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Head and neck squamous cell carcinoma (HNSCC) is a common, morbid, and frequently lethal malignancy. To uncover its mutational spectrum, we analyzed whole-exome sequencing data from 74 tumor-normal pairs. The majority exhibited a mutational profile consistent with tobacco exposure; human papillomavirus was detectable by sequencing DNA from infected tumors. In addition to identifying previously known HNSCC genes (TP53, CDKN2A, PTEN, PIK3CA, and HRAS), our analysis revealed many genes not previously implicated in this malignancy. At least 30% of cases harbored mutations in genes that regulate squamous differentiation (for example, NOTCH1, IRF6, and TP63), implicating its dysregulation as a major driver of HNSCC carcinogenesis. More generally, the results indicate the ability of large-scale sequencing to reveal fundamental tumorigenic mechanisms.  相似文献   
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Atlantic salmon (Salmo salar) fry, initial weight 0.16 g, were fed a semipurified diet with 0, 15, 30, 60 or 120 mg dl-α-tocopheryl acetate/kg. After 24 weeks, the first two of these groups were extinct, and the fish receiving 30 mg/kg were clearly vitamin E deficient. Vitamin E deficient fish had low hemoglobin levels, characterized by a combination of reduced cellular hemoglobin concentration, red cell volume and red cell number, and an increased number and fraction of immature red blood cells. The hemoglobin concentration decreased over the decreasing range of experimental dl-ga-tocopheryl acetate levels. Therefore, even if 60 mg dl-α-tocopheryl acetate/kg gave good survival, this level was clearly physiologically suboptimal. Ceroid accumulated in the liver of fish fed 30 mg vitamin E/kg, and autofluorescent inclusions were found in the red blood cells of fish fed 30 and 60 mg vitamin E/kg. Degeneration of skeletal muscle was not observed in the present study.  相似文献   
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Atlantic salmon (Salmo salar L.) parr were fed for one month on fish meal based diets supplemented with Cd (0, 0.7, or 204 mg Cd kg–1 DW) or Cu (0, 34, or 691 mg Cu kg–1 DW) to assess the effects of non-essential (Cd) and essential (Cu) dietary metals on lipid peroxidation and the oxidative defence system. Cadmium accumulated significantly in the liver, intestine, and kidney of 204 mg Cd kg–1exposed fish compared to controls. Copper accumulated significantly in the intestine, kidney, and liver of fish exposed to 691 mg Cu kg–1, and in the intestine of 34 mg Cu kg–1 exposed fish. Tissue Cu accumulation significantly increased intestinal and hepatic lipid peroxidation (as seen from thiobarbituric acid reactive substances, TBARS, levels) and subsequently decreased intestinal -tocopherol levels and increased intestinal and hepatic selenium dependent glutathione peroxidase (SeGSH-Px) activity. Dietary Cd significantly reduced SeGSH-Px activity in the intestine and liver of 204 mg Cd kg–1 exposed fish compared to controls. No significant increase in tissue TBARS or reduction of -tocopherol levels was observed in the intestine of fish exposed to dietary Cd, with exception of the highest exposure group (204 mg Cd kg–1). Dietary Cu caused depletion of tissue Se and glutathione levels, however the reduced availability of GSH and Se did not seem to explain the differences in SeGSH-Px activity. Dietary Cu had a direct effect on lipid peroxidation at a relatively low concentration (34 mg Cu kg–1). Cadmium indirectly affected tissue lipid peroxidation by damaging the oxidative defence system at the highest dietary concentration (204 mg Cd kg–1).  相似文献   
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• Introduction   

Heavy metal pollution is a strong driver of above- and belowground communities and triggers evolutionary adaptation in organisms. This review provides an overview of our knowledge on the effects of toxic concentrations of metals on ectomycorrhizal populations and communities.  相似文献   
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Pasteurella are an important cause of fatal infections in free-ranging bats, but the genetic diversity of bat-derived strains is unclear. In the current study, 81 Pasteurella strains associated with pneumonia, severe organ necroses and systemic infection in free-ranging European vespertilionid bats were characterized by biochemical and molecular typing methods. Genetic relationships and subspecies status of Pasteurella multocida strains were determined by comparative 16S rDNA and rpoB gene sequence analysis. In addition, 30 representatives of the bat-derived P. multocida strains were selected based on phenotypic and genotypic tests to be compared by pulsed-field gel electrophoresis using SmaI. Most (85%) of the Pasteurella strains obtained from free-ranging bats in this study represented P. multocida ssp. septica. P. multocida ssp. multocida and Pasteurella species B were also identified in a small number of isolates. PFGE analysis correlated well with the sequencing results and revealed a high genetic diversity among bat-derived strains of P. multocida ssp. septica. Strains sharing identical or closely related SmaI fragment patterns were cultured from bats of different species, geographic origins, and years of isolation. The presence of numerous different P. multocida strains allows the assumption that Pasteurella infections in vespertilionid bats are not solely based on intra- but also on inter-species transmission. And indeed, our results present evidence of P. multocida infections in bats following cat predation.  相似文献   
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Habitat loss and fragmentation in agricultural landscapes lead to severe declines of abundance and richness of many insect species in the remaining isolated semi-natural habitats. We analysed possible barrier effects of large hedges and corridor effects of narrow grass strips that were hypothesized to affect foraging and dispersal of hymenopterans. We selected calcareous grasslands in the vicinity of Göttingen (Germany), which harbour high Hymenoptera diversity and are starting points for foraging and dispersal in the landscape. We installed pan traps to sample bees (i) on the grasslands; (ii) on grassland edges behind adjacent hedges (potential barriers) and without hedges; (iii) on grass strips in 100 m distance to the grassland, which were connected or unconnected to the grassland; and (iv) unconnected (isolated) grass strips in 300 m and 750 m distance to test for corridor and isolation effects on abundance and species richness of foraging wild bees. Additionally we provided trap nests for bees, wasps and their parasitoids on the grasslands and the strips. Species abundance and richness declined with increasing isolation from grasslands for foraging solitary bees, trap-nesting bees, wasps and parasitoids, but not for foraging bumblebees. Hedges did not confine movement of foraging bees. We found no mitigating effects of (100 m) corridor strips on any of the observed groups. We conclude that conservation of semi-natural habitats as sources of bee and wasp diversity is important and that grass strips act as sinks rather than corridors when high quality patches are nearby.  相似文献   
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