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101.
Leah Wetherill Dongbing Lai Emma C. Johnson Andrey Anokhin Lance Bauer Kathleen K. Bucholz Danielle M. Dick Ahmad R. Hariri Victor Hesselbrock Chella Kamarajan John Kramer Samuel Kuperman Jacquelyn L. Meyers John I. Nurnberger Jr Marc Schuckit Denise M. Scott Robert E. Taylor Jay Tischfield Bernice Porjesz Alison M. Goate Howard J. Edenberg Tatiana Foroud Ryan Bogdan Arpana Agrawal 《Genes, Brain & Behavior》2019,18(6)
Genetic influences on alcohol and drug dependence partially overlap, however, specific loci underlying this overlap remain unclear. We conducted a genome‐wide association study (GWAS) of a phenotype representing alcohol or illicit drug dependence (ANYDEP) among 7291 European‐Americans (EA; 2927 cases) and 3132 African‐Americans (AA: 1315 cases) participating in the family‐based Collaborative Study on the Genetics of Alcoholism. ANYDEP was heritable (h 2 in EA = 0.60, AA = 0.37). The AA GWAS identified three regions with genome‐wide significant (GWS; P < 5E‐08) single nucleotide polymorphisms (SNPs) on chromosomes 3 (rs34066662, rs58801820) and 13 (rs75168521, rs78886294), and an insertion‐deletion on chromosome 5 (chr5:141988181). No polymorphisms reached GWS in the EA. One GWS region (chromosome 1: rs1890881) emerged from a trans‐ancestral meta‐analysis (EA + AA) of ANYDEP, and was attributable to alcohol dependence in both samples. Four genes (AA: CRKL, DZIP3, SBK3; EA: P2RX6) and four sets of genes were significantly enriched within biological pathways for hemostasis and signal transduction. GWS signals did not replicate in two independent samples but there was weak evidence for association between rs1890881 and alcohol intake in the UK Biobank. Among 118 AA and 481 EA individuals from the Duke Neurogenetics Study, rs75168521 and rs1890881 genotypes were associated with variability in reward‐related ventral striatum activation. This study identified novel loci for substance dependence and provides preliminary evidence that these variants are also associated with individual differences in neural reward reactivity. Gene discovery efforts in non‐European samples with distinct patterns of substance use may lead to the identification of novel ancestry‐specific genetic markers of risk. 相似文献
102.
Jonathan M. Large Kristian Birchall Nathalie S. Bouloc Andy T. Merritt Ela Smiljanic-Hurley Denise J. Tsagris Mary C. Wheldon Keith H. Ansell Peter J. Coombs Catherine A. Kettleborough David Whalley Lindsay B. Stewart Paul W. Bowyer David A. Baker Simon A. Osborne 《Bioorganic & medicinal chemistry letters》2019,29(3):509-514
Development of a class of bicyclic inhibitors of the Plasmodium falciparum cyclic GMP-dependent protein kinase (PfPKG), starting from known compounds with activity against a related parasite PKG orthologue, is reported. Examination of key sub-structural elements led to new compounds with good levels of inhibitory activity against the recombinant kinase and in vitro activity against the parasite. Key examples were shown to possess encouraging in vitro ADME properties, and computational analysis provided valuable insight into the origins of the observed activity profiles. 相似文献
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105.
Denise C.O.F. Valdetaro Thomas C. Harrington Leonardo S.S. Oliveira Lúcio M.S. Guimarães Douglas L. McNew Lucas V.A. Pimenta Rivadalve C. Gonçalves Daniel A. Schurt Acelino C. Alfenas 《Fungal biology》2019,123(2):170-182
Ceratocystis fimbriata Ellis & Halsted recently was recorded causing seed and seedling blight on Carapa guianensis Aubl. (andiroba), a tree species native to the Amazon Rainforest and prized for its valuable timber and medicinal seed oil. C. fimbriata more commonly causes wilt type diseases in woody hosts, especially on non-native host trees. However, on andiroba the disease occurs on seedlings and seeds, affecting the species regeneration. We studied 73 isolates of C. fimbriata on andiroba from three regions of the Amazon Basin to see if they represented natural or introduced populations. Analysis of ITS rDNA sequences and phylogenetic analysis of mating type genes revealed new haplotypes of C. fimbriata from the Latin American Clade that were closely related to other Brazilian populations of the fungus. In mating experiments, andiroba isolates were inter-fertile with tester strains of C. fimbriata from Brazil and elsewhere, confirming that they belong to a single biological species. Using microsatellite markers, 14 genotypes and populations with intermediate levels of genetic variability were found, suggesting that the fungus is indigenous to the Amazon Basin. Inoculation tests indicated that the andiroba isolates are host-specialized on andiroba, supporting the proposition of the special form C. fimbriata f. sp. carapa. 相似文献
106.
Denise P. Silva Gustavo Duarte Helena D.M. Villela Henrique F. Santos Phillipe M. Rosado Joo Gabriel Rosado Alexandre S. Rosado Edir M. Ferreira Adriana U. Soriano Raquel S. Peixoto 《Ecology and evolution》2019,9(9):5172-5185
Although numerous studies have been carried out on the impacts of oil spills on coral physiology, most have relied on laboratory assays. This scarcity is partly explained by the difficulty of reproducing realistic conditions in a laboratory setting or of performing experiments with toxic compounds in the field. Mesocosm systems provide the opportunity to carry out such studies with safe handling of contaminants while reproducing natural conditions required by living organisms. The mesocosm design is crucial and can lead to the development of innovative technologies to mitigate environmental impacts. Therefore, this study aimed to develop a mesocosm system for studies simulating oil spills with several key advantages, including true replication and the use of gravity to control flow‐through that reduces reliance on pumps that can clog thereby decreasing errors and costs. This adaptable system can be configured to (a) have continuous flow‐through; (b) operate as an open or closed system; (c) be fed by gravity; (d) have separate mesocosm sections that can be used for individual and simultaneous experiments; and (e) simulate the migration of oil from ocean oil spills to the nearby reefs. The mesocosm performance was assessed with two experiments using the hydrocoral Millepora alcicornis and different configurations to simulate two magnitudes of oil spills. With few exceptions, physical and chemical parameters remained stable within replicates and within treatments throughout the experiments. Physical and chemical parameters that expressed change during the experiment were still within the range of natural conditions observed in Brazilian marine environments. The photosynthetic potential (Fv/Fm) of the algae associated with M. alcicornis decreased in response to an 1% crude‐oil contamination, suggesting a successful delivery of the toxic contaminant to the targeted replicates. This mesocosm is customizable and adjustable for several types of experiments and proved to be effective for studies of oil spills. 相似文献
107.
Shanti Souriant Luciana Balboa Maeva Dupont Karine Pingris Denise Kviatcovsky Céline Cougoule Claire Lastrucci Aicha Bah Romain Gasser Renaud Poincloux Brigitte Raynaud-Messina Talal Al Saati Sandra Inwentarz Susana Poggi Eduardo Jose Moraña Pablo González-Montaner Marcelo Corti Bernard Lagane Christel Vérollet 《Cell reports》2019,26(13):3586-3599.e7
108.
Evidence for targeting common siRNA hotspots and GC preference by plant Dicer-like proteins 总被引:5,自引:0,他引:5
Small interfering (si)RNAs isolated from Brassica juncea leaves infected by Turnip mosaic virus (TuMV) were characterized by cloning and sequencing. The TuMV siRNA population was dominated by 21 and 22-nt long species originated mainly from the same siRNA hotspots, indicating operational similarity between the plant Dicer-like (DCL) enzymes. Robust GC bias was observed for TuMV siRNAs versus the virus genome, indicating that DCL was more likely to target GC-rich regions. Furthermore, dicot micro-(mi)RNAs displayed higher GC% than their DCL1 substrate RNAs, implicating that the GC bias may be ancient, therefore may be important for the RNAi technology. 相似文献
109.
This protocol describes a method for the dissection of egg chambers from intact Drosophila females and culture conditions that permit live imaging of them, with a particular emphasis on stage 9. This stage of development is characterized by oocyte growth and patterning, outer follicle cell rearrangement and migration of border cells. Although in vitro culture of egg chambers of later developmental stages has long been possible, until recently stage 9 egg chambers could only be kept alive for short periods, did not develop normally, and border cell migration failed entirely. We have established culture conditions that support overall egg chamber development including border cell migration in vitro. This protocol makes possible direct observation of molecular and cellular dynamics in both wild-type and mutant egg chambers, and opens the door to testing of pharmacological inhibitors and the use of biosensors. The entire protocol takes approximately 24 h while the preparation of egg chambers for live imaging requires only 15-20 min. 相似文献
110.
Kobayashi T Antar AA Boehme KW Danthi P Eby EA Guglielmi KM Holm GH Johnson EM Maginnis MS Naik S Skelton WB Wetzel JD Wilson GJ Chappell JD Dermody TS 《Cell host & microbe》2007,1(2):147-157
Mammalian orthoreoviruses (reoviruses) are highly tractable experimental models for studies of double-stranded (ds) RNA virus replication and pathogenesis. Reoviruses infect respiratory and intestinal epithelium and disseminate systemically in newborn animals. Until now, a strategy to rescue infectious virus from cloned cDNA has not been available for any member of the Reoviridae family of dsRNA viruses. We report the generation of viable reovirus following plasmid transfection of murine L929 (L) cells using a strategy free of helper virus and independent of selection. We used the reovirus reverse genetics system to introduce mutations into viral capsid proteins sigma1 and sigma3 and to rescue a virus that expresses a green fluorescent protein (GFP) transgene, thus demonstrating the tractability of this technology. The plasmid-based reverse genetics approach described here can be exploited for studies of reovirus replication and pathogenesis and used to develop reovirus as a vaccine vector. 相似文献