Uncertainty in United States coastal wetland greenhouse gas inventorying

© The Author(s), 2018. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Environmental Research Letters 13 (2018): 115005, doi:10.1088/1748-9326/aae157.Coastal wetlands store carbon dioxide (CO2) and emit CO2 and methane (CH4) making them an important part of greenhouse gas (GHG) inventorying. In the contiguous United States (CONUS), a coastal wetland inventory was recently calculated by combining maps of wetland type and change with soil, biomass, and CH4 flux data from a literature review. We assess uncertainty in this developing carbon monitoring system to quantify confidence in the inventory process itself and to prioritize future research. We provide a value-added analysis by defining types and scales of uncertainty for assumptions, burial and emissions datasets, and wetland maps, simulating 10 000 iterations of a simplified version of the inventory, and performing a sensitivity analysis. Coastal wetlands were likely a source of net-CO2-equivalent (CO2e) emissions from 2006–2011. Although stable estuarine wetlands were likely a CO2e sink, this effect was counteracted by catastrophic soil losses in the Gulf Coast, and CH4 emissions from tidal freshwater wetlands. The direction and magnitude of total CONUS CO2e flux were most sensitive to uncertainty in emissions and burial data, and assumptions about how to calculate the inventory. Critical data uncertainties included CH4 emissions for stable freshwater wetlands and carbon burial rates for all coastal wetlands. Critical assumptions included the average depth of soil affected by erosion events, the method used to convert CH4 fluxes to CO2e, and the fraction of carbon lost to the atmosphere following an erosion event. The inventory was relatively insensitive to mapping uncertainties. Future versions could be improved by collecting additional data, especially the depth affected by loss events, and by better mapping salinity and inundation gradients relevant to key GHG fluxes. Social Media Abstract: US coastal wetlands were a recent and uncertain source of greenhouse gasses because of CH4 and erosion.Financial support was provided primarily by NASA Carbon Monitoring Systems (NNH14AY67I) and the USGS Land Carbon Program, with additional support from The Smithsonian Institution, The Coastal Carbon Research Coordination Network (DEB-1655622), and NOAA Grant: NA16NMF4630103

Fixation and Spread of Somatic Mutations in Adult Human Colonic Epithelium.

We investigated the means and timing by which mutations become fixed in the human colonic epithelium by visualizing somatic clones and mathematical inference. Fixation requires two sequential steps. First, one of approximately seven active stem cells residing within each colonic crypt has to be mutated. Second, the mutated stem cell has to replace neighbors to populate the entire crypt in a process that takes several years. Subsequent clonal expansion due to crypt fission is infrequent for neutral mutations (around 0.7% of all crypts undergo fission in a single year). Pro-oncogenic mutations subvert both stem cell replacement to accelerate fixation and clonal expansion by crypt fission to achieve high mutant allele frequencies with age. The benchmarking of these behaviors allows the advantage associated with different gene-specific mutations to be compared irrespective of the cellular mechanisms by which they are conferred

Accuracy and precision of tidal wetland soil carbon mapping in the conterminous United States

© The Author(s), 2018. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Scientific Reports 8 (2018): 9478, doi:10.1038/s41598-018-26948-7.Tidal wetlands produce long-term soil organic carbon (C) stocks. Thus for carbon accounting purposes, we need accurate and precise information on the magnitude and spatial distribution of those stocks. We assembled and analyzed an unprecedented soil core dataset, and tested three strategies for mapping carbon stocks: applying the average value from the synthesis to mapped tidal wetlands, applying models fit using empirical data and applied using soil, vegetation and salinity maps, and relying on independently generated soil carbon maps. Soil carbon stocks were far lower on average and varied less spatially and with depth than stocks calculated from available soils maps. Further, variation in carbon density was not well-predicted based on climate, salinity, vegetation, or soil classes. Instead, the assembled dataset showed that carbon density across the conterminous united states (CONUS) was normally distributed, with a predictable range of observations. We identified the simplest strategy, applying mean carbon density (27.0 kg C m−3), as the best performing strategy, and conservatively estimated that the top meter of CONUS tidal wetland soil contains 0.72 petagrams C. This strategy could provide standardization in CONUS tidal carbon accounting until such a time as modeling and mapping advancements can quantitatively improve accuracy and precision.Synthesis efforts were funded by NASA Carbon Monitoring System (CMS; NNH14AY67I), USGS LandCarbon and the Smithsonian Institution. J.R.H. was additionally supported by the NSF-funded Coastal Carbon Research Coordination Network while completing this manuscript (DEB-1655622). J.M.S. coring efforts were funded by NSF (EAR-1204079). B.P.H. coring efforts were funded by Earth Observatory (Publication Number 197)

Variation in Organ-Specific \u3ci\u3ePIK3CA\u3c/i\u3e and \u3ci\u3eKRAS\u3c/i\u3e Mutant Levels in Normal Human Tissues Correlates With Mutation Prevalence in Corresponding Carcinomas

Large-scale sequencing efforts have described the mutational complexity of individual cancers and identified mutations prevalent in different cancers. As a complementary approach, allele specific competitive blocker PCR (ACB-PCR) is being used to quantify levels of hotspot cancer driver mutations (CDMs) with high sensitivity, to elucidate the tissue-specific properties of CDMs, their occurrence as tumor cell subpopulations, and their occurrence in normal tissues. Here we report measurements of PIK3CA H1047R mutant fraction (MF) in normal colonic mucosa, normal lung, colonic adenomas, colonic adenocarcinomas, and lung adenocarcinomas. We report PIK3CA E545K MF measurements in those tissues, as well as in normal breast, normal thyroid, mammary ductal carcinomas, and papillary thyroid carcinomas. We report KRAS G12D and G12V MF measurements in normal colon. These MF measurements were integrated with previously published ACB-PCR data on KRAS G12D, KRAS G12V, and PIK3CA H1047R. Analysis of these data revealed a correlation between the degree of interindividual variability in these mutations (as log10 MF standard deviation) in normal tissues and the frequencies with which the mutations are detected in carcinomas of the corresponding organs in the COSMIC database. This novel observation has important implications. It suggests that interindividual variability in mutation levels of normal tissues may be used as a metric to identify mutations with critical early roles in tissue-specific carcinogenesis. Additionally, it raises the possibility that personalized cancer therapeutics, developed to target specifically activated oncogenic products, might be repurposed as prophylactic therapies to reduce the accumulation of cells carrying CDMs and, thereby, reduce future cancer risk

Low-Frequency Mutational Heterogeneity of Invasive Ductal Carcinoma Subtypes: Information to Direct Precision Oncology

Information regarding the role of low-frequency hotspot cancer-driver mutations (CDMs) in breast carcinogenesis and therapeutic response is limited. Using the sensitive and quantitative Allele-specific Competitor Blocker PCR (ACB-PCR) approach, mutant fractions (MFs) of six CDMs (PIK3CA H1047R and E545K, KRAS G12D and G12V, HRAS G12D, and BRAF V600E) were quantified in invasive ductal carcinomas (IDCs; including ~20 samples per subtype). Measurable levels (i.e., ≥ 1 × 10−5, the lowest ACB-PCR standard employed) of the PIK3CA H1047R, PIK3CA E545K, KRAS G12D, KRAS G12V, HRAS G12D, and BRAF V600E mutations were observed in 34/81 (42%), 29/81 (36%), 51/81 (63%), 9/81 (11%), 70/81 (86%), and 48/81 (59%) of IDCs, respectively. Correlation analysis using available clinicopathological information revealed that PIK3CA H1047R and BRAF V600E MFs correlate positively with maximum tumor dimension. Analysis of IDC subtypes revealed minor mutant subpopulations of critical genes in the MAP kinase pathway (KRAS, HRAS, and BRAF) were prevalent across IDC subtypes. Few triple-negative breast cancers (TNBCs) had appreciable levels of PIK3CA mutation, suggesting that individuals with TNBC may be less responsive to inhibitors of the PI3K/AKT/mTOR pathway. These results suggest that low-frequency hotspot CDMs contribute significantly to the intertumoral and intratumoral genetic heterogeneity of IDCs, which has the potential to impact precision oncology approaches

Ovarian effects of prenatal exposure to benzo[a]pyrene: Roles of embryonic and maternal glutathione status.

Females deficient in the glutamate cysteine ligase modifier subunit (Gclm) of the rate-limiting enzyme in glutathione synthesis are more sensitive to ovarian follicle depletion and tumorigenesisby prenatal benzo[a]pyrene (BaP) exposure than Gclm+/+ mice. We investigated effects of prenatal exposure to BaP on reproductive development and ovarian mutations in Kras, a commonly mutated gene in epithelial ovarian tumors. Pregnantmice were dosed from gestational day 6.5 through 15.5 with 2mg/kg/day BaP or vehicle. Puberty onset occurred 5 days earlier in F1 daughters of all Gclm genotypes exposed to BaP compared to controls. Gclm+/- F1 daughters of Gclm+/- mothers and wildtype F1 daughters of wildtype mothers had similar depletion of ovarian follicles following prenatal exposure to BaP, suggesting that maternal Gclm genotype does not modify ovarian effects of prenatal BaP. We observed no BaP treatment or Gclm genotype related differences in ovarian Kras codon 12 mutations in F1 offspring

Breast Cancer Heterogeneity Examined by High-Sensitivity Quantification of PIK3CA, KRAS, HRAS, and BRAF Mutations in Normal Breast and Ductal Carcinomas

Mutant cancer subpopulations have the potential to derail durable patient responses to molecularly targeted cancer therapeutics, yet the prevalence and size of such subpopulations are largely unexplored. We employed the sensitive and quantitative Allele-specific Competitive Blocker PCR approach to characterize mutant cancer subpopulations in ductal carcinomas (DCs), examining five specific hotspot point mutations (PIK3CA H1047R, KRAS G12D, KRAS G12V, HRAS G12D, and BRAF V600E). As an approach to aid interpretation of the DC results, the mutations were also quantified in normal breast tissue. Overall, the mutations were prevalent in normal breast and DCs, with 9/9 DCs having measureable levels of at least three of the five mutations. HRAS G12D was significantly increased in DCs as compared to normal breast. The most frequent point mutation reported in DC by DNA sequencing, PIK3CA H1047R, was detected in all normal breast tissue and DC samples and was present at remarkably high levels (mutant fractions of 1.1 × 10−3 to 4.6 × 10−2) in 4/10 normal breast samples. In normal breast tissue samples, PIK3CA mutation levels were positively correlated with age. However, the PIK3CA H1047R mutant fraction distributions for normal breast tissues and DCs were similar. The results suggest PIK3CA H1047R mutant cells have a selective advantage in breast, contribute to breast cancer susceptibility, and drive tumor progression during breast carcinogenesis, even when present as only a subpopulation of tumor cells