Scott D

References (6)

Title : Domestic Pig Unlikely Reservoir for MERS-CoV - de Wit_2017_Emerg.Infect.Dis_23_985
Author(s) : de Wit E , Feldmann F , Horne E , Martellaro C , Haddock E , Bushmaker T , Rosenke K , Okumura A , Rosenke R , Saturday G , Scott D , Feldmann H
Ref : Emerg Infect Dis , 23 :985 , 2017
Abstract : We tested the suitability of the domestic pig as a model for Middle East respiratory syndrome coronavirus (MERS-CoV) infection. Inoculation did not cause disease, but a low level of virus replication, shedding, and seroconversion were observed. Pigs do not recapitulate human MERS-CoV and are unlikely to constitute a reservoir in nature.
ESTHER : de Wit_2017_Emerg.Infect.Dis_23_985
PubMedSearch : de Wit_2017_Emerg.Infect.Dis_23_985
PubMedID: 28318484

Title : Liver-Targeted Small-Molecule Inhibitors of Proprotein Convertase Subtilisin\/Kexin Type 9 Synthesis - McClure_2017_Angew.Chem.Int.Ed.Engl_56_16218
Author(s) : McClure KF , Piotrowski DW , Petersen D , Wei L , Xiao J , Londregan AT , Kamlet AS , Dechert-Schmitt AM , Raymer B , Ruggeri RB , Canterbury D , Limberakis C , Liras S , DaSilva-Jardine P , Dullea RG , Loria PM , Reidich B , Salatto CT , Eng H , Kimoto E , Atkinson K , King-Ahmad A , Scott D , Beaumont K , Chabot JR , Bolt MW , Maresca K , Dahl K , Arakawa R , Takano A , Halldin C
Ref : Angew Chem Int Ed Engl , 56 :16218 , 2017
Abstract : Targeting of the human ribosome is an unprecedented therapeutic modality with a genome-wide selectivity challenge. A liver-targeted drug candidate is described that inhibits ribosomal synthesis of PCSK9, a lipid regulator considered undruggable by small molecules. Key to the concept was the identification of pharmacologically active zwitterions designed to be retained in the liver. Oral delivery of the poorly permeable zwitterions was achieved by prodrugs susceptible to cleavage by carboxylesterase 1. The synthesis of select tetrazole prodrugs was crucial. A cell-free in vitro translation assay containing human cell lysate and purified target mRNA fused to a reporter was used to identify active zwitterions. In vivo PCSK9 lowering by oral dosing of the candidate prodrug and quantification of the drug fraction delivered to the liver utilizing an oral positron emission tomography (18) F-isotopologue validated our liver-targeting approach.
ESTHER : McClure_2017_Angew.Chem.Int.Ed.Engl_56_16218
PubMedSearch : McClure_2017_Angew.Chem.Int.Ed.Engl_56_16218
PubMedID: 29073340

Title : An endophenotype approach to the genetics of alcohol dependence: a genome wide association study of fast beta EEG in families of African ancestry - Meyers_2017_Mol.Psychiatry_22_1767
Author(s) : Meyers JL , Zhang J , Wang JC , Su J , Kuo SI , Kapoor M , Wetherill L , Bertelsen S , Lai D , Salvatore JE , Kamarajan C , Chorlian D , Agrawal A , Almasy L , Bauer L , Bucholz KK , Chan G , Hesselbrock V , Koganti L , Kramer J , Kuperman S , Manz N , Pandey A , Seay M , Scott D , Taylor RE , Dick DM , Edenberg HJ , Goate A , Foroud T , Porjesz B
Ref : Mol Psychiatry , 22 :1767 , 2017
Abstract : Fast beta (20-28 Hz) electroencephalogram (EEG) oscillatory activity may be a useful endophenotype for studying the genetics of disorders characterized by neural hyperexcitability, including substance use disorders (SUDs). However, the genetic underpinnings of fast beta EEG have not previously been studied in a population of African-American ancestry (AA). In a sample of 2382 AA individuals from 482 families drawn from the Collaborative Study on the Genetics of Alcoholism (COGA), we performed a genome-wide association study (GWAS) on resting-state fast beta EEG power. To further characterize our genetic findings, we examined the functional and clinical/behavioral significance of GWAS variants. Ten correlated single-nucleotide polymorphisms (SNPs) (r(2)>0.9) located in an intergenic region on chromosome 3q26 were associated with fast beta EEG power at P<5 x 10(-8). The most significantly associated SNP, rs11720469 (beta: -0.124; P<4.5 x 10(-9)), is also an expression quantitative trait locus for BCHE (butyrylcholinesterase), expressed in thalamus tissue. Four of the genome-wide SNPs were also associated with Diagnostic and Statistical Manual of Mental Disorders Alcohol Dependence in COGA AA families, and two (rs13093097, rs7428372) were replicated in an independent AA sample (Gelernter et al.). Analyses in the AA adolescent/young adult (offspring from COGA families) subsample indicated association of rs11720469 with heavy episodic drinking (frequency of consuming 5+ drinks within 24 h). Converging findings presented in this study provide support for the role of genetic variants within 3q26 in neural and behavioral disinhibition. These novel genetic findings highlight the importance of including AA populations in genetics research on SUDs and the utility of the endophenotype approach in enhancing our understanding of mechanisms underlying addiction susceptibility.
ESTHER : Meyers_2017_Mol.Psychiatry_22_1767
PubMedSearch : Meyers_2017_Mol.Psychiatry_22_1767
PubMedID: 28070124

Title : Host species restriction of Middle East respiratory syndrome coronavirus through its receptor, dipeptidyl peptidase 4 - van Doremalen_2014_J.Virol_88_9220
Author(s) : van Doremalen N , Miazgowicz KL , Milne-Price S , Bushmaker T , Robertson S , Scott D , Kinne J , McLellan JS , Zhu J , Munster VJ
Ref : J Virol , 88 :9220 , 2014
Abstract : UNLABELLED: Middle East respiratory syndrome coronavirus (MERS-CoV) emerged in 2012. Recently, the MERS-CoV receptor dipeptidyl peptidase 4 (DPP4) was identified and the specific interaction of the receptor-binding domain (RBD) of MERS-CoV spike protein and DPP4 was determined by crystallography. Animal studies identified rhesus macaques but not hamsters, ferrets, or mice to be susceptible for MERS-CoV. Here, we investigated the role of DPP4 in this observed species tropism. Cell lines of human and nonhuman primate origin were permissive of MERS-CoV, whereas hamster, ferret, or mouse cell lines were not, despite the presence of DPP4. Expression of human DPP4 in nonsusceptible BHK and ferret cells enabled MERS-CoV replication, whereas expression of hamster or ferret DPP4 did not. Modeling the binding energies of MERS-CoV spike protein RBD to DPP4 of human (susceptible) or hamster (nonsusceptible) identified five amino acid residues involved in the DPP4-RBD interaction. Expression of hamster DPP4 containing the five human DPP4 amino acids rendered BHK cells susceptible to MERS-CoV, whereas expression of human DPP4 containing the five hamster DPP4 amino acids did not. Using the same approach, the potential of MERS-CoV to utilize the DPP4s of common Middle Eastern livestock was investigated. Modeling of the DPP4 and MERS-CoV RBD interaction predicted the ability of MERS-CoV to bind the DPP4s of camel, goat, cow, and sheep. Expression of the DPP4s of these species on BHK cells supported MERS-CoV replication. This suggests, together with the abundant DPP4 presence in the respiratory tract, that these species might be able to function as a MERS-CoV intermediate reservoir. IMPORTANCE: The ongoing outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) has caused 701 laboratory-confirmed cases to date, with 249 fatalities. Although bats and dromedary camels have been identified as potential MERS-CoV hosts, the virus has so far not been isolated from any species other than humans. The inability of MERS-CoV to infect commonly used animal models, such as hamster, mice, and ferrets, indicates the presence of a species barrier. We show that the MERS-CoV receptor DPP4 plays a pivotal role in the observed species tropism of MERS-CoV and subsequently identified the amino acids in DPP4 responsible for this restriction. Using a combined modeling and experimental approach, we predict that, based on the ability of MERS-CoV to utilize the DPP4 of common Middle East livestock species, such as camels, goats, sheep, and cows, these form a potential MERS-CoV intermediate host reservoir species.
ESTHER : van Doremalen_2014_J.Virol_88_9220
PubMedSearch : van Doremalen_2014_J.Virol_88_9220
PubMedID: 24899185

Title : The sequence and analysis of duplication-rich human chromosome 16 - Martin_2004_Nature_432_988
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
Ref : Nature , 432 :988 , 2004
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.
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

Title : Molecular forms of acetylcholinesterase in Hirschsprung's disease - Bonham_1985_Clin.Chim.Acta_145_297
Author(s) : Bonham JR , Dale G , Scott D , Wagget J
Ref : Clinica Chimica Acta , 145 :297 , 1985
Abstract : We describe changes in the levels of different molecular forms of acetylcholinesterase in four cases of Hirschsprung's disease linked to the transition from aganglionic to normal bowel. In addition changes in a control case with histologically normal bowel is reported. In all patients with Hirschsprung's disease there is a marked increase in the level of the tetrameric form of the enzyme in the aganglionic region. The changing level of this form of the enzyme correlates well with the histochemical appearance suggesting that quantitative measurement of this molecular species might form the basis of an improved diagnostic test for the disease.
ESTHER : Bonham_1985_Clin.Chim.Acta_145_297
PubMedSearch : Bonham_1985_Clin.Chim.Acta_145_297
PubMedID: 3987032