Docking protein FRS2 links the protein tyrosine kinase RET and its oncogenic forms with the mitogen-activated protein kinase signaling cascade

The receptor tyrosine kinase RET functions as the signal transducing receptor for the GDNF (for "glial cell-derived neurotrophic factors") family of ligands. Mutations in the RET gene were implicated in Hirschsprung disease (HSCR), multiple endocrine neoplasia type 2 (MEN 2), and thyroid carcinomas. In this report we demonstrate that the docking protein FRS2 is tyrosine phosphorylated by ligand-stimulated and by constitutively activated oncogenic forms of RET. Complex formation between RET and FRS2 is mediated by binding of the phosphotyrosine-binding domain of FRS2 to pY1062, a residue in RET that also functions as a binding site for Shc. However, overexpression of FRS2 but not Shc potentiates mitogen-activated protein (MAP) kinase activation by RET oncoproteins. We demonstrate that oncogenic RET-PTC proteins are associated with FRS2 constitutively, leading to tyrosine phosphorylation of FRS2, MAP kinase stimulation, and cell proliferation. However, loss-of-function HSCR-associated RET mutants exhibit impaired FRS2 binding and reduced MAP kinase activation. These experiments demonstrate that FRS2 couples both ligand-regulated and oncogenic forms of RET, with the MAP kinase signaling cascade as part of the response of RET under normal biological conditions and pathological conditions, such as MEN 2 and papillary thyroid carcinomas.     

Modeling the effects of snowpack on heterotrophic respiration across northern temperate and high latitude regions: Comparison with measurements of atmospheric carbon dioxide in high latitudes

Simulations by global terrestrial biogeochemical models (TBMs) consistently underestimate the concentration of atmospheric carbon dioxide (CO₂ at high latitude monitoring stations during the non-growing season. We hypothesized that heterotrophic respiration is underestimated during the nongrowing season primarily because TBMs do not generally consider the insulative effects of snowpack on soil temperature. To evaluate this hypothesis, we compared the performance of baseline and modified versions of three TBMs in simulating the seasonal cycle of atmospheric CO₂ at high latitude CO₂ monitoring stations; the modified version maintained soil temperature at 0 °C when modeled snowpack was present. The three TBMs include the Carnegie-Ames-Stanford Approach (CASA), Century, and the Terrestrial Ecosystem Model (TEM). In comparison with the baseline simulation of each model, the snowpack simulations caused higher releases of CO₂ between November and March and greater uptake of CO₂ between June and August for latitudes north of 30° N. We coupled the monthly estimates of CO₂ exchange, the seasonal carbon dioxide flux fields generated by the HAMOCC3 seasonal ocean carbon cycle model, and fossil fuel source fields derived from standard sources to the three-dimensional atmospheric transport model TM2 forced by observed winds to simulate the seasonal cycle of atmospheric CO₂ at each of seven high latitude monitoring stations. In comparison to the CO₂ concentrations simulated with the baseline fluxes of each TBM, concentrations simulated using the snowpack fluxes are generally in better agreement with observed concentrations between August and March at each of the monitoring stations. Thus, representation of the insulative effects of snowpack in TBMs generally improves simulation of atmospheric CO₂ concentrations in high latitudes during both the late growing season and nongrowing season. These simulations highlight the global importance of biogeochemical processes during the nongrowing season in estimating carbon balance of ecosystems in northern high and temperate latitudes.     

A Preliminary Energy Return on Investment Analysis of Natural Gas from the Marcellus Shale

An analysis of the energy return on investment (EROI) of natural gas obtained from horizontal, hydraulically fractured wells in the Marcellus Shale was conducted using net external energy ratio methodology and available data and estimates of energy inputs and outputs. Used as sources of input data were estimates of carbon dioxide and nitrogen oxides emitted from the gas extraction processes, as well as fuel‐use reports from industry and other sources. Estimates of quantities of materials used and the associated embodied energy as well as other energy‐using steps were also developed from available data. Total input energy was compared with the energy expected to be made available to end users of the natural gas produced from a typical Marcellus well. The analysis indicates that the EROI of a typical well is likely between 64:1 and 112:1, with a mean of approximately 85:1. This range assumes an estimated ultimate recovery (EUR) of 3.0 billion cubic feet (Bcf) per well. EROI values are directly proportionate to EUR values. If the EUR is greater or lesser than 3 Bcf, the EROI would be proportionately higher or lower. EROI is also sensitive to the energy used or embedded in gathering and transmission pipelines and associated infrastructure and energy used for their construction, energy consumed in well drilling and well completion, and energy used for wastewater treatment.     

Intentional versus unintentional nitrogen use in the United States: trends, efficiency and implications

Human actions have both intentionally and unintentionally altered the global economy of nitrogen (N), with both positive and negative consequences for human health and welfare, the environment and climate change. Here we examine long-term trends in reactive N (Nr) creation and efficiencies of Nr use within the continental US. We estimate that human actions in the US have increased Nr inputs by at least ~5 times compared to pre-industrial conditions. Whereas N₂ fixation as a by-product of fossil fuel combustion accounted for ~1/4 of Nr inputs from the 1970s to 2000 (or ~7 Tg N year^?1), this value has dropped substantially since then (to <5 Tg N year^?1), owing to Clean Air Act amendments. As of 2007, national N use efficiency (NUE) of all combined N inputs was equal to ~40 %. This value increases to 55 % when considering intentional N inputs alone, with food, industrial goods, fuel and fiber production accounting for the largest Nr sinks, respectively. We estimate that 66 % of the N lost during the production of goods and services enters the air (as NO _x , NH₃, N₂O and N₂), with the remaining 34 % lost to various waterways. These Nr losses contribute to smog formation, acid rain, eutrophication, biodiversity declines and climate change. Hence we argue that an improved national NUE would: (i) benefit the US economy on the production side; (ii) reduce social damage costs; and (iii) help avoid some major climate change risks in the future.     

An Asymmetric Opening of HIV-1 Envelope Mediates Antibody-Dependent Cellular Cytotoxicity

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The Gut of Geographically Disparate Ciona intestinalis Harbors a Core Microbiota

It is now widely understood that all animals engage in complex interactions with bacteria (or microbes) throughout their various life stages. This ancient exchange can involve cooperation and has resulted in a wide range of evolved host-microbial interdependencies, including those observed in the gut. Ciona intestinalis, a filter-feeding basal chordate and classic developmental model that can be experimentally manipulated, is being employed to help define these relationships. Ciona larvae are first exposed internally to microbes upon the initiation of feeding in metamorphosed individuals; however, whether or not these microbes subsequently colonize the gut and whether or not Ciona forms relationships with specific bacteria in the gut remains unknown. In this report, we show that the Ciona gut not only is colonized by a complex community of bacteria, but also that samples from three geographically isolated populations reveal striking similarity in abundant operational taxonomic units (OTUs) consistent with the selection of a core community by the gut ecosystem.     

Uncertainty analysis of vegetation distribution in the northern high latitudes during the 21st century with a dynamic vegetation model

This study aims to assess how high-latitude vegetation may respond under various climate scenarios during the 21st century with a focus on analyzing model parameters induced uncertainty and how this uncertainty compares to the uncertainty induced by various climates. The analysis was based on a set of 10,000 Monte Carlo ensemble Lund-Potsdam-Jena (LPJ) simulations for the northern high latitudes (45(o)N and polewards) for the period 1900-2100. The LPJ Dynamic Global Vegetation Model (LPJ-DGVM) was run under contemporary and future climates from four Special Report Emission Scenarios (SRES), A1FI, A2, B1, and B2, based on the Hadley Centre General Circulation Model (GCM), and six climate scenarios, X901M, X902L, X903H, X904M, X905L, and X906H from the Integrated Global System Model (IGSM) at the Massachusetts Institute of Technology (MIT). In the current dynamic vegetation model, some parameters are more important than others in determining the vegetation distribution. Parameters that control plant carbon uptake and light-use efficiency have the predominant influence on the vegetation distribution of both woody and herbaceous plant functional types. The relative importance of different parameters varies temporally and spatially and is influenced by climate inputs. In addition to climate, these parameters play an important role in determining the vegetation distribution in the region. The parameter-based uncertainties contribute most to the total uncertainty. The current warming conditions lead to a complexity of vegetation responses in the region. Temperate trees will be more sensitive to climate variability, compared with boreal forest trees and C3 perennial grasses. This sensitivity would result in a unanimous northward greenness migration due to anomalous warming in the northern high latitudes. Temporally, boreal needleleaved evergreen plants are projected to decline considerably, and a large portion of C3 perennial grass is projected to disappear by the end of the 21st century. In contrast, the area of temperate trees would increase, especially under the most extreme A1FI scenario. As the warming continues, the northward greenness expansion in the Arctic region could continue.