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- Werren, John H, et al.
(författare)
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Functional and evolutionary insights from the genomes of three parasitoid Nasonia species.
- 2010
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 327:5963, s. 343-8
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Tidskriftsartikel (refereegranskat)abstract
- We report here genome sequences and comparative analyses of three closely related parasitoid wasps: Nasonia vitripennis, N. giraulti, and N. longicornis. Parasitoids are important regulators of arthropod populations, including major agricultural pests and disease vectors, and Nasonia is an emerging genetic model, particularly for evolutionary and developmental genetics. Key findings include the identification of a functional DNA methylation tool kit; hymenopteran-specific genes including diverse venoms; lateral gene transfers among Pox viruses, Wolbachia, and Nasonia; and the rapid evolution of genes involved in nuclear-mitochondrial interactions that are implicated in speciation. Newly developed genome resources advance Nasonia for genetic research, accelerate mapping and cloning of quantitative trait loci, and will ultimately provide tools and knowledge for further increasing the utility of parasitoids as pest insect-control agents.
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| 2. |
- Locy, Morgan L, et al.
(författare)
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Thioredoxin reductase inhibition elicits Nrf2-mediated responses in Clara cells : implications for oxidant-induced lung injury
- 2012
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Ingår i: Antioxidants and Redox Signaling. - Stockholm : Karolinska Institutet, Dept of Medical Biochemistry and Biophysics. - 1557-7716 .- 1523-0864.
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Tidskriftsartikel (refereegranskat)abstract
- Aims: Pulmonary oxygen toxicity contributes to lung injury in newborn and adult humans.We previously reported that thioredoxin reductase (TrxR1) inhibition with aurothioglucose (ATG) attenuates hyperoxic lung injury in adult mice. The present studies tested the hypothesis that TrxR1 inhibition protects against the effects of hyperoxia via nuclear factor E2-related factor 2 (Nrf2)-dependent mechanisms. Results: Both pharmacologic and siRNA-mediated TrxR1 inhibition induced robust Nrf2 responses in murine-transformed Clara cells (mtCC). While TrxR1 inhibition did not alter the susceptibility of cells to the effects of hyperoxia, glutathione (GSH) depletion after TrxR1 inhibition markedly enhanced the hyperoxic susceptibility of cultured mtCCs. Finally, in vivo data revealed dose-dependent increases in the expression of the Nrf2 target gene NADPH:quinone oxidoreductase 1 (NQO1) in the lungs of ATGtreated adult mice. Innovation: TrxR1 inhibition activates Nrf2-dependent antioxidant responses in mtCCs in vitro and in adult murine lungs in vivo, providing a plausible mechanism for the protective effects of TrxR1 inhibition in vivo. Conclusion: GSH-dependent enzyme systems in mtCCs may be of greater importance for protection against hyperoxic exposure than are TrxR-dependent systems. The induction of Nrf2 activation via TrxR1 inhibition represents a novel therapeutic strategy that attenuates oxidant-mediated lung injury. Similar expression levels of TrxR1 in newborn and adult mouse or human lungs broaden the potential clinical applicability of the present findings to both neonatal and adult oxidant lung injury.
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| 3. |
- MacGregor, Stuart, et al.
(författare)
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Genome-wide association study identifies a new melanoma susceptibility locus at 1q21.3
- 2011
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 43:11, s. 1114-1118
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Tidskriftsartikel (refereegranskat)abstract
- We performed a genome-wide association study of melanoma in a discovery cohort of 2,168 Australian individuals with melanoma and 4,387 control individuals. In this discovery phase, we confirm several previously characterized melanoma-associated loci at MC1R, ASIP and MTAP-CDKN2A. We selected variants at nine loci for replication in three independent case-control studies (Europe: 2,804 subjects with melanoma, 7,618 control subjects; United States 1: 1,804 subjects with melanoma, 1,026 control subjects; United States 2: 585 subjects with melanoma, 6,500 control subjects). The combined meta-analysis of all case-control studies identified a new susceptibility locus at 1q21.3 (rs7412746, P = 9.0 x 10(-11), OR in combined replication cohorts of 0.89 (95% CI 0.85-0.95)). We also show evidence suggesting that melanoma associates with 1q42.12 (rs3219090, P = 9.3 x 10(-8)). The associated variants at the 1q21.3 locus span a region with ten genes, and plausible candidate genes for melanoma susceptibility include ARNT and SETDB1. Variants at the 1q21.3 locus do not seem to be associated with human pigmentation or measures of nevus density.
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