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981.
James R. Bradford Chris J. Needham Philip Tedder Matthew A. Care Andrew J. Bulpitt David R. Westhead 《The Plant journal : for cell and molecular biology》2010,61(4):713-721
Despite recent advances, accurate gene function prediction remains an elusive goal, with very few methods directly applicable to the plant Arabidopsis thaliana. In this study, we present GO‐At (gene ontology prediction in A. thaliana), a method that combines five data types (co‐expression, sequence, phylogenetic profile, interaction and gene neighbourhood) to predict gene function in Arabidopsis. Using a simple, yet powerful two‐step approach, GO‐At first generates a list of genes ranked in descending order of probability of functional association with the query gene. Next, a prediction score is automatically assigned to each function in this list based on the assumption that functions appearing most frequently at the top of the list are most likely to represent the function of the query gene. In this way, the second step provides an effective alternative to simply taking the ‘best hit’ from the first list, and achieves success rates of up to 79%. GO‐At is applicable across all three GO categories: molecular function, biological process and cellular component, and can assign functions at multiple levels of annotation detail. Furthermore, we demonstrate GO‐At’s ability to predict functions of uncharacterized genes by identifying ten putative golgins/Golgi‐associated proteins amongst 8219 genes of previously unknown cellular component and present independent evidence to support our predictions. A web‐based implementation of GO‐At ( http://www.bioinformatics.leeds.ac.uk/goat ) is available, providing a unique resource for plant researchers to make predictions for uncharacterized genes and predict novel functions in Arabidopsis. 相似文献
982.
983.
Min Zhong Wang Shen Kenneth J. Barr Jennifer P. Arbitrario Michelle R. Arkin Minna Bui Teresa Chen Brian C. Cunningham Marc J. Evanchik Emily J. Hanan Ute Hoch Karen Huen Jennifer Hyde Jeffery L. Kumer Teresa Lac Chris E. Lawrence Jose R. Martell Johan D. Oslob Kumar Paulvannan Saileta Prabhu W. Mike Flanagan 《Bioorganic & medicinal chemistry letters》2010,20(17):5269-5273
This letter describes the discovery of a novel series of tetrahydroisoquinoline (THIQ)-derived small molecules that potently inhibit both human T-cell migration and super-antigen induced T-cell activation through disruption of the binding of integrin LFA-1 to its receptor, ICAM-1. In addition to excellent in vitro potency, 6q shows good pharmacokinetic properties and its ethyl ester (6t) demonstrates good oral bioavailability in both mouse and rat. Either intravenous administration of 6q or oral administration of its ethyl ester (6t) produced a significant reduction of neutrophil migration in a thioglycollate-induced murine peritonitis model. 相似文献
984.
985.
Alin M. Puinean Stephen P. Foster Linda Oliphant Ian Denholm Linda M. Field Neil S. Millar Martin S. Williamson Chris Bass 《PLoS genetics》2010,6(6)
The aphid Myzus persicae is a globally significant crop pest that has evolved high levels of resistance to almost all classes of insecticide. To date, the neonicotinoids, an economically important class of insecticides that target nicotinic acetylcholine receptors (nAChRs), have remained an effective control measure; however, recent reports of resistance in M. persicae represent a threat to the long-term efficacy of this chemical class. In this study, the mechanisms underlying resistance to the neonicotinoid insecticides were investigated using biological, biochemical, and genomic approaches. Bioassays on a resistant M. persicae clone (5191A) suggested that P450-mediated detoxification plays a primary role in resistance, although additional mechanism(s) may also contribute. Microarray analysis, using an array populated with probes corresponding to all known detoxification genes in M. persicae, revealed constitutive over-expression (22-fold) of a single P450 gene (CYP6CY3); and quantitative PCR showed that the over-expression is due, at least in part, to gene amplification. This is the first report of a P450 gene amplification event associated with insecticide resistance in an agriculturally important insect pest. The microarray analysis also showed over-expression of several gene sequences that encode cuticular proteins (2–16-fold), and artificial feeding assays and in vivo penetration assays using radiolabeled insecticide provided direct evidence of a role for reduced cuticular penetration in neonicotinoid resistance. Conversely, receptor radioligand binding studies and nucleotide sequencing of nAChR subunit genes suggest that target-site changes are unlikely to contribute to resistance to neonicotinoid insecticides in M. persicae. 相似文献
986.
Nitric oxide is a small gaseous signaling molecule which functions in the regulation of plant development and responses to biotic and abiotic stresses. Recently, we have shown that nitric oxide is required for development of functional nodules. Here, we show that inhibition of nitric oxide synthase enzymatic activity (using Nω-nitro-L-arginine) reduces nitric oxide content in soybean root nodules and this is coupled by reduction of endogenous cyclic guanosine monophosphate content in the nodules. We postulate that the regulation of soybean nodule development by nitric oxide is transduced via cyclic guanosine monophosphate through activation of nitric oxide-responsive soluble guanylate cyclase. Furthermore, we hypothesize that this signaling cascade is mediated via modulation of the activities of antioxidant metabolic pathways.Key words: cyclic guanosine monophosphate, nitric oxide synthase, nitric oxide, nitrogen fixation, nodulation efficiency, nodule functioning, reactive oxygen species 相似文献
987.
Jim Kaput Chris T. Evelo Giuditta Perozzi Ben van Ommen Richard Cotton 《Genes & nutrition》2010,5(4):275-283
Nutrigenomics is the science of analyzing and understanding gene–nutrient interactions, which because of the genetic heterogeneity, varying degrees of interaction among gene products, and the environmental diversity is a complex science. Although much knowledge of human diversity has been accumulated, estimates suggest that ~90% of genetic variation has not yet been characterized. Identification of the DNA sequence variants that contribute to nutrition-related disease risk is essential for developing a better understanding of the complex causes of disease in humans, including nutrition-related disease. The Human Variome Project (HVP; http://www.humanvariomeproject.org/) is an international effort to systematically identify genes, their mutations, and their variants associated with phenotypic variability and indications of human disease or phenotype. Since nutrigenomic research uses genetic information in the design and analysis of experiments, the HVP is an essential collaborator for ongoing studies of gene–nutrient interactions. With the advent of next generation sequencing methodologies and the understanding of the undiscovered variation in human genomes, the nutrigenomic community will be generating novel sequence data and results. The guidelines and practices of the HVP can guide and harmonize these efforts. 相似文献
988.
W. Chris Funk Eric D. Forsman Matthew Johnson Thomas D. Mullins Susan M. Haig 《Conservation Genetics》2010,11(3):1013-1021
The northern spotted owl (Strix occidentalis caurina) is one of the most controversial threatened subspecies ever listed under the US Endangered Species Act. Despite protection
of its remaining forest habitat, recent field studies show continued declines of northern spotted owls. One potential threat
to northern spotted owls which has not yet been shown is loss of genetic variation from population bottlenecks. Bottlenecks
can increase the probability of mating among related individuals, potentially causing inbreeding depression, and can decrease
adaptive potential. Here we report evidence for recent bottlenecks in northern spotted owls using a large genetic dataset
(352 individuals and 10 microsatellite loci). The signature of bottlenecks was strongest in the Washington Cascade Mountains,
in agreement with field data. Our results provide independent evidence that northern spotted owls have recently declined,
and suggest that loss of genetic variation is an emerging threat to the subspecies’ persistence. Reduced effective population
size (N
e) shown here in addition to field evidence for demographic decline highlights the increasing vulnerability of this bird to
extinction. 相似文献
989.
Andrew R. Whiteley Kim Hastings John K. Wenburg Chris A. Frissell Jamie C. Martin Fred W. Allendorf 《Conservation Genetics》2010,11(5):1929-1943
Following glacial recession in southeast Alaska, waterfalls created by isostatic rebound have isolated numerous replicate
populations of coastal cutthroat trout (Oncorhynchus clarkii clarkii) in short coastal streams. These replicate isolated populations offer an unusual opportunity to examine factors associated
with the maintenance of genetic diversity. We used eight microsatellites to examine genetic variation within and differentiation
among 12 population pairs sampled from above and below these natural migration barriers. Geological evidence indicated that
the above-barrier populations have been isolated for 8,000–12,500 years. Genetic differentiation among below-barrier populations
(F
ST = 0.10, 95% C.I. 0.08–0.12) was similar to a previous study of more southern populations of this species. Above-barrier populations
were highly differentiated from adjacent below-barrier populations (mean pairwise F
ST = 0.28; SD 0.18) and multiple lines of evidence were consistent with asymmetric downstream gene flow that varied among streams.
Each above-barrier population had reduced within-population genetic variation when compared to the adjacent below-barrier
population. Within-population genetic diversity was significantly correlated with the amount of available habitat in above-barrier
sites. Increased genetic differentiation of above-barrier populations with lower genetic diversity suggests that genetic drift
has been the primary cause of genetic divergence. Long-term estimates of N
e based on loss of heterozygosity over the time since isolation were large (3,170; range 1,077–7,606) and established an upper
limit for N
e if drift were the only evolutionary process responsible for loss of genetic diversity. However, it is likely that a combination
of mutation, selection, and gene flow have also contributed to the genetic diversity of above-barrier populations. Contemporary
above-barrier N
e estimates were much smaller than long-term N
e estimates, not correlated with within-population genetic diversity, and not consistent with the amount of genetic variation
retained, given the approximate 10,000-year period of isolation. The populations isolated by waterfalls in this study that
occur in larger stream networks have retained substantial genetic variation, which suggests that the amount of habitat in
headwater streams is an important consideration for maintaining the evolutionary potential of isolated populations. 相似文献
990.
Bruce SJ Breton I Decombaz J Boesch C Scheurer E Montoliu I Rezzi S Kochhar S Guy PA 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2010,878(29):3015-3023
A global metabolic profiling methodology based on gas chromatography coupled to time-of-flight mass spectrometry (GC-TOFMS) for human plasma was applied to a human exercise study focused on the effects of beverages containing glucose, galactose, or fructose taken after exercise and throughout a recovery period of 6 h and 45 min. One group of 10 well trained male cyclists performed 3 experimental sessions on separate days (randomized, single center). After performing a standardized depletion protocol on a bicycle, subjects consumed one of three different beverages: maltodextrin (MD)+glucose (2:1 ratio), MD+galactose (2:1), and MD+fructose (2:1), consumed at an average of ~1.25 g of carbohydrate (CHO) ingested per minute. Blood was taken straight after exercise and every 45 min within the recovery phase. With the resulting blood plasma, insulin, free fatty acid (FFA) profile, glucose, and GC-TOFMS global metabolic profiling measurements were performed. The resulting profiling data was able to match the results obtained from the other clinical measurements with the addition of being able to follow many different metabolites throughout the recovery period. The data quality was assessed, with all the labelled internal standards yielding values of <15% CV for all samples (n=335), apart from the labelled sucrose which gave a value of 15.19%. Differences between recovery treatments including the appearance of galactonic acid from the galactose based beverage were also highlighted. 相似文献