Alzheimer's Disease (AD) currently affects more than 5 million Americans, with numbers expected to grow dramatically as the population ages. The pathophysiological changes in AD patients begin ...decades before the onset of dementia, highlighting the urgent need for the development of early diagnostic methods. Compelling data demonstrate that increased levels of amyloid-beta compromise multiple cellular pathways; thus, the investigation of changes in various cellular networks is essential to advance our understanding of early disease mechanisms and to identify novel therapeutic targets. We applied a liquid chromatography/mass spectrometry-based non-targeted metabolomics approach to determine global metabolic changes in plasma and cerebrospinal fluid (CSF) from the same individuals with different AD severity. Metabolic profiling detected a total of significantly altered 342 plasma and 351 CSF metabolites, of which 22% were identified. Based on the changes of >150 metabolites, we found 23 altered canonical pathways in plasma and 20 in CSF in mild cognitive impairment (MCI) vs. cognitively normal (CN) individuals with a false discovery rate <0.05. The number of affected pathways increased with disease severity in both fluids. Lysine metabolism in plasma and the Krebs cycle in CSF were significantly affected in MCI vs. CN. Cholesterol and sphingolipids transport was altered in both CSF and plasma of AD vs. CN. Other 30 canonical pathways significantly disturbed in MCI and AD patients included energy metabolism, Krebs cycle, mitochondrial function, neurotransmitter and amino acid metabolism, and lipid biosynthesis. Pathways in plasma that discriminated between all groups included polyamine, lysine, tryptophan metabolism, and aminoacyl-tRNA biosynthesis; and in CSF involved cortisone and prostaglandin 2 biosynthesis and metabolism. Our data suggest metabolomics could advance our understanding of the early disease mechanisms shared in progression from CN to MCI and to AD.
Conceptual models suggest that stability of organic carbon (OC) in soil depends on the source of plant litter, occlusion within aggregates, incorporation in organo-mineral complexes, and location ...within the soil profile. Density fractionation is a useful tool to study the relevance of OC stabilization in aggregates and in association with minerals, but it has rarely been applied to full soil profiles. We aim to determine factors shaping the depth profiles of physically unprotected and mineral associated OC and test their relevance for OC stability across a range of European soils that vary in vegetation, soil types, parent material, and land use. At each of the 12 study sites, 10 soil cores were sampled to 60 cm depth and subjected to density separation. Bulk soil samples and density fractions (free light fractions – fLF, occluded light fractions – oLF, heavy fractions – HF) were analysed for OC, total nitrogen (TN), δ14C, and Δ14C. Bulk samples were also incubated to determine CO2 evolution per g OC in the samples (specific mineralization rates) as an indicator for OC stability. Depth profiles of OC in the light fraction (LF-OC) matched those of roots for undisturbed grassland and forest sites, suggesting that roots are shaping the depth distribution of LF-OC. Organic C in the HF declined less with soil depth than LF-OC and roots, especially at grassland sites. The decrease in Δ14C (increase in age) of HF-OC with soil depth was related to soil pH as well as to dissolved OC fluxes. This indicates that dissolved OC translocation contributes to the formation of subsoil HF-OC and shapes the Δ14C profiles. The LF at three sites were rather depleted in 14C, indicating the presence of fossil material such as coal and lignite, probably inherited from the parent material. At the other sites, modern Δ14C signatures and positive correlations between specific mineralization rates and fLF-OC indicate the fLF is a potentially available energy and nutrient source for subsurface microorganisms throughout the profile. Declining specific mineralization rates with soil depth confirm greater stability of OC in subsoils across sites. The overall importance of OC stabilization by binding to minerals was demonstrated by declining specific mineralization rates with increasing contributions of HF-OC to bulk soil OC, and the low Δ14C values of HF-OC. The stability of HF-OC was greater in subsoils than in topsoils; nevertheless, a portion of HF-OC was active throughout the profile. While quantitatively less important than OC in the HF, consistent older ages of oLF-OC than fLF-OC suggest that occlusion of LF-OC in aggregates also contributes to OC stability in subsoils. Overall, our results indicate that association with minerals is the most important factor in stabilization of OC in soils, irrespective of vegetation, soil type, and land use.
The authors of The Economic Effects of Constitutions use econometric tools to study what they call the "missing link" between constitutional systems and economic policy; the book is an ...uncompromisingly empirical sequel to their previous theoretical analysis of economic policy. Taking recent theoretical work as a point of departure, they ask which theoretical findings are supported and which are contradicted by the facts. The results are based on comparisons of political institutions across countries or time, in a large sample of contemporary democracies. They find that presidential/parliamentary and majoritarian/proportional dichotomies influence several economic variables: presidential regimes induce smaller public sectors, and proportional elections lead to greater and less targeted government spending and larger budget deficits. Moreover, the details of the electoral system (such as district magnitude and ballot structure) influence corruption and structural policies toward economic growth. Persson and Tabellini's goal is to draw conclusions about the causal effects of constitutions on policy outcomes. But since constitutions are not randomly assigned to countries, how the constitutional system was selected in the first place must be taken into account. This raises challenging methodological problems, which are addressed in the book. The study is therefore important not only in its findings but also in establishing a methodology for empirical analysis in the field of comparative politics.
The control of the betatron coupling is of importance for safe beam operation in the LHC. In this article we show recent advancements in methods and algorithms to measure and correct coupling. The ...benefit of using a more precise formula relating the resonance driving term f1001 to the ΔQ min is presented. The quality of the coupling measurements is increased, with about a factor 3, by selecting beam position monitor (BPM) pairs with phase advances close to pi/2 and through data cleaning using singular value decomposition with an optimal number of singular values. These improvements are beneficial for the implemented automatic coupling correction, which is based on injection oscillations, presented in the article. Furthermore, a proposed coupling feedback for the LHC is presented. The system will rely on the measurements from BPMs equipped with a new type of high resolution electronics, diode orbit and oscillation, which will be operational when the LHC restarts in 2015. The feedback will combine the coupling measurements from the available BPMs in order to calculate the best correction.
Measurements of plasma free fatty acids (FFA) concentration and isotopic enrichment are commonly used to evaluate FFA metabolism. Until now, gas chromatography-combustion-isotope ratio mass ...spectrometry (GC/C/IRMS) was the best method to measure isotopic enrichment in the methyl derivatives of 13C-labeled fatty acids. Although IRMS is excellent for analyzing enrichment, it requires time-consuming derivatization steps and is not optimal for measuring FFA concentrations. We developed a new, rapid, and reliable method for simultaneous quantification of 13C-labeled fatty acids in plasma using high-performance liquid chromatography-mass spectrometry (HPLC/MS). This method involves a very quick Dole extraction procedure and direct injection of the samples on the HPLC system. After chromatographic separation, the samples are directed to the mass spectrometer for electrospray ionization (ESI) and analysis in the negative mode using single ion monitoring. By employing equipment with two columns connected parallel to a mass spectrometer, we can double the throughput to the mass spectrometer, reducing the analysis time per sample to 5 min. Palmitate flux measured using this approach agreed well with the GC/C/IRMS method. This HPLC/MS method provides accurate and precise measures of FFA concentration and enrichment.
Liming can counteract acidification in forest soils, but the effects on soil C and N pools and fluxes over long periods are less well understood. Replicated plots in an acidic and N-rich 40-year-old ...Norway spruce (
Picea abies
) forest in SW Sweden (Hasslöv) were treated with 0, 3.45 and 8.75 Mg ha
−1
of dolomitic lime (D0, D2 and D3) in 1984. Between 1984 and 2016, soil organic C to 30 cm depth increased by 28 Mg ha
−1
(30% increase) in D0 and decreased by 9 Mg ha
−1
(9.4% decrease) in D3. The change in D2 was not significant (+ 2 Mg ha
−1
). Soil N pools changed proportionally to those in soil C pools. The C and N changes occurred almost exclusively in the top organic layer. Non-burrowing earthworms responded positively to liming and stimulated heterotrophic respiration in this layer in both D2 and D3. Burrowing earthworms in D3 further accelerated C and N turnover and loss of soil. The high soil C and N loss at our relatively N-rich site differs from studies of N-poor sites showing no C and N loss. Earthworms need both high pH and N-rich food to reach high abundance and biomass. This can explain why liming of N-rich soils often results in decreasing C and N pools, whereas liming of N-poor soils with few earthworms will not show any change in soil C and N. Extractable nitrate N was always higher in D3 than in D2 and D0. After 6 years (1990), potential nitrification was much higher in D3 (197 kg N ha
−1
) than in D0 (36 kg N ha
−1
), but this difference decreased during the following years, when also the unlimed organic layers showed high nitrification potential. Our experiment finds that high-dose liming of acidic N-rich forest soils produces an initial pulse of soil heterotrophic respiration and increases in earthworm biomass, which together cause long-term declines in soil C and N pools.
•Challenges for smart intensification of marginal land are manifold•Tools for precise agriculture will aid to detect pollutant hotspots and poor soils•Crop rotation and adapted crop choice will yield ...biomass•Amendments will sequester carbon and release fertilizer when needed•Potentials of marginal soils can be unlocked and lead to ecological and economical success
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The rapid increase of the world population constantly demands more food production from agricultural soils. This causes conflicts, since at the same time strong interest arises on novel bio-based products from agriculture, and new perspectives for rural landscapes with their valuable ecosystem services. Agriculture is in transition to fulfill these demands. In many countries, conventional farming, influenced by post-war food requirements, has largely been transformed into integrated and sustainable farming. However, since it is estimated that agricultural production systems will have to produce food for a global population that might amount to 9.1 billion by 2050 and over 10 billion by the end of the century, we will require an even smarter use of the available land, including fallow and derelict sites. One of the biggest challenges is to reverse non-sustainable management and land degradation. Innovative technologies and principles have to be applied to characterize marginal lands, explore options for remediation and re-establish productivity. With view to the heterogeneity of agricultural lands, it is more than logical to apply specific crop management and production practices according to soil conditions. Cross-fertilizing with conservation agriculture, such a novel approach will provide (1) increased resource use efficiency by producing more with less (ensuring food security), (2) improved product quality, (3) ameliorated nutritional status in food and feed products, (4) increased sustainability, (5) product traceability and (6) minimized negative environmental impacts notably on biodiversity and ecological functions. A sustainable strategy for future agriculture should concentrate on production of food and fodder, before utilizing bulk fractions for emerging bio-based products and convert residual stage products to compost, biochar and bioenergy. The present position paper discusses recent developments to indicate how to unlock the potentials of marginal land.
Abstract
This study was an investigation of the need for pre-treatment of a new raw water source for artificial groundwater recharge. The study was done through a column test, well sampling and ...survey data relating to 11 artificial recharge plants in Sweden. The column test showed that only 30% of the natural organic matter (NOM) was removed from the new raw water source during infiltration. The survey revealed that the new water source's quality was within the range requiring pre-treatment prior to infiltration. The well sampling results showed a significant correlation between the NOM content in the raw and treated waters for WTPs without pre-treatment (r = 0.78 and ρ = 0.04), indicating one of the short-term limitations of artificial recharge. The study results indicate that the new raw water source is unsuitable for direct use in artificial recharge and that treatment is required prior to infiltration.
Context:
Poor glycemic control in individuals with type 1 diabetes (T1D) is associated with both micro- and macrovascular complications, but good glycemic control does not fully prevent the risk of ...these complications.
Objective:
The objective of the study was to determine whether T1D with good glycemic control have persistent abnormalities of metabolites and pathways that exist in T1D with poor glycemic control.
Design:
We compared plasma metabolites in T1D with poor (glycated hemoglobin ≥ 8.5%, T1D− and good (glycated hemoglobin < 6.5%, T1D+) glycemic control with nondiabetic controls (ND).
Setting:
The study was conducted at the clinical research unit.
Patients or Other Participants:
T1D with poor (n = 14), T1D(−) and good, T1D(+) (n = 15) glycemic control and matched (for age, sex, and body mass index) ND participants were included in the study.
Intervention(s):
There were no intervention.
Main Outcome Measure(s):
Comparison of qualitative and quantitative profiling of metabolome was performed.
Results:
In T1D(−), 347 known metabolites belonging to 38 metabolic pathways involved in cholesterol, vitamin D, tRNA, amino acids (AAs), bile acids, urea, tricarboxylic acid cycle, immune response, and eicosanoids were different from ND. In T1D(+),154 known metabolites belonging to 26 pathways including glycolysis, gluconeogenesis, bile acids, tRNA biosynthesis, AAs, branch-chain AAs, retinol, and vitamin D metabolism remained altered from ND. Targeted measurements of AA metabolites, trichloroacetic acid, and free fatty acids showed directional changes similar to the untargeted metabolomics approach.
Conclusions:
Comprehensive metabolomic profiling identified extensive metabolomic abnormalities in T1D with poor glycemic control. Chronic good glycemic control failed to normalize many of these perturbations, suggesting a potential role for these persistent abnormalities in many complications in T1D.
The nonlinear dynamics of a circular accelerator such as the Large Hadron Collider (LHC) may significantly impact its performance. As the LHC progresses to more challenging regimes of operation it is ...to be expected that the nonlinear single particle dynamics in the transverse planes will play an increasing role in limiting the reach of the accelerator. As such it is vital that the nonlinear sources are well understood. The nonlinear fields of a circular accelerator may be probed through measurement of the amplitude detuning: the variation of tune with single particle emittance. This quantity may be assessed experimentally by exciting the beam to large amplitudes with kicks, and obtaining the tunes and actions from turn-by-turn data at Beam Position Monitors. The large amplitude excitations inherent to such a measurement also facilitate measurement of the dynamic aperture from an analysis of beam losses following the kicks. In 2012 these measurements were performed on the LHC Beam 2 at injection energy (450 GeV) with the nominal magnetic configuration. Nonlinear coupling was also observed. A second set of measurements were performed following the application of corrections for b_{4} and b_{5} errors. Analysis of the experimental results, and a comparison to simulation are presented herein.
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