Loss of angiotensin II receptor expression in dopamine neurons in Parkinson’s disease correlates with pathological progression and is accompanied by increases in Nox4- and 8-OH guanosine-related nucleic acid oxidation and caspase-3 activation

In rodent models of Parkinsons disease (PD), dopamine neuron loss is accompanied by increased expression of angiotensin II (AngII), its type 1 receptor (AT1), and NADPH oxidase (Nox) in the nigral dopamine neurons and microglia. AT1 blockers (ARBs) stymie such oxidative damage and neuron loss. Whether changes in the AngII/AT1/Nox4 axis contribute to Parkinson neuropathogenesis is unknown. Here, we studied the distribution of AT1 and Nox4 in dopamine neurons in two nigral subregions: the less affected calbindin-rich matrix and the first-affected calbindin-poor nigrosome 1 of three patients, who were clinically asymptomatic, but had nigral dopamine cell loss and Braak stages consistent with a neuropathological diagnosis of PD (prePD). For comparison, five clinically- and neuropathologically-confirmed PD patients and seven age-matched control patients (AMC) were examined.AT1 and Nox4 immunoreactivity was noted in dopamine neurons in both the matrix and the nigrosome 1. The total cellular levels of AT1 in surviving dopamine neurons in the matrix and nigrosome 1 declined from AMC>prePD>PD, suggesting that an AngII/AT1/Nox4 axis orders neurodegenerative progression. In this vein, the loss of dopamine neurons was paralleled by a decline in total AT1 per surviving dopamine neuron. Similarly, AT1 in the nuclei of surviving neurons in the nigral matrix declined with disease progression, i.e., AMC>prePD>PD. In contrast, in nigrosome 1, the expression of nuclear AT1 was unaffected and similar in all groups. The ratio of nuclear AT1 to total AT1 (nuclear + cytoplasmic + membrane) in dopamine neurons increased stepwise from AMC to prePD to PD. The proportional increase in nuclear AT1 in dopamine neurons in nigrosome 1 of prePD and PD patients was accompanied by elevated nuclear expression of Nox4, oxidative damage to DNA, and caspase-3-mediated cell loss.Our observations are consistent with the idea that AngII/AT1/Nox4 axis-mediated oxidative stress gives rise to the dopamine neuron dysfunction and loss characteristic of the neuropathological and clinical manifestations of PD and suggest that the chance for a neuron to survive increases in association with lower total as well as nuclear AT1 expression. Our results support the need for further evaluation of ARBs as disease-modifying agents in PD

Impacts of peat bulk density, ash deposition and rainwater chemistry on establishment of peatland mosses

Background and aims Peatland moss communities play an important role in ecosystem function. Drivers such as fire and atmospheric pollution have the capacity to influence mosses via multiple pathways. Here, we investigate physical and chemical processes which may influence establishment and growth of three key moss species in peatlands. Methods A controlled factorial experiment investigated the effects of different peat bulk density, ash deposition and rainwater chemistry treatments on the growth of Sphagnum capillifolium, S. fallax and Campylopus introflexus. Results Higher peat bulk density limited growth of both Sphagnum species. S. capillifolium and C. introflexus responded positively to ash deposition. Less polluted rain limited growth of C. introflexus. Biomass was well correlated with percentage cover in all three species. Conclusions Peat bulk density increases caused by fire or drainage can limit Sphagnum establishment and growth, potentially threatening peatland function. Ash inputs may have direct benefits for some Sphagnum species, but are also likely to increase competition from other bryophytes and vascular plants which may offset positive effects. Rainwater pollution may similarly increase competition to Sphagnum, and could enhance positive effects of ash addition on C. introflexus growth. Finally, cover can provide a useful approximation of biomass where destructive sampling is undesirable

Effects of fire on the hydrology, biogeochemistry, and ecology of peatland river systems

Peatlands are found around the world and cover ~3.4% of the Earth’s surface. In the UK, peatlands cover 17.2% or ~1.58 Mha of the land surface and occur mainly in upland areas covering the headwaters of most major British rivers. However, large areas are now subject to prescribed vegetation burning despite policy guidance that recommends a strong presumption against burning deep blanket peat. Wildfires occur sporadically but are forecast to increase in frequency in the future. This paper provides a synthesis of current knowledge about how UK peatland-dominated river catchments respond to fires caused by prescribed vegetation burning and uncontrolled wildfire. We provide insight into the effects of fire on the hydrology, biogeochemistry, and biota of peatland river ecosystems, and the peatland-soil-driven controls on these effects at the catchment-scale. Burning increases the depth to water table and water-table variability, although some small-scale studies indicate shallower water table in some places. More work is needed on fire effects on peatland river flow, but recent results suggest a complex response with smaller flow peaks for burned systems associated with most rainfall events, but enhanced peaks compared to unburned systems for the top quintile of rainfall events with the largest total rain. Evidence from biogeochemical studies suggests that fire leads to increased dissolved organic C concentrations in rivers. River biota responses primarily include significant reductions in the density of grazing mayflies but increases among detritivores including Chironomidae and Baetis mayflies. We provide a conceptual synthesis that links the main responses of terrestrial and aquatic systems to fire, and we summarize some major research gaps that should be prioritized to inform future policy around peatland management

The influence of slope and peatland vegetation type on riverine dissolved organic carbon and water colour at different scales

Peatlands are important sources of fluvial carbon. Previous research has shown that riverine dissolved organic carbon (DOC) concentrations are largely controlled by soil type. However, there has been little work to establish the controls of riverine DOC within blanket peatlands that have not undergone major disturbance from drainage or burning. A total of 119 peatland catchments were sampled for riverine DOC and water colour across three drainage basins during six repeated sampling campaigns. The topographic characteristics of each catchment were determined from digital elevation models. The dominant vegetation cover was mapped using 0.5 m resolution colour infrared aerial images, with ground-truthed validation revealing 82 % accuracy. Forward and backward stepwise regression modelling showed that mean slope was a strong (and negative) determinant of DOC and water colour in blanket peatland river waters. There was a weak role for plant functional type in determining DOC and water colour. At the basin scale, there were major differences between the models depending on the basin. The dominance of topographic predictors of DOC found in our study, combined with a weaker role of vegetation type, paves the way for developing improved planning tools for water companies operating in peatland catchments. Using topographic data and aerial imagery it will be possible to predict which tributaries will typically yield lower DOC concentrations and which are therefore more suitable and cost-effective as raw water intakes

Tailoring Gold Nanoparticle Characteristics and the Impact on Aqueous-Phase Oxidation of Glycerol

Poly(vinyl alcohol) (PVA)-stabilized Au nanoparticles (NPs) were synthesized by colloidal methods in which temperature variations (−75 to 75 °C) and mixed H2O/EtOH solvent ratios (0, 50, and 100 vol/vol) were used. The resulting Au NPs were immobilized on TiO2 (P25), and their catalytic performance was investigated for the liquid phase oxidation of glycerol. For each unique solvent system, there was a systematic increase in the average Au particle diameter as the temperature of the colloidal preparation increased. Generation of the Au NPs in H2O at 1 °C resulted in a high observed activity compared with current Au/TiO2 catalysts (turnover frequency = 915 h–1). Interestingly, Au catalysts with similar average particle sizes but prepared under different conditions had contrasting catalytic performance. For the most active catalyst, aberration-corrected high angle annular dark field scanning transmission electron microscopy analysis identified the presence of isolated Au clusters (from 1 to 5 atoms) for the first time using a modified colloidal method, which was supported by experimental and computational CO adsorption studies. It is proposed that the variations in the populations of these species, in combination with other solvent/PVA effects, is responsible for the contrasting catalytic properties

Upland grasslands in Northern England were atmospheric carbon sinks regardless of management regimes

Continuous exchange of carbon (C) in the forms of carbon dioxide (CO2) and methane (CH4) occurs between the atmosphere and the terrestrial ecosystem. These greenhouse gases (GHGs) contribute significantly to global warming when present in the atmosphere. Thus, there is growing interest in understanding better ways of managing terrestrial ecosystems so as to increase or fully utilize their capacity to sequester GHGs, or reduce emissions, and mitigate climate change. In this study, we examined the fluxes of CO2 and CH4 in two upland grassland locations (Nidderdale and Ribblesdale) in northern England with contrasting lithologies and under: 1) traditional hay meadow and 2) conventional pasture management. Net ecosystem exchange (NEE) and ecosystem respiration (ER) were measured for 12 months from June 2016 to May 2017, alongside other environmental variables such as soil temperature and moisture, and photosynthetically active radiation (PAR). Results showed that the grasslands were a net atmospheric C sink, with an uptake of 1822–2758 g CO2-eq m−2 year−1. This C uptake is greater than those reported in other European grasslands due to low ER. The Ribblesdale hay meadow had the lowest C uptake (1822 g CO2-eq m−2 year−1) likely due to low available soil nitrogen (N) resulting from the absence of N fertilization. This has implication for agri-environment schemes that discourage the use of inorganic N fertilizers. Warmer condition in Ribblesdale was implicated as the cause of higher C efflux relative to Nidderdale, which has implications for future climate change. The CH4 fluxes were very low (−0.36 to −0.44 g CH4 m−2 year−1) and did not differ significantly between management regimes. It is recommended that future research should prioritise the overall GHG balance of upland grasslands and their inter-annual and decadal variability

Negative effects of climate change on upland grassland productivity and carbon fluxes are not attenuated by nitrogen status

Effects of climate change on managed grassland carbon (C) fluxes and biomass production are not well understood. In this study, we investigated the individual and interactive effects of experimental warming (+3 °C above ambient summer daily range of 9–12 °C), supplemental precipitation (333 mm +15%) and drought (333 mm −23%) on plant biomass, microbial biomass C (MBC), net ecosystem exchange (NEE) and dissolved organic C (DOC) flux in soil cores from two upland grasslands of different soil nitrogen (N) status (0.54% and 0.37%) in the UK. After one month of acclimation to ambient summer temperature and precipitation, five replicate cores of each treatment were subjected to three months of experimental warming, drought and supplemental precipitation, based on the projected regional summer climate by the end of the 21st Century, in a fully factorial design. NEE and DOC flux were measured throughout the experimental duration, alongside other environmental variables including soil temperature and moisture. Plant biomass and MBC were determined at the end of the experiment. Results showed that warming plus drought resulted in a significant decline in belowground plant biomass (−29 to −37%), aboveground plant biomass (−35 to −77%) and NEE (−13 to −29%), regardless of the N status of the soil. Supplemental precipitation could not reverse the negative effects of warming on the net ecosystem C uptake and plant biomass production. This was attributed to physiological stress imposed by warming which suggests that future summer climate will reduce the C sink capacity of the grasslands. Due to the low moisture retention observed in this study, and to verify our findings, it is recommended that future experiments aimed at measuring soil C dynamics under climate change should be carried out under field conditions. Longer term experiments are recommended to account for seasonal and annual variability, and adaptive changes in biota

Soil organic carbon stock in grasslands: Effects of inorganic fertilizers, liming and grazing in different climate settings

Grasslands store about 34% of the global terrestrial carbon (C) and are vital for the provision of various ecosystem services such as forage and climate regulation. About 89% of this grassland C is stored in the soil and is affected by management activities but the effects of these management activities on C storage under different climate settings are not known. In this study, we synthesized the effects of fertilizer (nitrogen and phosphorus) application, liming and grazing regime on the stock of SOC in global grasslands, under different site specific climatic settings using a meta-analysis of 341 datasets. We found an overall significant reduction (−8.5%) in the stock of SOC in global managed grasslands, mainly attributable to grazing (−15.0%), and only partially attenuated by fertilizer addition (+6.7%) and liming (+5.8%), indicating that management to improve biomass production does not contribute sufficient organic matter to replace that lost by direct removal by animals. Management activities had the greatest effect in the tropics (−22.4%) due primarily to heavy grazing, and the least effect in the temperate zone (−4.5%). The negative management effect reduced significantly with increasing mean annual temperature and mean annual precipitation in the temperate zone, suggesting that temperate grassland soils are potential C sinks in the face of climate change. For a sustainable management of grasslands that will provide adequate forage for livestock and mitigate climate change through C sequestration, we recommend that future tropical grassland management policies should focus on reducing the intensity of grazing. Also, to verify our findings for temperate grasslands and to better inform land management policy, future research should focus on the impacts of the projected climate change on net greenhouse gas exchange and potential climate feedbacks

A signal sequence suppressor mutant that stabilizes an assembled state of the twin arginine translocase

\ua9 2017, National Academy of Sciences. All rights reserved. The twin-arginine protein translocation (Tat) system mediates transport of folded proteins across the cytoplasmic membrane of bacteria and the thylakoid membrane of chloroplasts. The Tat system of Escherichia coli is made up of TatA, TatB, and TatC components. TatBC comprise the substrate receptor complex, and active Tat translocases are formed by the substrate-induced association of TatA oligomers with this receptor. Proteins are targeted to TatBC by signal peptides containing an essential pair of arginine residues. We isolated substitutions, locating to the transmembrane helix of TatB that restored transport activity to Tat signal peptides with inactivating twin arginine substitutions. A subset of these variants also suppressed inactivating substitutions in the signal peptide binding site on TatC. The suppressors did not function by restoring detectable signal peptide binding to the TatBC complex. Instead, site-specific cross-linking experiments indicate that the suppressor substitutions induce conformational change in the complex and movement of the TatB subunit. The TatB F13Y substitution was associated with the strongest suppressing activity, even allowing transport of a Tat substrate lacking a signal peptide. In vivo analysis using a TatA-YFP fusion showed that the TatB F13Y substitution resulted in signal peptide-independent assembly of the Tat translocase. We conclude that Tat signal peptides play roles in substrate targeting and in triggering assembly of the active translocase

Array comparative genomic hybridization: results from an adult population with drug-resistant epilepsy and co-morbidities.

The emergence of array comparative genomic hybridization (array CGH) as a diagnostic tool in molecular genetics has facilitated recognition of microdeletions and microduplications as risk factors for both generalised and focal epilepsies. Furthermore, there is evidence that some microdeletions/duplications, such as the 15q13.3 deletion predispose to a range of neuropsychiatric disorders, including intellectual disability (ID), autism, schizophrenia and epilepsy. We hypothesised that array CGH would reveal relevant findings in an adult patient group with epilepsy and complex phenotypes