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121.
Stephanie L.H. Zeiger Erik S. Musiek Giuseppe Zanoni Giovanni Vidari Jason D. Morrow Ginger J. Milne BethAnn McLaughlin 《Free radical biology & medicine》2009,47(10):1422-1431
Stroke is the third leading cause of death in the United States, yet no neuroprotective agents for treatment are clinically available. There is a pressing need to understand the signaling molecules that mediate ischemic cell death and identify novel neuroprotective targets. Cyclopentenone isoprostanes (IsoPs), formed after free radical-mediated peroxidation of arachidonic acid, are used as markers of stress, but their bioactivity is poorly understood. We have recently shown that 15-A2t-IsoP is a potent neurotoxin in vitro and increases the free radical burden in neurons. In this work, we demonstrate that 15-A2t-IsoP is abundantly produced in stroke-infarcted human cortical tissue. Using primary neuronal cultures we found that minimally toxic exposure to 15-A2t-IsoP does not alter ATP content, but in combination with oxygen glucose deprivation resulted in a significant hyperpolarization of the mitochondrial membrane and dramatically increased neuronal cell death. In the presence of Ca2+, 15-A2t-IsoP led to a rapid induction of the permeability transition pore and release of cytochrome c. Taken with our previous work, these data support a model in which ischemia causes generation of reactive oxygen species, calcium influx, lipid peroxidation, and 15-A2t-IsoP formation. These factors combine to enhance opening of the permeability transition pore leading to cell death subsequent to mitochondrial cytochrome c release. These data are the first documentation of significant 15-A2t-IsoP formation after acute ischemic stroke and suggest that the addition of 15-A2t-IsoP to in vitro models of ischemia may help to more fully recapitulate stroke injury. 相似文献
122.
TOPALi v2: a rich graphical interface for evolutionary analyses of multiple alignments on HPC clusters and multi-core desktops 总被引:1,自引:0,他引:1
Milne I Lindner D Bayer M Husmeier D McGuire G Marshall DF Wright F 《Bioinformatics (Oxford, England)》2009,25(1):126-127
Summary: TOPALi v2 simplifies and automates the use of severalmethods for the evolutionary analysis of multiple sequence alignments.Jobs are submitted from a Java graphical user interface as TOPALiweb services to either run remotely on high-performance computingclusters or locally (with multiple cores supported). Methodsavailable include model selection and phylogenetic tree estimationusing the Bayesian inference and maximum likelihood (ML) approaches,in addition to recombination detection methods. The optimalsubstitution model can be selected for protein or nucleic acid(standard, or protein-coding using a codon position model) datausing accurate statistical criteria derived from ML co-estimationof the tree and the substitution model. Phylogenetic softwareavailable includes PhyML, RAxML and MrBayes. Availability: Freely downloadable from http://www.topali.orgfor Windows, Mac OS X, Linux and Solaris. Contact: iain.milne{at}scri.ac.uk
Associate Editor: Martin Bishop 相似文献
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124.
Caroline B. Milne Pan-Jun Kim James A. Eddy Nathan D. Price Dr. 《Biotechnology journal》2009,4(12):1653-1670
Driven by advancements in high-throughput biological technologies and the growing number of sequenced genomes, the construction of in silico models at the genome scale has provided powerful tools to investigate a vast array of biological systems and applications. Here, we review comprehensively the uses of such models in industrial and medical biotechnology, including biofuel generation, food production, and drug development. While the use of in silico models is still in its early stages for delivering to industry, significant initial successes have been achieved. For the cases presented here, genome-scale models predict engineering strategies to enhance properties of interest in an organism or to inhibit harmful mechanisms of pathogens. Going forward, genome-scale in silico models promise to extend their application and analysis scope to become a transformative tool in biotechnology. 相似文献
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126.
Emily HM Wong David K Smith Raul Rabadan Malik Peiris Leo LM Poon 《BMC evolutionary biology》2010,10(1):253
Background
The influenza A virus is an important infectious cause of morbidity and mortality in humans and was responsible for 3 pandemics in the 20th century. As the replication of the influenza virus is based on its host's machinery, codon usage of its viral genes might be subject to host selection pressures, especially after interspecies transmission. A better understanding of viral evolution and host adaptive responses might help control this disease. 相似文献127.
Hall LM Moran CN Milne GR Wilson J MacFarlane NG Forouhi NG Hariharan N Salt IP Sattar N Gill JM 《PloS one》2010,5(12):e14197
Background
South Asians are more insulin resistant than Europeans, which cannot be fully explained by differences in adiposity. We investigated whether differences in oxidative capacity and capacity for fatty acid utilisation in South Asians might contribute, using a range of whole-body and skeletal muscle measures.Methodology/Principal Findings
Twenty men of South Asian ethnic origin and 20 age and BMI-matched men of white European descent underwent exercise and metabolic testing and provided a muscle biopsy to determine expression of oxidative and lipid metabolism genes and of insulin signalling proteins. In analyses adjusted for age, BMI, fat mass and physical activity, South Asians, compared to Europeans, exhibited; reduced insulin sensitivity by 26% (p = 0.010); lower VO2max (40.6±6.6 vs 52.4±5.7 ml.kg−1.min−1, p = 0.001); and reduced fat oxidation during submaximal exercise at the same relative (3.77±2.02 vs 6.55±2.60 mg.kg−1.min−1 at 55% VO2max, p = 0.013), and absolute (3.46±2.20 vs 6.00±1.93 mg.kg−1.min−1 at 25 ml O2.kg−1.min−1, p = 0.021), exercise intensities. South Asians exhibited significantly higher skeletal muscle gene expression of CPT1A and FASN and significantly lower skeletal muscle protein expression of PI3K and PKB Ser473 phosphorylation. Fat oxidation during submaximal exercise and VO2max both correlated significantly with insulin sensitivity index and PKB Ser473 phosphorylation, with VO2max or fat oxidation during exercise explaining 10–13% of the variance in insulin sensitivity index, independent of age, body composition and physical activity.Conclusions/Significance
These data indicate that reduced oxidative capacity and capacity for fatty acid utilisation at the whole body level are key features of the insulin resistant phenotype observed in South Asians, but that this is not the consequence of reduced skeletal muscle expression of oxidative and lipid metabolism genes. 相似文献128.
129.
Background
Plant breeders use an increasingly diverse range of data types to identify lines with desirable characteristics suitable to be taken forward in plant breeding programmes. There are a number of key morphological and physiological traits, such as disease resistance and yield that need to be maintained and improved upon if a commercial variety is to be successful. Computational tools that provide the ability to integrate and visualize this data with pedigree structure, will enable breeders to make better decisions on the lines that are used in crossings to meet both the demands for increased yield/production and adaptation to climate change.Results
We have used a large and unique set of experimental barley (H. vulgare) data to develop a prototype pedigree visualization system. We then used this prototype to perform a subjective user evaluation with domain experts to guide and direct the development of an interactive pedigree visualization tool called Helium.Conclusions
We show that Helium allows users to easily integrate a number of data types along with large plant pedigrees to offer an integrated environment in which they can explore pedigree data. We have also verified that users were happy with the abstract representation of pedigrees that we have used in our visualization tool.Electronic supplementary material
The online version of this article (doi:10.1186/1471-2105-15-259) contains supplementary material, which is available to authorized users. 相似文献130.
Hanna W van Steenbergen Jessica AB van Nies Tom WJ Huizinga Monique Reijnierse Annette HM van der Helm-van Mil 《Arthritis research & therapy》2014,16(2):R92