A metagenomic analysis was performed on a soil profile from a wet tundra site in northern Alaska. The goal was to link existing biogeochemical knowledge of the system with the organisms and genes responsible for the relevant metabolic pathways. We specifically investigated how the importance of iron (Fe) oxides and humic substances (HS) as terminal electron acceptors in this ecosystem is expressed genetically, and how respiratory and fermentative processes varied with soil depth into the active layer and into the upper permafrost. Overall, the metagenomes reflected a microbial community enriched in a diverse range of anaerobic pathways, with a preponderance of known Fe reducing species at all depths in the profile. The abundance of sequences associated with anaerobic metabolic processes generally increased with depth, while aerobic cytochrome c oxidases decreased. Methanogenesis genes and methanogen genomes followed the pattern of CH4 fluxes : they increased steeply with depth into the active layer, but declined somewhat over the transition zone between the lower active layer and the upper permafrost. The latter was relatively enriched in fermentative and anaerobic respiratory pathways. A survey of decaheme cytochromes (MtrA, MtrC and their homologs) revealed that this is a promising approach to identifying potential reducers of Fe(III) or HS, and indicated a possible role for Acidobacteria as Fe reducers in these soils. Methanogens appear to coexist in the same layers, though in lower abundance, with Fe reducing bacteria and other potential competitors, including acetogens. These observations provide a rich set of hypotheses for further targeted study.
Cutaneous melanoma is increasing in incidence at one of the highest rates for any form of cancer in the USA, with a current lifetime incidence of 1 in 68. Although early-stage disease is often curable, the survival rate for advanced disease is low, with an average life expectancy of 6-10 months. Knowledge of the molecular alterations associated with melanoma development and progression is expected to lead to improved therapies and outcomes. Major progress in defining the molecular alterations associated with the evolution of melanoma came in 2002, through a systematic genome-wide assessment of cancer-associated pathways. Large-scale sequencing of growth-associated genes in a variety of cancers identified a high frequency (>60%) of activating mutations of the BRAF kinase gene in human melanomas. This discovery has prompted a large number of studies evaluating the biological significance of BRAF kinase mutations in the initiation and progression of melanoma, and their importance for the development of novel melanoma therapies. Here we review the most recent studies of BRAF kinase in the pathogenesis of melanoma and their implications for defining BRAF kinase as a therapeutic point of interest in melanoma.
Perioperative management of cardiovascular surgical procedures requiring cardiopulmonary bypass (CPB) in patients with hemophilia A poses a clinical challenge in coagulation management. Use of CPB requires the administration of an anticoagulant, usually unfractionated heparin, and also causes dilutional coagulopathy, platelet dysfunction or platelet consumption coagulopathy. Hypothermia and activation of the inflammatory cascade also affect coagulation. The effects of CPB on circulating levels of factor VIII have not been clearly defined. In this review, the effects of CPB and hemodilution on FVIII are shown in a case presentation, and perioperative laboratory testing in patients with hemophilia A having cardiac surgery is discussed along with perioperative and postoperative coagulation management.
Permafrost is an extreme habitat yet it hosts microbial populations that remain active over millennia. Using permafrost collected from a Pleistocene chronosequence (19 to 33 ka), we hypothesized that the functional genetic potential of microbial communities in permafrost would reflect microbial strategies to metabolize permafrost soluble organic matter (OM) in situ over geologic time. We also hypothesized that changes in the metagenome across the chronosequence would correlate with shifts in carbon chemistry, permafrost age, and paleoclimate at the time of permafrost formation. We combined high-resolution characterization of water-soluble OM by Fourier-transform ion-cyclotron-resonance mass spectrometry (FT-ICR MS), quantification of organic anions in permafrost water extracts, and metagenomic sequencing to better understand the relationships between the molecular-level composition of potentially bioavailable OM, the microbial community, and permafrost age. Both age and paleoclimate had marked effects on both the molecular composition of dissolved OM and the microbial community. The relative abundance of genes associated with hydrogenotrophic methanogenesis, carbohydrate active enzyme families, nominal oxidation state of carbon (NOSC), and number of identifiable molecular formulae significantly decreased with increasing age. In contrast, genes associated with fermentation of short chain fatty acids (SCFAs), the concentration of SCFAs and ammonium all significantly increased with age. We present a conceptual model of microbial metabolism in permafrost based on fermentation of OM and the buildup of organic acids that helps to explain the unique chemistry of ancient permafrost soils. These findings imply long-term in situ microbial turnover of ancient permafrost OM and that this pooled biolabile OM could prime ancient permafrost soils for a larger and more rapid microbial response to thaw compared to younger permafrost soils.
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