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Sökning: WFRF:(Morgan Kevin)

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1.
  • Beal, Jacob, et al. (författare)
  • Robust estimation of bacterial cell count from optical density
  • 2020
  • Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
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4.
  • Sodergren, Erica, et al. (författare)
  • The genome of the sea urchin Strongylocentrotus purpuratus.
  • 2006
  • Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 314:5801, s. 941-52
  • Tidskriftsartikel (refereegranskat)abstract
    • We report the sequence and analysis of the 814-megabase genome of the sea urchin Strongylocentrotus purpuratus, a model for developmental and systems biology. The sequencing strategy combined whole-genome shotgun and bacterial artificial chromosome (BAC) sequences. This use of BAC clones, aided by a pooling strategy, overcame difficulties associated with high heterozygosity of the genome. The genome encodes about 23,300 genes, including many previously thought to be vertebrate innovations or known only outside the deuterostomes. This echinoderm genome provides an evolutionary outgroup for the chordates and yields insights into the evolution of deuterostomes.
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5.
  • Abeysinghe, Kasun S., et al. (författare)
  • Mercury flow through an Asian rice-based food web
  • 2017
  • Ingår i: Environmental Pollution. - : ELSEVIER SCI LTD. - 0269-7491 .- 1873-6424. ; 229, s. 219-228
  • Tidskriftsartikel (refereegranskat)abstract
    • Mercury (Hg) is a globally-distributed pollutant, toxic to humans and animals. Emissions are particularly high in Asia, and the source of exposure for humans there may also be different from other regions, including rice as well as fish consumption, particularly in contaminated areas. Yet the threats Asian wildlife face in rice-based ecosystems are as yet unclear. We sought to understand how Hg flows through rice-based food webs in historic mining and non-mining regions of Guizhou, China. We measured total Hg (THg) and methylmercury (MeHg) in soil, rice, 38 animal species (27 for MeHg) spanning multiple trophic levels, and examined the relationship between stable isotopes and Hg concentrations. Our results confirm biomagnification of THg/MeHg, with a high trophic magnification slope. Invertivorous songbirds had concentrations of THg in their feathers that were 15x and 3x the concentration reported to significantly impair reproduction, at mining and non-mining sites, respectively. High concentrations in specialist rice consumers and in granivorous birds, the later as high as in piscivorous birds,, suggest rice is a primary source of exposure. Spiders had the highest THg concentrations among invertebrates and may represent a vector through which Hg is passed to vertebrates, especially songbirds. Our findings suggest there could be significant population level health effects and consequent biodiversity loss in sensitive ecosystems, like agricultural wetlands, across Asia, and invertivorous songbirds would be good subjects for further studies investigating this possibility.
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6.
  • Ainsworth, Elizabeth A., et al. (författare)
  • Next generation of elevated [CO2] experiments with crops: a critical investment for feeding the future world
  • 2008
  • Ingår i: Plant, Cell and Environment. - : Wiley. - 0140-7791 .- 1365-3040. ; 31:9, s. 1317-1324
  • Tidskriftsartikel (refereegranskat)abstract
    • A rising global population and demand for protein-rich diets are increasing pressure to maximize agricultural productivity. Rising atmospheric [CO2] is altering global temperature and precipitation patterns, which challenges agricultural productivity. While rising [CO2] provides a unique opportunity to increase the productivity of C-3 crops, average yield stimulation observed to date is well below potential gains. Thus, there is room for improving productivity. However, only a fraction of available germplasm of crops has been tested for CO2 responsiveness. Yield is a complex phenotypic trait determined by the interactions of a genotype with the environment. Selection of promising genotypes and characterization of response mechanisms will only be effective if crop improvement and systems biology approaches are closely linked to production environments, that is, on the farm within major growing regions. Free air CO2 enrichment (FACE) experiments can provide the platform upon which to conduct genetic screening and elucidate the inheritance and mechanisms that underlie genotypic differences in productivity under elevated [CO2]. We propose a new generation of large-scale, low-cost per unit area FACE experiments to identify the most CO2-responsive genotypes and provide starting lines for future breeding programmes. This is necessary if we are to realize the potential for yield gains in the future.
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7.
  • Baker, Crystal, et al. (författare)
  • Effects of Alzheimer's peptide and alpha 1-antichymotrypsin on astrocyte gene expression
  • 2007
  • Ingår i: Neurobiology of Aging. - : Elsevier BV. - 1558-1497 .- 0197-4580. ; 28:1, s. 51-61
  • Tidskriftsartikel (refereegranskat)abstract
    • We employed gene array technology to investigate the effects of alpha 1-antichymotrypsin (ACT), soluble or fibrillar Alzheimer's peptide (A beta(1-42)) alone and the combination of ACT/A beta(1-42) on human astrocytes. Using a 1.2-fold change as significance threshold, 398 astrocyte genes showed altered expression in response to these treatments compared to controls. Of the 276 genes affected by the ACT/soluble A beta(1-42) combination, 195 (70.6%) were suppressed. The ACT/fibrillar A beta(1-42) combination affected expression of 64 genes of which 58 (90.5%) were up-regulated. The most prominent gene expression changes in response to the ACT/soluble A beta(1-42), were the down-regulation of at least 60 genes involved in transcription, signal transduction, apoptosis and neurogenesis. The ACT/fibril A beta(1-42) increased the expression of genes involved in transcription regulation and signal transduction. Surprisingly, gene expression of astrocytes exposed to soluble or fibrillar A beta(1-42) alone was largely unaffected. Thus, the molecular forms generated by the combination of ACT/A beta(1-42) alter expression of astrocyte genes more profoundly in breadth and magnitude than soluble or fibrillar A beta(1-42) alone, suggesting that pathogenic effects of A beta(1-42) may occur as a consequence of its association with other proteins. (c) 2005 Elsevier Inc. All rights reserved.
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8.
  • Birney, Ewan, et al. (författare)
  • Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project
  • 2007
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 447:7146, s. 799-816
  • Tidskriftsartikel (refereegranskat)abstract
    • We report the generation and analysis of functional data from multiple, diverse experiments performed on a targeted 1% of the human genome as part of the pilot phase of the ENCODE Project. These data have been further integrated and augmented by a number of evolutionary and computational analyses. Together, our results advance the collective knowledge about human genome function in several major areas. First, our studies provide convincing evidence that the genome is pervasively transcribed, such that the majority of its bases can be found in primary transcripts, including non-protein-coding transcripts, and those that extensively overlap one another. Second, systematic examination of transcriptional regulation has yielded new understanding about transcription start sites, including their relationship to specific regulatory sequences and features of chromatin accessibility and histone modification. Third, a more sophisticated view of chromatin structure has emerged, including its inter-relationship with DNA replication and transcriptional regulation. Finally, integration of these new sources of information, in particular with respect to mammalian evolution based on inter- and intra-species sequence comparisons, has yielded new mechanistic and evolutionary insights concerning the functional landscape of the human genome. Together, these studies are defining a path for pursuit of a more comprehensive characterization of human genome function.
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9.
  • Bras, Jose, et al. (författare)
  • Genetic analysis implicates APOE, SNCA and suggests lysosomal dysfunction in the etiology of dementia with Lewy bodies.
  • 2014
  • Ingår i: Human molecular genetics. - : Oxford University Press (OUP). - 1460-2083 .- 0964-6906. ; 23:23, s. 6139-6146
  • Tidskriftsartikel (refereegranskat)abstract
    • Clinical and neuropathological similarities between dementia with Lewy bodies (DLB), Parkinson's and Alzheimer's diseases (PD and AD, respectively) suggest that these disorders may share etiology. To test this hypothesis, we have performed an association study of 54 genomic regions, previously implicated in PD or AD, in a large cohort of DLB cases and controls. The cohort comprised 788 DLB cases and 2624 controls. To minimize the issue of potential misdiagnosis, we have also performed the analysis including only neuropathologically proven DLB cases (667 cases). The results show that the APOE is a strong genetic risk factor for DLB, confirming previous findings, and that the SNCA and SCARB2 loci are also associated after a study-wise Bonferroni correction, although these have a different association profile than the associations reported for the same loci in PD. We have previously shown that the p.N370S variant in GBA is associated with DLB, which, together with the findings at the SCARB2 locus, suggests a role for lysosomal dysfunction in this disease. These results indicate that DLB has a unique genetic risk profile when compared with the two most common neurodegenerative diseases and that the lysosome may play an important role in the etiology of this disorder. We make all these data available.
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10.
  • Craddock, Nick, et al. (författare)
  • Genome-wide association study of CNVs in 16,000 cases of eight common diseases and 3,000 shared controls
  • 2010
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 464:7289, s. 713-720
  • Tidskriftsartikel (refereegranskat)abstract
    • Copy number variants (CNVs) account for a major proportion of human genetic polymorphism and have been predicted to have an important role in genetic susceptibility to common disease. To address this we undertook a large, direct genome-wide study of association between CNVs and eight common human diseases. Using a purpose-designed array we typed,19,000 individuals into distinct copy-number classes at 3,432 polymorphic CNVs, including an estimated similar to 50% of all common CNVs larger than 500 base pairs. We identified several biological artefacts that lead to false-positive associations, including systematic CNV differences between DNAs derived from blood and cell lines. Association testing and follow-up replication analyses confirmed three loci where CNVs were associated with disease-IRGM for Crohn's disease, HLA for Crohn's disease, rheumatoid arthritis and type 1 diabetes, and TSPAN8 for type 2 diabetes-although in each case the locus had previously been identified in single nucleotide polymorphism (SNP)-based studies, reflecting our observation that most common CNVs that are well-typed on our array are well tagged by SNPs and so have been indirectly explored through SNP studies. We conclude that common CNVs that can be typed on existing platforms are unlikely to contribute greatly to the genetic basis of common human diseases.
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