Inflammatory cytokine, IL-1β, regulates glial glutamate transporter via microRNA-181a in vitro

Glutamate overload triggers synaptic and neuronal loss that potentially contributes to neurodegenerative diseases including Alzheimer's disease (AD). Glutamate clearance and regulation at synaptic clefts is primarily mediated by glial glutamate transporter 1 (GLT-1). We determined that inflammatory cytokines significantly upregulated GLT-1 through microRNA-181a-mediated post-transcriptional modifications. Unveiling the key underlying mechanisms modulating GLT-1 helps better understand its physiological and pathological interactions with cytokines. Primary murine astrocyte and neuron co-culture received 20 ng/mL IL-1β, TNF-α, or IL-6 for 48 h. Soluble proteins or total RNA were extracted after treatment for further analyses. Treatment with inflammatory cytokines, IL-1β and TNF-α, but not IL-6, significantly increased GLT-1 steady-state levels (p≤0.05) without affecting mRNA levels, suggesting the cytokine-induced GLT-1 was regulated through post-transcriptional modifications. Among the candidate microRNAs predicted to modulate GLT-1, only microRNA-181a was significantly decreased following the IL-1β treatment (p≤0.05). Co-treatment of microRNA-181a mimic in IL-1β-treated primary astrocytes and neurons effectively blocked the IL-1β-induced upregulation of GLT-1. Lastly, we attempted to determine the link between GLT-1 and microRNA-181a in human AD brains. A significant reduction of GLT-1 was found in AD hippocampus tissues, and the ratio of mature microRNA-181a over primary microRNA-181a had an increasing tendency in AD. MicroRNA-181a controls rapid modifications of GLT-1 levels in astrocytes. Cytokine-induced inhibition of microRNA-181a and subsequent upregulation of GLT-1 may have physiological implications in synaptic plasticity while aberrant maturation of microRNA-181a may be involved in pathological consequences in AD

Ceftriaxone ameliorates tau pathology and cognitive decline via restoration of glial glutamate transporter in a mouse model of Alzheimer's disease

Glial glutamate transporter, GLT-1, is the major Na+-driven glutamate transporter to control glutamate levels in synapses and prevent glutamate-induced excitotoxicity implicated in neurodegenerative disorders including Alzheimer's disease (AD). Significant functional loss of GLT-1 has been reported to correlate well with synaptic degeneration and severity of cognitive impairment among AD patients, yet the underlying molecular mechanism and its pathological consequence in AD are not well understood. Here, we find the temporal decrease in GLT-1 levels in the hippocampus of the 3xTg-AD mouse model and that the pharmacological upregulation of GLT-1 significantly ameliorates the age-dependent pathological tau accumulation, restores synaptic proteins, and rescues cognitive decline with minimal effects on Ab pathology. In primary neuron and astrocyte coculture, naturally secreted A beta species significantly downregulate GLT-1 steady-state and expression levels. Taken together, our data strongly suggest that GLT-1 restoration is neuroprotective and A beta-induced astrocyte dysfunction represented by a functional loss of GLT-1 may serve as one of the major pathological links between Ab and tau patholog

Historical U.S. Cropland Areas and the Potential for Bioenergy Production on Abandoned Croplands

Agriculture is historically a dominant form of global environmental degradation, and the potential for increased future degradation may be driven by growing demand for food and biofuels. While these impacts have been explored using global gridded maps of croplands, such maps are based on relatively coarse spatial data. Here, we apply high-resolution cropland inventories for the conterminous U.S. with a land-use model to develop historical gridded cropland areas for the years 1850–2000 and year 2000 abandoned cropland maps. While the historical cropland maps are consistent with generally accepted land-use trends, our U.S. abandoned cropland estimates of 68 Mha are as much as 70% larger than previous gridded estimates due to a reduction in aggregation effects. Renewed cultivation on the subset of abandoned croplands that have not become forests or urban lands represents one approach to mitigating the future expansion of agriculture. Potential bioenergy production from these abandoned lands using a wide range of biomass yields and conversion efficiencies has an upper-limit of 5–30% of the current U.S. primary energy demand or 4–30% of the current U.S. liquid fuel demand

Inflammatory Cytokine IL-1β Downregulates Endothelial LRP1 via MicroRNA-mediated Gene Silencing

Effective clearance of neurotoxic amyloid-beta (Aβ) from the brain is a critical process to prevent Alzheimer's disease (AD). One major clearance mechanism is Aβ transcytosis mediated by low-density lipoprotein receptor-related protein 1 (LRP1) in capillary endothelial cells. A marked loss of endothelial LRP1 is found in AD brains and is believed to significantly impair Aβ clearance. Recently, we demonstrated that pro-inflammatory cytokines IL-1β, IL-6 and TNF-α, significantly down-regulated LRP1 in human primary microvascular endothelial cells (MVECs). In this study, we sought to determine the underlying molecular mechanism by which IL-1β led to LRP1 loss in MVECs. Reduced LRP1 protein and transcript were detected up to 24 h post-exposure and returned to the baseline levels after 48 h post-exposure with 1 ng/ml IL-1β. This reduction was in part mediated by microRNA-205-5p, -200b-3p, and -200c-3p, as these microRNAs were concomitantly upregulated in MVECs exposed to IL-1β. Synthetic microRNA-205-5p, -200b-3p, and -200c-3p mimics recapitulated LRP1 loss in MVECs without IL-1β, and their synthetic antagomirs effectively reversed IL-1β-mediated LRP1 loss. Importantly, we found that the expression of these three microRNAs was controlled by NF-κB as pharmacological NF-κB inhibitor, BMS-345541, inhibited the IL-1β-mediated upregulation of these microRNAs and rescued LRP1 expression. siRNA-mediated silencing of IκB in MVECs elevated microRNA-200b-3p and decreased LRP1 transcript, partially confirming our overall findings. In conclusion, our study provides a mechanism by which pro-inflammatory IL-1β instigates the suppression of LRP1 expression in MVECs. Our findings could implicate spatiotemporal loss of LRP1 and impairment of the LRP1-mediated clearance mechanism by endothelial cells

Regulation of T cells and cytokines by the interleukin-10 (IL-10)-family cytokines IL-19, IL-20, IL-22, IL-24 and IL-26

PubMedID: 16365913The family of IL-10-related cytokines includes several human members, IL-19, IL-20, IL-22, IL-24 and IL-26, and a series of herpesviral and poxviral paralogs. Some of these cytokines share common receptor subunits. In this study, we investigated the effects of these cytokines on naive T cell differentiation, antigen-specific T cell suppression, survival and expression of surface markers in comparison to IL-10 and cytomegalovirus (CMV)-IL-10. Human CD45RA+ T cells were stimulated in the presence of IL-10-family cytokines in sequential 12-day cycles. After three to four cycles of stimulation, IL-10 and CMV-IL-10 led to increased IFN-? and IL-10 but decreased IL-4 and IL-13. Interestingly, long-term exposure of T cells to IL-19, IL-20 and IL-22 down-regulated IFN-? but upregulated IL-4 and IL-13 in T cells and supported the polarization of naive T cells to Th2-like cells. In contrast, neutralization of endogenous IL-22 activity by IL-22-binding protein decreased IL-4, IL-13 and IFN-? synthesis. The antigen-specific suppressor activity of IL-10 and CMV-IL-10 was not observed for any of the other IL-10-family cytokines. These data demonstrate that IL-19, IL-20 and IL-22 may participate in T cell-mediated diseases by distinct regulation of T cell cytokine profiles. © 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Seasonal energy storage using bioenergy production from abandoned croplands

Bioenergy has the unique potential to provide a dispatchable and carbon-negative component to renewable energy portfolios. However, the sustainability, spatial distribution, and capacity for bioenergy are critically dependent on highly uncertain land-use impacts of biomass agriculture. Biomass cultivation on abandoned agriculture lands is thought to reduce land-use impacts relative to biomass production on currently used croplands. While coarse global estimates of abandoned agriculture lands have been used for large-scale bioenergy assessments, more practical technological and policy applications will require regional, high-resolution information on land availability. Here, we present US county-level estimates of the magnitude and distribution of abandoned cropland and potential bioenergy production on this land using remote sensing data, agriculture inventories, and land-use modeling. These abandoned land estimates are 61% larger than previous estimates for the US, mainly due to the coarse resolution of data applied in previous studies. We apply the land availability results to consider the capacity of biomass electricity to meet the seasonal energy storage requirement in a national energy system that is dominated by wind and solar electricity production. Bioenergy from abandoned croplands can supply most of the seasonal storage needs for a range of energy production scenarios, regions, and biomass yield estimates. These data provide the basis for further down-scaling using models of spatially gridded land-use areas as well as a range of applications for the exploration of bioenergy sustainability

Large variability in ecosystem models explains uncertainty in a critical parameter for quantifying GPP with carbonyl sulphide

Regional gross primary productivity (GPP) estimates are crucial to estimating carbon-climate feedbacks but are highly uncertain with existing methods. An emerging approach uses atmospheric carbonyl sulphide (COS) as a tracer for carbon dioxide: COS plant uptake is simulated by scaling GPP. A critical parameter for this method is leaf-scale relative uptake (LRU). Plant chamber and eddy covariance studies find a narrow range of LRU values but some atmospheric modelling studies assign values well outside this range. Here we study this discrepancy by conducting new regional chemical transport simulations for North America using the underlying data from previous studies. We find the wide range of ecosystem model GPP estimates can explain the discrepancy in LRU values. We also find that COS concentration uncertainty is more sensitive to GPP uncertainty than to LRU parameter uncertainty. These results support the COS tracer technique as a useful approach for constraining GPP estimates

Energy and water co-benefits from covering canals with solar panels

Solar-power development over canals is an emerging response to the energy-water-food nexus that can result in multiple benefits for water and energy infrastructure. Case studies of over-canal solar photovoltaic (PV) arrays have demonstrated enhanced PV performance due to the cooler microclimate next to the canal. Further, shade from the PV panels has been shown to mitigate evaporation and could mitigate aquatic weed growth. However, the evaporation savings and financial co-benefits have not been quantified across major canal systems. Here we use regional hydrologic and techno-economic simulations of solar PV panels covering California’s 6350 km canal network, which is the world’s largest conveyance system and covers a wide range of climates, insolation rates, and water costs. We find that over-canal solar could reduce annual evaporation by an average of 39 ± 12 thousand m3 per kilometer of canals. Furthermore, the financial benefits from shading the canals outweigh the added costs of cable-support structures required to span canals. The net present value (NPV) of over-canal solar exceeds conventional over-ground solar by 20% to 50%, challenging the convention of leaving canals uncovered and calling into question our understanding of the most economic locations to locate solar power.&nbsp

Energy and water co-benefits from covering canals with solar panels

Solar-power development over canals is an emerging response to the energy-water-food nexus that can result in multiple benefits for water and energy infrastructure. Case studies of over-canal solar photovoltaic (PV) arrays have demonstrated enhanced PV performance due to the cooler microclimate next to the canal. Further, shade from the PV panels has been shown to mitigate evaporation and could mitigate aquatic weed growth. However, the evaporation savings and financial co-benefits have not been quantified across major canal systems. Here we use regional hydrologic and techno-economic simulations of solar PV panels covering California’s 6350 km canal network, which is the world’s largest conveyance system and covers a wide range of climates, insolation rates, and water costs. We find that over-canal solar could reduce annual evaporation by an average of 39 ± 12 thousand m3 per kilometer of canals. Furthermore, the financial benefits from shading the canals outweigh the added costs of cable-support structures required to span canals. The net present value (NPV) of over-canal solar exceeds conventional over-ground solar by 20% to 50%, challenging the convention of leaving canals uncovered and calling into question our understanding of the most economic locations to locate solar power.&nbsp