Verification of a Methodology for Targeting Brush Control to Maximize Water Yield Through Hydrologic Modeling

Brush control strategies have been implemented for many traditional grasslands that have been impaired by wooded species. However, little information is known concerning what site specific characteristics may be most beneficial for increasing water yields by returning shrub encroached areas to native grasslands. This paper discusses a number of potential targeting criteria for successful brush management and outlines a methodology for testing the role of steep slope, brush density, and shallow soils on successful use of vegetation replacement for increasing water yield

Host Species Restriction of Middle East Respiratory Syndrome Coronavirus through Its Receptor, Dipeptidyl Peptidase 4

Middle East respiratory syndrome coronavirus (MERS-CoV) emerged in 2012. Recently, the MERS-CoV receptor dipeptidyl peptidase 4 (DPP4) was identified and the specific interaction of the receptor-binding domain (RBD) of MERS-CoV spike protein and DPP4 was determined by crystallography. Animal studies identified rhesus macaques but not hamsters, ferrets, or mice to be susceptible for MERS-CoV. Here, we investigated the role of DPP4 in this observed species tropism. Cell lines of human and nonhuman primate origin were permissive of MERS-CoV, whereas hamster, ferret, or mouse cell lines were not, despite the presence of DPP4. Expression of human DPP4 in nonsusceptible BHK and ferret cells enabled MERS-CoV replication, whereas expression of hamster or ferret DPP4 did not. Modeling the binding energies of MERS-CoV spike protein RBD to DPP4 of human (susceptible) or hamster (nonsusceptible) identified five amino acid residues involved in the DPP4-RBD interaction. Expression of hamster DPP4 containing the five human DPP4 amino acids rendered BHK cells susceptible to MERS-CoV, whereas expression of human DPP4 containing the five hamster DPP4 amino acids did not. Using the same approach, the potential of MERS-CoV to utilize the DPP4s of common Middle Eastern livestock was investigated. Modeling of the DPP4 and MERS-CoV RBD interaction predicted the ability of MERS-CoV to bind the DPP4s of camel, goat, cow, and sheep. Expression of the DPP4s of these species on BHK cells supported MERS-CoV replication. This suggests, together with the abundant DPP4 presence in the respiratory tract, that these species might be able to function as a MERS-CoV intermediate reservoir

Ecosystems as Commodity Frontiers - Challenges Faced by Land Set Aside as Protected Areas (PAs) in the Dubai Emirate, United Arab Emirates (UAE)

This chapter examines natural habitats in Dubai, UAE that the state has demarcated as protected areas (PAs) in an attempt to utilize them for recreational/economic purposes while also mitigating habitat fragmentation. The authors employ the concept of the ‘commodity frontier’ to demonstrate how these PAs have contributed to the ongoing commodification of land that began with the rise of modern agriculture in the mid-twentieth century. The rise of the oil economy in the mid-twentieth century stimulated significant development that, over time, has resulted in ecological degradation. In line with state conservation agendas aimed at greening the desert and preserving biodiversity, PAs also serve as a mechanism for promoting tourism. Ironically, these activities have in turn put further pressure on the country’s natural resources and desert ecology. The authors also present an example of a PA that has been effectively managed and could serve as a model of sustainable development

Infection with Mers-Cov Causes Lethal Pneumonia in the Common Marmoset

The availability of a robust disease model is essential for the development of countermeasures for Middle East respiratory syndrome coronavirus (MERS-CoV). While a rhesus macaque model of MERS-CoV has been established, the lack of uniform, severe disease in this model complicates the analysis of countermeasure studies. Modeling of the interaction between the MERS-CoV spike glycoprotein and its receptor dipeptidyl peptidase 4 predicted comparable interaction energies in common marmosets and humans. The suitability of the marmoset as a MERS-CoV model was tested by inoculation via combined intratracheal, intranasal, oral and ocular routes. Most of the marmosets developed a progressive severe pneumonia leading to euthanasia of some animals. Extensive lesions were evident in the lungs of all animals necropsied at different time points post inoculation. Some animals were also viremic; high viral loads were detected in the lungs of all infected animals, and total RNAseq demonstrated the induction of immune and inflammatory pathways. This is the first description of a severe, partially lethal, disease model of MERS-CoV, and as such will have a major impact on the ability to assess the efficacy of vaccines and treatment strategies as well as allowing more detailed pathogenesis studies

Unified Structural Representation of the southern California crust and upper mantle

We present a new, 3D description of crust and upper mantle velocity structure in southern California implemented as a Unified Structural Representation (USR). The USR is comprised of detailed basin velocity descriptions that are based on tens of thousands of direct velocity (Vp, Vs) measurements and incorporates the locations and displacement of major fault zones that influence basin structure. These basin descriptions were used to developed tomographic models of crust and upper mantle velocity and density structure, which were subsequently iterated and improved using 3D waveform adjoint tomography. A geotechnical layer (GTL) based on Vs30 measurements and consistent with the underlying velocity descriptions was also developed as an optional model component. The resulting model provides a detailed description of the structure of the southern California crust and upper mantle that reflects the complex tectonic history of the region. The crust thickens eastward as Moho depth varies from 10 to 40 km reflecting the transition from oceanic to continental crust. Deep sedimentary basins and underlying areas of thin crust reflect Neogene extensional tectonics overprinted by transpressional deformation and rapid sediment deposition since the late Pliocene. To illustrate the impact of this complex structure on strong ground motion forecasting, we simulate rupture of a proposed M 7.9 earthquake source in the Western Transverse Ranges. The results show distinct basin amplification and focusing of energy that reflects crustal structure described by the USR that is not captured by simpler velocity descriptions. We anticipate that the USR will be useful for a broad range of simulation and modeling efforts, including strong ground motion forecasting, dynamic rupture simulations, and fault system modeling. The USR is available through the Southern California Earthquake Center (SCEC) website (http://www.scec.org)

High-Content, High-Throughput Analysis of Cell Cycle Perturbations Induced by the HSP90 Inhibitor XL888

BACKGROUND: Many proteins that are dysregulated or mutated in cancer cells rely on the molecular chaperone HSP90 for their proper folding and activity, which has led to considerable interest in HSP90 as a cancer drug target. The diverse array of HSP90 client proteins encompasses oncogenic drivers, cell cycle components, and a variety of regulatory factors, so inhibition of HSP90 perturbs multiple cellular processes, including mitogenic signaling and cell cycle control. Although many reports have investigated HSP90 inhibition in the context of the cell cycle, no large-scale studies have examined potential correlations between cell genotype and the cell cycle phenotypes of HSP90 inhibition. METHODOLOGY/PRINCIPAL FINDINGS: To address this question, we developed a novel high-content, high-throughput cell cycle assay and profiled the effects of two distinct small molecule HSP90 inhibitors (XL888 and 17-AAG [17-allylamino-17-demethoxygeldanamycin]) in a large, genetically diverse panel of cancer cell lines. The cell cycle phenotypes of both inhibitors were strikingly similar and fell into three classes: accumulation in M-phase, G2-phase, or G1-phase. Accumulation in M-phase was the most prominent phenotype and notably, was also correlated with TP53 mutant status. We additionally observed unexpected complexity in the response of the cell cycle-associated client PLK1 to HSP90 inhibition, and we suggest that inhibitor-induced PLK1 depletion may contribute to the striking metaphase arrest phenotype seen in many of the M-arrested cell lines. CONCLUSIONS/SIGNIFICANCE: Our analysis of the cell cycle phenotypes induced by HSP90 inhibition in 25 cancer cell lines revealed that the phenotypic response was highly dependent on cellular genotype as well as on the concentration of HSP90 inhibitor and the time of treatment. M-phase arrest correlated with the presence of TP53 mutations, while G2 or G1 arrest was more commonly seen in cells bearing wt TP53. We draw upon previous literature to suggest an integrated model that accounts for these varying observations

Regulating Electricity Imports into RGGI: Toward a Legal, Workable Solution

This white paper evaluates the legal workability and constitutionality of what is frequently considered the most feasible mechanism for RGGI to use in regulating imports: an obligation on RGGI “load serving entities” (LSEs) – those companies responsible for supplying electricity to end-use customers – to purchase allowances to account for the emissions associated with the electricity they sell that is imported. Ultimately, although there are many design complexities yet to be worked out, we find that an LSE-centered approach could present a viable pathway forward for RGGI states’ regulation of imports. It is likely to create long-term price signals about the value of clean energy and to help prevent emissions “leakage.” And importantly, an LSE-centered mechanism has a good chance of being found constitutional under the dormant Commerce Clause and Federal Power Act preemption. However, an LSE-centered approach also has some features that may be considered drawbacks: it would likely increase consumer prices within RGGI without sending any immediate price signals to out-of-state generators to incentivize their emissions reductions (instead, such price signals will develop over time as new clean generation and demand-side resources come on-line). Given these features, RGGI states will want to think carefully about whether an LSE-centered imports mechanism accomplishes their goals

Regulating Imports into RGGI: Toward a Legal, Workable Solution

This white paper evaluates the legal workability and constitutionality of what is frequently considered the most feasible mechanism for RGGI to use in regulating imports: an obligation on RGGI “load serving entities” (LSEs) – those companies responsible for supplying electricity to end-use customers – to purchase allowances to account for the emissions associated with the electricity they sell that is imported. Ultimately, although there are many design complexities yet to be worked out, we find that an LSE-centered approach could present a viable pathway forward for RGGI states’ regulation of imports. It is likely to create long-term price signals about the value of clean energy and to help prevent emissions “leakage.” And importantly, an LSE-centered mechanism has a good chance of being found constitutional under the dormant Commerce Clause and Federal Power Act preemption. However, an LSE-centered approach also has some features that may be considered drawbacks: it would likely increase consumer prices within RGGI without sending any immediate price signals to out-of-state generators to incentivize their emissions reductions (instead, such price signals will develop over time as new clean generation and demand-side resources come on-line). Given these features, RGGI states will want to think carefully about whether an LSE-centered imports mechanism accomplishes their goals

Verification of a Methodology for Targeting Brush Control to Maximize Water Yield Through Hydrologic Modeling

Brush control strategies have been implemented for many traditional grasslands that have been impaired by wooded species. However, little information is known concerning what site specific characteristics may be most beneficial for increasing water yields by returning shrub encroached areas to native grasslands. This paper discusses a number of potential targeting criteria for successful brush management and outlines a methodology for testing the role of steep slope, brush density, and shallow soils on successful use of vegetation replacement for increasing water yield