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Sökning: WFRF:(Goldstone Jared D.)

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1.
  • 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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2.
  • Celander, Malin C., 1962, et al. (författare)
  • SPECIES EXTRAPOLATION FOR THE 21ST CENTURY
  • 2011
  • Ingår i: Environmental Toxicology and Chemistry. ; 30:1, s. 52-63
  • Tidskriftsartikel (refereegranskat)abstract
    • Safety factors are used in ecological risk assessments to extrapolate from the toxic responses of laboratory test species to all species representing that group in the environment. More accurate extrapolation of species responses is important. Advances in understanding the mechanistic basis for toxicological responses and identifying molecular response pathways can provide a basis for extrapolation across species and, in part, an explanation for the variability in whole organism responses to toxicants. We highlight potential short- and medium-term development goals to meet our long-term aspiration of truly predictive in silico extrapolation across wildlife species' response to toxicants. A conceptual approach for considering cross-species extrapolation is presented. Critical information is required to establish evidence-based species extrapolation, including identification of critical molecular pathways and regulatory networks that are linked to the biological mode of action and species' homologies. A case study is presented that examines steroidogenesis inhibition in fish after exposure to fadrozole or prochloraz. Similar effects for each compound among fathead minnow, medaka, and zebrafish were attributed to similar inhibitor pharmacokinetic/pharmacodynamic distributions and sequences of cytochrome P45019A1/2 (CYP19A1/2). Rapid advances in homology modeling allow the prediction of interactions of chemicals with enzymes, for example, CYP19 aromatase, which would eventually allow a prediction of potential aromatase toxicity of new compounds across a range of species. Eventually, predictive models will be developed to extrapolate across species, although substantial research is still required. Knowledge gaps requiring research include defining differences in life histories (e.g., reproductive strategies), understanding tissue-specific gene expression, and defining the role of metabolism on toxic responses and how these collectively affect the power of interspecies extrapolation methods. Environ. Toxicol. Chem. 2011;30:52-63. © 2010 SETAC.
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3.
  • Denslow, Nancy D., et al. (författare)
  • SPECIES EXTRAPOLATION FOR THE 21ST CENTURY
  • 2009
  • Ingår i: SETAC North America 30th Annual Meeting Human-Environment Interactions: New Orleans, Louisiana USA, 19-23 November 2009..
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • Ecological risk assessment is facing the need for increasing sophistication that will require a scientific rationale for making appropriate informed extrapolations. This will inevitably require sound biological linkages amongst species in their responses to chemical stressors. It is important to acknowledge the tools and knowledge are currently here for extrapolations based on omics data to begin. However, limitations in our understanding of the complexity molecular target expression form and function with their response to the multitude of mechanisms of actions mean that our ambitions in this field require considerable further development. A conceptual approach is presented and illustrated with a case study with an aromatase inhibiting mode of action. This paper aims to highlight the potential short and medium term development goals in order to meet our long term aspiration for in silico extrapolation across species response to toxicants.
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4.
  • Bainy, Afonso C.D., et al. (författare)
  • Functional characterization of a full length pregnane X receptor, expression in vivo, and identification of PXR alleles, in Zebrafish (Danio rerio)
  • 2013
  • Ingår i: Aquatic Toxicology. - : Elsevier BV. - 0166-445X. ; 142-143, s. 447-457
  • Tidskriftsartikel (refereegranskat)abstract
    • The pregnane X receptor (PXR) (nuclear receptor NR1I2) is a ligand activated transcription factor, mediating responses to diverse xenobiotic and endogenous chemicals. The properties of PXR in fish are not fully understood. Here we report on cloning and characterization of full-length PXR of zebrafish, Danio rerio, and pxr expression in vivo. Initial efforts gave a cDNA encoding a 430 amino acid protein identified as zebrafish pxr by phylogenetic and synteny analysis. The sequence of the cloned Pxr DNA binding domain (DBD) was highly conserved, with 74% identity to human PXR-DBD, while the ligand-binding domain (LBD) of the cloned sequence was only 44% identical to human PXR-LBD. Sequence variation among clones in the initial effort prompted sequencing of multiple clones from a single fish. There were two prominent variants, one sequence with S183, Y218 and H383 and the other with I183, C218 and N383, which we designate as alleles pxr*1 (nr1i2*1) and pxr*2 (nr1i2*2), respectively. In COS-7 cells co-transfected with a PXR-responsive reporter gene, the full-length Pxr*1 (the more common variant) was activated by known PXR agonists clotrimazole and pregnenolone 16α-carbonitrile but to a lesser extent than the full-length human PXR. Activation of full-length Pxr*1 was only 10% of that with the Pxr*1 LBD. Quantitative real time PCR analysis showed prominent expression of pxr in liver and eye, as well as brain and intestine of adult zebrafish. The pxr was expressed in heart and kidney at levels similar to that in intestine. The expression of pxr in liver was weakly induced by ligands for mammalian PXR or constitutive androstane receptor (NR1I3). The results establish a foundation for PXR studies in this vertebrate model. PXR allelic variation and the differences between the full-length PXR and the LBD in reporter assays have implications for assessing the action of PXR ligands in zebrafish.
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  • Resultat 1-4 av 4

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