Gene expression profiling of microglia infected by a highly neurovirulent murine leukemia virus: implications for neuropathogenesis

BACKGROUND: Certain murine leukemia viruses (MLVs) are capable of inducing progressive spongiform motor neuron disease in susceptible mice upon infection of the central nervous system (CNS). The major CNS parenchymal target of these neurovirulent retroviruses (NVs) are the microglia, whose infection is largely coincident with neuropathological changes. Despite this close association, the role of microglial infection in disease induction is still unknown. In this paper, we investigate the interaction of the highly virulent MLV, FrCasE, with microglia ex vivo to evaluate whether infection induces specific changes that could account for neurodegeneration. Specifically, we compared microglia infected with FrCasE, a related non-neurovirulent virus (NN) F43/Fr57E, or mock-infected, both at a basic virological level, and at the level of cellular gene expression using quantitative real time RT-PCR (qRT-PCR) and Afffymetrix 430A mouse gene chips. RESULTS: Basic virological comparison of NN, NV, and mock-infected microglia in culture did not reveal differences in virus expression that provided insight into neuropathogenesis. Therefore, microglial analysis was extended to ER stress gene induction based on previous experiments demonstrating ER stress induction in NV-infected mouse brains and cultured fibroblasts. Analysis of message levels for the ER stress genes BiP (grp78), CHOP (Gadd153), calreticulin, and grp58 in cultured microglia, and BiP and CHOP in microglia enriched fractions from infected mouse brains, indicated that FrCasE infection did not induce these ER stress genes either in vitro or in vivo. To broadly identify physiological changes resulting from NV infection of microglia in vitro, we undertook a gene array screen of more than 14,000 well-characterized murine genes and expressed sequence tags (ESTs). This analysis revealed only a small set of gene expression changes between infected and uninfected cells (<18). Remarkably, gene array comparison of NN- and NV-infected microglia revealed only 3 apparent gene expression differences. Validation experiments for these genes by Taqman real-time RT-PCR indicated that only single Ig IL-1 receptor related protein (SIGIRR) transcript was consistently altered in culture; however, SIGIRR changes were not observed in enriched microglial fractions from infected brains. CONCLUSION: The results from this study indicate that infection of microglia by the highly neurovirulent virus, FrCasE, does not induce overt physiological changes in this cell type when assessed ex vivo. In particular, NV does not induce microglial ER stress and thus, FrCasE-associated CNS ER stress likely results from NV interactions with another cell type or from neurodegeneration directly. The lack of NV-induced microglial gene expression changes suggests that FrCasE either affects properties unique to microglia in situ, alters the expression of microglial genes not represented in this survey, or affects microglial cellular processes at a post-transcriptional level. Alternatively, NV-infected microglia may simply serve as an unaffected conduit for persistent dissemination of virus to other neural cells where they produce acute neuropathogenic effects

Educating Health Professionals about Disability: A Review of Interventions

Health professionals need to understand the human rights and health needs of disabled people. This review of evidence on interventions demonstrates that a range of often innovative approaches have been trialled. Lectures by faculty are less effective in changing attitudes than contact with disabled people themselves. Existing examples of good practice need to be scaled up, and better and more long-term evaluations of impact are required

Potential of global croplands and bioenergy crops for climate change mitigation through deployment for enhanced weathering.

Conventional row crop agriculture for both food and fuel is a source of carbon dioxide (CO2) and nitrous oxide (N2O) to the atmosphere, and intensifying production on agricultural land increases the potential for soil C loss and soil acidification due to fertilizer use. Enhanced weathering (EW) in agricultural soils-applying crushed silicate rock as a soil amendment-is a method for combating global climate change while increasing nutrient availability to plants. EW uses land that is already producing food and fuel to sequester carbon (C), and reduces N2O loss through pH buffering. As biofuel use increases, EW in bioenergy crops offers the opportunity to sequester CO2 while reducing fossil fuel combustion. Uncertainties remain in the long-term effects and global implications of large-scale efforts to directly manipulate Earth's atmospheric CO2 composition, but EW in agricultural lands is an opportunity to employ these soils to sequester atmospheric C while benefitting crop production and the global climate

Consensus, uncertainties and challenges for perennial bioenergy crops and land-use

Perennial bioenergy crops have significant potential to reduce greenhouse gas (GHG) emissions and contribute to climate change mitigation by substituting for fossil fuels; yet delivering significant GHG savings will require substantial land-use change, globally. Over the last decade, research has delivered improved understanding of the environmental benefits and risks of this transition to perennial bioenergy crops, addressing concerns that the impacts of land conversion to perennial bioenergy crops could result in increased rather than decreased GHG emissions. For policymakers to assess the most cost-effective and sustainable options for deployment and climate change mitigation, synthesis of these studies is needed to support evidence-based decision making. In 2015, a workshop was convened with researchers, policymakers and industry/business representatives from the UK, EU and internationally. Outcomes from global research on bioenergy land-use change were compared to identify areas of consensus, key uncertainties, and research priorities. Here, we discuss the strength of evidence for and against six consensus statements summarising the effects of land-use change to perennial bioenergy crops on the cycling of carbon, nitrogen and water, in the context of the whole life-cycle of bioenergy production. Our analysis suggests that the direct impacts of dedicated perennial bioenergy crops on soil carbon and nitrous oxide are increasingly well understood and are often consistent with significant life cycle GHG mitigation from bioenergy relative to conventional energy sources. We conclude that the GHG balance of perennial bioenergy crop cultivation will often be favourable, with maximum GHG savings achieved where crops are grown on soils with low carbon stocks and conservative nutrient application, accruing additional environmental benefits such as improved water quality. The analysis reported here demonstrates there is a mature and increasingly comprehensive evidence base on the environmental benefits and risks of bioenergy cultivation which can support the development of a sustainable bioenergy industry

CO2 fertilization of Sphagnum peat mosses is modulated by water table level and other environmental factors

Sphagnum mosses account for most accumulated dead organic matter in peatlands. Therefore, understanding their responses to increasing atmospheric CO2 is needed for estimating peatland C balances under climate change. A key process is photorespiration: a major determinant of net photosynthetic C assimilation that depends on the CO2 to O-2 ratio. We used climate chambers to investigate photorespiratory responses of Sphagnum fuscum hummocks to recent increases in atmospheric CO2 (from 280 to 400 ppm) under different water table, temperature, and light intensity levels. We tested the photorespiratory variability using a novel method based on deuterium isotopomers (D6(S)/D6(R) ratio) of photosynthetic glucose. The effect of elevated CO2 on photorespiration was highly dependent on water table. At low water table (-20 cm), elevated CO2 suppressed photorespiration relative to C assimilation, thus substantially increasing the net primary production potential. In contrast, a high water table (similar to 0 cm) favored photorespiration and abolished this CO2 effect. The response was further tested for Sphagnum majus lawns at typical water table levels (similar to 0 and -7 cm), revealing no effect of CO2 under those conditions. Our results indicate that hummocks, which typically experience low water table levels, benefit from the 20th century's increase in atmospheric CO2

A process-based model of conifer forest structure and function with special emphasis on leaf lifespan

We describe the University of Sheffield Conifer Model (USCM), a process-based approach for simulating conifer forest carbon, nitrogen, and water fluxes by up-scaling widely applicable relationships between leaf lifespan and function. The USCM is designed to predict and analyze the biogeochemistry and biophysics of conifer forests that dominated the ice-free high-latitude regions under the high pCO2 “greenhouse” world 290–50 Myr ago. It will be of use in future research investigating controls on the contrasting distribution of ancient evergreen and deciduous forests between hemispheres, and their differential feedbacks on polar climate through the exchange of energy and materials with the atmosphere. Emphasis is placed on leaf lifespan because this trait can be determined from the anatomical characteristics of fossil conifer woods and influences a range of ecosystem processes. Extensive testing of simulated net primary production and partitioning, leaf area index, evapotranspiration, nitrogen uptake, and land surface energy partitioning showed close agreement with observations from sites across a wide climatic gradient. This indicates the generic utility of our model, and adequate representation of the key processes involved in forest function using only information on leaf lifespan, climate, and soils

Intensification differentially affects the delivery of multiple ecosystem services in subtropical and temperate grasslands

Intensification, the process of intensifying land management to enhance agricultural goods, results in “intensive” pastures that are planted with productive grasses and fertilized. These intensive pastures provide essential ecosystem services, including forage production for livestock. Understanding the synergies and tradeoffs of pasture intensification on the delivery of services across climatic regions is crucial to shape policies and incentives for better management of natural resources. Here, we investigated how grassland intensification affects key components of provisioning (forage productivity and quality), supporting (plant diversity) and regulating services (CO2 and CH4 fluxes) by comparing these services between intensive versus extensive pastures in subtropical and temperate pastures in the USDA Long-term Agroecosystem Research (LTAR) Network sites in Florida and Oklahoma, USA over multiple years. Our results suggest that grassland intensification led to a decrease in measured supporting and regulating services, but increased forage productivity in temperate pastures and forage digestibility in subtropical pastures. Intensification decreased the net CO2 sink of subtropical pastures while it did not affect the sink capacity of temperate pastures; and it also increased environmental CH4 emissions from subtropical pastures and reduced CH4 uptake in temperate pastures. Intensification enhanced the global warming potential associated with C fluxes of pastures in both ecoregions. Our study demonstrates that comparisons of agroecosystems in contrasting ecoregions can reveal important drivers of ecosystem services and general or region-specific opportunities and solutions to maintaining agricultural production and reducing environmental footprints. Further LTAR network-scale comparisons of multiple ecosystem services across croplands and grazinglands intensively vs extensively managed are warranted to inform the sustainable intensification of agriculture within US and beyond. Our results highlight that achieving both food security and environmental stewardship will involve the conservation of less intensively managed pastures while adopting sustainable strategies in intensively managed pastures

Enhanced weathering in the U.S. Corn Belt delivers carbon removal with agronomic benefits

Enhanced weathering (EW) with crushed basalt on farmlands is a promising scalable atmospheric carbon dioxide removal strategy that urgently requires performance assessment with commercial farming practices. Our large-scale replicated EW field trial in the heart of the U.S. Corn Belt shows cumulative time-integrated carbon sequestration of 15.4 +/- 4.1 t CO2 ha-1 over four years, with additional emissions mitigation of ~0.1 - 0.4 t CO2,e ha-1 yr-1 for soil nitrous oxide, a potent long-lived greenhouse gas. Maize and soybean yields increased 12-16% with EW following improved soil fertility, decreased soil acidification, and upregulation of root nutrient transport genes. Our findings suggest that widespread adoption of EW across farming sectors has the potential to contribute significantly to net-zero greenhouse gas emissions goals and global food and soil security

SPACE: the SPectroscopic, All-Sky Cosmic Explorer

We describe the scientific motivations, the mission concept and the instrumentation of SPACE, a class-M mission proposed for concept study at the first call of the ESA Cosmic-Vision 2015-2025 planning cycle. SPACE aims at producing the largest three-dimensional evolutionary map of the Universe over the past 10 billion years by taking near-IR spectra and measuring redshifts of more than half a billion galaxies at 0 < z < 2 down to AB approximately 23 over 37r sr of the sky. In addition, SPACE will also target a smaller sky field, performing a deep spectroscopic survey of millions of galaxies to AB approximately 26 and at 2 < z < l0+. Owing to the depth, redshift range, volume coverage and quality of its spectra, SPACE will reveal with unique sensitivity most of the fundamental cosmological signatures, including the power spectrum of density fluctuations and its turnover, the baryonic acoustic oscillations imprinted when matter and radiation decoupled, the distance-luminosity relation of cosmological supernovae, the evolution of the cosmic expansion rate, the growth rate of cosmic large-scale structure, the large scale distribution of galaxies. The datasets from the SPACE mission will represent a long lasting legacy that will be data mined for many years to come