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Formate dehydrogenases (FDHs) are capable of performing the reversible oxidation of formate and are enzymes of great interest for fuel cell applications and for the production of reduced carbon compounds as energy sources from CO2. Metal containing FDHs in general contain a highly conserved active site, comprising a molybdenum (or tungsten) center coordinated by two molybdopterin guanine dinucleotide molecules, a sulfido and a (seleno-)cysteine ligand, in addition to a histidine and arginine residue in the second coordination sphere. So far, the role of these amino acids in catalysis has not been studied in detail, because of the lack of suitable expression systems and the lability or oxygen sensitivity of the enzymes. Here, the roles of these active site residues is revealed using the Mo-containing FDH from Rhodobacter capsulatus. Our results show that the cysteine ligand at the Mo ion is displaced by the formate substrate during the reaction, the arginine has a direct role in substrate binding and stabilization, and the histidine elevates the pK(a) of the active site cysteine. We further found that in addition to reversible formate oxidation, the enzyme is further capable of reducing nitrate to nitrite. We propose a mechanistic scheme that combines both functionalities and provides important insights into the distinct mechanisms of C-H bond cleavage and oxygen atom transfer catalyzed by formate dehydrogenase.
In this Thesis, the properties of aqueous hemicellulose polysaccharides are investigated using computer simulations. The high swelling capacity of materials composed of these molecules allows the generation of directed motion in plant materials entirely controlled by water uptake.
To explore the molecular origin of this swelling capacity, a computational model with atomistic resolution for hemicellulose polysaccharides is build and validated in comparison with experiments. Using this model, simulations of small polysaccharides are employed to gain an understanding of the interactions of these molecules with water, the influence of water on their conformational freedom, and the swelling capacity quantified in terms of osmotic pressure. It is revealed that the branched hemicellulose polysaccharides show different hydration characteristics compared to linear polysaccharides.
To study swelling properties on length and time scales that exceed the limitations imposed by atomistic simulations, a procedure to obtain transferable coarse-grain models is developed. The transferability of the coarse-grain models over both different degrees of polymerization as well as different solute concentrations is demonstrated. Therefore, the procedure allows the construction of large coarse-grained systems based on small atomistic reference systems. Finally, the coarse-grain model is applied to demonstrate that linear and branched polysaccharides show a different swelling behavior when coupled to a water bath.
One hallmark of aging is the accumulation of protein aggregates, promoted by the unfolding of oxidized proteins. Unraveling the mechanism by which oxidized proteins are degraded may provide a basis to delay the early onset of features, such as protein aggregate formation, that contribute to the aging phenotype. In order to prevent aggregation of oxidized proteins, cells recur to the 20S proteasome, an efficient turnover proteolysis complex. It has previously been shown that upon oxidative stress the 26S proteasome, another form, dissociates into the 20S form. A critical player implicated in its dissociation is the Heat Shock Protein 70 (Hsp70), which promotes an increase in free 20S proteasome and, therefore, an increased capability to degrade oxidized proteins. The aim of this study was to test whether or not Hsp70 is involved in cooperating with the 20S proteasome for a selective degradation of oxidatively damaged proteins. Our results demonstrate that Hsp70 expression is induced in HT22 cells as a result of mild oxidative stress conditions. Furthermore, Hsp70 prevents the accumulation of oxidized proteins and directly promotes their degradation by the 20S proteasome. In contrast the expression of the Heat shock cognate protein 70 (Hsc70) was not changed in recovery after oxidative stress and Hsc70 has no influence on the removal of oxidatively damaged proteins. We were able to demonstrate in HT22 cells, in brain homogenates from 129/SV mice and in vitro, that there is an increased interaction of Hsp70 with oxidized proteins, but also with the 20S proteasome, indicating a role of Hsp70 in mediating the interaction of oxidized proteins with the 20S proteasome. Thus, our data clearly implicate an involvement of Hsp70 oxidatively damaged protein degradation by the 20S proteasome. c) 2016 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
The Groningen gas field serves as a natural laboratory for production-induced earthquakes, because no earthquakes were observed before the beginning of gas production. Increasing gas production rates resulted in growing earthquake activity and eventually in the occurrence of the 2012M(w) 3.6 Huizinge earthquake. At least since this event, a detailed seismic hazard and risk assessment including estimation of the maximum earthquake magnitude is considered to be necessary to decide on the future gas production. In this short note, we first apply state-of-the-art methods of mathematical statistics to derive confidence intervals for the maximum possible earthquake magnitude m(max). Second, we calculate the maximum expected magnitude M-T in the time between 2016 and 2024 for three assumed gas-production scenarios. Using broadly accepted physical assumptions and 90% confidence level, we suggest a value of m(max) 4.4, whereas M-T varies between 3.9 and 4.3, depending on the production scenario.
The matrix metalloproteinases (MMP) MMP-2 and MMP-9 are physiological regulators of vascular remodelling. Their dysregulation could contribute to vascular calcification. We examined the role of the MMP-2 and MMP-9 in uraemic vascular calcification in vivo and in vitro. The impact of pharmacological MMP inhibition on the development of media calcifications was explored in an aggressive animal model of uraemic calcification. In addition, the selective effects of addition and inhibition, respectively, of MMP-2 and MMP-9 on calcium-/phosphate-induced calcifications were studied in a murine cell line of vascular smooth muscle cells (VSMCs). High-dose calcitriol treatment of uraemic rats given a high phosphate diet induced massive calcifications, apoptosis and increased gene expressions of MMP-2, MMP-9 and of osteogenic transcription factors and proteins in aortic VSMC. The MMP inhibitor doxycycline prevented the VSMC transdifferentiation to osteoblastic cells, suppressed transcription of mediators of matrix remodelling and almost completely blocked aortic calcifications while further increasing apoptosis. Similarly, specific inhibitors of either MMP-2 or -9, or of both gelatinases (Ro28-2653) and a selective knockdown of MMP-2/-9 mRNA expression blocked calcification of murine VSMC induced by calcification medium (CM). In contrast to MMP inhibition, recombinant MMP-2 or MMP-9 enhanced CM-induced calcifications and the secretion of gelatinases. These data indicate that both gelatinases provide essential signals for phenotypic VSMC conversion, matrix remodelling and the initiation of vascular calcification. Their inhibition seems a promising strategy in the prevention of vascular calcifications.
Large, compressional earthquakes cause surface uplift aswell as widespread mass wasting. Knowledge of their trade-off is fragmentary. Combining a seismologically consistent model of earthquake-triggered landsliding and an analytical solution of coseismic surface displacement, we assess how the mass balance of single earthquakes and earthquake sequences depends on fault size and other geophysical parameters. We find that intermediate size earthquakes (M-w 6-7.3) may cause more erosion than uplift, controlled primarily by seismic source depth and landscape steepness, and less so by fault dip and rake. Such earthquakes can limit topographic growth, but our model indicates that both smaller and larger earthquakes (M-w < 6, M-w > 7.3) systematically cause mountain building. Earthquake sequences with a Gutenberg-Richter distribution have a greater tendency to lead to predominant erosion, than repeating earthquakes of the same magnitude, unless a fault can produce earthquakes with M-w > 8 or more.
The 2014 April 1, M-w 8.1 Iquique (Chile) earthquake struck in the Northern Chile seismic gap. With a rupture length of less than 200 km, it left unbroken large segments of the former gap. Early studies were able to model the main rupture features but results are ambiguous with respect to the role of aseismic slip and left open questions on the remaining hazard at the Northern Chile gap. A striking observation of the 2014 earthquake has been its extensive preparation phase, with more than 1300 events with magnitude above M-L 3, occurring during the 15 months preceding the main shock. Increasing seismicity rates and observed peak magnitudes accompanied the last three weeks before the main shock. Thanks to the large data sets of regional recordings, we assess the precursor activity, compare foreshocks and aftershocks and model rupture preparation and rupture effects. To tackle inversion challenges for moderate events with an asymmetric network geometry, we use full waveforms techniques to locate events, map the seismicity rate and derive source parameters, obtaining moment tensors for more than 300 events (magnitudes M-w 4.0-8.1) in the period 2013 January 1-2014 April 30. This unique data set of fore- and aftershocks is investigated to distinguish rupture process models and models of strain and stress rotation during an earthquake. Results indicate that the spatial distributions of foreshocks delineated the shallower part of the rupture areas of the main shock and its largest aftershock, well matching the spatial extension of the aftershocks cloud. Most moment tensors correspond to almost pure double couple thrust mechanisms, consistent with the slab orientation. Whereas no significant differences are observed among thrust mechanisms in different areas, nor among thrust foreshocks and aftershocks, the early aftershock sequence is characterized by the presence of normal fault mechanisms, striking parallel to the trench but dipping westward. These events likely occurred in the shallow wedge structure close to the slab interface and are consequence of the increased extensional stress in this region after the largest events. The overall stress inversion result suggests a minor stress rotation after the main shock, but a significant release of the deviatoric stress. The temporal change in the distribution of focal mechanisms can also be explained in terms of the spatial heterogeneity of the stress field: under such interpretation, the potential of a large megathrust earthquake breaking a larger segment offshore Northern Chile remains high.
Teacher judgments in terms of grades, proficiency assessments, and recommending placement in ability groups can have important consequences for a child’s future educational path. Whether or not students’ sociodemographic background characteristics are systematically related to teacher judgments has been a controversial topic of discussion. Using data from the TIMSS-Transition Study (N = 3285 fourth graders) administered across 13 German federal states in the 2006–2007 school year and survey data from parents and teachers, we investigated whether or not the average classroom socioeconomic status is reflected in teacher judgments and also examined possible underlying processes. We also probed the role of teachers’ own socioeconomic backgrounds (at the age of 16) in their later susceptibility to differentially judge students from different socioeconomic backgrounds and in differentially composed classrooms. Multilevel regression analyses revealed that, after controlling for differences in achievement (as indicated by standardized tests), teachers’ judgments were associated with the classrooms’ socioeconomic composition, and this finding could not be attributed to the average levels of motivation or behavior in the classroom. Teachers were similarly likely to exhibit such differential judgments regardless of their own socioeconomic background. These findings are discussed in the context of their implications for educational policy.
We analyze the link between R&D, innovation, and productivity in MSMEs with a special focus on micro firms with fewer than 10 employees; usually constituting the majority of firms in industrialized economies. Using the German KfW SME-panel, we examine to what extent micro firms are different from other firms in terms of innovativeness. We find that while firms engage in innovative activities with smaller probability, the smaller they are, for those firms that do make such investment, R&D intensity is larger the smaller firms are. For all MSMEs, the predicted R&D intensity is positively correlated with the probability of reporting innovation, with a larger effect size for product than for process innovations. Moreover, micro firms benefit in a comparable way from innovation processes as larger firms, as they are similarly able to increase their labor productivity. Overall, the link between R&D, innovation, and productivity in micro firms does not largely differ from their larger counterparts. (C) 2016 Elsevier B.V. All rights reserved.
The dispute between social versus religious interpretations of anti-Semitism pervaded the whole history of scholarly research. Whereas socio-historical interpretations had underlined the social aspects, current studies on anti-Semitism focus on religious motifs. The thesis that anti-Semitism was a result of a religious conflict, however, is far more alleged than substantially proved by the sources. So it seems necessary to go back to the sources. Therefore this paper analyzes the language of the Venetian Catholic newspaper Il Veneto Cattolico/La Difesa from the foundation of the newspaper in 1867 up to the First World War. Just a few years before the term anti-Semitism was coined, Catholic journalists of Venice had created the new semantic of secular anti-Semitism. They turned back to religious issues when they tried to systematize their anti-Jewish sentiments. Thus one can observe in the coverage of the Venetian Catholic journals the invention of an anti-Semitic tradition.
Gut bacteria exert beneficial and harmful effects in metabolic diseases as deduced from the comparison of germfree and conventional mice and from fecal transplantation studies. Compositional microbial changes in diseased subjects have been linked to adiposity, type 2 diabetes and dyslipidemia. Promotion of an increased expression of intestinal nutrient transporters or a modified lipid and bile acid metabolism by the intestinal microbiota could result in an increased nutrient absorption by the host. The degradation of dietary fiber and the subsequent fermentation of monosaccharides to short-chain fatty acids (SCFA) is one of the most controversially discussed mechanisms of how gut bacteria impact host physiology. Fibers reduce the energy density of the diet, and the resulting SCFA promote intestinal gluconeogenesis, incretin formation and subsequently satiety. However, SCFA also deliver energy to the host and support liponeogenesis. Thus far, there is little knowledge on bacterial species that promote or prevent metabolic disease. Clostridium ramosum and Enterococcus cloacae were demonstrated to promote obesity in gnotobiotic mouse models, whereas bifidobacteria and Akkermansia muciniphila were associated with favorable phenotypes in conventional mice, especially when oligofructose was fed. How diet modulates the gut microbiota towards a beneficial or harmful composition needs further research. Gnotobiotic animals are a valuable tool to elucidate mechanisms underlying diet-host-microbe interactions.
The interplay between soil structure, roots, and microbiota as a determinant of plant-soil feedback
(2016)
Plant-soil feedback (PSF) can influence plant community structure via changes in the soil microbiome. However, how these feedbacks depend on the soil environment remains poorly understood. We hypothesized that disintegrating a naturally aggregated soil may influence the outcome of PSF by affecting microbial communities. Furthermore, we expected plants to differentially interact with soil structure and the microbial communities due to varying root morphology. We carried out a feedback experiment with nine plant species (five forbs and four grasses) where the training phase consisted of aggregated versus disintegrated soil. In the feedback phase, a uniform soil was inoculated in a fully factorial design with soil washings from conspecific- versus heterospecific-trained soil that had been either disintegrated or aggregated. This way, the effects of prior soil structure on plant performance in terms of biomass production and allocation were examined. In the training phase, soil structure did not affect plant biomass. But on disintegrated soil, plants with lower specific root length (SRL) allocated more biomass aboveground. PSF in the feedback phase was negative overall. With training on disintegrated soil, conspecific feedback was positively correlated with SRL and significantly differed between grasses and forbs. Plants with higher SRL were likely able to easily explore the disintegrated soil with smaller pores, while plants with lower SRL invested in belowground biomass for soil exploration and seemed to be more susceptible to fungal pathogens. This suggests that plants with low SRL could be more limited by PSF on disintegrated soils of early successional stages. This study is the first to examine the influence of soil structure on PSF. Our results suggest that soil structure determines the outcome of PSF mediated by SRL. We recommend to further explore the effects of soil structure and propose to include root performance when working with PSF.
Botanic gardens have been exchanging seeds through seed catalogues for centuries. In many gardens, these catalogues remain an important source of plant material. Living collections have become more relevant for genetic analysis and derived research, since genomics of non-model organisms heavily rely on living material. The range of species that is made available annually on all seed lists combined, provides an unsurpassed source of instantly accessible plant material for research collections. Still, the Index Seminum has received criticism in the past few decades. The current exchange model dictates that associated data is manually entered into each database. The amount of time involved and the human errors occurring in this process are difficult to justify when the data was initially produced as a report from another database. The authors propose that an online marketplace for seed exchange should be established, with enhanced search possibilities and downloadable accession data in a standardised format. Such online service should preferably be supervised and coordinated by Botanic Gardens Conservation International (BGCI). This manuscript is the outcome of a workshop on July 9th, 2015, at the European botanic gardens congress "Eurogard VII" in Paris, where the first two authors invited members of the botanic garden community to discuss how the anachronistic Index Seminum can be transformed into an improved and modern tool for seed exchange.
Variation in the size, shape, and positioning of leaves as the major photosynthetic organs strongly impacts crop yield, and optimizing these aspects is a central aim of cereal breeding [1, 2]. Leaf growth in grasses is driven by cell proliferation and cell expansion in a basal growth zone [3]. Although several factors influencing final leaf size and shape have been identified from rice and maize [4-14], what limits grass leaf growth in the longitudinal or transverse directions during leaf development remains poorly understood. To identify factors involved in this process, we characterized the barley mutant broad leaf1 (blf1). Mutants form wider but slightly shorter leaves due to changes in the numbers of longitudinal cell files and of cells along the leaf length. These differences arise during primordia outgrowth because of more cell divisions in the width direction increasing the number of cell files. Positional cloning, analysis of independent alleles, and transgenic complementation confirm that BLF1 encodes a presumed transcriptional regulator of the INDETERMINATE DOMAIN family. In contrast to loss-of-function mutants, moderate overexpression of BLF1 decreases leaf width below wild-type levels. A functional BLF1-vYFP fusion protein expressed from the endogenous promoter shows a dynamic expression pattern in the shoot apical meristem and young leaf primordia. Thus, we propose that the BLF1 gene regulates barley leaf size by restricting cell proliferation in the leaf-width direction. Given the agronomic importance of canopy traits in cereals, identifying functionally different BLF1 alleles promises to allow for the generation of optimized cereal ideotypes.
The three-space theory of problem solving predicts that the quality of a learner's model and the goal specificity of a task interact on knowledge acquisition. In Experiment 1 participants used a computer simulation of a lever system to learn about torques. They either had to test hypotheses (nonspecific goal), or to produce given values for variables (specific goal). In the good- but not in the poor-model condition they saw torque depicted as an area. Results revealed the predicted interaction. A nonspecific goal only resulted in better learning when a good model of torques was provided. In Experiment 2 participants learned to manipulate the inputs of a system to control its outputs. A nonspecific goal to explore the system helped performance when compared to a specific goal to reach certain values when participants were given a good model, but not when given a poor model that suggested the wrong hypothesis space. Our findings support the three-space theory. They emphasize the importance of understanding for problem solving and stress the need to study underlying processes.
Landscapes can be viewed as spatially heterogeneous areas encompassing terrestrial and aquatic domains. To date, most landscape carbon (C) fluxes have been estimated by accounting for terrestrial ecosystems, while aquatic ecosystems have been largely neglected. However, a robust assessment of C fluxes on the landscape scale requires the estimation of fluxes within and between both landscape components. Here, we compiled data from the literature on C fluxes across the air–water interface from various landscape components. We simulated C emissions and uptake for five different scenarios which represent a gradient of increasing spatial heterogeneity within a temperate young moraine landscape: (I) a homogeneous landscape with only cropland and large lakes; (II) separation of the terrestrial domain into cropland and forest; (III) further separation into cropland, forest, and grassland; (IV) additional division of the aquatic area into large lakes and peatlands; and (V) further separation of the aquatic area into large lakes, peatlands, running waters, and small water bodies These simulations suggest that C fluxes at the landscape scale might depend on spatial heterogeneity and landscape diversity, among other factors. When we consider spatial heterogeneity and diversity alone, small inland waters appear to play a pivotal and previously underestimated role in landscape greenhouse gas emissions that may be regarded as C hot spots. Approaches focusing on the landscape scale will also enable improved projections of ecosystems’ responses to perturbations, e.g., due to global change and anthropogenic activities, and evaluations of the specific role individual landscape components play in regional C fluxes. WIREs Water 2016, 3:601–617. doi: 10.1002/wat2.1147
Fragestellung: Es soll die Qualität der Berichterstattung über Suizide und Suizidversuche in deutschsprachigen Jugendmagazinen näher untersucht werden und Veränderungen der Suizidzahlen unter Jugendlichen in Österreich nach dem Erscheinen von Berichten erfasst werden. Methodik: Suizidberichte aus fünf großen deutschsprachigen Jugendmagazinen wurden mithilfe qualitativer Inhaltsanalyse im Hinblick auf Geschlecht, dargestellte Motive, Suizid(versuchs)methoden, positive und negative Darstellungsweisen, Schuldzuweisungen und Abweichungen von Medienempfehlungen zur Berichterstattung über Suizid analysiert. Die Suizidzahlen 2 Wochen vor und nach dem Erscheinen von Suizidberichten wurden verglichen. Ergebnisse: 59 Berichte wurden identifiziert. Die häufigste Berichterstattung zum Thema Suizid fand sich in der Zeitschrift Bravo, wobei es zu einer leichten Überrepräsentation weiblicher Suizide und insgesamt zu einer Unterrepräsentation von Suizidversuchen kam. Entsprechend der Epidemiologie suizidalen Verhaltens wurde Sturz in die Tiefe am häufigsten bei Mädchen und Erhängen bei den Jungen beschrieben. Bei den dargestellten Motiven zeigte sich, dass wichtige Faktoren wie psychiatrische Erkrankungen kaum Erwähnung fanden. Während Suizidentinnen häufig positiv dargestellt wurden, wurden Suizidenten häufiger negativ dargestellt. Implizite Schuldzuweisungen wurden vorwiegend den Eltern zugeschrieben. Es zeigte sich kein Hinweis auf einen Werther-Effekt nach Berichterstattung. Schlussfolgerungen: Die weitgehende Divergenz zwischen der Epidemiologie von Suizidalität Jugendlicher und im deutschsprachigen Raum derzeit vorherrschenden Mediendarstellungen verdeutlicht wichtige Ansatzpunkte für Präventions- und Aufklärungsarbeit in der Bevölkerung.
The impact of soil microbiota on plant species performance and diversity in semi-natural grasslands
(2016)
Contrary to earlier studies dealing with the cultural identity development of diasporic minorities, this paper assesses the impact of homogeneity on intra-group cohesion and ethnic orientation. To this end, Oromo-Americans, an ethnic group originally located within the national borders of Ethiopia, will be compared to Armenian-Americans, British-Pakistanis and Somali-Americans. Despite different circumstances, all four groups share the experience of displacement owing to war and destitution. Additionally, all groups are confronted with the ramifications of a visible minority status. In the process of comparing these groups, their degrees of homogeneity in regard to language and religion - central aspects of culture and cultural identity - will be examined and juxtaposed at a macro level. Based on the correlative relationship of group homogeneity and social cohesion, I argue that the more homogeneous a group is in terms of language and religion, the more close-knit it will be. Consequently, exiled minorities who share the same language and religion are more likely to develop and retain a strong ethnic orientation than groups who are heterogeneous with regard to language and/or religion.
The semantics of focus particles like only requires a set of alternatives (Rooth, 1992). In two experiments, we investigated the impact of such particles on the retrieval of alternatives that are mentioned in the prior context or unmentioned. The first experiment used a probe recognition task and showed that focus particles interfere with the recognition of mentioned alternatives and the rejection of unmentioned alternatives relative to a condition without a particle. A second lexical decision experiment demonstrated priming effects for mentioned and unmentioned alternatives (compared with an unrelated condition) while focus particles caused additional interference effects. Overall, our results indicate that focus particles trigger an active search for alternatives and lead to a competition between mentioned alternatives, unmentioned alternatives, and the focused element.
The semantics of focus particles like only requires a set of alternatives (Rooth, 1992). In two experiments, we investigated the impact of such particles on the retrieval of alternatives that are mentioned in the prior context or unmentioned. The first experiment used a probe recognition task and showed that focus particles interfere with the recognition of mentioned alternatives and the rejection of unmentioned alternatives relative to a condition without a particle. A second lexical decision experiment demonstrated priming effects for mentioned and unmentioned alternatives (compared with an unrelated condition) while focus particles caused additional interference effects. Overall, our results indicate that focus particles trigger an active search for alternatives and lead to a competition between mentioned alternatives, unmentioned alternatives, and the focused element.
Reconstructing and understanding the Human Physiome virtually is a complex mathematical problem, and a highly demanding computational challenge. Mathematical models spanning from the molecular level through to whole populations of individuals must be integrated, then personalized. This requires interoperability with multiple disparate and geographically separated data sources, and myriad computational software tools. Extracting and producing knowledge from such sources, even when the databases and software are readily available, is a challenging task. Despite the difficulties, researchers must frequently perform these tasks so that available knowledge can be continually integrated into the common framework required to realize the Human Physiome. Software and infrastructures that support the communities that generate these, together with their underlying standards to format, describe and interlink the corresponding data and computer models, are pivotal to the Human Physiome being realized. They provide the foundations for integrating, exchanging and re-using data and models efficiently, and correctly, while also supporting the dissemination of growing knowledge in these forms. In this paper, we explore the standards, software tooling, repositories and infrastructures that support this work, and detail what makes them vital to realizing the Human Physiome.
The role that climate and environmental history may have played in influencing human evolution has been the focus of considerable interest and controversy among paleoanthropologists for decades. Prior attempts to understand the environmental history side of this equation have centered around the study of outcrop sediments and fossils adjacent to where fossil hominins (ancestors or close relatives of modern humans) are found, or from the study of deep sea drill cores. However, outcrop sediments are often highly weathered and thus are unsuitable for some types of paleoclimatic records, and deep sea core records come from long distances away from the actual fossil and stone tool remains. The Hominin Sites and Paleolakes Drilling Project (HSPDP) was developed to address these issues. The project has focused its efforts on the eastern African Rift Valley, where much of the evidence for early hominins has been recovered. We have collected about 2 km of sediment drill core from six basins in Kenya and Ethiopia, in lake deposits immediately adjacent to important fossil hominin and archaeological sites. Collectively these cores cover in time many of the key transitions and critical intervals in human evolutionary history over the last 4 Ma, such as the earliest stone tools, the origin of our own genus Homo, and the earliest anatomically modern Homo sapiens. Here we document the initial field, physical property, and core description results of the 2012-2014 HSPDP coring campaign.
The role that climate and environmental history may have played in influencing human evolution has been the focus of considerable interest and controversy among paleoanthropologists for decades. Prior attempts to understand the environmental history side of this equation have centered around the study of outcrop sediments and fossils adjacent to where fossil hominins (ancestors or close relatives of modern humans) are found, or from the study of deep sea drill cores. However, outcrop sediments are often highly weathered and thus are unsuitable for some types of paleoclimatic records, and deep sea core records come from long distances away from the actual fossil and stone tool remains. The Hominin Sites and Paleolakes Drilling Project (HSPDP) was developed to address these issues. The project has focused its efforts on the eastern African Rift Valley, where much of the evidence for early hominins has been recovered. We have collected about 2 km of sediment drill core from six basins in Kenya and Ethiopia, in lake deposits immediately adjacent to important fossil hominin and archaeological sites. Collectively these cores cover in time many of the key transitions and critical intervals in human evolutionary history over the last 4 Ma, such as the earliest stone tools, the origin of our own genus Homo, and the earliest anatomically modern Homo sapiens. Here we document the initial field, physical property, and core description results of the 2012-2014 HSPDP coring campaign.
We propose a theory of how the speech gesture determines change in a functionally relevant variable of vocal tract state (e.g., constriction degree). A core postulate of the theory is that the gesture determines how the variable evolves in time independent of any executive timekeeper. That is, the theory involves intrinsic timing of speech gestures. We compare the theory against others in which an executive timekeeper determines change in vocal tract state. Theories that employ an executive timekeeper have been proposed to correct for disparities between theoretically predicted and experimentally observed velocity profiles. Such theories of extrinsic timing make the gesture a nonautonomous dynamical system. For a nonautonomous dynamical system, the change in state depends not just on the state but also on time. We show that this nonautonomous extension makes surprisingly weak kinematic predictions both qualitatively and quantitatively. We propose instead that the gesture is a theoretically simpler nonlinear autonomous dynamical system. For the proposed nonlinear autonomous dynamical system, the change in state depends nonlinearly on the state and does not depend on time. This new theory provides formal expression to the notion of intrinsic timing. Furthermore, it predicts experimentally observed relations among kinematic variables.
The aim of this work is the evaluation of the geothermal potential of Luxembourg. The approach consists in a joint interpretation of different types of information necessary for a first rather qualitative assessment of deep geothermal reservoirs in Luxembourg and the adjoining regions in the surrounding countries of Belgium, France and Germany. For the identification of geothermal reservoirs by exploration, geological, thermal, hydrogeological and structural data are necessary. Until recently, however, reliable information about the thermal field and the regional geology, and thus about potential geothermal reservoirs, was lacking. Before a proper evaluation of the geothermal potential can be performed, a comprehensive survey of the geology and an assessment of the thermal field are required.
As a first step, the geology and basin structure of the Mesozoic Trier–Luxembourg Basin (TLB) is reviewed and updated using recently published information on the geology and structures as well as borehole data available in Luxembourg and the adjoining regions. A Bouguer map is used to get insight in the depth, morphology and structures in the Variscan basement buried beneath the Trier–Luxembourg Basin. The geological section of the old Cessange borehole is reinterpreted and provides, in combination with the available borehole data, consistent information for the production of isopach maps. The latter visualize the synsedimentary evolution of the Trier–Luxembourg Basin. Complementary, basin-wide cross sections illustrate the evolution and structure of the Trier–Luxembourg Basin. The knowledge gained does not support the old concept of the Weilerbach Mulde. The basin-wide cross sections, as well as the structural and sedimentological observations in the Trier–Luxembourg Basin suggest that the latter probably formed above a zone of weakness related to a buried Rotliegend graben. The inferred graben structure designated by SE-Luxembourg Graben (SELG) is located in direct southwestern continuation of the Wittlicher Rotliegend-Senke.
The lack of deep boreholes and subsurface temperature prognosis at depth is circumnavigated by using thermal modelling for inferring the geothermal resource at depth. For this approach, profound structural, geological and petrophysical input data are required. Conceptual geological cross sections encompassing the entire crust are constructed and further simplified and extended to lithospheric scale for their utilization as thermal models. The 2-D steady state and conductive models are parameterized by means of measured petrophysical properties including thermal conductivity, radiogenic heat production and density. A surface heat flow of 75 ∓ 7 (2δ) mW m–2 for verification of the thermal models could be determined in the area. The models are further constrained by the geophysically-estimated depth of the lithosphere–asthenosphere boundary (LAB) defined by the 1300 °C isotherm. A LAB depth of 100 km, as seismically derived for the Ardennes, provides the best fit with the measured surface heat flow. The resulting mantle heat flow amounts to ∼40 mW m–2. Modelled temperatures are in the range of 120–125 °C at 5 km depth and of 600–650 °C at the crust/mantle discontinuity (Moho). Possible thermal consequences of the 10–20 Ma old Eifel plume, which apparently caused upwelling of the asthenospheric mantle to 50–60 km depth, were modelled in a steady-state thermal scenario resulting in a surface heat flow of at least 91 mW m–2 (for the plume top at 60 km) in the Eifel region. Available surface heat-flow values are significantly lower (65–80 mW m–2) and indicate that the plume-related heating has not yet entirely reached the surface.
Once conceptual geological models are established and the thermal regime is assessed, the geothermal potential of Luxembourg and the surrounding areas is evaluated by additional consideration of the hydrogeology, the stress field and tectonically active regions. On the one hand, low-enthalpy hydrothermal reservoirs in Mesozoic reservoirs in the Trier–Luxembourg Embayment (TLE) are considered. On the other hand, petrothermal reservoirs in the Lower Devonian basement of the Ardennes and Eifel regions are considered for exploitation by Enhanced/Engineered Geothermal Systems (EGS). Among the Mesozoic aquifers, the Buntsandstein aquifer characterized by temperatures of up to 50 °C is a suitable hydrothermal reservoir that may be exploited by means of heat pumps or provide direct heat for various applications. The most promising area is the zone of the SE–Luxembourg Graben. The aquifer is warmest underneath the upper Alzette River valley and the limestone plateau in Lorraine, where the Buntsandstein aquifer lies below a thick Mesozoic cover. At the base of an inferred Rotliegend graben in the same area, temperatures of up to 75 °C are expected. However, geological and hydraulic conditions are uncertain. In the Lower Devonian basement, thick sandstone-/quartzite-rich formations with temperatures >90 °C are expected at depths >3.5 km and likely offer the possibility of direct heat use. The setting of the Südeifel (South Eifel) region, including the Müllerthal region near Echternach, as a tectonically active zone may offer the possibility of deep hydrothermal reservoirs in the fractured Lower Devonian basement. Based on the recent findings about the structure of the Trier–Luxembourg Basin, the new concept presents the Müllerthal–Südeifel Depression (MSD) as a Cenozoic structure that remains tectonically active and subsiding, and therefore is relevant for geothermal exploration. Beyond direct use of geothermal heat, the expected modest temperatures at 5 km depth (about 120 °C) and increased permeability by EGS in the quartzite-rich Lochkovian could prospectively enable combined geothermal heat production and power generation in Luxembourg and the western realm of the Eifel region.
The production of toxic metabolites by cyanobacterial blooms represents a significant threat to the health of humans and ecosystems worldwide. Here we summarize the current state of the knowledge regarding the genetics, biosynthesis and regulation of well-characterized cyanotoxins, including the microcystins, nodularin, cylindrospermopsin, saxitoxins and antitoxins, as well as the lesser-known marine toxins (e.g. lyngbyatoxin, aplysiatoxin, jamaicamides, barbamide, curacin, hectochlorin and apratoxins). (C) 2015 Elsevier B.V. All rights reserved.
The agricultural transition profoundly changed human societies. We sequenced and analysed the first genome (1.39x) of an early Neolithic woman from Ganj Dareh, in the Zagros Mountains of Iran, a site with early evidence for an economy based on goat herding, ca. 10,000 BP. We show that Western Iran was inhabited by a population genetically most similar to hunter-gatherers from the Caucasus, but distinct from the Neolithic Anatolian people who later brought food production into Europe. The inhabitants of Ganj Dareh made little direct genetic contribution to modern European populations, suggesting those of the Central Zagros were somewhat isolated from other populations of the Fertile Crescent. Runs of homozygosity are of a similar length to those from Neolithic farmers, and shorter than those of Caucasus and Western Hunter-Gatherers, suggesting that the inhabitants of Ganj Dareh did not undergo the large population bottleneck suffered by their northern neighbours. While some degree of cultural diffusion between Anatolia, Western Iran and other neighbouring regions is possible, the genetic dissimilarity between early Anatolian farmers and the inhabitants of Ganj Dareh supports a model in which Neolithic societies in these areas were distinct.
Arf-like proteins (ARLs) are ubiquitously expressed small G proteins of the RAS superfamily. In photoreceptors, ARL2 and ARL3 participate in the trafficking of lipidated membrane-associated proteins and colocalize in the inner segment with UNC119A and PDE delta. UNC119A and PDE delta are acyl-and prenyl-binding proteins, respectively, involved in trafficking of acylated (transducin-alpha subunit, nephrocystin NPHP3) and prenylated proteins (GRK1, PDE6). Germline Arl3 knockout mice do not survive beyond postnatal day 21 and display ciliary defects in multiple organs (kidney, liver and pancreas) as well as retinal degeneration. Conditional knockouts will be necessary to delineate mechanisms of protein transport in retina disease.
Endocardial cells are cardiac endothelial cells that line the interior of the heart tube. Historically, their contribution to cardiac development has mainly been considered from a morphological perspective. However, recent studies have begun to define novel instructive roles of the endocardium, as a sensor and signal transducer of biophysical forces induced by blood flow, and as an angiocrine signalling centre that is involved in myocardial cellular morphogenesis, regeneration and reprogramming. In this Review, we discuss how the endocardium develops, how endocardial-myocardial interactions influence the developing embryonic heart, and how the dysregulation of blood flowresponsive endocardial signalling can result in pathophysiological changes.
In June 2013, widespread flooding and consequent damage and losses occurred in Central Europe, especially in Germany. This paper explores what data are available to investigate the adverse impacts of the event, what kind of information can be retrieved from these data and how well data and information fulfil requirements that were recently proposed for disaster reporting on the European and international levels. In accordance with the European Floods Directive (2007/60/EC), impacts on human health, economic activities (and assets), cultural heritage and the environment are described on the national and sub-national scale. Information from governmental reports is complemented by communications on traffic disruptions and surveys of flood-affected residents and companies.
Overall, the impacts of the flood event in 2013 were manifold. The study reveals that flood-affected residents suffered from a large range of impacts, among which mental health and supply problems were perceived more seriously than financial losses. The most frequent damage type among affected companies was business interruption. This demonstrates that the current scientific focus on direct (financial) damage is insufficient to describe the overall impacts and severity of flood events.
The case further demonstrates that procedures and standards for impact data collection in Germany are widely missing. Present impact data in Germany are fragmentary, heterogeneous, incomplete and difficult to access. In order to fulfil, for example, the monitoring and reporting requirements of the Sendai Framework for Disaster Risk Reduction 2015-2030 that was adopted in March 2015 in Sendai, Japan, more efforts on impact data collection are needed.
In June 2013, widespread flooding and consequent damage and losses occurred in Central Europe, especially in Germany. This paper explores what data are available to investigate the adverse impacts of the event, what kind of information can be retrieved from these data and how well data and information fulfil requirements that were recently proposed for disaster reporting on the European and international levels. In accordance with the European Floods Directive (2007/60/EC), impacts on human health, economic activities (and assets), cultural heritage and the environment are described on the national and sub-national scale. Information from governmental reports is complemented by communications on traffic disruptions and surveys of flood-affected residents and companies.
Overall, the impacts of the flood event in 2013 were manifold. The study reveals that flood-affected residents suffered from a large range of impacts, among which mental health and supply problems were perceived more seriously than financial losses. The most frequent damage type among affected companies was business interruption. This demonstrates that the current scientific focus on direct (financial) damage is insufficient to describe the overall impacts and severity of flood events.
The case further demonstrates that procedures and standards for impact data collection in Germany are widely missing. Present impact data in Germany are fragmentary, heterogeneous, incomplete and difficult to access. In order to fulfil, for example, the monitoring and reporting requirements of the Sendai Framework for Disaster Risk Reduction 2015–2030 that was adopted in March 2015 in Sendai, Japan, more efforts on impact data collection are needed.
The origin of the magnetic field in massive O-type stars is still under debate. To model the physical processes responsible for the generation of O star magnetic fields, it is important to understand whether correlations between the presence of a magnetic field and stellar evolutionary state, rotation velocity, kinematical status, and surface composition can be identified. The O4 Ief supergiant zeta Pup is a fast rotator and a runaway star, which may be a product of a past binary interaction, possibly having had an encounter with the cluster Trumper 10 some 2 Myr ago. The currently available observational material suggests that certain observed phenomena in this star may be related to the presence of a magnetic field. We acquired spectropolarimetric observations of zeta Pup with FORS 2 mounted on the 8 m Antu telescope of the Very Large Telescope to investigate if a magnetic field is indeed present in this star. We show that many spectral lines are highly variable and probably vary with the recently detected period of 1.78 day. No magnetic field is detected in zeta Pup, as no magnetic field measurement has a significance level higher than 2.4 sigma. Still, we studied the probability of a single sinusoidal explaining the variation of the longitudinal magnetic field measurements.
The multifaceted concept of ‘form’ plays a central tole in the linguistic work of Wilhelm von Humboldt (1767–1835), where it is deeply entwined with aesthetic questions. H. Steinthal's (1823–1899) interpretation of linguistic form, however, made it the servant of psychology. The Formungstrieb (drive to formation) of Georg von der Gabelentz (1840–1893) challenged Steinthal's conception and placed a renewed emphasis on aesthetics. In this endeavour, Gabelentz drew on the work of such figures as August Friedrich Pott (1802–1887), Hans Conon von der Gabelentz (1807–1874) and William Dwight Whitney (1827–1894). In this paper, we examine Gabelentz' Formungstrieb and place it in its historical context.
Parental care is widespread among vertebrates and the observed patterns of parental care and investment are extremely diverse. Among amphibians, caecilians (Gymnophiona) exhibit considerable variation in reproductive modes, including both oviparity and viviparity, combined with highly unusual investment strategies (e.g. skin-feeding and intrauterine feeding). In the present study, current knowledge on the reproductive modes is integrated into an analysis of the evolutionary scenario of parental investment of caecilians. Phylogenetically basal caecilians possessing a biphasic life cycle that includes an aquatic larval stage invest in macrolecithal eggs directly corresponding to size at hatching. Some phylogenetically derived caecilians (i.e. the Teresomata) have a smaller clutch size and show a reduction to either medium-yolked (mesolecithal) or small-yolked (microlecithal) eggs. Via alternative pathways of parental investment, such as intrauterine feeding in viviparous taxa and maternal dermatotrophy in oviparous taxa, teresomatan caecilians increase both offspring size and quality. However, more data regarding reproductive biology are needed to obtain a fully resolved understanding of the evolution of reproduction in caecilian amphibians. (C) 2016 The Linnean Society of London
Since spring 2014 the relations between the EU and Russia are stuck in an Ice Age. From a Western point of view, especially the annexation of Crimea by Russia and the intervention in the conflict in Ukraine are responsible. The EU has frozen their relations to Russia and applied sanctions against it. Russia reacted in the same way. Can this vicious circle be broken without betraying the values of the EU? This book presents the analysis and ideas of social scientists from Germany, Poland and Russia. The reasons for this crisis are seen quite differently but all try to find a way out of the current confrontation.
The Eukaryotic-Specific ISD11 Is a Complex-Orphan Protein with Ability to Bind the Prokaryotic IscS
(2016)
The eukaryotic protein Isd11 is a chaperone that binds and stabilizes the central component of the essential metabolic pathway responsible for formation of iron-sulfur clusters in mitochondria, the desulfurase Nfs1. Little is known about the exact role of Isd11. Here, we show that human Isd11 (ISD11) is a helical protein which exists in solution as an equilibrium between monomer, dimeric and tetrameric species when in the absence of human Nfs1 (NFS1). We also show that, surprisingly, recombinant ISD11 expressed in E. coli co-purifies with the bacterial orthologue of NFS1, IscS. Binding is weak but specific suggesting that, despite the absence of Isd11 sequences in bacteria, there is enough conservation between the two desulfurases to retain a similar mode of interaction. This knowledge may inform us on the conservation of the mode of binding of Isd11 to the desulfurase. We used evolutionary evidence to suggest Isd11 residues involved in the interaction.
The eukaryotic-specific Isd11 is a complex- orphan protein with ability to bind the prokaryotic IscS
(2016)
The eukaryotic protein Isd11 is a chaperone that binds and stabilizes the central component of the essential metabolic pathway responsible for formation of iron-sulfur clusters in mitochondria, the desulfurase Nfs1. Little is known about the exact role of Isd11. Here, we show that human Isd11 (ISD11) is a helical protein which exists in solution as an equilibrium between monomer, dimeric and tetrameric species when in the absence of human Nfs1 (NFS1). We also show that, surprisingly, recombinant ISD11 expressed in E. coli co-purifies with the bacterial orthologue of NFS1, IscS. Binding is weak but specific suggesting that, despite the absence of Isd11 sequences in bacteria, there is enough conservation between the two desulfurases to retain a similar mode of interaction. This knowledge may inform us on the conservation of the mode of binding of Isd11 to the desulfurase. We used evolutionary evidence to suggest Isd11 residues involved in the interaction.
The xanthine oxidase (XO) family comprises molybdenum-dependent enzymes that usually form homodimers (or dimers of heterodimers/trimers) organized in three domains that harbor two [2Fe-2S] clusters, one FAD, and a Mo cofactor. In this work, we crystallized an unusual member of the family, the periplasmic aldehyde oxidoreductase PaoABC from Escherichia coli. This is the first example of an E. coli protein containing a molybdopterin-cytosine-dinucleotide cofactor and is the only heterotrimer of the XO family so far structurally characterized. The crystal structure revealed the presence of an unexpected [4Fe-4S] cluster, anchored to an additional 40 residues subdomain. According to phylogenetic analysis, proteins containing this cluster are widely spread in many bacteria phyla, putatively through repeated gene transfer events. The active site of PaoABC is highly exposed to the surface with no aromatic residues and an arginine (PaoC-R440) making a direct interaction with PaoC-E692, which acts as a base catalyst. In order to understand the importance of R440, kinetic assays were carried out, and the crystal structure of the PaoC-R440H variant was also determined.
In this study, the stable conformers of neutral anserine were searched by molecular dynamics simulations and energy minimization calculations using the MM2 force field. Thermochemical calculations at B3LYP/6-31G(d) level of theory followed these preliminary calculations. The results confirmed that neutral anserine has quite a flexible structure and many stable gauche and trans conformers at room temperature. Nevertheless, two are considerably more favourable in energy than the others and expected to dominate the gas-phase and matrix IR spectra of the molecule. The corresponding structural and vibrational spectral data for these two conformers of neutral anserine, whose relative stabilities were also examined by high-accuracy energy calculations carried out using G3MP2B3 method, and for the most stable conformer of anserine in zwitterion form were calculated at B3LYP/6-311++G(d,p) level of theory. The calculated harmonic force constants were refined using the Scaled Quantum Mechanical Force Field (SQM-FF) method and then used to produce the refined wavenumbers, potential energy distributions (PEDs) and IR and Raman intensities. These refined data together with the scaled harmonic wavenumbers obtained using another method, Dual Scale factors (DS), enabled us to correctly analyse the observed IR and Raman spectra of anserine and revealed the effects of conformation and zwitterionic tautomerism on its structural and vibrational spectral data. (C) 2016 Elsevier B.V. All rights reserved.
Restoring degraded lands in rural environments that are heavily managed to meet subsistence needs is a challenge due to high rates of disturbance and resource extraction. This study investigates the efficacy of erosion control structures (ECSs) as restoration tools in the context of a watershed rehabilitation and wet meadow (bofedal) restoration program in the Bolivian Andes. In an effort to enhance water security and increase grazing stability, Aymara indigenous communities built over 15,000 check dams, 9,100 terraces, 5,300 infiltration ditches, and 35 pasture improvement trials. Communities built ECSs at different rates, and we compared vegetation change in the highest restoration management intensity, lowest restoration management intensity, and nonproject control communities. We used line transects to measure changes in vegetation cover and standing water in gullies with check dams and without check dams, and related these ground measurements to a time series (1986-2009) of normalized difference vegetation index derived from Landsat TM5 images. Evidence suggests that check dams increase bofedal vegetation and standing water at a local scale, and lead to increased greenness at a basin scale when combined with other ECSs. Watershed rehabilitation enhances ecosystem services significant to local communities (grazing stability, water security), which creates important synergies when conducting land restoration in rural development settings.
Background: Comprehension of reversible sentences that have derived word order has often been reported as impaired in agrammatic aphasia. Most accounts of this phenomenon refer to the syntactic differences between derived and base word order of the arguments. However, it has been demonstrated that in agrammatic spontaneous speech in standard Indonesian (SI) passives are produced at a rate that is proportional to that of healthy speakers. The main difference between passives in SI and in other languages is the frequency with which passives are used: passives in SI are highly frequent. The high frequency can be explained by the fact that passives are used for politeness reasons, saliency of the passive morphology, earlier acquisition, and formal simplicity of the passive structure.
Aims: The purpose of the current study is to investigate comprehension of the passive as a derived structure in SI and the influence of frequency.
Methods & Procedures: A sentence-to-picture matching task was developed to test four reversible sentence types (active, passive, subject cleft and object cleft). There are three variables that are of interest, that is, word order, embedding and relative frequency of structures. Eleven agrammatic speakers classified as suffering from Broca’s aphasia were tested.
Outcomes & Results: The passive sentences were comprehended equally well as the active sentences. Embedding had limited effects: subject clefts were understood as well as actives and passives. Object clefts, however, were understood poorly and significantly worse than the three other sentence types.
Conclusions: The sentence comprehension deficit pattern shown in SI individuals with Broca’s aphasia introduces frequency of a syntactic structure as an additional factor to consider. Whether frequency or pragmatic constraints protects against erosion of the passive in Broca’s aphasia in SI remains an open question.
Over the past ~40 years, several attempts were made to reintroduce Eurasian lynx to suitable habitat within their former distribution range in Western Europe. In general, limited numbers of individuals have been released to establish new populations. To evaluate the effects of reintroductions on the genetic status of lynx populations we used 12 microsatellite loci to study lynx populations in the Bohemian–Bavarian and Vosges–Palatinian forests. Compared with autochthonous lynx populations, these two reintroduced populations displayed reduced genetic diversity, particularly the Vosges–Palatinian population. Our genetic data provide further evidence to support the status of ‘endangered’ and ‘critically endangered’ for the Bohemian–Bavarian and Vosges–Palatinian populations, respectively. Regarding conservation management, we highlight the need to limit poaching, and advocate additional translocations to bolster genetic variability.
The differential cross-section for gravitational photon-photon scattering calculated in perturbative quantum gravity is shown to depend on the degree of polarization entanglement of the two photons. The interaction between photons in the symmetric Bell state is stronger than between not entangled photons. In contrast, the interaction between photons in the anti-symmetric Bell state is weaker than between not entangled photons. The results are interpreted in terms of quantum interference, and it is shown how they fit into the idea of distance-dependent forces. Copyright (C) EPLA, 2016
In the present study, we summarize and evaluate the endeavors from recent years to estimate the maximum possible earthquake magnitude m(max) from observed data. In particular, we use basic and physically motivated assumptions to identify best cases and worst cases in terms of lowest and highest degree of uncertainty of m(max). In a general framework, we demonstrate that earthquake data and earthquake proxy data recorded in a fault zone provide almost no information about m(max) unless reliable and homogeneous data of a long time interval, including several earthquakes with magnitude close to m(max), are available. Even if detailed earthquake information from some centuries including historic and paleoearthquakes are given, only very few, namely the largest events, will contribute at all to the estimation of m(max), and this results in unacceptably high uncertainties. As a consequence, estimators of m(max) in a fault zone, which are based solely on earthquake-related information from this region, have to be dismissed.
Dipeptidyl peptidase (DPP)-4 inhibitors delay chronic kidney disease (CKD) progression in experimental diabetic nephropathy in a glucose-independent manner. Here we compared the effects of the DPP-4 inhibitor linagliptin versus telmisartan in preventing CKD progression in non-diabetic rats with 5/6 nephrectomy. Animals were allocated to 1 of 4 groups: sham operated plus placebo; 5/6 nephrectomy plus placebo; 5/6 nephrectomy plus linagliptin; and 5/6 nephrectomy plus telmisartan. Interstitial fibrosis was significantly decreased by 48% with linagliptin but a non-significant 24% with telmisartan versus placebo. The urine albumin-to-creatinine ratio was significantly decreased by 66% with linagliptin and 92% with telmisartan versus placebo. Blood pressure was significantly lowered by telmisartan, but it was not affected by linagliptin. As shown by mass spectrometry, the number of altered peptide signals for linagliptin in plasma was 552 and 320 in the kidney. For telmisartan, there were 108 peptide changes in plasma and 363 in the kidney versus placebo. Linagliptin up-regulated peptides derived from collagen type I, apolipoprotein C1, and heterogeneous nuclear ribonucleoproteins A2/B1, a potential downstream target of atrial natriuretic peptide, whereas telmisartan up-regulated angiotensin II. A second study was conducted to confirm these findings in 5/6 nephrectomy wild-type and genetically deficient DPP-4 rats treated with linagliptin or placebo. Linagliptin therapy in wild-type rats was as effective as DPP-4 genetic deficiency in terms of albuminuria reduction. Thus, linagliptin showed comparable efficacy to telmisartan in preventing CKD progression in non-diabetic rats with 5/6 nephrectomy. However, the underlying pathways seem to be different. Copyright (C) 2016, International Society of Nephrology. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
In Sources of the Self Charles Taylor makes clear that both hypergoods and moral sources are essential to the moral life. Although hypergoods and moral sources are not the same thing, Taylor’s descriptions of these concepts are quite similar, and so their distinction requires interpretation. I propose that we interpret the difference on the basis of another distinction that is central to Taylor’s thinking: that between immanence and transcendence. Whereas a moral source transcends us, a hypergood is the value of our immanent way of relating to that moral source. This interpretation requires that we first differentiate between a narrow and a wide sense of “moral source.”