Author Report for: Xie GNo contact information in database for Xie G
Ou J, Peng Y, Yang W, Zhang Y, Hao J, Li F, Chen Y, Zhao Y, Xie X and Liang H <8 more author(s)> Ou J, Peng Y, Yang W, Zhang Y, Hao J, Li F, Chen Y, Zhao Y, Xie X, Wu S, Zha L, Luo X, Xie G, Wang L, Sun W, Zhou Q, Li J, Liang H (- 8) Ref: Nat Commun, 10:1078, 2019 : PubMed ESTHER: Ou_2019_Nat.Commun_10_1078 PubMedSearch: Ou 2019 Nat.Commun 10 1078 PubMedID: 30842415 Gene_locus related to this paper: human-ABHD5 Abstract The efficacy of Fluorouracil (FU) in the treatment of colorectal cancer (CRC) is greatly limited by drug resistance. Autophagy has been implicated in chemoresistance, but the role of selective autophagic degradation in regulating chemoresistance remains unknown. In this study, we revealed a critical role of ABHD5 in charging CRC sensitivity to FU via regulating autophagic uracil yield. We demonstrated that ABHD5 localizes to lysosome and interacts with PDIA5 to prevent PDIA5 from interacting with RNASET2 and inactivating RNASET2. ABHD5 deficiency releases PDIA5 to directly interact with RNASET2 and leave RNASET2 in an inactivate state, which impairs RNASET2-mediated autophagic uracil yield and promotes CRC cells to uptake FU as an exogenous uracil, thus increasing their sensitivity to FU. Our findings for the first time reveal a novel role of ABHD5 in regulating lysosome function, highlighting the significance of ABHD5 as a compelling biomarker predicting the sensitivity of CRCs to FU-based chemotherapy. Title: Loss of Abhd5 Promotes Colorectal Tumor Development and Progression by Inducing Aerobic Glycolysis and Epithelial-Mesenchymal Transition Ou J, Miao H, Ma Y, Guo F, Deng J, Wei X, Zhou J, Xie G, Shi H and Yu L <2 more author(s)> Ou J, Miao H, Ma Y, Guo F, Deng J, Wei X, Zhou J, Xie G, Shi H, Xue B, Liang H, Yu L (- 2) Ref: Cell Rep, 24:2795, 2018 : PubMed ESTHER: Ou_2018_Cell.Rep_24_2795 PubMedSearch: Ou 2018 Cell.Rep 24 2795 PubMedID: 30184511 Gene_locus related to this paper: human-ABHD5 Title: Synthesis and Evaluation of Novel Ligustrazine Derivatives as Multi-Targeted Inhibitors for the Treatment of Alzheimer's Disease Wu W, Liang X, Xie G, Chen L, Liu W, Luo G, Zhang P, Yu L, Zheng X and Yi W <2 more author(s)> Wu W, Liang X, Xie G, Chen L, Liu W, Luo G, Zhang P, Yu L, Zheng X, Ji H, Zhang C, Yi W (- 2) Ref: Molecules, 23:, 2018 : PubMed ESTHER: Wu_2018_Molecules_23_ PubMedSearch: Wu 2018 Molecules 23 PubMedID: 30301153 Abstract A series of novel ligustrazine derivatives 8a(-)r were designed, synthesized, and evaluated as multi-targeted inhibitors for anti-Alzheimer's disease (AD) drug discovery. The results showed that most of them exhibited a potent ability to inhibit both ChEs, with a high selectivity towards AChE. In particular, compounds 8q and 8r had the greatest inhibitory abilities for AChE, with IC50 values of 1.39 and 0.25 nM, respectively, and the highest selectivity towards AChE (for 8q, IC50 BuChE/IC50 AChE = 2.91 x 10(6); for 8r, IC50 BuChE/IC50 AChE = 1.32 x 10(7)). Of note, 8q and 8r also presented potent inhibitory activities against Abeta aggregation, with IC50 values of 17.36 microM and 49.14 microM, respectively. Further cellular experiments demonstrated that the potent compounds 8q and 8r had no obvious cytotoxicity in either HepG2 cells or SH-SY5Y cells, even at a high concentration of 500 muM. Besides, a combined Lineweaver-Burk plot and molecular docking study revealed that these compounds might act as mixed-type inhibitors to exhibit such effects via selectively targeting both the catalytic active site (CAS) and the peripheral anionic site (PAS) of AChEs. Taken together, these results suggested that further development of these compounds should be of great interest. Title: Monoacylglycerol lipase inhibitor JZL184 regulates apoptosis and migration of colorectal cancer cells Ma M, Bai J, Ling Y, Chang W, Xie G, Li R, Wang G, Tao K Ref: Mol Med Rep, 13:2850, 2016 : PubMed ESTHER: Ma_2016_Mol.Med.Rep_13_2850 PubMedSearch: Ma 2016 Mol.Med.Rep 13 2850 PubMedID: 26847687 Inhibitor(s) related to this paper: JZL184 Abstract Monoacylglycerol lipase (MAGL) is involved in the degradation of triacylglycerol. Previous studies have demonstrated that MAGL regulates tumor growth and metastasis via fatty acid networks, and is associated with colorectal cancer. JZL184 is a MAGL inhibitor, which in the present study was administered to colorectal cancer cell lines, resulting in decreased tumor proliferation, increased apoptosis and increased tumor cell sensitivity to 5-fluorouracil. Bcell lymphoma 2 (Bcl2) and Bcl2associated X protein (Bax) are key proteins in apoptosis. The expression levels of Bcl2/Bax were determined in colorectal cancer cell lines following JZL184 administration, and it was observed that the mRNA and protein expression levels of Bcl2 were decreased, whereas the expression levels of Bax were increased. These results indicated that JZL184 may induce tumor cell apoptosis by regulating the expression of Bcl2 and Bax. Epithelial-mesenchymal transition (EMT) is closely associated with metastasis. Administration of JZL184 in various malignant colorectal cancer cell lines suppressed migration and altered the expression of EMT markers; Ecadherin was increased, whereas the expression levels of vimentin and zinc finger protein SNAI1 were decreased. These results suggested that JZL184 was able to regulate the EMT process, in order to control the migration of colorectal cancer cells, particularly in tumors with a stronger metastatic capability. Therefore, in colorectal cancer, MAGL may be considered a potential therapeutic target and JZL184 may be a possible therapeutic agent. Title: Macrophage ABHD5 promotes colorectal cancer growth by suppressing spermidine production by SRM Miao H, Ou J, Peng Y, Zhang X, Chen Y, Hao L, Xie G, Wang Z, Pang X and Liang H <6 more author(s)> Miao H, Ou J, Peng Y, Zhang X, Chen Y, Hao L, Xie G, Wang Z, Pang X, Ruan Z, Li J, Yu L, Xue B, Shi H, Shi C, Liang H (- 6) Ref: Nat Commun, 7:11716, 2016 : PubMed ESTHER: Miao_2016_Nat.Commun_7_11716 PubMedSearch: Miao 2016 Nat.Commun 7 11716 PubMedID: 27189574 Abstract Metabolic reprogramming in stromal cells plays an essential role in regulating tumour growth. The metabolic activities of tumour-associated macrophages (TAMs) in colorectal cancer (CRC) are incompletely characterized. Here, we identify TAM-derived factors and their roles in the development of CRC. We demonstrate that ABHD5, a lipolytic co-activator, is ectopically expressed in CRC-associated macrophages. We demonstrate in vitro and in mouse models that macrophage ABHD5 potentiates growth of CRC cells. Mechanistically, ABHD5 suppresses spermidine synthase (SRM)-dependent spermidine production in macrophages by inhibiting the reactive oxygen species-dependent expression of C/EBPvarepsilon, which activates transcription of the srm gene. Notably, macrophage-specific ABHD5 transgene-induced CRC growth in mice can be prevented by an additional SRM transgene in macrophages. Altogether, our results show that the lipolytic factor ABHD5 suppresses SRM-dependent spermidine production in TAMs and potentiates the growth of CRC. The ABHD5/SRM/spermidine axis in TAMs might represent a potential target for therapy. Title: ABHD5 interacts with BECN1 to regulate autophagy and tumorigenesis of colon cancer independent of PNPLA2 Peng Y, Miao H, Wu S, Yang W, Zhang Y, Xie G, Xie X, Li J, Shi C and Ou J <4 more author(s)> Peng Y, Miao H, Wu S, Yang W, Zhang Y, Xie G, Xie X, Li J, Shi C, Ye L, Sun W, Wang L, Liang H, Ou J (- 4) Ref: Autophagy, 12:2167, 2016 : PubMed ESTHER: Peng_2016_Autophagy_12_2167 PubMedSearch: Peng 2016 Autophagy 12 2167 PubMedID: 27559856 Gene_locus related to this paper: human-ABHD5 Abstract Autophagy critically contributes to metabolic reprogramming and chromosomal stability. It has been reported that monoallelic loss of the essential autophagy gene BECN1 (encoding BECN1/Beclin 1) promotes cancer development and progression. However, the mechanism by which BECN1 is inactivated in malignancy remains largely elusive. We have previously reported a tumor suppressor role of ABHD5 (abhydrolase domain containing 5), a co-activator of PNPLA2 (patatin like phospholipase domain containing 2) in colorectal carcinoma (CRC). Here we report a noncanonical role of ABHD5 in regulating autophagy and CRC tumorigenesis. ABHD5 directly competes with CASP3 for binding to the cleavage sites of BECN1, and consequently prevents BECN1 from being cleaved by CASP3. ABHD5 deficiency provides CASP3 an advantage to cleave and inactivate BECN1, thus impairing BECN1-induced autophagic flux and augmenting genomic instability, which subsequently promotes tumorigenesis. Notably, clinical data also confirm that ABHD5 proficiency is significantly correlated with the expression levels of BECN1, LC3-II and CASP3 in human CRC tissues. Our findings suggest that ABHD5 possesses a PNPLA2-independent function in regulating autophagy and tumorigenesis, further establishing the tumor suppressor role of ABHD5, and offering an opportunity to develop new approaches aimed at preventing CRC carcinogenesis. Title: Genomic sequences of six botulinum neurotoxin-producing strains representing three clostridial species illustrate the mobility and diversity of botulinum neurotoxin genes Smith TJ, Hill KK, Xie G, Foley BT, Williamson CH, Foster JT, Johnson SL, Chertkov O, Teshima H and Smith LA <3 more author(s)> Smith TJ, Hill KK, Xie G, Foley BT, Williamson CH, Foster JT, Johnson SL, Chertkov O, Teshima H, Gibbons HS, Johnsky LA, Karavis MA, Smith LA (- 3) Ref: Infect Genet Evol, 30:102, 2015 : PubMed ESTHER: Smith_2015_Infect.Genet.Evol_30_102 PubMedSearch: Smith 2015 Infect.Genet.Evol 30 102 PubMedID: 25489752 Gene_locus related to this paper: 9clot-a0a0c1u9k6 Abstract The whole genomes for six botulinum neurotoxin-producing clostridial strains were sequenced to provide references for under-represented toxin types, bivalent strains or unusual toxin complexes associated with a bont gene. The strains include three Clostridium botulinum Group I strains (CDC 297, CDC 1436, and Prevot 594), a Group II C. botulinum strain (Eklund 202F), a Group IV Clostridium argentinense strain (CDC 2741), and a Group V Clostridium baratii strain (Sullivan). Comparisons of the Group I genomic sequences revealed close relationships and conservation of toxin gene locations with previously published Group I C. botulinum genomes. The bont/F6 gene of strain Eklund 202F was determined to be a chimeric toxin gene composed of bont/F1 and bont/F2. The serotype G strain CDC 2741 remained unfinished in 20 contigs with the bont/G located within a 1.15Mb contig, indicating a possible chromosomal location for this toxin gene. Within the genome of C. baratii Sullivan strain, direct repeats of IS1182 insertion sequence (IS) elements were identified flanking the bont/F7 toxin complex that may be the mechanism of bont insertion into C. baratii. Highlights of the six strains are described and release of their genomic sequences will allow further study of unusual neurotoxin-producing clostridial strains. Title: Phospho-NSAIDs Have Enhanced Efficacy in Mice Lacking Plasma Carboxylesterase: Implications for their Clinical Pharmacology Wong CC, Cheng KW, Papayannis I, Mattheolabakis G, Huang L, Xie G, Ouyang N, Rigas B Ref: Pharm Res, 32:1663, 2015 : PubMed ESTHER: Wong_2015_Pharm.Res_32_1663 PubMedSearch: Wong 2015 Pharm.Res 32 1663 PubMedID: 25392229 Abstract PURPOSE: The purpose of the study was to evaluate the metabolism, pharmacokinetics and efficacy of phospho-NSAIDs in Ces1c-knockout mice. Title: Loss of abhd5 promotes colorectal tumor development and progression by inducing aerobic glycolysis and epithelial-mesenchymal transition Ou J, Miao H, Ma Y, Guo F, Deng J, Wei X, Zhou J, Xie G, Shi H and Yu L <2 more author(s)> Ou J, Miao H, Ma Y, Guo F, Deng J, Wei X, Zhou J, Xie G, Shi H, Xue B, Liang H, Yu L (- 2) Ref: Cell Rep, 9:1798, 2014 : PubMed ESTHER: Ou_2014_Cell.Rep_9_1798 PubMedSearch: Ou 2014 Cell.Rep 9 1798 PubMedID: 25482557 Gene_locus related to this paper: human-ABHD5 Abstract How cancer cells shift metabolism to aerobic glycolysis is largely unknown. Here, we show that deficiency of alpha/beta-hydrolase domain-containing 5 (Abhd5), an intracellular lipolytic activator that is also known as comparative gene identification 58 (CGI-58), promotes this metabolic shift and enhances malignancies of colorectal carcinomas (CRCs). Silencing of Abhd5 in normal fibroblasts induces malignant transformation. Intestine-specific knockout of Abhd5 in Apc(Min/+) mice robustly increases tumorigenesis and malignant transformation of adenomatous polyps. In colon cancer cells, Abhd5 deficiency induces epithelial-mesenchymal transition by suppressing the AMPKalpha-p53 pathway, which is attributable to increased aerobic glycolysis. In human CRCs, Abhd5 expression falls substantially and correlates negatively with malignant features. Our findings link Abhd5 to CRC pathogenesis and suggest that cancer cells develop aerobic glycolysis by suppressing Abhd5-mediated intracellular lipolysis. Title: Genome Sequences of Two Carbapenemase-Resistant Klebsiella pneumoniae ST258 Isolates Ramirez MS, Xie G, Johnson S, Davenport K, van Duin D, Perez F, Bonomo RA, Chain P, Tolmasky ME Ref: Genome Announc, 2:, 2014 : PubMed ESTHER: Ramirez_2014_Genome.Announc_2_e00558 PubMedSearch: Ramirez 2014 Genome.Announc 2 e00558 PubMedID: 24948759 Abstract Klebsiella pneumoniae, an ESKAPE group (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) pathogen, has acquired multiple antibiotic resistance genes and is becoming a serious public health threat. Here, we report the genome sequences of two representative strains of K. pneumoniae from the emerging K. pneumoniae carbapenemase (KPC) outbreak in northeast Ohio belonging to sequence type 258 (ST258) (isolates Kb140 and Kb677, which were isolated from blood and urine, respectively). Both isolates harbor a blaKPC gene, and strain Kb140 carries blaKPC-2, while Kb677 carries blaKPC-3. Title: [Effect of Huperzine A on neural lesion of acute organophosphate poisoning in mice] Liu L, Wang J, Xie G, Sun J Ref: Wei Sheng Yan Jiu, 42:419, 2013 : PubMed ESTHER: Liu_2013_Wei.Sheng.Yan.Jiu_42_419 PubMedSearch: Liu 2013 Wei.Sheng.Yan.Jiu 42 419 PubMedID: 23805518 Abstract OBJECTIVE: Effects of neurophathologic changes and expression of Glu and 60 nNOS were observed in acute isocarbophos and phoxim poisoning in mice. Title: Comparative in vitro metabolism of phospho-tyrosol-indomethacin by mice, rats and humans Xie G, Zhou D, Cheng KW, Wong CC, Rigas B Ref: Biochemical Pharmacology, 85:1195, 2013 : PubMed ESTHER: Xie_2013_Biochem.Pharmacol_85_1195 PubMedSearch: Xie 2013 Biochem.Pharmacol 85 1195 PubMedID: 23399640 Abstract Phospho-tyrosol-indomethacin (PTI; MPI 621), a novel anti-cancer agent, is more potent and safer than conventional indomethacin. Here, we show that PTI was extensively metabolized in vitro and in vivo. PTI was rapidly hydrolyzed by carboxylesterases to generate indomethacin as its major metabolite in the liver microsomes and rats. PTI additionally undergoes cytochromes P450 (CYP)-mediated hydroxylation at its tyrosol moiety and O-demethylation at its indomethacin moiety. Of the five major human CYPs, CYP3A4 and CYP2D6 catalyze the hydroxylation and O-demethylation reactions of PTI, respectively; whereas CYP1A2, 2C9 and 2C19 are inactive towards PTI. In contrast to PTI, indomethacin is primarily O-demethylated by CYP2C9, which prefers acidic substrates. The hydrolyzed and O-demethylated metabolites of PTI are further glucuronidated and sulfated, facilitating drug elimination and detoxification. We observed substantial inter-species differences in the metabolic rates of PTI. Among the liver microsomes from various species, PTI was the most rapidly hydrolyzed, hydroxylated and O-demethylated in mouse, human and rat liver microsomes, respectively. These results reflect the differential expression patterns of carboxylesterase and CYP isoforms among these species. Of the human microsomes from various tissues, PTI underwent more rapid carboxylesterase- and CYP-catalyzed reactions in liver and intestine microsomes than in kidney and lung microsomes. Together, our results establish the metabolic pathways of PTI, reveal significant inter-species differences in its metabolism, and provide insights into the underlying biochemical mechanisms. Title: Salsolinol modulation of dopamine neurons Xie G, Krnjevic K, Ye JH Ref: Front Behavioral Neuroscience, 7:52, 2013 : PubMed ESTHER: Xie_2013_Front.Behav.Neurosci_7_52 PubMedSearch: Xie 2013 Front.Behav.Neurosci 7 52 PubMedID: 23745110 Abstract Salsolinol, a tetrahydroisoquinoline present in the human and rat brains, is the condensation product of dopamine and acetaldehyde, the first metabolite of ethanol. Previous evidence obtained in vivo links salsolinol with the mesolimbic dopaminergic (DA) system: salsolinol is self-administered into the posterior of the ventral tegmental area (pVTA) of rats; intra-VTA administration of salsolinol induces a strong conditional place preference and increases dopamine release in the nucleus accumbens (NAc). However, the underlying neuronal mechanisms are unclear. Here we present an overview of some of the recent research on this topic. Electrophysiological studies reveal that DA neurons in the pVTA are a target of salsolinol. In acute brain slices from rats, salsolinol increases the excitability and accelerates the ongoing firing of dopamine neurons in the pVTA. Intriguingly, this action of salsolinol involves multiple pre- and post-synaptic mechanisms, including: (1) depolarizing dopamine neurons; (2) by activating mu opioid receptors on the GABAergic inputs to dopamine neurons - which decreases GABAergic activity - dopamine neurons are disinhibited; and (3) enhancing presynaptic glutamatergic transmission onto dopamine neurons via activation of dopamine type 1 receptors, probably situated on the glutamatergic terminals. These novel mechanisms may contribute to the rewarding/reinforcing properties of salsolinol observed in vivo. Title: Genome Sequences of Two Klebsiella pneumoniae Isolates from Different Geographical Regions, Argentina (Strain JHCK1) and the United States (Strain VA360) Xie G, Ramirez MS, Marshall SH, Hujer KM, Lo CC, Johnson S, Li PE, Davenport K, Endimiani A and Chain PS <2 more author(s)> Xie G, Ramirez MS, Marshall SH, Hujer KM, Lo CC, Johnson S, Li PE, Davenport K, Endimiani A, Bonomo RA, Tolmasky ME, Chain PS (- 2) Ref: Genome Announc, 1:, 2013 : PubMed ESTHER: Xie_2013_Genome.Announc_1_E00168 PubMedSearch: Xie 2013 Genome.Announc 1 E00168 PubMedID: 23640195 Gene_locus related to this paper: klep7-a6t9v6, klep7-y1077, klepn-a0a016qwx4, klepn-w8uta0 Abstract We report the sequences of two Klebsiella pneumoniae clinical isolates, strains JHCK1 and VA360, from a newborn with meningitis in Buenos Aires, Argentina, and from a tertiary care medical center in Cleveland, OH, respectively. Both isolates contain one chromosome and at least five plasmids; isolate VA360 contains the Klebsiella pneumoniae carbapenemase (KPC) gene. Title: Genomic comparison of Escherichia coli O104:H4 isolates from 2009 and 2011 reveals plasmid, and prophage heterogeneity, including shiga toxin encoding phage stx2 Ahmed SA, Awosika J, Baldwin C, Bishop-Lilly KA, Biswas B, Broomall S, Chain PS, Chertkov O, Chokoshvili O and Gibbons HS <35 more author(s)> Ahmed SA, Awosika J, Baldwin C, Bishop-Lilly KA, Biswas B, Broomall S, Chain PS, Chertkov O, Chokoshvili O, Coyne S, Davenport K, Detter JC, Dorman W, Erkkila TH, Folster JP, Frey KG, George M, Gleasner C, Henry M, Hill KK, Hubbard K, Insalaco J, Johnson S, Kitzmiller A, Krepps M, Lo CC, Luu T, McNew LA, Minogue T, Munk CA, Osborne B, Patel M, Reitenga KG, Rosenzweig CN, Shea A, Shen X, Strockbine N, Tarr C, Teshima H, van Gieson E, Verratti K, Wolcott M, Xie G, Sozhamannan S, Gibbons HS (- 35) Ref: PLoS ONE, 7:e48228, 2012 : PubMed ESTHER: Ahmed_2012_PLoS.ONE_7_E48228 PubMedSearch: Ahmed 2012 PLoS.ONE 7 E48228 PubMedID: 23133618 Gene_locus related to this paper: ecoli-MCMK, ecoli-ycfp, ecoli-yqia, ecoli-YfhR Abstract In May of 2011, an enteroaggregative Escherichia coli O104:H4 strain that had acquired a Shiga toxin 2-converting phage caused a large outbreak of bloody diarrhea in Europe which was notable for its high prevalence of hemolytic uremic syndrome cases. Several studies have described the genomic inventory and phylogenies of strains associated with the outbreak and a collection of historical E. coli O104:H4 isolates using draft genome assemblies. We present the complete, closed genome sequences of an isolate from the 2011 outbreak (2011C-3493) and two isolates from cases of bloody diarrhea that occurred in the Republic of Georgia in 2009 (2009EL-2050 and 2009EL-2071). Comparative genome analysis indicates that, while the Georgian strains are the nearest neighbors to the 2011 outbreak isolates sequenced to date, structural and nucleotide-level differences are evident in the Stx2 phage genomes, the mer/tet antibiotic resistance island, and in the prophage and plasmid profiles of the strains, including a previously undescribed plasmid with homology to the pMT virulence plasmid of Yersinia pestis. In addition, multiphenotype analysis showed that 2009EL-2071 possessed higher resistance to polymyxin and membrane-disrupting agents. Finally, we show evidence by electron microscopy of the presence of a common phage morphotype among the European and Georgian strains and a second phage morphotype among the Georgian strains. The presence of at least two stx2 phage genotypes in host genetic backgrounds that may derive from a recent common ancestor of the 2011 outbreak isolates indicates that the emergence of stx2 phage-containing E. coli O104:H4 strains probably occurred more than once, or that the current outbreak isolates may be the result of a recent transfer of a new stx2 phage element into a pre-existing stx2-positive genetic background. Title: GABAergic actions mediate opposite ethanol effects on dopaminergic neurons in the anterior and posterior ventral tegmental area Guan Y, Xiao C, Krnjevic K, Xie G, Zuo W, Ye JH Ref: Journal of Pharmacology & Experimental Therapeutics, 341:33, 2012 : PubMed ESTHER: Guan_2012_J.Pharmacol.Exp.Ther_341_33 PubMedSearch: Guan 2012 J.Pharmacol.Exp.Ther 341 33 PubMedID: 22209891 Abstract It is known that the posterior ventral tegmental area (p-VTA) differs from the anterior VTA (a-VTA) in that rats learn to self-administer ethanol into the p-VTA, but not into the a-VTA. Because activation of VTA dopaminergic neurons by ethanol is a cellular mechanism underlying the reinforcement of ethanol consumption, we hypothesized that ethanol may exert different effects on dopaminergic neurons in the p-VTA and a-VTA. In patch-clamp recordings in midbrain slices from young rats (postnatal days 22-32), we detected no significant difference in electrophysiological properties between p-VTA and a-VTA dopaminergic neurons. However, acute exposure to ethanol (21-86 mM) stimulated p-VTA dopaminergic neurons but suppressed a-VTA dopaminergic neurons. Conversely, ethanol (>21 mM) dose-dependently reduced the frequency of the GABAergic spontaneous inhibitory postsynaptic currents (sIPSCs) generated by inhibitory neuronal firing but not miniature inhibitory postsynaptic currents (mIPSCs) in p-VTA dopaminergic neurons. By contrast, ethanol increased the frequency and amplitude of both sIPSCs and mIPSCs in a-VTA dopaminergic neurons. All of these effects of ethanol were abolished by a GABA(A) receptor antagonist. There was a strong negative correlation between ethanol-evoked modulation of sIPSCs and neuronal firing in VTA dopaminergic neurons. These results indicate that GABAergic inputs play an important role in ethanol's actions in the VTA. The differential effects of ethanol on sIPSCs and neuronal firing in the p-VTA and a-VTA could be the basis for ethanol reinforcement via the p-VTA. Title: Carboxylesterases 1 and 2 hydrolyze phospho-nonsteroidal anti-inflammatory drugs: relevance to their pharmacological activity Wong CC, Cheng KW, Xie G, Zhou D, Zhu CH, Constantinides PP, Rigas B Ref: Journal of Pharmacology & Experimental Therapeutics, 340:422, 2012 : PubMed ESTHER: Wong_2012_J.Pharmacol.Exp.Ther_340_422 PubMedSearch: Wong 2012 J.Pharmacol.Exp.Ther 340 422 PubMedID: 22085648 Abstract Phospho-nonsteroidal anti-inflammatory drugs (phospho-NSAIDs) are novel NSAID derivatives with improved anticancer activity and reduced side effects in preclinical models. Here, we studied the metabolism of phospho-NSAIDs by carboxylesterases and assessed the impact of carboxylesterases on the anticancer activity of phospho-NSAIDs in vitro and in vivo. The expression of human liver carboxylesterase (CES1) and intestinal carboxylesterase (CES2) in human embryonic kidney 293 cells resulted in the rapid intracellular hydrolysis of phospho-NSAIDs. Kinetic analysis revealed that CES1 is more active in the hydrolysis of phospho-sulindac, phospho-ibuprofen, phospho-naproxen, phospho-indomethacin, and phospho-tyrosol-indomethacin that possessed a bulky acyl moiety, whereas the phospho-aspirins are preferentially hydrolyzed by CES2. Carboxylesterase expression leads to a significant attenuation of the in vitro cytotoxicity of phospho-NSAIDs, suggesting that the integrity of the drug is critical for anticancer activity. Benzil and bis-p-nitrophenyl phosphate (BNPP), two carboxylesterase inhibitors, abrogated the effect of carboxylesterases and resensitized carboxylesterase-expressing cells to the potent cytotoxic effects of phospho-NSAIDs. In mice, coadministration of phospho-sulindac and BNPP partially protected the former from esterase-mediated hydrolysis, and this combination more effectively inhibited the growth of AGS human gastric xenografts in nude mice (57%) compared with phospho-sulindac alone (28%) (p = 0.037). Our results show that carboxylesterase mediates that metabolic inactivation of phospho-NSAIDs, and the inhibition of carboxylesterases improves the efficacy of phospho-NSAIDs in vitro and in vivo. Title: Salsolinol stimulates dopamine neurons in slices of posterior ventral tegmental area indirectly by activating mu-opioid receptors Xie G, Hipolito L, Zuo W, Polache A, Granero L, Krnjevic K, Ye JH Ref: Journal of Pharmacology & Experimental Therapeutics, 341:43, 2012 : PubMed ESTHER: Xie_2012_J.Pharmacol.Exp.Ther_341_43 PubMedSearch: Xie 2012 J.Pharmacol.Exp.Ther 341 43 PubMedID: 22209890 Abstract Previous studies in vivo have shown that salsolinol, the condensation product of acetaldehyde and dopamine, has properties that may contribute to alcohol abuse. Although opioid receptors, especially the mu-opioid receptors (MORs), may be involved, the cellular mechanisms mediating the effects of salsolinol have not been fully explored. In the current study, we used whole-cell patch-clamp recordings to examine the effects of salsolinol on dopamine neurons of the ventral tegmental area (VTA) in acute brain slices from Sprague-Dawley rats. Salsolinol (0.01-1 muM) dose-dependently and reversibly increased the ongoing firing of dopamine neurons; this effect was blocked by naltrexone, an antagonist of MORs, and gabazine, an antagonist of GABA(A) receptors. We further showed that salsolinol reduced the frequency without altering the amplitude of spontaneous GABA(A) receptor-mediated inhibitory postsynaptic currents in dopamine neurons. The salsolinol-induced reduction was blocked by both naltrexone and [D-Ala2,N-Me-Phe4,Gly5-ol]enkephalin, an agonist of MORs. Thus, salsolinol excites VTA-dopamine neurons indirectly by activating MORs, which inhibit GABA neurons in the VTA. This form of disinhibition seems to be a novel mechanism underlying the effects of salsolinol. Title: Interkingdom gene transfer may contribute to the evolution of phytopathogenicity in botrytis cinerea Zhu B, Zhou Q, Xie G, Zhang G, Zhang X, Wang Y, Sun G, Li B, Jin G Ref: Evol Bioinform Online, 8:105, 2012 : PubMed ESTHER: Zhu_2012_Evol.Bioinform.Online_8_105 PubMedSearch: Zhu 2012 Evol.Bioinform.Online 8 105 PubMedID: 22346340 Abstract The ascomycete Botrytis cinerea is a phytopathogenic fungus infecting and causing significant yield losses in a number of crops. The genome of B. cinerea has been fully sequenced while the importance of horizontal gene transfer (HGT) to extend the host range in plant pathogenic fungi has been recently appreciated. However, recent data confirm that the B. cinerea fungus shares conserved virulence factors with other fungal plant pathogens with narrow host range. Therefore, interkingdom HGT may contribute to the evolution of phytopathogenicity in B. cinerea. In this study, a stringent genome comparison pipeline was used to identify potential genes that have been obtained by B. cinerea but not by other fungi through interkingdom HGT. This search led to the identification of four genes: a UDP-glucosyltransferase (UGT), a lipoprotein and two alpha/beta hydrolase fold proteins. Phylogenetic analysis of the four genes suggests that B. cinerea acquired UGT from plants and the other 3 genes from bacteria. Based on the known gene functions and literature searching, a correlation between gene acquision and the evolution of pathogenicity in B. cinerea can be postulated. Title: Complete Genome Sequence of a thermotolerant sporogenic lactic acid bacterium, Bacillus coagulans strain 36D1 Rhee MS, Moritz BE, Xie G, Glavina Del Rio T, Dalin E, Tice H, Bruce D, Goodwin L, Chertkov O and Shanmugam KT <9 more author(s)> Rhee MS, Moritz BE, Xie G, Glavina Del Rio T, Dalin E, Tice H, Bruce D, Goodwin L, Chertkov O, Brettin T, Han C, Detter C, Pitluck S, Land ML, Patel M, Ou M, Harbrucker R, Ingram LO, Shanmugam KT (- 9) Ref: Stand Genomic Sci, 5:331, 2011 : PubMed ESTHER: Rhee_2011_Stand.Genomic.Sci_5_331 PubMedSearch: Rhee 2011 Stand.Genomic.Sci 5 331 PubMedID: 22675583 Gene_locus related to this paper: bacco-c1p801, bacco-g2tqg6 Abstract Bacillus coagulans is a ubiquitous soil bacterium that grows at 50-55 degrees C and pH 5.0 and ferments various sugars that constitute plant biomass to L (+)-lactic acid. The ability of this sporogenic lactic acid bacterium to grow at 50-55 degrees C and pH 5.0 makes this organism an attractive microbial biocatalyst for production of optically pure lactic acid at industrial scale not only from glucose derived from cellulose but also from xylose, a major constituent of hemicellulose. This bacterium is also considered as a potential probiotic. Complete genome sequence of a representative strain, B. coagulans strain 36D1, is presented and discussed. Title: Whole genome sequences of two Xylella fastidiosa strains (M12 and M23) causing almond leaf scorch disease in California Chen J, Xie G, Han S, Chertkov O, Sims D, Civerolo EL Ref: Journal of Bacteriology, 192:4534, 2010 : PubMed ESTHER: Chen_2010_J.Bacteriol_192_4534 PubMedSearch: Chen 2010 J.Bacteriol 192 4534 PubMedID: 20601474 Gene_locus related to this paper: xylfa-cxest, xylfa-metx, xylfa-pip, xylfa-XF0015, xylfa-XF1029, xylfa-XF1253, xylfa-XF1282, xylfa-XF1356, xylfa-XF2330, xylfa-XF2551 Abstract Xylella fastidiosa is a Gram-negative plant-pathogenic bacterium causing many economically important diseases, including almond leaf scorch disease (ALSD) in California. Genome information greatly facilitates research on this nutritionally fastidious organism. Here we report the complete genome sequences of two ALSD strains of this bacterium, M12 and M23. Title: Comparative genomics of clinical and environmental Vibrio mimicus Hasan NA, Grim CJ, Haley BJ, Chun J, Alam M, Taviani E, Hoq M, Munk AC, Saunders E and Colwell RR <8 more author(s)> Hasan NA, Grim CJ, Haley BJ, Chun J, Alam M, Taviani E, Hoq M, Munk AC, Saunders E, Brettin TS, Bruce DC, Challacombe JF, Detter JC, Han CS, Xie G, Nair GB, Huq A, Colwell RR (- 8) Ref: Proc Natl Acad Sci U S A, 107:21134, 2010 : PubMed ESTHER: Hasan_2010_Proc.Natl.Acad.Sci.U.S.A_107_21134 PubMedSearch: Hasan 2010 Proc.Natl.Acad.Sci.U.S.A 107 21134 PubMedID: 21078967 Gene_locus related to this paper: vibch-VC2610, vibch-VC2718, vibch-VCA0688, vibch-y1892, vibch-y2276, vibmi-d0gt41, vibmi-u4zh77 Abstract Whether Vibrio mimicus is a variant of Vibrio cholerae or a separate species has been the subject of taxonomic controversy. A genomic analysis was undertaken to resolve the issue. The genomes of V. mimicus MB451, a clinical isolate, and VM223, an environmental isolate, comprise ca. 4,347,971 and 4,313,453 bp and encode 3,802 and 3,290 ORFs, respectively. As in other vibrios, chromosome I (C-I) predominantly contains genes necessary for growth and viability, whereas chromosome II (C-II) bears genes for adaptation to environmental change. C-I harbors many virulence genes, including some not previously reported in V. mimicus, such as mannose-sensitive hemagglutinin (MSHA), and enterotoxigenic hemolysin (HlyA); C-II encodes a variant of Vibrio pathogenicity island 2 (VPI-2), and Vibrio seventh pandemic island II (VSP-II) cluster of genes. Extensive genomic rearrangement in C-II indicates it is a hot spot for evolution and genesis of speciation for the genus Vibrio. The number of virulence regions discovered in this study (VSP-II, MSHA, HlyA, type IV pilin, PilE, and integron integrase, IntI4) with no notable difference in potential virulence genes between clinical and environmental strains suggests these genes also may play a role in the environment and that pathogenic strains may arise in the environment. Significant genome synteny with prototypic pre-seventh pandemic strains of V. cholerae was observed, and the results of phylogenetic analysis support the hypothesis that, in the course of evolution, V. mimicus and V. cholerae diverged from a common ancestor with a prototypic sixth pandemic genomic backbone. Title: Large direct repeats flank genomic rearrangements between a new clinical isolate of Francisella tularensis subsp. tularensis A1 and Schu S4 Nalbantoglu U, Sayood K, Dempsey MP, Iwen PC, Francesconi SC, Barabote RD, Xie G, Brettin TS, Hinrichs SH, Fey PD Ref: PLoS ONE, 5:e9007, 2010 : PubMed ESTHER: Nalbantoglu_2010_PLoS.ONE_5_E9007 PubMedSearch: Nalbantoglu 2010 PLoS.ONE 5 E9007 PubMedID: 20140244 Gene_locus related to this paper: fratt-q5ngu5 Abstract Francisella tularensis subspecies tularensis consists of two separate populations A1 and A2. This report describes the complete genome sequence of NE061598, an F. tularensis subspecies tularensis A1 isolated in 1998 from a human with clinical disease in Nebraska, United States of America. The genome sequence was compared to Schu S4, an F. tularensis subspecies tularensis A1a strain originally isolated in Ohio in 1941. It was determined that there were 25 nucleotide polymorphisms (22 SNPs and 3 indels) between Schu S4 and NE061598; two of these polymorphisms were in potential virulence loci. Pulsed-field gel electrophoresis analysis demonstrated that NE061598 was an A1a genotype. Other differences included repeat sequences (n = 11 separate loci), four of which were contained in coding sequences, and an inversion and rearrangement probably mediated by insertion sequences and the previously identified direct repeats I, II, and III. Five new variable-number tandem repeats were identified; three of these five were unique in NE061598 compared to Schu S4. Importantly, there was no gene loss or gain identified between NE061598 and Schu S4. Interpretation of these data suggests there is significant sequence conservation and chromosomal synteny within the A1 population. Further studies are needed to determine the biological properties driving the selective pressure that maintains the chromosomal structure of this monomorphic pathogen. Title: Complete genome sequence of Francisella tularensis subspecies holarctica FTNF002-00 Barabote RD, Xie G, Brettin TS, Hinrichs SH, Fey PD, Jay JJ, Engle JL, Godbole SD, Noronha JM and Dempsey MP <3 more author(s)> Barabote RD, Xie G, Brettin TS, Hinrichs SH, Fey PD, Jay JJ, Engle JL, Godbole SD, Noronha JM, Scheuermann RH, Zhou LW, Lion C, Dempsey MP (- 3) Ref: PLoS ONE, 4:e7041, 2009 : PubMed ESTHER: Barabote_2009_PLoS.ONE_4_E7041 PubMedSearch: Barabote 2009 PLoS.ONE 4 E7041 PubMedID: 19756146 Gene_locus related to this paper: fratt-q5ngu5 Abstract Francisella tularensis subspecies holarctica FTNF002-00 strain was originally obtained from the first known clinical case of bacteremic F. tularensis pneumonia in Southern Europe isolated from an immunocompetent individual. The FTNF002-00 complete genome contains the RD(23) deletion and represents a type strain for a clonal population from the first epidemic tularemia outbreak in Spain between 1997-1998. Here, we present the complete sequence analysis of the FTNF002-00 genome. The complete genome sequence of FTNF002-00 revealed several large as well as small genomic differences with respect to two other published complete genome sequences of F. tularensis subsp. holarctica strains, LVS and OSU18. The FTNF002-00 genome shares >99.9% sequence similarity with LVS and OSU18, and is also approximately 5 MB smaller by comparison. The overall organization of the FTNF002-00 genome is remarkably identical to those of LVS and OSU18, except for a single 3.9 kb inversion in FTNF002-00. Twelve regions of difference ranging from 0.1-1.5 kb and forty-two small insertions and deletions were identified in a comparative analysis of FTNF002-00, LVS, and OSU18 genomes. Two small deletions appear to inactivate two genes in FTNF002-00 causing them to become pseudogenes; the intact genes encode a protein of unknown function and a drug:H(+) antiporter. In addition, we identified ninety-nine proteins in FTNF002-00 containing amino acid mutations compared to LVS and OSU18. Several non-conserved amino acid replacements were identified, one of which occurs in the virulence-associated intracellular growth locus subunit D protein. Many of these changes in FTNF002-00 are likely the consequence of direct selection that increases the fitness of this subsp. holarctica clone within its endemic population. Our complete genome sequence analyses lay the foundation for experimental testing of these possibilities. Title: Genome, transcriptome, and secretome analysis of wood decay fungus Postia placenta supports unique mechanisms of lignocellulose conversion Martinez D, Challacombe J, Morgenstern I, Hibbett D, Schmoll M, Kubicek CP, Ferreira P, Ruiz-Duenas FJ, Martinez AT and Cullen D <43 more author(s)> Martinez D, Challacombe J, Morgenstern I, Hibbett D, Schmoll M, Kubicek CP, Ferreira P, Ruiz-Duenas FJ, Martinez AT, Kersten P, Hammel KE, Vanden Wymelenberg A, Gaskell J, Lindquist E, Sabat G, Bondurant SS, Larrondo LF, Canessa P, Vicuna R, Yadav J, Doddapaneni H, Subramanian V, Pisabarro AG, Lavin JL, Oguiza JA, Master E, Henrissat B, Coutinho PM, Harris P, Magnuson JK, Baker SE, Bruno K, Kenealy W, Hoegger PJ, Kues U, Ramaiya P, Lucas S, Salamov A, Shapiro H, Tu H, Chee CL, Misra M, Xie G, Teter S, Yaver D, James T, Mokrejs M, Pospisek M, Grigoriev IV, Brettin T, Rokhsar D, Berka R, Cullen D (- 43) Ref: Proc Natl Acad Sci U S A, 106:1954, 2009 : PubMed ESTHER: Martinez_2009_Proc.Natl.Acad.Sci.U.S.A_106_1954 PubMedSearch: Martinez 2009 Proc.Natl.Acad.Sci.U.S.A 106 1954 PubMedID: 19193860 Gene_locus related to this paper: pospm-b8p1f3, pospm-b8p2q7, pospm-b8p4n0, pospm-b8p4n9, pospm-b8p5g9, pospm-b8p5r9, pospm-b8p6h2, pospm-b8p7b1, pospm-b8p7c4, pospm-b8p8w7, pospm-b8p9j1, pospm-b8p164, pospm-b8p280, pospm-b8p423.1, pospm-b8p423.2, pospm-b8p858, pospm-b8pam2, pospm-b8pam5, pospm-b8pb68, pospm-b8pbm3, pospm-b8pc54, pospm-b8pc56, pospm-b8pce4, pospm-b8pd91, pospm-b8pdk6, pospm-b8ph32, pospm-b8ph43, pospm-b8phc9, pospm-b8php7, pospm-b8phy5, pospm-b8pjg8, pospm-b8pji9, pospm-b8plr5, pospm-b8pmk3, pospm-b8pfg0, pospm-b8pg35, pospm-b8pa20.1, pospm-b8pa20.2, pospm-b8p4g8, pospm-b8phn6 Abstract Brown-rot fungi such as Postia placenta are common inhabitants of forest ecosystems and are also largely responsible for the destructive decay of wooden structures. Rapid depolymerization of cellulose is a distinguishing feature of brown-rot, but the biochemical mechanisms and underlying genetics are poorly understood. Systematic examination of the P. placenta genome, transcriptome, and secretome revealed unique extracellular enzyme systems, including an unusual repertoire of extracellular glycoside hydrolases. Genes encoding exocellobiohydrolases and cellulose-binding domains, typical of cellulolytic microbes, are absent in this efficient cellulose-degrading fungus. When P. placenta was grown in medium containing cellulose as sole carbon source, transcripts corresponding to many hemicellulases and to a single putative beta-1-4 endoglucanase were expressed at high levels relative to glucose-grown cultures. These transcript profiles were confirmed by direct identification of peptides by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Also up-regulated during growth on cellulose medium were putative iron reductases, quinone reductase, and structurally divergent oxidases potentially involved in extracellular generation of Fe(II) and H(2)O(2). These observations are consistent with a biodegradative role for Fenton chemistry in which Fe(II) and H(2)O(2) react to form hydroxyl radicals, highly reactive oxidants capable of depolymerizing cellulose. The P. placenta genome resources provide unparalleled opportunities for investigating such unusual mechanisms of cellulose conversion. More broadly, the genome offers insight into the diversification of lignocellulose degrading mechanisms in fungi. Comparisons with the closely related white-rot fungus Phanerochaete chrysosporium support an evolutionary shift from white-rot to brown-rot during which the capacity for efficient depolymerization of lignin was lost. Title: Novel features of the polysaccharide-digesting gliding bacterium Flavobacterium johnsoniae as revealed by genome sequence analysis McBride MJ, Xie G, Martens EC, Lapidus A, Henrissat B, Rhodes RG, Goltsman E, Wang W, Xu J and Stein JL <4 more author(s)> McBride MJ, Xie G, Martens EC, Lapidus A, Henrissat B, Rhodes RG, Goltsman E, Wang W, Xu J, Hunnicutt DW, Staroscik AM, Hoover TR, Cheng YQ, Stein JL (- 4) Ref: Applied Environmental Microbiology, 75:6864, 2009 : PubMed ESTHER: McBride_2009_Appl.Environ.Microbiol_75_6864 PubMedSearch: McBride 2009 Appl.Environ.Microbiol 75 6864 PubMedID: 19717629 Gene_locus related to this paper: flaj1-a5fb12, flaj1-a5fmd7, flaj1-a5fns3 Abstract The 6.10-Mb genome sequence of the aerobic chitin-digesting gliding bacterium Flavobacterium johnsoniae (phylum Bacteroidetes) is presented. F. johnsoniae is a model organism for studies of bacteroidete gliding motility, gene regulation, and biochemistry. The mechanism of F. johnsoniae gliding is novel, and genome analysis confirms that it does not involve well-studied motility organelles, such as flagella or type IV pili. The motility machinery is composed of Gld proteins in the cell envelope that are thought to comprise the "motor" and SprB, which is thought to function as a cell surface adhesin that is propelled by the motor. Analysis of the genome identified genes related to sprB that may encode alternative adhesins used for movement over different surfaces. Comparative genome analysis revealed that some of the gld and spr genes are found in nongliding bacteroidetes and may encode components of a novel protein secretion system. F. johnsoniae digests proteins, and 125 predicted peptidases were identified. F. johnsoniae also digests numerous polysaccharides, and 138 glycoside hydrolases, 9 polysaccharide lyases, and 17 carbohydrate esterases were predicted. The unexpected ability of F. johnsoniae to digest hemicelluloses, such as xylans, mannans, and xyloglucans, was predicted based on the genome analysis and confirmed experimentally. Numerous predicted cell surface proteins related to Bacteroides thetaiotaomicron SusC and SusD, which are likely involved in binding of oligosaccharides and transport across the outer membrane, were also identified. Genes required for synthesis of the novel outer membrane flexirubin pigments were identified by a combination of genome analysis and genetic experiments. Genes predicted to encode components of a multienzyme nonribosomal peptide synthetase were identified, as were novel aspects of gene regulation. The availability of techniques for genetic manipulation allows rapid exploration of the features identified for the polysaccharide-digesting gliding bacteroidete F. johnsoniae. Title: Three genomes from the phylum Acidobacteria provide insight into the lifestyles of these microorganisms in soils Ward NL, Challacombe JF, Janssen PH, Henrissat B, Coutinho PM, Wu M, Xie G, Haft DH, Sait M and Kuske CR <36 more author(s)> Ward NL, Challacombe JF, Janssen PH, Henrissat B, Coutinho PM, Wu M, Xie G, Haft DH, Sait M, Badger J, Barabote RD, Bradley B, Brettin TS, Brinkac LM, Bruce D, Creasy T, Daugherty SC, Davidsen TM, DeBoy RT, Detter JC, Dodson RJ, Durkin AS, Ganapathy A, Gwinn-Giglio M, Han CS, Khouri H, Kiss H, Kothari SP, Madupu R, Nelson KE, Nelson WC, Paulsen I, Penn K, Ren Q, Rosovitz MJ, Selengut JD, Shrivastava S, Sullivan SA, Tapia R, Thompson LS, Watkins KL, Yang Q, Yu C, Zafar N, Zhou L, Kuske CR (- 36) Ref: Applied Environmental Microbiology, 75:2046, 2009 : PubMed ESTHER: Ward_2009_Appl.Environ.Microbiol_75_2046 PubMedSearch: Ward 2009 Appl.Environ.Microbiol 75 2046 PubMedID: 19201974 Gene_locus related to this paper: korve-q1ihr9, korve-q1ii02, korve-q1iit0, korve-q1ilk4, korve-q1imj9, korve-q1ims4, korve-q1iqj0, korve-q1isy7, korve-q1itj5, korve-q1itz6, korve-q1ivc8, acic5-c1f1u6, acic5-c1f2i7, acic5-c1f4m6, acic5-c1f4y4, acic5-c1f5a7, acic5-c1f5u2, acic5-c1f7a9, acic5-c1f7x6, acic5-c1f8y9, acic5-c1f9m2, acic5-c1f594, acic5-c1f609, acic5-c1f692, acic5-c1f970, acic5-c1fa52, korve-q1iiw2, korve-q1ivn9, solue-q01nb0, solue-q01qj6, solue-q01r37, solue-q01rq8, solue-q01rz0, solue-q01t44, solue-q01t57, solue-q01ts5, solue-q01tv4, solue-q01vd8, solue-q01vr3, solue-q01vw5, solue-q01w12, solue-q01wt9, solue-q01y40, solue-q01ym8, solue-q01z24, solue-q01z97, solue-q01zl4, solue-q01zm0, solue-q01zm5, solue-q01zm7, solue-q02aa4, solue-q02ab9, solue-q02b72, solue-q02bs8, solue-q02bt7, solue-q02cp0, solue-q02d61, solue-q020h3, solue-q020i8, solue-q021i6, solue-q022b1, solue-q022p8, solue-q022q2, solue-q022q3, solue-q022x2, solue-q022x5, solue-q022x6, solue-q022x8, solue-q023e7, solue-q024d9, solue-q025c1, solue-q026j1, solue-q026k6, solue-q026r6, solue-q027p2, solue-q027r8, solue-q01zt5, korve-q1itw6, solue-q01yh7, solue-q02ad6, korve-q1imj6, korve-q1iuf6, acic5-c1f891, solue-q026h7 Abstract The complete genomes of three strains from the phylum Acidobacteria were compared. Phylogenetic analysis placed them as a unique phylum. They share genomic traits with members of the Proteobacteria, the Cyanobacteria, and the Fungi. The three strains appear to be versatile heterotrophs. Genomic and culture traits indicate the use of carbon sources that span simple sugars to more complex substrates such as hemicellulose, cellulose, and chitin. The genomes encode low-specificity major facilitator superfamily transporters and high-affinity ABC transporters for sugars, suggesting that they are best suited to low-nutrient conditions. They appear capable of nitrate and nitrite reduction but not N(2) fixation or denitrification. The genomes contained numerous genes that encode siderophore receptors, but no evidence of siderophore production was found, suggesting that they may obtain iron via interaction with other microorganisms. The presence of cellulose synthesis genes and a large class of novel high-molecular-weight excreted proteins suggests potential traits for desiccation resistance, biofilm formation, and/or contribution to soil structure. Polyketide synthase and macrolide glycosylation genes suggest the production of novel antimicrobial compounds. Genes that encode a variety of novel proteins were also identified. The abundance of acidobacteria in soils worldwide and the breadth of potential carbon use by the sequenced strains suggest significant and previously unrecognized contributions to the terrestrial carbon cycle. Combining our genomic evidence with available culture traits, we postulate that cells of these isolates are long-lived, divide slowly, exhibit slow metabolic rates under low-nutrient conditions, and are well equipped to tolerate fluctuations in soil hydration. Title: Cloning, expression and characterization of an organic solvent tolerant lipase from Pseudomonas fluorescens JCM5963 Zhang A, Cao R, Diao N, Xie G, Gao G, Gao S Ref: J Mol Catal B Enzym, 56:78, 2009 : PubMed ESTHER: Zhang_2009_J.Mol.Catal.B.Enzym_56_78 PubMedSearch: Zhang 2009 J.Mol.Catal.B.Enzym 56 78 Gene_locus related to this paper: psef5-q4kj24 Abstract A novel lipase gene from an organic solvent degradable strain Pseudomonas fluorescens JCM5963 was cloned, sequenced, and overexpressed as an N-terminus His-tag fusion protein in E. coli. The alignment of amino acid sequences revealed that the protein contained a lipase motif and shared a medium or high similarity with lipases from other Pseudomonas strains. It could be defined as a member of subfamily I.1 lipase. Most of the recombinant proteins expressed as enzymatically active aggregates soluble in 20 mM Tris-HCl buffer (pH 8.0) containing sodium deoxycholate are remarkably different from most subfamily I.1 and I.2 members of Pseudomonas lipases expressed as inactive inclusion body formerly described in E. coli. The recombinant lipase (rPFL) was purified to homogeneity by Ni-NTA affinity chromatography and Sephacryl S-200 gel filtration chromatography. The purified lipase was stable in broad ranges of temperatures and pH values, with the optimal temperature and pH value being 55 C and 9.0, respectively. Its activity was found to increase in the presence of metal ions such as Ca2+, Sn2+ and some non-ionic surfactants. In addition, rPFL was activated by and remained stable in a series of water-miscible organic solvents solutions and highly tolerant to some water-immiscible organic solvents. These features render this novel lipase attraction for biotechnological applications in the field of organic synthesis and detergent additives. Title: Acetylcholine release by human colon cancer cells mediates autocrine stimulation of cell proliferation Cheng K, Samimi R, Xie G, Shant J, Drachenberg C, Wade M, Davis RJ, Nomikos G, Raufman JP Ref: American Journal of Physiology Gastrointest Liver Physiol, 295:G591, 2008 : PubMed ESTHER: Cheng_2008_Am.J.Physiol.Gastrointest.Liver.Physiol_295_G591 PubMedSearch: Cheng 2008 Am.J.Physiol.Gastrointest.Liver.Physiol 295 G591 PubMedID: 18653726 Abstract Most colon cancers overexpress M3 muscarinic receptors (M3R), and post-M3R signaling stimulates human colon cancer cell proliferation. Acetylcholine (ACh), a muscarinic receptor ligand traditionally regarded as a neurotransmitter, may be produced by nonneuronal cells. We hypothesized that ACh release by human colon cancer cells results in autocrine stimulation of proliferation. H508 human colon cancer cells, which have robust M3R expression, were used to examine effects of muscarinic receptor antagonists, acetylcholinesterase inhibitors, and choline transport inhibitors on cell proliferation. A nonselective muscarinic receptor antagonist (atropine), a selective M3R antagonist (p-fluorohexahydro-sila-difenidol hydrochloride), and a choline transport inhibitor (hemicholinum-3) all inhibited unstimulated H508 colon cancer cell proliferation by approximately 40% (P<0.005). In contrast, two acetylcholinesterase inhibitors (eserine-hemisulfate and bis-9-amino-1,2,3,4-tetrahydroacridine) increased proliferation by 2.5- and 2-fold, respectively (P<0.005). By using quantitative real-time PCR, expression of choline acetyltransferase (ChAT), a critical enzyme for ACh synthesis, was identified in H508, WiDr, and Caco-2 colon cancer cells. By using high-performance liquid chromatography-electrochemical detection, released ACh was detected in H508 and Caco-2 cell culture media. Immunohistochemistry in surgical specimens revealed weak or no cytoplasmic staining for ChAT in normal colon enterocytes (n=25) whereas half of colon cancer specimens (n=24) exhibited moderate to strong staining (P<0.005). We conclude that ACh is an autocrine growth factor in colon cancer. Mechanisms that regulate colon epithelial cell production and release of ACh warrant further investigation. Title: Genome sequencing and analysis of the biomass-degrading fungus Trichoderma reesei (syn. Hypocrea jecorina) Martinez D, Berka RM, Henrissat B, Saloheimo M, Arvas M, Baker SE, Chapman J, Chertkov O, Coutinho PM and Brettin TS <35 more author(s)> Martinez D, Berka RM, Henrissat B, Saloheimo M, Arvas M, Baker SE, Chapman J, Chertkov O, Coutinho PM, Cullen D, Danchin EG, Grigoriev IV, Harris P, Jackson M, Kubicek CP, Han CS, Ho I, Larrondo LF, de Leon AL, Magnuson JK, Merino S, Misra M, Nelson B, Putnam N, Robbertse B, Salamov AA, Schmoll M, Terry A, Thayer N, Westerholm-Parvinen A, Schoch CL, Yao J, Barabote R, Nelson MA, Detter C, Bruce D, Kuske CR, Xie G, Richardson P, Rokhsar DS, Lucas SM, Rubin EM, Dunn-Coleman N, Ward M, Brettin TS (- 35) Ref: Nat Biotechnol, 26:553, 2008 : PubMed ESTHER: Martinez_2008_Nat.Biotechnol_26_553 PubMedSearch: Martinez 2008 Nat.Biotechnol 26 553 PubMedID: 18454138 Gene_locus related to this paper: hypjq-g0rh85, hypjq-cip2, hypjq-g0r9d1, hypjq-g0r810, hypjq-g0rbm4, hypjq-g0rez4, hypjq-g0rfr3, hypjq-g0rg60, hypjq-g0rij9, hypjq-g0riu1, hypjq-g0rl87, hypjq-g0rlh4, hypjq-g0rme5, hypjq-g0rwy5, hypje-axylest, hypje-q7z9m3, hypjq-g0r6x2, hypje-a0a024s1b8, hypjr-a0a024s1s9, hypjq-g0rxi5 Abstract Trichoderma reesei is the main industrial source of cellulases and hemicellulases used to depolymerize biomass to simple sugars that are converted to chemical intermediates and biofuels, such as ethanol. We assembled 89 scaffolds (sets of ordered and oriented contigs) to generate 34 Mbp of nearly contiguous T. reesei genome sequence comprising 9,129 predicted gene models. Unexpectedly, considering the industrial utility and effectiveness of the carbohydrate-active enzymes of T. reesei, its genome encodes fewer cellulases and hemicellulases than any other sequenced fungus able to hydrolyze plant cell wall polysaccharides. Many T. reesei genes encoding carbohydrate-active enzymes are distributed nonrandomly in clusters that lie between regions of synteny with other Sordariomycetes. Numerous genes encoding biosynthetic pathways for secondary metabolites may promote survival of T. reesei in its competitive soil habitat, but genome analysis provided little mechanistic insight into its extraordinary capacity for protein secretion. Our analysis, coupled with the genome sequence data, provides a roadmap for constructing enhanced T. reesei strains for industrial applications such as biofuel production. Title: Esterase SeE of Streptococcus equi ssp. equi is a novel nonspecific carboxylic ester hydrolase Xie G, Liu M, Zhu H, Lei B Ref: FEMS Microbiology Letters, 289:181, 2008 : PubMed ESTHER: Xie_2008_FEMS.Microbiol.Lett_289_181 PubMedSearch: Xie 2008 FEMS.Microbiol.Lett 289 181 PubMedID: 19054107 Abstract Extracellular carboxylic ester hydrolases are produced by many bacterial pathogens and have been shown recently to be important for virulence of some pathogens. However, these hydrolases are poorly characterized in enzymatic activity. This study prepared and characterized the secreted ester hydrolase of Streptococcus equi ssp. equi (designated SeE for S. equi esterase). SeE hydrolyzes ethyl acetate, acetylsalicylic acid, and tributyrin but not ethyl butyrate. This substrate specificity pattern does not match those of the three conventional types of nonspecific carboxylic ester hydrolases (carboxylesterases, arylesterases, and acetylesterases). To determine whether SeE has lipase activity, a number of triglycerides and vinyl esters were tested in SeE-catalyzed hydrolysis. SeE does not hydrolyze triglycerides and vinyl esters of long-chain carboxylic acids nor display interfacial activation, indicating that SeE is not a lipase. Like the conventional carboxylesterases, SeE is inhibited by di-isopropylfluorophosphate. These findings indicate that SeE is a novel carboxylesterase with optimal activity for acetyl esters. Title: The complete genome sequence of Bacillus thuringiensis Al Hakam Challacombe JF, Altherr MR, Xie G, Bhotika SS, Brown N, Bruce D, Campbell CS, Campbell ML, Chen J and Brettin TS <38 more author(s)> Challacombe JF, Altherr MR, Xie G, Bhotika SS, Brown N, Bruce D, Campbell CS, Campbell ML, Chen J, Chertkov O, Cleland C, Dimitrijevic M, Doggett NA, Fawcett JJ, Glavina T, Goodwin LA, Green LD, Han CS, Hill KK, Hitchcock P, Jackson PJ, Keim P, Kewalramani AR, Longmire J, Lucas S, Malfatti S, Martinez D, McMurry K, Meincke LJ, Misra M, Moseman BL, Mundt M, Munk AC, Okinaka RT, Parson-Quintana B, Reilly LP, Richardson P, Robinson DL, Saunders E, Tapia R, Tesmer JG, Thayer N, Thompson LS, Tice H, Ticknor LO, Wills PL, Gilna P, Brettin TS (- 38) Ref: Journal of Bacteriology, 189:3680, 2007 : PubMed ESTHER: Challacombe_2007_J.Bacteriol_189_3680 PubMedSearch: Challacombe 2007 J.Bacteriol 189 3680 PubMedID: 17337577 Gene_locus related to this paper: bacah-a0rcd1, bacah-a0rer5, bacah-a0rev7, bacan-BA1019, bacan-BA1242, bacan-BA2392, bacan-BA2607, bacan-BA3343, bacan-BA3863, bacan-BA3877, bacan-BA4324, bacan-BA4338, bacan-BA4577, bacan-BA5009, bacan-BA5110, bacan-BA5136, bacan-DHBF, bacc1-q73a27, bacc1-q73c93, bacce-BC0192, bacce-BC1788, bacce-BC1954, bacce-BC2141, bacce-BC2171, bacce-BC4730, bacce-BC4862, bacce-BC5130, bacce-PHAC, bacce-q72yu1, baccr-pepx, bachk-q6hcl3, bachk-q6hgn4, bachk-q6hgp9, bachk-q6hig3, bachk-q6hit8 Abstract Bacillus thuringiensis is an insect pathogen that is widely used as a biopesticide (E. Schnepf, N. Crickmore, J. Van Rie, D. Lereclus, J. Baum, J. Feitelson, D. R. Zeigler, and D. H. Dean, Microbiol. Mol. Biol. Rev. 62:775-806, 1998). Here we report the finished, annotated genome sequence of B. thuringiensis Al Hakam, which was collected in Iraq by the United Nations Special Commission (L. Radnedge, P. Agron, K. Hill, P. Jackson, L. Ticknor, P. Keim, and G. Andersen, Appl. Environ. Microbiol. 69:2755-2764, 2003). Title: Complete genome sequence of Haemophilus somnus (Histophilus somni) strain 129Pt and comparison to Haemophilus ducreyi 35000HP and Haemophilus influenzae Rd Challacombe JF, Duncan AJ, Brettin TS, Bruce D, Chertkov O, Detter JC, Han CS, Misra M, Richardson P and Inzana TJ <3 more author(s)> Challacombe JF, Duncan AJ, Brettin TS, Bruce D, Chertkov O, Detter JC, Han CS, Misra M, Richardson P, Tapia R, Thayer N, Xie G, Inzana TJ (- 3) Ref: Journal of Bacteriology, 189:1890, 2007 : PubMed ESTHER: Challacombe_2007_J.Bacteriol_189_1890 PubMedSearch: Challacombe 2007 J.Bacteriol 189 1890 PubMedID: 17172329 Gene_locus related to this paper: haes1-q0i317, haes1-q0i470, haes2-b0utw7, haes2-b0uvn0, haes2-b0uwc2 Abstract Haemophilus somnus can be either a commensal of bovine mucosal surfaces or an opportunistic pathogen. Pathogenic strains of H. somnus are a significant cause of systemic disease in cattle. We report the genome sequence of H. somnus 129Pt, a nonpathogenic commensal preputial isolate, and the results of a genome-wide comparative analysis of H. somnus 129Pt, Haemophilus influenzae Rd, and Haemophilus ducreyi 35000HP. We found unique genes in H. somnus 129Pt involved in lipooligosaccharide biosynthesis, carbohydrate uptake and metabolism, cation transport, amino acid metabolism, ubiquinone and menaquinone biosynthesis, cell surface adhesion, biosynthesis of cofactors, energy metabolism, and electron transport. There were also many genes in common among the three organisms. Our comparative analyses of H. somnus 129Pt, H. influenzae Rd, and H. ducreyi 35000HP revealed similarities and differences in the numbers and compositions of genes involved in metabolism, host colonization, and persistence. These results lay a foundation for research on the host specificities and niche preferences of these organisms. Future comparisons between H. somnus 129Pt and virulent strains will aid in the development of protective strategies and vaccines to protect cattle against H. somnus disease. Title: Analysis of the neurotoxin complex genes in Clostridium botulinum A1-A4 and B1 strains: BoNT/A3, /Ba4 and /B1 clusters are located within plasmids Smith TJ, Hill KK, Foley BT, Detter JC, Munk AC, Bruce DC, Doggett NA, Smith LA, Marks JD and Brettin TS <1 more author(s)> Smith TJ, Hill KK, Foley BT, Detter JC, Munk AC, Bruce DC, Doggett NA, Smith LA, Marks JD, Xie G, Brettin TS (- 1) Ref: PLoS ONE, 2:e1271, 2007 : PubMed ESTHER: Smith_2007_PLoS.ONE_2_E1271 PubMedSearch: Smith 2007 PLoS.ONE 2 E1271 PubMedID: 18060065 Gene_locus related to this paper: clob1-a7fqm2, clob1-a7fv94, clobl-a7gbn0, clobh-pip, clobh-a5i3m0, clob1-a7fvd9, clobl-a7gbt4 Abstract BACKGROUND: Clostridium botulinum and related clostridial species express extremely potent neurotoxins known as botulinum neurotoxins (BoNTs) that cause long-lasting, potentially fatal intoxications in humans and other mammals. The amino acid variation within the BoNT is used to categorize the species into seven immunologically distinct BoNT serotypes (A-G) which are further divided into subtypes. The BoNTs are located within two generally conserved gene arrangements known as botulinum progenitor complexes which encode toxin-associated proteins involved in toxin stability and expression. METHODOLOGY/PRINCIPAL FINDINGS: Because serotype A and B strains are responsible for the vast majority of human botulism cases worldwide, the location, arrangement and sequences of genes from eight different toxin complexes representing four different BoNT/A subtypes (BoNT/A1-Ba4) and one BoNT/B1 strain were examined. The bivalent Ba4 strain contained both the BoNT/A4 and BoNT/bvB toxin clusters. The arrangements of the BoNT/A3 and BoNT/A4 subtypes differed from the BoNT/A1 strains and were similar to those of BoNT/A2. However, unlike the BoNT/A2 subtype, the toxin complex genes of BoNT/A3 and BoNT/A4 were found within large plasmids and not within the chromosome. In the Ba4 strain, both BoNT toxin clusters (A4 and bivalent B) were located within the same 270 kb plasmid, separated by 97 kb. Complete genomic sequencing of the BoNT/B1 strain also revealed that its toxin complex genes were located within a 149 kb plasmid and the BoNT/A3 complex is within a 267 kb plasmid. CONCLUSIONS/SIGNIFICANCE: Despite their size differences and the BoNT genes they contain, the three plasmids containing these toxin cluster genes share significant sequence identity. The presence of partial insertion sequence (IS) elements, evidence of recombination/gene duplication events, and the discovery of the BoNT/A3, BoNT/Ba4 and BoNT/B1 toxin complex genes within plasmids illustrate the different mechanisms by which these genes move among diverse genetic backgrounds of C. botulinum. Title: Genome sequence of the cellulolytic gliding bacterium Cytophaga hutchinsonii Xie G, Bruce DC, Challacombe JF, Chertkov O, Detter JC, Gilna P, Han CS, Lucas S, Misra M and McBride MJ <8 more author(s)> Xie G, Bruce DC, Challacombe JF, Chertkov O, Detter JC, Gilna P, Han CS, Lucas S, Misra M, Myers GL, Richardson P, Tapia R, Thayer N, Thompson LS, Brettin TS, Henrissat B, Wilson DB, McBride MJ (- 8) Ref: Applied Environmental Microbiology, 73:3536, 2007 : PubMed ESTHER: Xie_2007_Appl.Environ.Microbiol_73_3536 PubMedSearch: Xie 2007 Appl.Environ.Microbiol 73 3536 PubMedID: 17400776 Gene_locus related to this paper: cyth3-q11pu3, cyth3-q11rb1, cyth3-q11sp5, cyth3-q11sp6, cyth3-q11ty5, cyth3-q11vh6, cyth3-q11vj5, cyth3-q11w17, cyth3-q11xy0 Abstract The complete DNA sequence of the aerobic cellulolytic soil bacterium Cytophaga hutchinsonii, which belongs to the phylum Bacteroidetes, is presented. The genome consists of a single, circular, 4.43-Mb chromosome containing 3,790 open reading frames, 1,986 of which have been assigned a tentative function. Two of the most striking characteristics of C. hutchinsonii are its rapid gliding motility over surfaces and its contact-dependent digestion of crystalline cellulose. The mechanism of C. hutchinsonii motility is not known, but its genome contains homologs for each of the gld genes that are required for gliding of the distantly related bacteroidete Flavobacterium johnsoniae. Cytophaga-Flavobacterium gliding appears to be novel and does not involve well-studied motility organelles such as flagella or type IV pili. Many genes thought to encode proteins involved in cellulose utilization were identified. These include candidate endo-beta-1,4-glucanases and beta-glucosidases. Surprisingly, obvious homologs of known cellobiohydrolases were not detected. Since such enzymes are needed for efficient cellulose digestion by well-studied cellulolytic bacteria, C. hutchinsonii either has novel cellobiohydrolases or has an unusual method of cellulose utilization. Genes encoding proteins with cohesin domains, which are characteristic of cellulosomes, were absent, but many proteins predicted to be involved in polysaccharide utilization had putative D5 domains, which are thought to be involved in anchoring proteins to the cell surface. Title: Pathogenomic sequence analysis of Bacillus cereus and Bacillus thuringiensis isolates closely related to Bacillus anthracis Han CS, Xie G, Challacombe JF, Altherr MR, Bhotika SS, Brown N, Bruce D, Campbell CS, Campbell ML and Gilna P <38 more author(s)> Han CS, Xie G, Challacombe JF, Altherr MR, Bhotika SS, Brown N, Bruce D, Campbell CS, Campbell ML, Chen J, Chertkov O, Cleland C, Dimitrijevic M, Doggett NA, Fawcett JJ, Glavina T, Goodwin LA, Green LD, Hill KK, Hitchcock P, Jackson PJ, Keim P, Kewalramani AR, Longmire J, Lucas S, Malfatti S, McMurry K, Meincke LJ, Misra M, Moseman BL, Mundt M, Munk AC, Okinaka RT, Parson-Quintana B, Reilly LP, Richardson P, Robinson DL, Rubin E, Saunders E, Tapia R, Tesmer JG, Thayer N, Thompson LS, Tice H, Ticknor LO, Wills PL, Brettin TS, Gilna P (- 38) Ref: Journal of Bacteriology, 188:3382, 2006 : PubMed ESTHER: Han_2006_J.Bacteriol_188_3382 PubMedSearch: Han 2006 J.Bacteriol 188 3382 PubMedID: 16621833 Gene_locus related to this paper: bacan-BA0954, bacan-BA2607, bacce-BC0968, bacce-BC3133, bacce-BC5130, bacce-c2mr40, baccz-q63gk2 Abstract Bacillus anthracis, Bacillus cereus, and Bacillus thuringiensis are closely related gram-positive, spore-forming bacteria of the B. cereus sensu lato group. While independently derived strains of B. anthracis reveal conspicuous sequence homogeneity, environmental isolates of B. cereus and B. thuringiensis exhibit extensive genetic diversity. Here we report the sequencing and comparative analysis of the genomes of two members of the B. cereus group, B. thuringiensis 97-27 subsp. konkukian serotype H34, isolated from a necrotic human wound, and B. cereus E33L, which was isolated from a swab of a zebra carcass in Namibia. These two strains, when analyzed by amplified fragment length polymorphism within a collection of over 300 of B. cereus, B. thuringiensis, and B. anthracis isolates, appear closely related to B. anthracis. The B. cereus E33L isolate appears to be the nearest relative to B. anthracis identified thus far. Whole-genome sequencing of B. thuringiensis 97-27and B. cereus E33L was undertaken to identify shared and unique genes among these isolates in comparison to the genomes of pathogenic strains B. anthracis Ames and B. cereus G9241 and nonpathogenic strains B. cereus ATCC 10987 and B. cereus ATCC 14579. Comparison of these genomes revealed differences in terms of virulence, metabolic competence, structural components, and regulatory mechanisms. Title: Crystal Structure of an Acylpeptide Hydrolase/Esterase from Aeropyrum pernix K1. Bartlam M, Wang G, Yang H, Gao R, Zhao X, Xie G, Cao S, Feng Y, Rao Z Ref: Structure(Camb), 12:1481, 2004 : PubMed ESTHER: Bartlam_2004_Structure.(Camb)_12_1481 PubMedSearch: Bartlam 2004 Structure.(Camb) 12 1481 PubMedID: 15296741 Gene_locus related to this paper: aerpe-APE1547 Abstract Acylpeptide hydrolases (APH; also known as acylamino acid releasing enzyme) catalyze the removal of an N-acylated amino acid from blocked peptides. The crystal structure of an APH from the thermophilic archaeon Aeropyrum pernix K1 to 2.1 A resolution confirms it to be a member of the prolyl oligopeptidase family of serine proteases. The structure of apAPH is a symmetric homodimer with each subunit comprised of two domains. The N-terminal domain is a regular seven-bladed beta-propeller, while the C-terminal domain has a canonical alpha/beta hydrolase fold and includes the active site and a conserved Ser445-Asp524-His556 catalytic triad. The complex structure of apAPH with an organophosphorus substrate, p-nitrophenyl phosphate, has also been determined. The complex structure unambiguously maps out the substrate binding pocket and provides a basis for substrate recognition by apAPH. A conserved mechanism for protein degradation from archaea to mammals is suggested by the structural features of apAPH. Title: The DNA sequence and biology of human chromosome 19 Grimwood J, Gordon LA, Olsen A, Terry A, Schmutz J, Lamerdin J, Hellsten U, Goodstein D, Couronne O and Lucas SM <88 more author(s)> Grimwood J, Gordon LA, Olsen A, Terry A, Schmutz J, Lamerdin J, Hellsten U, Goodstein D, Couronne O, Tran-Gyamfi M, Aerts A, Altherr M, Ashworth L, Bajorek E, Black S, Branscomb E, Caenepeel S, Carrano A, Caoile C, Chan YM, Christensen M, Cleland CA, Copeland A, Dalin E, Dehal P, Denys M, Detter JC, Escobar J, Flowers D, Fotopulos D, Garcia C, Georgescu AM, Glavina T, Gomez M, Gonzales E, Groza M, Hammon N, Hawkins T, Haydu L, Ho I, Huang W, Israni S, Jett J, Kadner K, Kimball H, Kobayashi A, Larionov V, Leem SH, Lopez F, Lou Y, Lowry S, Malfatti S, Martinez D, McCready P, Medina C, Morgan J, Nelson K, Nolan M, Ovcharenko I, Pitluck S, Pollard M, Popkie AP, Predki P, Quan G, Ramirez L, Rash S, Retterer J, Rodriguez A, Rogers S, Salamov A, Salazar A, She X, Smith D, Slezak T, Solovyev V, Thayer N, Tice H, Tsai M, Ustaszewska A, Vo N, Wagner M, Wheeler J, Wu K, Xie G, Yang J, Dubchak I, Furey TS, DeJong P, Dickson M, Gordon D, Eichler EE, Pennacchio LA, Richardson P, Stubbs L, Rokhsar DS, Myers RM, Rubin EM, Lucas SM (- 88) Ref: Nature, 428:529, 2004 : PubMed ESTHER: Grimwood_2004_Nature_428_529 PubMedSearch: Grimwood 2004 Nature 428 529 PubMedID: 15057824 Abstract Chromosome 19 has the highest gene density of all human chromosomes, more than double the genome-wide average. The large clustered gene families, corresponding high G + C content, CpG islands and density of repetitive DNA indicate a chromosome rich in biological and evolutionary significance. Here we describe 55.8 million base pairs of highly accurate finished sequence representing 99.9% of the euchromatin portion of the chromosome. Manual curation of gene loci reveals 1,461 protein-coding genes and 321 pseudogenes. Among these are genes directly implicated in mendelian disorders, including familial hypercholesterolaemia and insulin-resistant diabetes. Nearly one-quarter of these genes belong to tandemly arranged families, encompassing more than 25% of the chromosome. Comparative analyses show a fascinating picture of conservation and divergence, revealing large blocks of gene orthology with rodents, scattered regions with more recent gene family expansions and deletions, and segments of coding and non-coding conservation with the distant fish species Takifugu. Title: The sequence and analysis of duplication-rich human chromosome 16 Martin J, Han C, Gordon LA, Terry A, Prabhakar S, She X, Xie G, Hellsten U, Chan YM and Pennacchio LA <112 more author(s)> Martin J, Han C, Gordon LA, Terry A, Prabhakar S, She X, Xie G, Hellsten U, Chan YM, Altherr M, Couronne O, Aerts A, Bajorek E, Black S, Blumer H, Branscomb E, Brown NC, Bruno WJ, Buckingham JM, Callen DF, Campbell CS, Campbell ML, Campbell EW, Caoile C, Challacombe JF, Chasteen LA, Chertkov O, Chi HC, Christensen M, Clark LM, Cohn JD, Denys M, Detter JC, Dickson M, Dimitrijevic-Bussod M, Escobar J, Fawcett JJ, Flowers D, Fotopulos D, Glavina T, Gomez M, Gonzales E, Goodstein D, Goodwin LA, Grady DL, Grigoriev I, Groza M, Hammon N, Hawkins T, Haydu L, Hildebrand CE, Huang W, Israni S, Jett J, Jewett PB, Kadner K, Kimball H, Kobayashi A, Krawczyk MC, Leyba T, Longmire JL, Lopez F, Lou Y, Lowry S, Ludeman T, Manohar CF, Mark GA, McMurray KL, Meincke LJ, Morgan J, Moyzis RK, Mundt MO, Munk AC, Nandkeshwar RD, Pitluck S, Pollard M, Predki P, Parson-Quintana B, Ramirez L, Rash S, Retterer J, Ricke DO, Robinson DL, Rodriguez A, Salamov A, Saunders EH, Scott D, Shough T, Stallings RL, Stalvey M, Sutherland RD, Tapia R, Tesmer JG, Thayer N, Thompson LS, Tice H, Torney DC, Tran-Gyamfi M, Tsai M, Ulanovsky LE, Ustaszewska A, Vo N, White PS, Williams AL, Wills PL, Wu JR, Wu K, Yang J, DeJong P, Bruce D, Doggett NA, Deaven L, Schmutz J, Grimwood J, Richardson P, Rokhsar DS, Eichler EE, Gilna P, Lucas SM, Myers RM, Rubin EM, Pennacchio LA (- 112) Ref: Nature, 432:988, 2004 : PubMed ESTHER: Martin_2004_Nature_432_988 PubMedSearch: Martin 2004 Nature 432 988 PubMedID: 15616553 Gene_locus related to this paper: human-CES1, human-CES2, human-CES3, human-CES4A, human-CES5A Abstract Human chromosome 16 features one of the highest levels of segmentally duplicated sequence among the human autosomes. We report here the 78,884,754 base pairs of finished chromosome 16 sequence, representing over 99.9% of its euchromatin. Manual annotation revealed 880 protein-coding genes confirmed by 1,670 aligned transcripts, 19 transfer RNA genes, 341 pseudogenes and three RNA pseudogenes. These genes include metallothionein, cadherin and iroquois gene families, as well as the disease genes for polycystic kidney disease and acute myelomonocytic leukaemia. Several large-scale structural polymorphisms spanning hundreds of kilobase pairs were identified and result in gene content differences among humans. Whereas the segmental duplications of chromosome 16 are enriched in the relatively gene-poor pericentromere of the p arm, some are involved in recent gene duplication and conversion events that are likely to have had an impact on the evolution of primates and human disease susceptibility. | |||||||
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