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31.
32.
Andreas Houben Carolyn R. Leach Dawn Verlin Ruth Rofe Jeremy N. Timmis 《Chromosoma》1997,106(8):513-519
Dot-like micro B chromosomes of Brachycome dichromosomatica were analysed for their sequence composition. Southern hybridization patterns of a total micro B probe to genomic DNA from
plants with and without micro Bs demonstrated that the micro Bs shared sequences with the A chromosomes. In addition to telomere,
rDNA and common A and B chromosome sequences, a new B-specific, highly methylated tandem repeat (Bdm29) was detected. After
in situ hybridization with Bdm29 the entire micro B chromosome was labelled and clustering of the condensed micro Bs could
be observed at interphase. A high number of Bdm29-like sequences were also found in the larger B chromosomes of B. dichromosomatica and in other Bs within the genus Brachycome.
Received: 30 May 1997; in revised form: 20 August 1997 / Accepted: 20 August 1997 相似文献
33.
RNA interference is a cellular mechanism regulating levels of mRNAs. It has been widely exploited to knock down specific protein targets. The selected interfering RNA sequence greatly influences its ability to knock down the target. Here we present a method for constructing multiple testing plasmids which express small hairpin RNAs (shRNA) targeting different regions of an mRNA. A simple fluorescence test in cultured cells allows convenient evaluation of mRNA knockdown by many different shRNAs on 96-well plates. We show that software predicted shRNAs have varying efficacies and only 2 of the 7 tested shRNAs significantly knocked down their targets. 相似文献
34.
It is useful to have robust gene-environment interaction tests that can utilize a variety of family structures in an efficient way. This article focuses on tests for gene-environment interaction in the presence of main genetic and environmental effects. The objective is to develop powerful tests that can combine trio data with parental genotypes and discordant sibships when parents' genotypes are missing. We first make a modest improvement on a method for discordant sibs (discordant on phenotype), but the approach does not allow one to use families when all offspring are affected, e.g., trios. We then make a modest improvement on a Mendelian transmission-based approach that is inefficient when discordant sibs are available, but can be applied to any nuclear family. Finally, we propose a hybrid approach that utilizes the most efficient method for a specific family type, then combines over families. We utilize this hybrid approach to analyze a chronic obstructive pulmonary disorder dataset to test for gene-environment interaction in the Serpine2 gene with smoking. The methods are freely available in the R package fbati. 相似文献
35.
Shawn J. Stachel Melissa S. Egbertson Jenny Wai Michelle Machacek Dawn M. Toolan John Swestock Donnie M. Eddins Vanita Puri Georgia McGaughey Hua-Poo Su Debbie Perlow Deping Wang Lei Ma Gopal Parthasarathy John C. Reid Pravien D. Abeywickrema Sean M. Smith Jason M. Uslaner 《Bioorganic & medicinal chemistry letters》2018,28(6):1122-1126
An internal HTS effort identified a novel PDE2 inhibitor series that was subsequently optimized for improved PDE2 activity and off-target selectivity. The optimized lead, compound 4, improved cognitive performance in a rodent novel object recognition task as well as a non-human primate object retrieval task. In addition, co-crystallization studies of close analog of 4 in the PDE2 active site revealed unique binding interactions influencing the high PDE isoform selectivity. 相似文献
36.
37.
Glenn Rhodes Hester Bosma David Studholme Dawn L. Arnold Robert W. Jackson Roger W. Pickup 《Environmental microbiology》2014,16(8):2374-2388
The rulAB operon of Pseudomonas spp. confers fitness traits on the host and has been suggested to be a hotspot for insertion of mobile elements that carry avirulence genes. Here, for the first time, we show that rulB on plasmid pWW0 is a hotspot for the active site‐specific integration of related integron‐like elements (ILEs) found in six environmental pseudomonads (strains FH1–FH6). Integration into rulB on pWW0 occurred at position 6488 generating a 3 bp direct repeat. ILEs from FH1 and FH5 were 9403 bp in length and contained eight open reading frames (ORFs), while the ILE from FH4 was 16 233 bp in length and contained 16 ORFs. In all three ILEs, the first 5.1 kb (containing ORFs 1–4) were structurally conserved and contained three predicted site‐specific recombinases/integrases and a tetR homologue. Downstream of these resided ORFs of the ‘variable side’ with structural and sequence similarity to those encoding survival traits on the fitness enhancing plasmid pGRT1 (ILEFH1 and ILEFH5) and the NR‐II virulence region of genomic island PAGI‐5 (ILEFH4). Collectively, these ILEs share features with the previously described type III protein secretion system effector ILEs and are considered important to host survival and transfer of fitness enhancing and (a)virulence genes between bacteria. 相似文献
38.
Derek J. Nunez Mark A. Bush David A. Collins Susan L. McMullen Dawn Gillmor Glen Apseloff George Atiee Leonor Corsino Linda Morrow Paul L. Feldman 《PloS one》2014,9(4)
GPR119 receptor agonists improve glucose metabolism and alter gut hormone profiles in animal models and healthy subjects. We therefore investigated the pharmacology of GSK1292263 (GSK263), a selective GPR119 agonist, in two randomized, placebo-controlled studies that enrolled subjects with type 2 diabetes. Study 1 had drug-naive subjects or subjects who had stopped their diabetic medications, and Study 2 had subjects taking metformin. GSK263 was administered as single (25–800 mg; n = 45) or multiple doses (100–600 mg/day for 14 days; n = 96). Placebo and sitagliptin 100 mg/day were administered as comparators. In Study 1, sitagliptin was co-administered with GSK263 or placebo on Day 14 of dosing. Oral glucose and meal challenges were used to assess the effects on plasma glucose, insulin, C-peptide, glucagon, peptide tyrosine-tyrosine (PYY), glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP). After 13 days of dosing, GSK263 significantly increased plasma total PYY levels by ∼five-fold compared with placebo, reaching peak concentrations of ∼50 pM after each of the three standardized meals with the 300 mg BID dose. Co-dosing of GSK263 and metformin augmented peak concentrations to ∼100 pM at lunchtime. GSK263 had no effect on active or total GLP-1 or GIP, but co-dosing with metformin increased post-prandial total GLP-1, with little effect on active GLP-1. Sitagliptin increased active GLP-1, but caused a profound suppression of total PYY, GLP-1, and GIP when dosed alone or with GSK263. This suppression of peptides was reduced when sitagliptin was co-dosed with metformin. GSK263 had no significant effect on circulating glucose, insulin, C-peptide or glucagon levels. We conclude that GSK263 did not improve glucose control in type 2 diabetics, but it had profound effects on circulating PYY. The gut hormone effects of this GPR119 agonist were modulated when co-dosed with metformin and sitagliptin. Metformin may modulate negative feedback loops controlling the secretion of enteroendocrine peptides.
Trial Registration:
Clinicaltrials.gov Clinicaltrials.gov NCT01119846 NCT01128621相似文献39.
40.
Knight R Jansson J Field D Fierer N Desai N Fuhrman JA Hugenholtz P van der Lelie D Meyer F Stevens R Bailey MJ Gordon JI Kowalchuk GA Gilbert JA 《Nature biotechnology》2012,30(6):513-520
Metagenomics holds enormous promise for discovering novel enzymes and organisms that are biomarkers or drivers of processes relevant to disease, industry and the environment. In the past two years, we have seen a paradigm shift in metagenomics to the application of cross-sectional and longitudinal studies enabled by advances in DNA sequencing and high-performance computing. These technologies now make it possible to broadly assess microbial diversity and function, allowing systematic investigation of the largely unexplored frontier of microbial life. To achieve this aim, the global scientific community must collaborate and agree upon common objectives and data standards to enable comparative research across the Earth's microbiome. Improvements in comparability of data will facilitate the study of biotechnologically relevant processes, such as bioprospecting for new glycoside hydrolases or identifying novel energy sources. 相似文献