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Garnet of eclogite (formerly termed garnet clinopyroxenite) hosted in lenses of orogenic garnet peridotite from the Granulitgebirge, NW Bohemian Massif, contains unique inclusions of granitic melt, now either glassy or crystallized. Analysed glasses and re‐homogenized inclusions are hydrous, peraluminous, and enriched in highly incompatible elements characteristic of the continental crust such as Cs, Li, B, Pb, Rb, Th, and U. The original melt thus represents a pristine, chemically evolved metasomatic agent, which infiltrated the mantle via deep continental subduction during the Variscan orogeny. The bulk chemical composition of the studied eclogites is similar to that of Fe‐rich basalt and the enrichment in LILE and U suggest a subduction‐related component. All these geochemical features confirm metasomatism. In comparison with many other garnet+clinopyroxene‐bearing lenses in peridotites of the Bohemian Massif, the studied samples from Rubinberg and Klatschmühle are more akin to eclogite than pyroxenites, as reflected in high jadeite content in clinopyroxene, relatively low Mg, Cr, and Ni but relatively high Ti. However, trace elements of both bulk rock and individual mineral phases show also important differences making these samples rather unique. Metasomatism involving a melt requiring a trace element pattern very similar to the composition reported here has been suggested for the source region of rocks of the so‐called durbachite suite, that is, ultrapotassic melanosyenites, which are found throughout the high‐grade Variscan basement. Moreover, the Th, U, Pb, Nb, Ta, and Ti patterns of these newly studied melt inclusions (MI) strongly resemble those observed for peridotite and its enclosed pyroxenite from the T‐7 borehole (Staré, České Středhoři Mountains) in N Bohemia. This suggests that a similar kind of crustal‐derived melt also occurred here. This study of granitic MI in eclogites from peridotites has provided the first direct characterization of a preserved metasomatic melt, possibly responsible for the metasomatism of several parts of the mantle in the Variscides.
We report a new synthetic route to a series of a-carboxynitrobenzyl photocaged L-aspartates for application in time-resolved structural biology. The resulting compounds were characterised in terms of UV/Vis absorption properties, aqueous solubility and stability, and photocleavage rates (tau = ms to ms) and quantum yields (phi = 0.05 to 0.14).
In crop modeling and yield predictions, the heterogeneity of agricultural landscapes is usually not accounted for. This heterogeneity often arises from landscape elements like forests, hedges, or single trees and shrubs that cast shadows. Shading from forested areas or shrubs has effects on transpiration, temperature, and soil moisture, all of which affect the crop yield in the adjacent arable land. Transitional gradients of solar irradiance can be described as a function of the distance to the zero line (edge), the cardinal direction, and the height of trees. The magnitude of yield reduction in transition zones is highly influenced by solar irradiance-a factor that is not yet implemented in crop growth models on a landscape level. We present a spatially explicit model for shading caused by forested areas, in agricultural landscapes. With increasing distance to forest, solar irradiance and yield increase. Our model predicts that the shading effect from the forested areas occurs up to 15 m from the forest edge, for the simulated wheat yields, and up to 30 m, for simulated maize. Moreover, we estimated the spatial extent of transition zones, to calculate the regional yield reduction caused by shading of the forest edges, which amounted to 5% to 8% in an exemplary region.
Colombia's agriculture, forestry and other land use sector accounts for nearly half of its total greenhouse gas (GHG) emissions. The importance of smallholder deforestation is comparatively high in relation to its regional counterparts, and livestock agriculture represents the largest driver of primary forest depletion. Silvopastoral systems (SPSs) are presented as agroecological solutions that synergistically enhance livestock productivity, improve local farmers' livelihoods and hold the potential to reduce pressure on forest conversion. The department of Caquetá represents Colombia's most important deforestation hotspot. Targeting smallholder livestock farms through survey data, in this work we investigate the GHG mitigation potential of implementing SPSs for smallholder farms in this region. Specifically, we assess whether the carbon sequestration taking place in the soil and biomass of SPSs is sufficient to offset the per-hectare increase in livestock GHG emissions resulting from higher stocking rates. To address these questions we use data on livestock population characteristics and historic land cover changes reported from a survey covering 158 farms and model the carbon sequestration occurring in three different scenarios of progressively-increased SPS complexity using the CO2 fix model. We find that, even with moderate tree planting densities, the implementation of SPSs can reduce GHG emissions by 2.6 Mg CO2e ha−1 yr−1 in relation to current practices, while increasing agriculture productivity and contributing to the restoration of severely degraded landscapes.
Hungry cities: how local food self-sufficiency relates to climate change, diets, and urbanisation
(2019)
Using a newly developed model approach and combining it with remote sensing, population, and climate data, first insights are provided into how local diets, urbanisation, and climate change relates to local urban food self-sufficiency. In plain terms, by utilizing the global peri-urban (PU) food production potential approximately lbn urban residents (30% of global urban population) can be locally nourished, whereby further urbanisation is by far the largest pressure factor on PU agriculture, followed by a change of diets, and climate change. A simple global food transport model which optimizes transport and neglects differences in local emission intensities indicates that CO2 emissions related to food transport can be reduced by a factor of 10.
The question of whether urbanization contributes to increasing carbon dioxide emissions has been mainly investigated via scaling relationships with population or population density. However, these approaches overlook the correlations between population and area, and ignore possible interactions between these quantities. Here, we propose a generalized framework that simultaneously considers the effects of population and area along with possible interactions between these urban metrics. Our results significantly improve the description of emissions and reveal the coupled role between population and density on emissions. These models show that variations in emissions associated with proportionate changes in population or density may not only depend on the magnitude of these changes but also on the initial values of these quantities. For US areas, the larger the city, the higher is the impact of changing its population or density on its emissions; but population changes always have a greater effect on emissions than population density.
The speed-curvature power law is a celebrated law of motor control expressing a relation between the kinematic property of speed and the geometric property of curvature. We aimed to assess whether speech movements obey this law just as movements from other domains do. We describe a metronome-driven speech elicitation paradigm designed to cover a wide range of speeds. We recorded via electromagnetic articulometry speech movements in sequences of the form /CV…/ from nine speakers (five German, four English) speaking at eight distinct rates. First, we demonstrate that the paradigm of metronome-driven manipulations results in speech movement data consistent with earlier reports on the kinematics of speech production. Second, analysis of our data in their full three-dimensions and using advanced numerical differentiation methods offers stronger evidence for the law than that reported in previous studies devoted to its assessment. Finally, we demonstrate the presence of a clear rate dependency of the power law’s parameters. The robustness of the speed-curvature relation in our datasets lends further support to the hypothesis that the power law is a general feature of human movement. We place our results in the context of other work in movement control and consider implications for models of speech production.
Farber disease is a rare lysosomal storage disorder resulting from acid ceramidase deficiency and subsequent ceramide accumulation. No treatments for Farber disease are clinically available, and affected patients have a severely shortened lifespan. We have recently reported a novel acid ceramidase deficiency model that mirrors the human disease closely. Acid sphingomyelinase is the enzyme that generates ceramide upstream of acid ceramidase in the lysosomes. Using our acid ceramidase deficiency model, we tested if acid sphingomyelinase could be a potential novel therapeutic target for the treatment of Farber disease. A number of functional acid sphingomyelinase inhibitors are clinically available and have been used for decades to treat major depression. Using these as a therapeutic for Farber disease, thus, has the potential to improve central nervous symptoms of the disease as well, something all other treatment options for Farber disease can’t achieve so far. As a proof-of-concept study, we first cross-bred acid ceramidase deficient mice with acid sphingomyelinase deficient mice in order to prevent ceramide accumulation. Double-deficient mice had reduced ceramide accumulation, fewer disease manifestations, and prolonged survival. We next targeted acid sphingomyelinase pharmacologically, to test if these findings would translate to a setting with clinical applicability. Surprisingly, the treatment of acid ceramidase deficient mice with the acid sphingomyelinase inhibitor amitriptyline was toxic to acid ceramidase deficient mice and killed them within a few days of treatment. In conclusion, our study provides the first proof-of-concept that acid sphingomyelinase could be a potential new therapeutic target for Farber disease to reduce disease manifestations and prolong survival. However, we also identified previously unknown toxicity of the functional acid sphingomyelinase inhibitor amitriptyline in the context of Farber disease, strongly cautioning against the use of this substance class for Farber disease patients.
As structural membrane components and signaling effector molecules sphingolipids influence a plethora of host cell functions, and by doing so also the replication of viruses. Investigating the effects of various inhibitors of sphingolipid metabolism in primary human peripheral blood lymphocytes (PBL) and the human B cell line BJAB we found that not only the sphingosine kinase (SphK) inhibitor SKI-II, but also the acid ceramidase inhibitor ceranib-2 efficiently inhibited measles virus (MV) replication. Virus uptake into the target cells was not grossly altered by the two inhibitors, while titers of newly synthesized MV were reduced by approximately 1 log (90%) in PBL and 70-80% in BJAB cells. Lipidomic analyses revealed that in PBL SKI-II led to increased ceramide levels, whereas in BJAB cells ceranib-2 increased ceramides. SKI-II treatment decreased sphingosine-1-phosphate (S1P) levels in PBL and BJAB cells. Furthermore, we found that MV infection of lymphocytes induced a transient (0.5-6 h) increase in S1P, which was prevented by SKI-II. Investigating the effect of the inhibitors on the metabolic (mTORC1) activity we found that ceranib-2 reduced the phosphorylation of p70 S6K in PBL, and that both inhibitors, ceranib-2 and SKI-II, reduced the phosphorylation of p70 S6K in BJAB cells. As mTORC1 activity is required for efficient MV replication, this effect of the inhibitors is one possible antiviral mechanism. In addition, reduced intracellular S1P levels affect a number of signaling pathways and functions including Hsp90 activity, which was reported to be required for MV replication. Accordingly, we found that pharmacological inhibition of Hsp90 with the inhibitor 17-AAG strongly impaired MV replication in primary PBL. Thus, our data suggest that treatment of lymphocytes with both, acid ceramidase and SphK inhibitors, impair MV replication by affecting a number of cellular activities including mTORC1 and Hsp90, which alter the metabolic state of the cells causing a hostile environment for the virus.
The activity of neutral sphingomyelinase-2 (NSM2) to catalyze the conversion of sphingomyelin (SM) to ceramide and phosphocholine at the cytosolic leaflet of plasma membrane (PM) is important in T cell receptor (TCR) signaling. We recently identified PKC zeta as a major NSM2 downstream effector which regulates microtubular polarization. It remained, however, unclear to what extent NSM2 activity affected overall composition of PM lipids and downstream effector lipids in antigen stimulated T cells. Here, we provide a detailed lipidomics analyses on PM fractions isolated from TCR stimulated wild type and NSM2 deficient (Delta NSM) Jurkat T cells. This revealed that in addition to that of sphingolipids, NSM2 depletion also affected concentrations of many other lipids. In particular, NSM2 ablation resulted in increase of lyso-phosphatidylcholine (LPC) and lyso-phosphatidylethanolamine (LPE) which both govern PM biophysical properties. Crucially, TCR dependent upregulation of the important T cell signaling lipid diacylglycerol (DAG), which is fundamental for activation of conventional and novel PKCs, was abolished in Delta NSM cells. Moreover, NSM2 activity was found to play an important role in PM cholesterol transport to the endoplasmic reticulum (ER) and production of cholesteryl esters (CE) there. Most importantly, CE accumulation was essential to sustain human T cell proliferation. Accordingly, inhibition of CE generating enzymes, the cholesterol acetyltransferases ACAT1/SOAT1 and ACAT2/SOAT2, impaired TCR driven expansion of both CD4(+) and CD8(+) T cells. In summary, our study reveals an important role of NSM2 in regulating T cell functions by its multiple effects on PM lipids and cholesterol homeostasis.
Objective: Aging is accompanied by loss of brown adipocytes and a decline in their thermogenic potential, which may exacerbate the development of adiposity and other metabolic disorders. Presently, only limited evidence exists describing the molecular alterations leading to impaired brown adipogenesis with aging and the contribution of these processes to changes of systemic energy metabolism.
Methods: Samples of young and aged murine brown and white adipose tissue were used to compare age-related changes of brown adipogenic gene expression and thermogenesis-related lipid mobilization. To identify potential markers of brown adipose tissue aging, non-targeted proteomic and metabolomic as well as targeted lipid analyses were conducted on young and aged tissue samples. Subsequently, the effects of several candidate lipid classes on brown adipocyte function were examined.
Results: Corroborating previous reports of reduced expression of uncoupling protein-1, we observe impaired signaling required for lipid mobilization in aged brown fat after adrenergic stimulation. Omics analyses additionally confirm the age-related impairment of lipid homeostasis and reveal the accumulation of specific lipid classes, including certain sphingolipids, ceramides, and dolichols in aged brown fat. While ceramides as well as enzymes of dolichol metabolism inhibit brown adipogenesis, inhibition of sphingosine 1-phosphate receptor 2 induces brown adipocyte differentiation.
Conclusions: Our functional analyses show that changes in specific lipid species, as observed during aging, may contribute to reduced thermogenic potential. They thus uncover potential biomarkers of aging as well as molecular mechanisms that could contribute to the degradation of brown adipocytes, thereby providing potential treatment strategies of age-related metabolic conditions.
Dermal Delivery of the High-Molecular-Weight Drug Tacrolimus by Means of Polyglycerol-Based Nanogels
(2019)
Polyglycerol-based thermoresponsive nanogels (tNGs) have been shown to have excellent skin hydration properties and to be valuable delivery systems for sustained release of drugs into skin. In this study, we compared the skin penetration of tacrolimus formulated in tNGs with a commercial 0.1% tacrolimus ointment. The penetration of the drug was investigated in ex vivo abdominal and breast skin, while different methods for skin barrier disruption were investigated to improve skin permeability or simulate inflammatory conditions with compromised skin barrier. The amount of penetrated tacrolimus was measured in skin extracts by liquid chromatography tandem-mass spectrometry (LC-MS/MS), whereas the inflammatory markers IL-6 and IL-8 were detected by enzyme-linked immunosorbent assay (ELISA). Higher amounts of tacrolimus penetrated in breast as compared to abdominal skin or in barrier-disrupted as compared to intact skin, confirming that the stratum corneum is the main barrier for tacrolimus skin penetration. The anti-proliferative effect of the penetrated drug was measured in skin tissue/Jurkat cells co-cultures. Interestingly, tNGs exhibited similar anti-proliferative effects as the 0.1% tacrolimus ointment. We conclude that polyglycerol-based nanogels represent an interesting alternative to paraffin-based formulations for the treatment of inflammatory skin conditions.
Local probes of the electronic ground state are essential for understanding hydrogen bonding in aqueous environments. When tuned to the dissociative core-excited state at the O1s pre-edge of water, resonant inelastic X-ray scattering back to the electronic ground state exhibits a long vibrational progression due to ultrafast nuclear dynamics. We show how the coherent evolution of the OH bonds around the core-excited oxygen provides access to high vibrational levels in liquid water. The OH bonds stretch into the long-range part of the potential energy curve, which makes the X-ray probe more sensitive than infra-red spectroscopy to the local environment. We exploit this property to effectively probe hydrogen bond strength via the distribution of intramolecular OH potentials derived from measurements. In contrast, the dynamical splitting in the spectral feature of the lowest valence-excited state arises from the short-range part of the OH potential curve and is rather insensitive to hydrogen bonding.
Electronic health is one of the most popular applications of information and communication technologies and it has contributed immensely to health delivery through the provision of quality health service and ubiquitous access at a lower cost. Even though this mode of health service is increasingly becoming known or used in developing nations, these countries are faced with a myriad of challenges when implementing and deploying e-health services on both small and large scale. It is estimated that the Africa population alone carries the highest percentage of the world’s global diseases despite its certain level of e-health adoption. This paper aims at analyzing the progress so far and the current state of e-health in developing countries particularly Africa and propose a framework for further improvement.
Past climate and continentality inferred from ice wedges at Batagay Highlands, interior Yakutia
(2019)
Ice wedges in the Yana Highlands of interior Yakutia - the most continental region of the Northern Hemisphere - were investigated to elucidate changes in winter climate and continentality that have taken place since the Middle Pleistocene. The Batagay megaslump exposes ice wedges and composite wedges that were sampled from three cryostratigraphic units: the lower ice complex of likely pre-Marine Isotope Stage (MIS) 6 age, the upper ice complex (Yedoma) and the upper sand unit (both MIS 3 to 2). A terrace of the nearby Adycha River provides a Late Holocene (MIS 1) ice wedge that serves as a modern reference for interpretation. The stable-isotope composition of ice wedges in the MIS 3 upper ice complex at Batagay is more depleted (mean delta O-18 about -35 parts per thousand) than those from 17 other ice-wedge study sites across coastal and central Yakutia. This observation points to lower winter temperatures and therefore higher continentality in the Yana Highlands during MIS 3. Likewise, more depleted isotope values are found in Holocene wedge ice (mean delta O-18 about -29 parts per thousand) compared to other sites in Yakutia. Ice-wedge isotopic signatures of the lower ice complex mean delta O-18 about -33 parts per thousand) and of the MIS 3-2 upper sand unit (mean delta O-18 from about -33 parts per thousand to -30 parts per thousand) are less distinctive regionally. The latter unit preserves traces of fast formation in rapidly accumulating sand sheets and of post-depositional isotopic fractionation.
Germany and the United Kingdom have domestic shale gas reserves which they may exploit in the future to complement their national energy strategies. However gas production releases volatile organic compounds (VOC) and nitrogen oxides (NOx), which through photochemical reaction form ground-level ozone, an air pollutant that can trigger adverse health effects e.g. on the respiratory system. This study explores the range of impacts of a potential shale gas industry in these two countries on local and regional ambient ozone. To this end, comprehensive emission scenarios are used as the basis for input to an online-coupled regional chemistry transport model (WRF-Chem). Here we simulate shale gas scenarios over summer (June, July, August) 2011, exploring the effects of varying VOC emissions, gas speciation, and concentration of NOx emissions over space and time, on ozone formation. An evaluation of the model setup is performed, which exhibited the model’s ability to predict surface meteorological and chemical variables well compared with observations, and consistent with other studies. When different shale gas scenarios were employed, the results show a peak increase in maximum daily 8-hour average ozone from 3.7 to 28.3 μg m–3. In addition, we find that shale gas emissions can force ozone exceedances at a considerable percentage of regulatory measurement stations locally (up to 21% in Germany and 35% in the United Kingdom) and in distant countries through long-range transport, and increase the cumulative health-related metric SOMO35 (maximum percent increase of ~28%) throughout the region. Findings indicate that VOC emissions are important for ozone enhancement, and to a lesser extent NOx, meaning that VOC regulation for a future European shale gas industry will be of especial importance to mitigate unfavorable health outcomes. Overall our findings demonstrate that shale gas production in Europe can worsen ozone air quality on both the local and regional scales.
The Alpine orogen formed as a result of the collision between the Adriatic and European plates. Significant crustal heterogeneity exists within the region due to the long history of interplay between these plates, other continental and oceanic blocks in the region, and inherited crustal features from earlier orogenies. Deformation relating to the collision continues to the present day. Here, a seismically constrained, 3-D structural and density model of the lithosphere of the Alps and their respective forelands, derived from integrating numerous geoscientific datasets, was adjusted to match the observed gravity field. It is shown that the distribution of seismicity and deformation within the region correlates well to thickness and density changes within the crust, and that the present-day Adriatic crust is both thinner and denser (22.5 km, 2800 kg m(-3) ) than the European crust (27.5 km, 2750 kg m(-3)). Alpine crust derived from each respective plate is found to show the same trend, with zones of Adriatic provenance (Austro-Alpine unit and Southern Alps) found to be denser and those of European provenance (Helvetic zone and Tauern Window) to be less dense. This suggests that the respective plates and related terranes had similar crustal properties to the present-day ones prior to orogenesis. The model generated here is available for open-access use to further discussions about the crust in the region.
Influence of the Main Border Faults on the 3D Hydraulic Field of the Central Upper Rhine Graben
(2019)
The Upper Rhine Graben (URG) is an active rift with a high geothermal potential. Despite being a well-studied area, the three-dimensional interaction of the main controlling factors of the thermal and hydraulic regime is still not fully understood. Therefore, we have used a data-based 3D structural model of the lithological configuration of the central URG for some conceptual numerical experiments of 3D coupled simulations of fluid and heat transport. To assess the influence of the main faults bordering the graben on the hydraulic and the deep thermal field, we carried out a sensitivity analysis on fault width and permeability. Depending on the assigned width and permeability of the main border faults, fluid velocity and temperatures are affected only in the direct proximity of the respective border faults. Hence, the hydraulic characteristics of these major faults do not significantly influence the graben-wide groundwater flow patterns. Instead, the different scenarios tested provide a consistent image of the main characteristics of fluid and heat transport as they have in common: (1) a topography-driven basin-wide fluid flow perpendicular to the rift axis from the graben shoulders to the rift center, (2) a N/NE-directed flow parallel to the rift axis in the center of the rift and, (3) a pronounced upflow of hot fluids along the rift central axis, where the streams from both sides of the rift merge. This upflow axis is predicted to occur predominantly in the center of the URG (northern and southern model area) and shifted towards the eastern boundary fault (central model area).
The Sentinel Application Platform (SNAP) architecture facilitates Earth Observation data processing. In this work, we present results from a new Snow Processor for SNAP. We also describe physical principles behind the developed snow property retrieval technique based on the analysis of Ocean and Land Colour Instrument (OLCI) onboard Sentinel-3A/B measurements over clean and polluted snow fields. Using OLCI spectral reflectance measurements in the range 400-1020 nm, we derived important snow properties such as spectral and broadband albedo, snow specific surface area, snow extent and grain size on a spatial grid of 300 m. The algorithm also incorporated cloud screening and atmospheric correction procedures over snow surfaces. We present validation results using ground measurements from Antarctica, the Greenland ice sheet and the French Alps. We find the spectral albedo retrieved with accuracy of better than 3% on average, making our retrievals sufficient for a variety of applications. Broadband albedo is retrieved with the average accuracy of about 5% over snow. Therefore, the uncertainties of satellite retrievals are close to experimental errors of ground measurements. The retrieved surface grain size shows good agreement with ground observations. Snow specific surface area observations are also consistent with our OLCI retrievals. We present snow albedo and grain size mapping over the inland ice sheet of Greenland for areas including dry snow, melted/melting snow and impurity rich bare ice. The algorithm can be applied to OLCI Sentinel-3 measurements providing an opportunity for creation of long-term snow property records essential for climate monitoring and data assimilation studies-especially in the Arctic region, where we face rapid environmental changes including reduction of snow/ice extent and, therefore, planetary albedo.
The advance of high-throughput RNA-Sequencing techniques enables researchers to analyze the complete gene activity in particular cells. From the insights of such analyses, researchers can identify disease-specific expression profiles, thus understand complex diseases like cancer, and eventually develop effective measures for diagnosis and treatment. The high dimensionality of gene expression data poses challenges to its computational analysis, which is addressed with measures of gene selection. Traditional gene selection approaches base their findings on statistical analyses of the actual expression levels, which implies several drawbacks when it comes to accurately identifying the underlying biological processes. In turn, integrative approaches include curated information on biological processes from external knowledge bases during gene selection, which promises to lead to better interpretability and improved predictive performance. Our work compares the performance of traditional and integrative gene selection approaches. Moreover, we propose a straightforward approach to integrate external knowledge with traditional gene selection approaches. We introduce a framework enabling the automatic external knowledge integration, gene selection, and evaluation. Evaluation results prove our framework to be a useful tool for evaluation and show that integration of external knowledge improves overall analysis results.