Smith K

References (8)

Title : Taenia larvae possess distinct acetylcholinesterase profiles with implications for host cholinergic signalling - de Lange_2020_PLoS.Negl.Trop.Dis_14_e0008966
Author(s) : de Lange A , Prodjinotho UF , Tomes H , Hagen J , Jacobs BA , Smith K , Horsnell W , Sikasunge C , Hockman D , Selkirk ME , Prazeres da Costa C , Raimondo JV
Ref : PLoS Negl Trop Dis , 14 :e0008966 , 2020
Abstract : Larvae of the cestodes Taenia solium and Taenia crassiceps infect the central nervous system of humans. Taenia solium larvae in the brain cause neurocysticercosis, the leading cause of adult-acquired epilepsy worldwide. Relatively little is understood about how cestode-derived products modulate host neural and immune signalling. Acetylcholinesterases, a class of enzyme that breaks down acetylcholine, are produced by a host of parasitic worms to aid their survival in the host. Acetylcholine is an important signalling molecule in both the human nervous and immune systems, with powerful modulatory effects on the excitability of cortical networks. Therefore, it is important to establish whether cestode derived acetylcholinesterases may alter host neuronal cholinergic signalling. Here we make use of multiple techniques to profile acetylcholinesterase activity in different extracts of both Taenia crassiceps and Taenia solium larvae. We find that the larvae of both species contain substantial acetylcholinesterase activity. However, acetylcholinesterase activity is lower in Taenia solium as compared to Taenia crassiceps larvae. Further, whilst we observed acetylcholinesterase activity in all fractions of Taenia crassiceps larvae, including on the membrane surface and in the excreted/secreted extracts, we could not identify acetylcholinesterases on the membrane surface or in the excreted/secreted extracts of Taenia solium larvae. Bioinformatic analysis revealed conservation of the functional protein domains in the Taenia solium acetylcholinesterases, when compared to the homologous human sequence. Finally, using whole-cell patch clamp recordings in rat hippocampal brain slice cultures, we demonstrate that Taenia larval derived acetylcholinesterases can break down acetylcholine at a concentration which induces changes in neuronal signalling. Together, these findings highlight the possibility that Taenia larval acetylcholinesterases can interfere with cholinergic signalling in the host, potentially contributing to pathogenesis in neurocysticercosis.
ESTHER : de Lange_2020_PLoS.Negl.Trop.Dis_14_e0008966
PubMedSearch : de Lange_2020_PLoS.Negl.Trop.Dis_14_e0008966
PubMedID: 33347447
Gene_locus related to this paper: taesa-ACHE , taesa-TsaChel , taeso-Tso3 , taeso-Tso2 , taeso-Tso1 , taeas-a0a0r3w4n6

Title : Exploitation of a Novel Binding Pocket in Human Lipoprotein-Associated Phospholipase A2 (Lp-PLA2) Discovered through X-ray Fragment Screening - Woolford_2016_J.Med.Chem_59_5356
Author(s) : Woolford AJ , Pero JE , Aravapalli S , Berdini V , Coyle JE , Day PJ , Dodson AM , Grondin P , Holding FP , Lee LY , Li P , Manas ES , Marino J, Jr. , Martin AC , McCleland BW , McMenamin RL , Murray CW , Neipp CE , Page LW , Patel VK , Potvain F , Rich S , Rivero RA , Smith K , Somers DO , Trottet L , Velagaleti R , Williams G , Xie R
Ref : Journal of Medicinal Chemistry , 59 :5356 , 2016
Abstract : Elevated levels of human lipoprotein-associated phospholipase A2 (Lp-PLA2) are associated with cardiovascular disease and dementia. A fragment screen was conducted against Lp-PLA2 in order to identify novel inhibitors. Multiple fragment hits were observed in different regions of the active site, including some hits that bound in a pocket created by movement of a protein side chain (approximately 13 A from the catalytic residue Ser273). Using structure guided design, we optimized a fragment that bound in this pocket to generate a novel low nanomolar chemotype, which did not interact with the catalytic residues.
ESTHER : Woolford_2016_J.Med.Chem_59_5356
PubMedSearch : Woolford_2016_J.Med.Chem_59_5356
PubMedID: 27167608
Gene_locus related to this paper: human-PLA2G7

Title : Genome-wide association study identifies multiple susceptibility loci for pulmonary fibrosis - Fingerlin_2013_Nat.Genet_45_613
Author(s) : Fingerlin TE , Murphy E , Zhang W , Peljto AL , Brown KK , Steele MP , Loyd JE , Cosgrove GP , Lynch D , Groshong S , Collard HR , Wolters PJ , Bradford WZ , Kossen K , Seiwert SD , du Bois RM , Garcia CK , Devine MS , Gudmundsson G , Isaksson HJ , Kaminski N , Zhang Y , Gibson KF , Lancaster LH , Cogan JD , Mason WR , Maher TM , Molyneaux PL , Wells AU , Moffatt MF , Selman M , Pardo A , Kim DS , Crapo JD , Make BJ , Regan EA , Walek DS , Daniel JJ , Kamatani Y , Zelenika D , Smith K , McKean D , Pedersen BS , Talbert J , Kidd RN , Markin CR , Beckman KB , Lathrop M , Schwarz MI , Schwartz DA
Ref : Nat Genet , 45 :613 , 2013
Abstract : We performed a genome-wide association study of non-Hispanic, white individuals with fibrotic idiopathic interstitial pneumonias (IIPs; n = 1,616) and controls (n = 4,683), with follow-up replication analyses in 876 cases and 1,890 controls. We confirmed association with TERT at 5p15, MUC5B at 11p15 and the 3q26 region near TERC, and we identified seven newly associated loci (Pmeta = 2.4 x 10(-8) to 1.1 x 10(-19)), including FAM13A (4q22), DSP (6p24), OBFC1 (10q24), ATP11A (13q34), DPP9 (19p13) and chromosomal regions 7q22 and 15q14-15. Our results suggest that genes involved in host defense, cell-cell adhesion and DNA repair contribute to risk of fibrotic IIPs.
ESTHER : Fingerlin_2013_Nat.Genet_45_613
PubMedSearch : Fingerlin_2013_Nat.Genet_45_613
PubMedID: 23583980

Title : Draft genome of the filarial nematode parasite Brugia malayi - Ghedin_2007_Science_317_1756
Author(s) : Ghedin E , Wang S , Spiro D , Caler E , Zhao Q , Crabtree J , Allen JE , Delcher AL , Guiliano DB , Miranda-Saavedra D , Angiuoli SV , Creasy T , Amedeo P , Haas B , El-Sayed NM , Wortman JR , Feldblyum T , Tallon L , Schatz M , Shumway M , Koo H , Salzberg SL , Schobel S , Pertea M , Pop M , White O , Barton GJ , Carlow CK , Crawford MJ , Daub J , Dimmic MW , Estes CF , Foster JM , Ganatra M , Gregory WF , Johnson NM , Jin J , Komuniecki R , Korf I , Kumar S , Laney S , Li BW , Li W , Lindblom TH , Lustigman S , Ma D , Maina CV , Martin DM , McCarter JP , McReynolds L , Mitreva M , Nutman TB , Parkinson J , Peregrin-Alvarez JM , Poole C , Ren Q , Saunders L , Sluder AE , Smith K , Stanke M , Unnasch TR , Ware J , Wei AD , Weil G , Williams DJ , Zhang Y , Williams SA , Fraser-Liggett C , Slatko B , Blaxter ML , Scott AL
Ref : Science , 317 :1756 , 2007
Abstract : Parasitic nematodes that cause elephantiasis and river blindness threaten hundreds of millions of people in the developing world. We have sequenced the approximately 90 megabase (Mb) genome of the human filarial parasite Brugia malayi and predict approximately 11,500 protein coding genes in 71 Mb of robustly assembled sequence. Comparative analysis with the free-living, model nematode Caenorhabditis elegans revealed that, despite these genes having maintained little conservation of local synteny during approximately 350 million years of evolution, they largely remain in linkage on chromosomal units. More than 100 conserved operons were identified. Analysis of the predicted proteome provides evidence for adaptations of B. malayi to niches in its human and vector hosts and insights into the molecular basis of a mutualistic relationship with its Wolbachia endosymbiont. These findings offer a foundation for rational drug design.
ESTHER : Ghedin_2007_Science_317_1756
PubMedSearch : Ghedin_2007_Science_317_1756
PubMedID: 17885136
Gene_locus related to this paper: bruma-a8ndk6 , bruma-a8njt8 , bruma-a8nl88 , bruma-a8npi4 , bruma-a8npi6 , bruma-a8p6g9 , bruma-a8pah3 , bruma-a8pc38 , bruma-a8pek5 , bruma-a8piq4 , bruma-a8pnw8 , bruma-a8psu4 , bruma-a8pte1 , bruma-a8q606 , bruma-a8q632 , bruma-a8q937 , bruma-a8qav5 , bruma-a8qbd9 , bruma-a8qgj6 , bruma-a8qh78 , bruma-a8q143 , bruma-a0a024mej5 , bruma-a0a0k0jju9 , bruma-a0a0i9n517

Title : The genome of M. acetivorans reveals extensive metabolic and physiological diversity - Galagan_2002_Genome.Res_12_532
Author(s) : Galagan JE , Nusbaum C , Roy A , Endrizzi MG , Macdonald P , FitzHugh W , Calvo S , Engels R , Smirnov S , Atnoor D , Brown A , Allen N , Naylor J , Stange-Thomann N , DeArellano K , Johnson R , Linton L , McEwan P , McKernan K , Talamas J , Tirrell A , Ye W , Zimmer A , Barber RD , Cann I , Graham DE , Grahame DA , Guss AM , Hedderich R , Ingram-Smith C , Kuettner HC , Krzycki JA , Leigh JA , Li W , Liu J , Mukhopadhyay B , Reeve JN , Smith K , Springer TA , Umayam LA , White O , White RH , Conway de Macario E , Ferry JG , Jarrell KF , Jing H , Macario AJ , Paulsen I , Pritchett M , Sowers KR , Swanson RV , Zinder SH , Lander E , Metcalf WW , Birren B
Ref : Genome Res , 12 :532 , 2002
Abstract : Methanogenesis, the biological production of methane, plays a pivotal role in the global carbon cycle and contributes significantly to global warming. The majority of methane in nature is derived from acetate. Here we report the complete genome sequence of an acetate-utilizing methanogen, Methanosarcina acetivorans C2A. Methanosarcineae are the most metabolically diverse methanogens, thrive in a broad range of environments, and are unique among the Archaea in forming complex multicellular structures. This diversity is reflected in the genome of M. acetivorans. At 5,751,492 base pairs it is by far the largest known archaeal genome. The 4524 open reading frames code for a strikingly wide and unanticipated variety of metabolic and cellular capabilities. The presence of novel methyltransferases indicates the likelihood of undiscovered natural energy sources for methanogenesis, whereas the presence of single-subunit carbon monoxide dehydrogenases raises the possibility of nonmethanogenic growth. Although motility has not been observed in any Methanosarcineae, a flagellin gene cluster and two complete chemotaxis gene clusters were identified. The availability of genetic methods, coupled with its physiological and metabolic diversity, makes M. acetivorans a powerful model organism for the study of archaeal biology. [Sequence, data, annotations and analyses are available at]
ESTHER : Galagan_2002_Genome.Res_12_532
PubMedSearch : Galagan_2002_Genome.Res_12_532
PubMedID: 11932238
Gene_locus related to this paper: metac-MA0077 , metac-MA0362 , metac-MA0419 , metac-MA0736 , metac-MA0993 , metac-MA1571 , metac-MA1856 , metac-MA1857 , metac-MA2002 , metac-MA2343 , metac-MA2629 , metac-MA2691 , metac-MA2743 , metac-MA2933 , metac-MA3611 , metac-MA3635 , metac-MA3920 , metac-META

Title : Complete genome sequence of Pseudomonas aeruginosa PAO1, an opportunistic pathogen - Stover_2000_Nature_406_959
Author(s) : Stover CK , Pham XQ , Erwin AL , Mizoguchi SD , Warrener P , Hickey MJ , Brinkman FS , Hufnagle WO , Kowalik DJ , Lagrou M , Garber RL , Goltry L , Tolentino E , Westbrock-Wadman S , Yuan Y , Brody LL , Coulter SN , Folger KR , Kas A , Larbig K , Lim R , Smith K , Spencer D , Wong GK , Wu Z , Paulsen IT , Reizer J , Saier MH , Hancock RE , Lory S , Olson MV
Ref : Nature , 406 :959 , 2000
Abstract : Pseudomonas aeruginosa is a ubiquitous environmental bacterium that is one of the top three causes of opportunistic human infections. A major factor in its prominence as a pathogen is its intrinsic resistance to antibiotics and disinfectants. Here we report the complete sequence of P. aeruginosa strain PAO1. At 6.3 million base pairs, this is the largest bacterial genome sequenced, and the sequence provides insights into the basis of the versatility and intrinsic drug resistance of P. aeruginosa. Consistent with its larger genome size and environmental adaptability, P. aeruginosa contains the highest proportion of regulatory genes observed for a bacterial genome and a large number of genes involved in the catabolism, transport and efflux of organic compounds as well as four potential chemotaxis systems. We propose that the size and complexity of the P. aeruginosa genome reflect an evolutionary adaptation permitting it to thrive in diverse environments and resist the effects of a variety of antimicrobial substances.
ESTHER : Stover_2000_Nature_406_959
PubMedSearch : Stover_2000_Nature_406_959
PubMedID: 10984043
Gene_locus related to this paper: pseae-clipa , pseae-CPO , pseae-metx , pseae-PA0201 , pseae-PA0231 , pseae-PA0308 , pseae-PA0368 , pseae-PA0480 , pseae-PA0502 , pseae-PA0543 , pseae-PA0599 , pseae-PA0829 , pseae-PA1166 , pseae-PA1211 , pseae-PA1239 , pseae-PA1291 , pseae-PA1304 , pseae-PA1510 , pseae-PA1558 , pseae-PA1597 , pseae-PA1621 , pseae-PA1622 , pseae-PA1680 , pseae-PA1771 , pseae-PA1888 , pseae-PA1907 , pseae-PA1990 , pseae-PA2086 , pseae-PA2098 , pseae-PA2168 , pseae-PA2302 , pseae-PA2411 , pseae-PA2425 , pseae-PA2451 , pseae-PA2540 , pseae-PA2682 , pseae-PA2689 , pseae-PA2745 , pseae-PA2764 , pseae-PA2927 , pseae-PA2934 , pseae-PA2949 , pseae-PA3053 , pseae-PA3132 , pseae-PA3226 , pseae-PA3301 , pseae-PA3324 , pseae-PA3327 , pseae-PA3429 , pseae-PA3509 , pseae-PA3586 , pseae-PA3628 , pseae-PA3695 , pseae-PA3734 , pseae-PA3829 , pseae-PA3859 , pseae-PA3994 , pseae-PA4008 , pseae-PA4152 , pseae-PA4440 , pseae-PA4968 , pseae-PA5080 , pseae-PA5384 , pseae-PA5513 , pseae-PCHC , pseae-PCHF , pseae-PHAC1 , pseae-PHAC2 , pseae-phaD , pseae-phag , pseae-PVDD , pseae-q9i4b9 , pseae-q9i538 , pseae-rhla , pseae-Y2218 , pseae-q9hyv3 , pseae-q9i252 , pseae-q9i6m9

Title : Histologic assessment of dose-related diffusion and muscle fiber response after therapeutic botulinum A toxin injections - Borodic_1994_Mov.Dis_9_31
Author(s) : Borodic GE , Ferrante R , Pearce LB , Smith K
Ref : Movement Disorders , 9 :31 , 1994
Abstract : Fiber diameter variability, acetylcholinesterase staining properties, and average fiber diameter were determined 5 weeks after varying doses of botulinum A toxin were administered into albino rabbit longissimus dorsi muscle. The average fiber diameter within the muscle appeared to be a function of the dose of botulinum toxin injected. Fiber diameter variability correlated with the dose of botulinum toxin administered. Both fiber diameter variability and acetylcholinesterase spread characteristics showed a distinct diffusion gradient over a defined field within a muscle. At lower doses (1 IU), collapse of the diffusion gradient occurred over a 15-30-mm segment of muscle. At higher doses (5-10 IU), diffusion of botulinum A toxin effect occurred throughout the entire muscle with no apparent end point. This study demonstrated that botulinum A toxin produces a gradient of denervation in a given muscle and that both the magnitude of denervation and the extent of the gradient are dose dependent. Furthermore, both muscle fiber diameter variability and acetylcholinesterase staining were useful as measures of chemodenervation.
ESTHER : Borodic_1994_Mov.Dis_9_31
PubMedSearch : Borodic_1994_Mov.Dis_9_31
PubMedID: 8139603

Title : HLA-DQ beta-chain polymorphism linked to myasthenia gravis - Bell_1986_Lancet_1_1058
Author(s) : Bell J , Rassenti L , Smoot S , Smith K , Newby C , Hohlfeld R , Toyka K , McDevitt H , Steinman L
Ref : Lancet , 1 :1058 , 1986
Abstract : The HLA-DR3 haplotype is associated with increased risk of myasthenia gravis (MG) and a number of other autoimmune diseases, including insulin-dependent diabetes mellitus (IDDM), coeliac disease, and premature ovarian failure (POF). With a cDNA probe for a DQ beta gene, a 15 kb Hinc II restriction fragment has been demonstrated in genomic DNA from 7 of 16 HLA-DR3 patients with MG, 1 of 19 healthy DR3 controls, and none of 24 DR3 patients with IDDM, coeliac disease, or POF. The HLA-DQ polymorphism may be closely linked to a genetic locus regulating immune responsiveness to acetylcholine receptor and susceptibility to MG.
ESTHER : Bell_1986_Lancet_1_1058
PubMedSearch : Bell_1986_Lancet_1_1058
PubMedID: 2871336