective alterations in glia, neurons and synapses in BTBR forebrain, along with reduced neurogenesis in the adult hippocampus. Of all markers examined, the most distinctive changes were seen in the neurodevelopmental proteins NG2, PSA-NCAM, NeuroD and DCX. Our results are consistent with aberrant development of the nervous system in BTBR mice, and may reveal novel substrates to link callosal abnormalities and autistic behaviors. The changes that we observed in the BTBR mice suggest potential novel therapeutic strategies for intervention in autism spectrum disorders.
ESTHER : Stephenson_2011_Mol.Autism_2_7
PubMedSearch : Stephenson_2011_Mol.Autism_2_7
PubMedID: 21575186

Title : Accurate determination of the anticancer prodrug simmitecan and its active metabolite chimmitecan in various plasma samples based on immediate deactivation of blood carboxylesterases - Hu_2011_J.Chromatogr.A_1218_6646
Author(s) : Hu Z , Sun Y , Du F , Niu W , Xu F , Huang Y , Li C
Ref : Journal of Chromatography A , 1218 :6646 , 2011
Abstract : Simmitecan (L-P) is an anticancer ester prodrug, which involves activation to chimmitecan (L-2-Z). In the current study, a liquid chromatography/tandem mass spectrometry-based method was developed for simultaneous determination of L-P and L-2-Z in various plasma samples. Because L-P is rapidly converted to L-2-Z by blood carboxylesterase during and after sampling, which hampers accurate determination of L-P and L-2-Z in the biological samples, different carboxylesterase inhibitors were tested. As a result, bis(4-nitrophenyl)phosphate gave the best results with respect to inhibitory capability, hemolysis, and matrix effects and was used to deactivate blood carboxylesterases when sampling. The plasma samples were precipitated with acetonitrile and the resulting supernatants were separated using a pulse gradient method on a C18 column. Irinotecan and camptothecin were used as internal standards for quantification of L-P and L-2-Z, respectively. Protonated L-P, L-2-Z and their internal standards were generated by electrospray ionization and their precursor-product ion pairs (m/z 599-->124, 405-->361, 587-->195, and 349-->305, respectively) were used for measurement. The newly developed bioanalytical assay processed favorable accuracy and precision with lower limits of quantification of 2.1 nM for L-P and 3.4 nM for L-2-Z, and was successfully applied to pharmacokinetic studies in tumor-bearing nude mice, rats, and dogs. There are substantial species differences in the ester activity. The experimental strategies illustrated in our report may be adopted for measurement of other prodrugs (including irinotecan) or drugs subject to ester hydrolysis, as well as their metabolites, in biological matrices.
ESTHER : Hu_2011_J.Chromatogr.A_1218_6646
PubMedSearch : Hu_2011_J.Chromatogr.A_1218_6646
PubMedID: 21839460

Title : The B73 maize genome: complexity, diversity, and dynamics - Schnable_2009_Science_326_1112
Author(s) : Schnable PS , Ware D , Fulton RS , Stein JC , Wei F , Pasternak S , Liang C , Zhang J , Fulton L , Graves TA , Minx P , Reily AD , Courtney L , Kruchowski SS , Tomlinson C , Strong C , Delehaunty K , Fronick C , Courtney B , Rock SM , Belter E , Du F , Kim K , Abbott RM , Cotton M , Levy A , Marchetto P , Ochoa K , Jackson SM , Gillam B , Chen W , Yan L , Higginbotham J , Cardenas M , Waligorski J , Applebaum E , Phelps L , Falcone J , Kanchi K , Thane T , Scimone A , Thane N , Henke J , Wang T , Ruppert J , Shah N , Rotter K , Hodges J , Ingenthron E , Cordes M , Kohlberg S , Sgro J , Delgado B , Mead K , Chinwalla A , Leonard S , Crouse K , Collura K , Kudrna D , Currie J , He R , Angelova A , Rajasekar S , Mueller T , Lomeli R , Scara G , Ko A , Delaney K , Wissotski M , Lopez G , Campos D , Braidotti M , Ashley E , Golser W , Kim H , Lee S , Lin J , Dujmic Z , Kim W , Talag J , Zuccolo A , Fan C , Sebastian A , Kramer M , Spiegel L , Nascimento L , Zutavern T , Miller B , Ambroise C , Muller S , Spooner W , Narechania A , Ren L , Wei S , Kumari S , Faga B , Levy MJ , McMahan L , Van Buren P , Vaughn MW , Ying K , Yeh CT , Emrich SJ , Jia Y , Kalyanaraman A , Hsia AP , Barbazuk WB , Baucom RS , Brutnell TP , Carpita NC , Chaparro C , Chia JM , Deragon JM , Estill JC , Fu Y , Jeddeloh JA , Han Y , Lee H , Li P , Lisch DR , Liu S , Liu Z , Nagel DH , McCann MC , SanMiguel P , Myers AM , Nettleton D , Nguyen J , Penning BW , Ponnala L , Schneider KL , Schwartz DC , Sharma A , Soderlund C , Springer NM , Sun Q , Wang H , Waterman M , Westerman R , Wolfgruber TK , Yang L , Yu Y , Zhang L , Zhou S , Zhu Q , Bennetzen JL , Dawe RK , Jiang J , Jiang N , Presting GG , Wessler SR , Aluru S , Martienssen RA , Clifton SW , McCombie WR , Wing RA , Wilson RK
Ref : Science , 326 :1112 , 2009
Abstract : We report an improved draft nucleotide sequence of the 2.3-gigabase genome of maize, an important crop plant and model for biological research. Over 32,000 genes were predicted, of which 99.8% were placed on reference chromosomes. Nearly 85% of the genome is composed of hundreds of families of transposable elements, dispersed nonuniformly across the genome. These were responsible for the capture and amplification of numerous gene fragments and affect the composition, sizes, and positions of centromeres. We also report on the correlation of methylation-poor regions with Mu transposon insertions and recombination, and copy number variants with insertions and/or deletions, as well as how uneven gene losses between duplicated regions were involved in returning an ancient allotetraploid to a genetically diploid state. These analyses inform and set the stage for further investigations to improve our understanding of the domestication and agricultural improvements of maize.
ESTHER : Schnable_2009_Science_326_1112
PubMedSearch : Schnable_2009_Science_326_1112
PubMedID: 19965430
Gene_locus related to this paper: maize-b4ffc7 , maize-b6u7e1 , maize-c0pcy5 , maize-c0pgf7 , maize-c0pgw1 , maize-c0pfl3 , maize-b4fpr7 , maize-k7vy73 , maize-a0a096swr3 , maize-k7v3i9 , maize-b6u9v9 , maize-a0a3l6e780 , maize-b4fv80 , maize-a0a1d6nse2 , maize-c4j9a1 , maize-k7uba1

Title : Generation and annotation of the DNA sequences of human chromosomes 2 and 4 - Hillier_2005_Nature_434_724
Author(s) : Hillier LW , Graves TA , Fulton RS , Fulton LA , Pepin KH , Minx P , Wagner-McPherson C , Layman D , Wylie K , Sekhon M , Becker MC , Fewell GA , Delehaunty KD , Miner TL , Nash WE , Kremitzki C , Oddy L , Du H , Sun H , Bradshaw-Cordum H , Ali J , Carter J , Cordes M , Harris A , Isak A , Van Brunt A , Nguyen C , Du F , Courtney L , Kalicki J , Ozersky P , Abbott S , Armstrong J , Belter EA , Caruso L , Cedroni M , Cotton M , Davidson T , Desai A , Elliott G , Erb T , Fronick C , Gaige T , Haakenson W , Haglund K , Holmes A , Harkins R , Kim K , Kruchowski SS , Strong CM , Grewal N , Goyea E , Hou S , Levy A , Martinka S , Mead K , McLellan MD , Meyer R , Randall-Maher J , Tomlinson C , Dauphin-Kohlberg S , Kozlowicz-Reilly A , Shah N , Swearengen-Shahid S , Snider J , Strong JT , Thompson J , Yoakum M , Leonard S , Pearman C , Trani L , Radionenko M , Waligorski JE , Wang C , Rock SM , Tin-Wollam AM , Maupin R , Latreille P , Wendl MC , Yang SP , Pohl C , Wallis JW , Spieth J , Bieri TA , Berkowicz N , Nelson JO , Osborne J , Ding L , Sabo A , Shotland Y , Sinha P , Wohldmann PE , Cook LL , Hickenbotham MT , Eldred J , Williams D , Jones TA , She X , Ciccarelli FD , Izaurralde E , Taylor J , Schmutz J , Myers RM , Cox DR , Huang X , McPherson JD , Mardis ER , Clifton SW , Warren WC , Chinwalla AT , Eddy SR , Marra MA , Ovcharenko I , Furey TS , Miller W , Eichler EE , Bork P , Suyama M , Torrents D , Waterston RH , Wilson RK
Ref : Nature , 434 :724 , 2005
Abstract : Human chromosome 2 is unique to the human lineage in being the product of a head-to-head fusion of two intermediate-sized ancestral chromosomes. Chromosome 4 has received attention primarily related to the search for the Huntington's disease gene, but also for genes associated with Wolf-Hirschhorn syndrome, polycystic kidney disease and a form of muscular dystrophy. Here we present approximately 237 million base pairs of sequence for chromosome 2, and 186 million base pairs for chromosome 4, representing more than 99.6% of their euchromatic sequences. Our initial analyses have identified 1,346 protein-coding genes and 1,239 pseudogenes on chromosome 2, and 796 protein-coding genes and 778 pseudogenes on chromosome 4. Extensive analyses confirm the underlying construction of the sequence, and expand our understanding of the structure and evolution of mammalian chromosomes, including gene deserts, segmental duplications and highly variant regions.
ESTHER : Hillier_2005_Nature_434_724
PubMedSearch : Hillier_2005_Nature_434_724
PubMedID: 15815621
Gene_locus related to this paper: human-ABHD1 , human-LDAH , human-ABHD18 , human-KANSL3 , human-PGAP1 , human-PREPL

Title : Comparison of genome degradation in Paratyphi A and Typhi, human-restricted serovars of Salmonella enterica that cause typhoid - McClelland_2004_Nat.Genet_36_1268
Author(s) : McClelland M , Sanderson KE , Clifton SW , Latreille P , Porwollik S , Sabo A , Meyer R , Bieri T , Ozersky P , McLellan M , Harkins CR , Wang C , Nguyen C , Berghoff A , Elliott G , Kohlberg S , Strong C , Du F , Carter J , Kremizki C , Layman D , Leonard S , Sun H , Fulton L , Nash W , Miner T , Minx P , Delehaunty K , Fronick C , Magrini V , Nhan M , Warren W , Florea L , Spieth J , Wilson RK
Ref : Nat Genet , 36 :1268 , 2004
Abstract : Salmonella enterica serovars often have a broad host range, and some cause both gastrointestinal and systemic disease. But the serovars Paratyphi A and Typhi are restricted to humans and cause only systemic disease. It has been estimated that Typhi arose in the last few thousand years. The sequence and microarray analysis of the Paratyphi A genome indicates that it is similar to the Typhi genome but suggests that it has a more recent evolutionary origin. Both genomes have independently accumulated many pseudogenes among their approximately 4,400 protein coding sequences: 173 in Paratyphi A and approximately 210 in Typhi. The recent convergence of these two similar genomes on a similar phenotype is subtly reflected in their genotypes: only 30 genes are degraded in both serovars. Nevertheless, these 30 genes include three known to be important in gastroenteritis, which does not occur in these serovars, and four for Salmonella-translocated effectors, which are normally secreted into host cells to subvert host functions. Loss of function also occurs by mutation in different genes in the same pathway (e.g., in chemotaxis and in the production of fimbriae).
ESTHER : McClelland_2004_Nat.Genet_36_1268
PubMedSearch : McClelland_2004_Nat.Genet_36_1268
PubMedID: 15531882
Gene_locus related to this paper: salen-OPDB , salty-AES , salty-BIOH , salty-DLHH , salty-ENTF , salty-FES , salty-IROD , salty-IROE , salty-P74847 , salty-PLDB , salty-STM2547 , salty-STM4506 , salty-STY1441 , salty-STY2428 , salty-STY3846 , salty-yafa , salty-YBFF , salty-ycfp , salty-YFBB , salty-YHET , salty-YQIA

Title : A sensitive method for the determination of the novel cholinesterase inhibitor ZT-1 and its active metabolite huperzine A in rat blood using liquid chromatography\/tandem mass spectrometry - Li_2004_Rapid.Commun.Mass.Spectrom_18_651
Author(s) : Li C , Du F , Yu C , Xu X , Zheng J , Xu F , Zhu D
Ref : Rapid Commun Mass Spectrom , 18 :651 , 2004
Abstract : ZT-1 has been developed as a novel acetylcholinesterase inhibitor, but is rapidly degraded to huperzine A (Hup A) in water or aqueous organic solvents. A sensitive method has been developed for simultaneous determination of ZT-1 and its active metabolite Hup A in blood, and was applied to the investigation of the pharmacokinetics of ZT-1 in rats. The method involves immediate hydrogenation of ZT-1 with sodium borohydride to the stable form rZT-1 following blood sampling. The NaBH4-treated blood sample is then submitted to liquid-liquid extraction, and the resultant extract is analyzed by liquid chromatography with electrospray ionization and tandem mass spectrometry. Huperzine B is used as internal standard for the quantification. ZT-1 was found to be rapidly absorbed in the intestinal tract, with a time to reach the peak blood concentration (Tpeak) of 5 min after an intragastric dose of ZT-1 embedded in povidone to rats at 0.5 mg ZT-1/kg. The mean maximum blood concentration (Cmax) and area under the blood level-time curve (AUC(0 --> 8)) of ZT-1 were 1.57 ng/mL and 0.48 ng. h/mL, respectively. The Tpeak, Cmax, and AUC values of the metabolite Hup A were 0.22 h, 109.9 ng/mL, and 96.3 ng. h/mL, respectively. Following an intravenous dose of 0.1 mg ZT-1/kg rat body weight, the blood concentration of ZT-1 was higher than that of Hup A, and the AUC(0 --> 8) values were 26.2 ng. h/mL for ZT-1 and 6.0 ng. h/mL for Hup A. The elimination half-lives (T1/2) of ZT-1 and Hup A were 0.68 and 1.47 h, respectively. The oral bioavailability (F) of intact ZT-1 in rats treated with ZT-1 embedded in povidone was very low, 0.37%.
ESTHER : Li_2004_Rapid.Commun.Mass.Spectrom_18_651
PubMedSearch : Li_2004_Rapid.Commun.Mass.Spectrom_18_651
PubMedID: 15052575

Title : The DNA sequence of human chromosome 7 - Hillier_2003_Nature_424_157
Author(s) : Hillier LW , Fulton RS , Fulton LA , Graves TA , Pepin KH , Wagner-McPherson C , Layman D , Maas J , Jaeger S , Walker R , Wylie K , Sekhon M , Becker MC , O'Laughlin MD , Schaller ME , Fewell GA , Delehaunty KD , Miner TL , Nash WE , Cordes M , Du H , Sun H , Edwards J , Bradshaw-Cordum H , Ali J , Andrews S , Isak A , Vanbrunt A , Nguyen C , Du F , Lamar B , Courtney L , Kalicki J , Ozersky P , Bielicki L , Scott K , Holmes A , Harkins R , Harris A , Strong CM , Hou S , Tomlinson C , Dauphin-Kohlberg S , Kozlowicz-Reilly A , Leonard S , Rohlfing T , Rock SM , Tin-Wollam AM , Abbott A , Minx P , Maupin R , Strowmatt C , Latreille P , Miller N , Johnson D , Murray J , Woessner JP , Wendl MC , Yang SP , Schultz BR , Wallis JW , Spieth J , Bieri TA , Nelson JO , Berkowicz N , Wohldmann PE , Cook LL , Hickenbotham MT , Eldred J , Williams D , Bedell JA , Mardis ER , Clifton SW , Chissoe SL , Marra MA , Raymond C , Haugen E , Gillett W , Zhou Y , James R , Phelps K , Iadanoto S , Bubb K , Simms E , Levy R , Clendenning J , Kaul R , Kent WJ , Furey TS , Baertsch RA , Brent MR , Keibler E , Flicek P , Bork P , Suyama M , Bailey JA , Portnoy ME , Torrents D , Chinwalla AT , Gish WR , Eddy SR , McPherson JD , Olson MV , Eichler EE , Green ED , Waterston RH , Wilson RK
Ref : Nature , 424 :157 , 2003
Abstract : Human chromosome 7 has historically received prominent attention in the human genetics community, primarily related to the search for the cystic fibrosis gene and the frequent cytogenetic changes associated with various forms of cancer. Here we present more than 153 million base pairs representing 99.4% of the euchromatic sequence of chromosome 7, the first metacentric chromosome completed so far. The sequence has excellent concordance with previously established physical and genetic maps, and it exhibits an unusual amount of segmentally duplicated sequence (8.2%), with marked differences between the two arms. Our initial analyses have identified 1,150 protein-coding genes, 605 of which have been confirmed by complementary DNA sequences, and an additional 941 pseudogenes. Of genes confirmed by transcript sequences, some are polymorphic for mutations that disrupt the reading frame.
ESTHER : Hillier_2003_Nature_424_157
PubMedSearch : Hillier_2003_Nature_424_157
PubMedID: 12853948
Gene_locus related to this paper: human-ABHD11 , human-ACHE , human-CPVL , human-DPP6 , human-MEST

Title : Complete genome sequence of Salmonella enterica serovar Typhimurium LT2 - McClelland_2001_Nature_413_852
Author(s) : McClelland M , Sanderson KE , Spieth J , Clifton SW , Latreille P , Courtney L , Porwollik S , Ali J , Dante M , Du F , Hou S , Layman D , Leonard S , Nguyen C , Scott K , Holmes A , Grewal N , Mulvaney E , Ryan E , Sun H , Florea L , Miller W , Stoneking T , Nhan M , Waterston R , Wilson RK
Ref : Nature , 413 :852 , 2001
Abstract : Salmonella enterica subspecies I, serovar Typhimurium (S. typhimurium), is a leading cause of human gastroenteritis, and is used as a mouse model of human typhoid fever. The incidence of non-typhoid salmonellosis is increasing worldwide, causing millions of infections and many deaths in the human population each year. Here we sequenced the 4,857-kilobase (kb) chromosome and 94-kb virulence plasmid of S. typhimurium strain LT2. The distribution of close homologues of S. typhimurium LT2 genes in eight related enterobacteria was determined using previously completed genomes of three related bacteria, sample sequencing of both S. enterica serovar Paratyphi A (S. paratyphi A) and Klebsiella pneumoniae, and hybridization of three unsequenced genomes to a microarray of S. typhimurium LT2 genes. Lateral transfer of genes is frequent, with 11% of the S. typhimurium LT2 genes missing from S. enterica serovar Typhi (S. typhi), and 29% missing from Escherichia coli K12. The 352 gene homologues of S. typhimurium LT2 confined to subspecies I of S. enterica-containing most mammalian and bird pathogens-are useful for studies of epidemiology, host specificity and pathogenesis. Most of these homologues were previously unknown, and 50 may be exported to the periplasm or outer membrane, rendering them accessible as therapeutic or vaccine targets.
ESTHER : McClelland_2001_Nature_413_852
PubMedSearch : McClelland_2001_Nature_413_852
PubMedID: 11677609
Gene_locus related to this paper: salen-OPDB , salti-q8z717 , salty-AES , salty-BIOH , salty-ENTF , salty-FES , salty-IROD , salty-IROE , salty-P74847 , salty-PLDB , salty-STM0332 , salty-STM2547 , salty-STM3079 , salty-STM4506 , salty-STY1441 , salty-STY2428 , salty-STY3846 , salty-yafa , salty-YBFF , salty-ycfp , salty-YFBB , salty-YHET , salty-YJFP , salty-YQIA

Title : An engineered Tetrahymena tRNAGln for in vivo incorporation of unnatural amino acids into proteins by nonsense suppression - Saks_1996_J.Biol.Chem_271_23169
Author(s) : Saks ME , Sampson JR , Nowak MW , Kearney PC , Du F , Abelson JN , Lester HA , Dougherty DA
Ref : Journal of Biological Chemistry , 271 :23169 , 1996
Abstract : A new tRNA, THG73, has been designed and evaluated as a vehicle for incorporating unnatural amino acids site-specifically into proteins expressed in vivo using the stop codon suppression technique. The construct is a modification of tRNAGln(CUA) from Tetrahymena thermophila, which naturally recognizes the stop codon UAG. Using electrophysiological studies of mutations at several sites of the nicotinic acetylcholine receptor, it is established that THG73 represents a major improvement over previous nonsense suppressors both in terms of efficiency and fidelity of unnatural amino acid incorporation. Compared with a previous tRNA used for in vivo suppression, THG73 is as much as 100-fold less likely to be acylated by endogenous synthetases of the Xenopus oocyte. This effectively eliminates a major concern of the in vivo suppression methodology, the undesirable incorporation of natural amino acids at the suppression site. In addition, THG73 is 4-10-fold more efficient at incorporating unnatural amino acids in the oocyte system. Taken together, these two advances should greatly expand the range of applicability of the in vivo nonsense suppression methodology.
ESTHER : Saks_1996_J.Biol.Chem_271_23169
PubMedSearch : Saks_1996_J.Biol.Chem_271_23169
PubMedID: 8798511