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Search: WFRF:(Chappell James) > (2016)

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1.
  • Luo, Yiqi, et al. (author)
  • Toward more realistic projections of soil carbon dynamics by Earth system models
  • 2016
  • In: Global Biogeochemical Cycles. - 0886-6236. ; 30:1, s. 40-56
  • Journal article (peer-reviewed)abstract
    • Soil carbon (C) is a critical component of Earth system models (ESMs), and its diverse representations are a major source of the large spread across models in the terrestrial C sink from the third to fifth assessment reports of the Intergovernmental Panel on Climate Change (IPCC). Improving soil C projections is of a high priority for Earth system modeling in the future IPCC and other assessments. To achieve this goal, we suggest that (1) model structures should reflect real-world processes, (2) parameters should be calibrated to match model outputs with observations, and (3) external forcing variables should accurately prescribe the environmental conditions that soils experience. First, most soil C cycle models simulate C input from litter production and C release through decomposition. The latter process has traditionally been represented by first-order decay functions, regulated primarily by temperature, moisture, litter quality, and soil texture. While this formulation well captures macroscopic soil organic C (SOC) dynamics, better understanding is needed of their underlying mechanisms as related to microbial processes, depth-dependent environmental controls, and other processes that strongly affect soil C dynamics. Second, incomplete use of observations in model parameterization is a major cause of bias in soil C projections from ESMs. Optimal parameter calibration with both pool- and flux-based data sets through data assimilation is among the highest priorities for near-term research to reduce biases among ESMs. Third, external variables are represented inconsistently among ESMs, leading to differences in modeled soil C dynamics. We recommend the implementation of traceability analyses to identify how external variables and model parameterizations influence SOC dynamics in different ESMs. Overall, projections of the terrestrial C sink can be substantially improved when reliable data sets are available to select the most representative model structure, constrain parameters, and prescribe forcing fields.
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2.
  • Shaffer, Carrie L., et al. (author)
  • Peptidomimetic Small Molecules Disrupt Type IV Secretion System Activity in Diverse Bacterial Pathogens
  • 2016
  • In: mBio. - 2161-2129 .- 2150-7511. ; 7:2
  • Journal article (peer-reviewed)abstract
    • Bacteria utilize complex type IV secretion systems (T4SSs) to translocate diverse effector proteins or DNA into target cells. Despite the importance of T4SSs in bacterial pathogenesis, the mechanism by which these translocation machineries deliver cargo across the bacterial envelope remains poorly understood, and very few studies have investigated the use of synthetic molecules to disrupt T4SS-mediated transport. Here, we describe two synthetic small molecules (C10 and KSK85) that disrupt T4SS-dependent processes in multiple bacterial pathogens. Helicobacter pylori exploits a pilus appendage associated with the cag T4SS to inject an oncogenic effector protein (CagA) and peptidoglycan into gastric epithelial cells. In H. pylori, KSK85 impedes biogenesis of the pilus appendage associated with the cag T4SS, while C10 disrupts cag T4SS activity without perturbing pilus assembly. In addition to the effects in H. pylori, we demonstrate that these compounds disrupt interbacterial DNA transfer by conjugative T4SSs in Escherichia coli and impede vir T4SS-mediated DNA delivery by Agrobacterium tumefaciens in a plant model of infection. Of note, C10 effectively disarmed dissemination of a derepressed IncF plasmid into a recipient bacterial population, thus demonstrating the potential of these compounds in mitigating the spread of antibiotic resistance determinants driven by conjugation. To our knowledge, this study is the first report of synthetic small molecules that impair delivery of both effector protein and DNA cargos by diverse T4SSs. IMPORTANCE Many human and plant pathogens utilize complex nanomachines called type IV secretion systems (T4SSs) to transport proteins and DNA to target cells. In addition to delivery of harmful effector proteins into target cells, T4SSs can disseminate genetic determinants that confer antibiotic resistance among bacterial populations. In this study, we sought to identify compounds that disrupt T4SS-mediated processes. Using the human gastric pathogen H. pylori as a model system, we identified and characterized two small molecules that prevent transfer of an oncogenic effector protein to host cells. We discovered that these small molecules also prevented the spread of antibiotic resistance plasmids in E. coli populations and diminished the transfer of tumor-inducing DNA from the plant pathogen A. tumefaciens to target cells. Thus, these compounds are versatile molecular tools that can be used to study and disarm these important bacterial machines.
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