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Recombinant adeno-associated viruses (rAAV) provide outstanding options for customization and superior capabilities for gene therapy. To access their full potential, facile genetic manipulation is pivotal, including capsid loop modifications. Therefore, we assessed capsid tolerance to modifications of the structural VP proteins in terms of stability and plasticity. Flexible glycine-serine linkers of increasing sizes were, at the genetic level, introduced into the 587 loop region of the VP proteins of serotype 2, the best studied AAV representative. Analyses of biological function and thermal stability with respect to genome release of viral particles revealed structural plasticity. In addition, insertion of the 29 kDa enzyme beta-lactamase into the loop region was tested with a complete or a mosaic modification setting. For the mosaic approach, investigation of VP2 trans expression revealed that a Kozak sequence was required to prevent leaky scanning. Surprisingly, even the full capsid modification with beta-lactamase allowed for the assembly of capsids with a concomitant increase in size. Enzyme activity assays revealed lactamase functionality for both rAAV variants, which demonstrates the structural robustness of this platform technology.
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.
This article looks at Émile Zola’s novel cycle Les Rougon-Macquart and argues that it describes its subject, the Second Empire, as a warming climate tending toward climate catastrophe. Zola’s affinity to the notion of climate is shown to be linked to his poetic employment of the concept of ‘milieu’, inspired by Hippolyte Taine. Close readings of selected passages from the Rougon-Macquart are used to work out the climatic difference between ‘the old’ and ‘the new Paris’, and the process of warming that characterises the Second Empire. Octave Mouret’s department store holds a special place in the article, as it is analysed through what the article suggests calling a ‘meteorotopos’: a location of intensified climatic conditions that accounts for an increased interaction between human and non-human actors. The department store is also one of the many sites in the novel cycle that locally prefigure the ‘global’ climate catastrophe of Paris burning, in which the Second Empire perishes.
The actin cytoskeleton and its response to external chemical stimuli is fundamental to the mechano-biology of eukaryotic cells and their functions. One of the key players that governs the dynamics of the actin network is the motor protein myosin II. Based on a phase space embedding we have identified from experiments three phases in the cytoskeletal dynamics of starved Dictyostelium discoideum in response to a precisely controlled chemotactic stimulation. In the first two phases the dynamics of actin and myosin II in the cortex is uncoupled, while in the third phase the time scale for the recovery of cortical actin is determined by the myosin II dynamics. We report a theoretical model that captures the experimental observations quantitatively. The model predicts an increase in the optimal response time of actin with decreasing myosin II-actin coupling strength highlighting the role of myosin II in the robust control of cell contraction.
Tumor-associated macrophages (TAMs) promote tumor growth and metastasis by suppressing tumor immune surveillance. Herein, we provide evidence that the immunosuppressive phenotype of TAMs is controlled by long-chain fatty acid metabolism, specifically unsaturated fatty acids, here exemplified by oleate. Consequently, en-route enriched lipid droplets were identified as essential organelles, which represent effective targets for chemical inhibitors to block in vitro polarization of TAMs and tumor growth in vivo. In line, analysis of human tumors revealed that myeloid cells infiltrating colon cancer but not gastric cancer tissue indeed accumulate lipid droplets. Mechanistically, our data indicate that oleate-induced polarization of myeloid cells depends on the mammalian target of the rapamycin pathway. Thus, our findings reveal an alternative therapeutic strategy by targeting the pro-tumoral myeloid cells on a metabolic level.
Background. In horses and ponies numerous medical conditions are known to be linked with inflammation in different tissues, especially in the liver. Besides affecting other metabolic pathways such as the expression of certain interleukins (IL), inflammation is associated with stress of the endoplasmic reticulum (ER). In particular, ER stress leads to adaptive stress response and can be measured by several markers of inflammatory and stress signalling pathways, like nuclear factor kappa B (NF-kB). Objectives. To investigate lipopolysaccharide (LPS)-induced inflammatory reactions and their modulation in horses and ponies by feeding a polyphenol-rich supplement consisting of green tea and curcuma. Methods. In a cross-over study, 11 animals were allocated to either a placebo or a supplement group and supplemented with 10 g of a blend of green tea and curcuma extract (GCE) or a placebo (calcium carbonate) once daily. After 21 days of supplementation, all animals underwent a LPS challenge to induce moderate systemic inflammation. Blood samples and liver biopsies were taken at standardized time points: 24 hours before and 12 hours after LPS challenge. Inflammatory blood parameters such as serum amyloid A (SAA), haptoglobin and retinol binding protein 4 (RBP4) were measured in serum. Hepatic mRNA levels of selected markers of inflammation such as haptoglobin, tumor necrosis factor alpha (TNF-alpha), IL-1 beta, IL-6, cluster of differentiation 68 (CD68), fibroblast growth factor 21 (FGF-21), NF-kappa B, activating transcription factor 4 (ATF4) were quantified by RT-qPCR. In addition, liver biopsies were examined histologically for inflammatory alterations. Results. Blood markers of acute inflammatory response increased after LPS challenge. In the liver, the proinflammatory cytokine IL-1 beta showed significantly lower mRNA levels after LPS challenge in the supplemented group (P = 0.04) compared to the placebo group. Levels of the hepatic CD68 mRNA increased significantly in the placebo group (P = 0.04). There were no significant differences between supplemented and placebo groups concerning other markers of inflammation and markers of ER stress within the liver. The number of hepatic macrophages were not different after LPS challenge in both feeding groups. Conclusion. LPS was able to induce inflammation but seemed less suitable to induce ER stress in the horses and ponies. The polyphenol-rich supplement showed some potential to reduce inflammatory responses. Nevertheless, the supplementation did not exert an overall anti-inflammatory effect in horses and ponies.
BackgroundPachycladon cheesemanii is a close relative of Arabidopsis thaliana and is an allotetraploid perennial herb which is widespread in the South Island of New Zealand. It grows at altitudes of up to 1000m where it is subject to relatively high levels of ultraviolet (UV)-B radiation. To gain first insights into how Pachycladon copes with UV-B stress, we sequenced its genome and compared the UV-B tolerance of two Pachycladon accessions with those of two A. thaliana accessions from different altitudes.ResultsA high-quality draft genome of P. cheesemanii was assembled with a high percentage of conserved single-copy plant orthologs. Synteny analysis with genomes from other species of the Brassicaceae family found a close phylogenetic relationship of P. cheesemanii with Boechera stricta from Brassicaceae lineage I. While UV-B radiation caused a greater growth reduction in the A. thaliana accessions than in the P. cheesemanii accessions, growth was not reduced in one P. cheesemanii accession. The homologues of A. thaliana UV-B radiation response genes were duplicated in P. cheesemanii, and an expression analysis of those genes indicated that the tolerance mechanism in P. cheesemanii appears to differ from that in A. thaliana.ConclusionAlthough the P. cheesemanii genome shows close similarity with that of A. thaliana, it appears to have evolved novel strategies allowing the plant to tolerate relatively high UV-B radiation.
Both climate-change damages and climate-change mitigation will incur economic costs. While the risk of severe damages increases with the level of global warming (Dell et al., 2014; IPCC, 2014b, 2018; Lenton et al., 2008), mitigating costs increase steeply with more stringent warming limits (IPCC, 2014a; Luderer et al., 2013; Rogelj et al., 2015). Here, we show that the global warming limit that minimizes this century's total economic costs of climate change lies between 1.9 and 2 ∘C, if temperature changes continue to impact national economic growth rates as observed in the past and if instantaneous growth effects are neither compensated nor amplified by additional growth effects in the following years. The result is robust across a wide range of normative assumptions on the valuation of future welfare and inequality aversion. We combine estimates of climate-change impacts on economic growth for 186 countries (applying an empirical damage function from Burke et al., 2015) with mitigation costs derived from a state-of-the-art energy–economy–climate model with a wide range of highly resolved mitigation options (Kriegler et al., 2017; Luderer et al., 2013, 2015). Our purely economic assessment, even though it omits non-market damages, provides support for the international Paris Agreement on climate change. The political goal of limiting global warming to “well below 2 degrees” is thus also an economically optimal goal given above assumptions on adaptation and damage persistence.
Background/objective
Dry land-training (e.g., plyometric jump training) can be a useful mean to improve swimming performance. This study examined the effects of an 8-week plyometric jump training (PJT) program on jump and sport-specific performances in prepubertal female swimmers.
Methods
Twenty-two girls were randomly assigned to either a plyometric jump training group (PJTG; n = 12, age: 10.01 ± 0.57 years, maturity-offset = -1.50 ± 0.50, body mass = 36.39 ± 6.32 kg, body height = 146.90 ± 7.62 cm, body mass index = 16.50 ± 1.73 kg/m2) or an active control (CG; n = 10, age: 10.50 ± 0.28 years, maturity-offset = -1.34 ± 0.51, body mass = 38.41 ± 9.42 kg, body height = 143.60 ± 5.05 cm, body mass index = 18.48 ± 3.77 kg/m2). Pre- and post-training, tests were conducted for the assessment of muscle power (e.g., countermovement-jump [CMJ], standing-long-jump [SLJ]). Sport-specific-performances were tested using the timed 25 and 50-m front crawl with a diving-start, timed 25-m front crawl without push-off from the wall (25-m WP), and a timed 25-m kick without push-off from the wall (25-m KWP).
Results
Findings showed a significant main effect of time for the CMJ (d = 0.78), the SLJ (d = 0.91), 25-m front crawl test (d = 2.5), and the 25-m-KWP (d = 1.38) test. Significant group × time interactions were found for CMJ, SLJ, 25-m front crawl, 50-m front crawl, 25-m KWP, and 25-m WP test (d = 0.29–1.63) in favor of PJTG (d = 1.34–3.50). No significant pre-post changes were found for CG (p > 0.05).
Conclusion
In sum, PJT is effective in improving muscle power and sport-specific performances in prepubertal swimmers. Therefore, PJT should be included from an early start into the regular training program of swimmers.
Movement ecology aims to provide common terminology and an integrative framework of movement research across all groups of organisms. Yet such work has focused on unitary organisms so far, and thus the important group of filamentous fungi has not been considered in this context. With the exception of spore dispersal, movement in filamentous fungi has not been integrated into the movement ecology field. At the same time, the field of fungal ecology has been advancing research on topics like informed growth, mycelial translocations, or fungal highways using its own terminology and frameworks, overlooking the theoretical developments within movement ecology. We provide a conceptual and terminological framework for interdisciplinary collaboration between these two disciplines, and show how both can benefit from closer links: We show how placing the knowledge from fungal biology and ecology into the framework of movement ecology can inspire both theoretical and empirical developments, eventually leading towards a better understanding of fungal ecology and community assembly. Conversely, by a greater focus on movement specificities of filamentous fungi, movement ecology stands to benefit from the challenge to evolve its concepts and terminology towards even greater universality. We show how our concept can be applied for other modular organisms (such as clonal plants and slime molds), and how this can lead towards comparative studies with the relationship between organismal movement and ecosystems in the focus.
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.
Starch and Glycogen Analyses
(2020)
For complex carbohydrates, such as glycogen and starch, various analytical methods and techniques exist allowing the detailed characterization of these storage carbohydrates. In this article, we give a brief overview of the most frequently used methods, techniques, and results. Furthermore, we give insights in the isolation, purification, and fragmentation of both starch and glycogen. An overview of the different structural levels of the glucans is given and the corresponding analytical techniques are discussed. Moreover, future perspectives of the analytical needs and the challenges of the currently developing scientific questions are included
Corporate Citizenship
(2020)
Corporate citizenship, which is firms’ societal engagement beyond customer and shareholder interests, is a prominent topic in management practice and has led to extensive research. This increased interest resulted in a complex and fragmented scholarly literature. In order to structure and map the field quantitatively, we conducted a temporal analysis of publications and citations, an analysis of the productivity of involved disciplines, an analysis of the productivity of publication forms including journal impact factors, an author productivity and citation analysis, a co-author analysis, an article citation analysis, an article co-citation analysis, and a keyword co-occurrence analysis. Results of these bibliometric analyses show that corporate citizenship research seems to have been in a phase of stagnation since 2014 and shows a rather low degree of interdisciplinarity. Papers are predominantly published in high impact journals. Authors show little collaboration with other researchers. Current research relates to other business ethics topics, addresses philosophical foundations, and starts to relate to human resource management and organization studies.
Climate change is affecting the rate of carbon cycling, particularly in the Arctic. Permafrost degradation through deeper thaw and physical disturbances results in the release of carbon dioxide and methane to the atmosphere and to an increase in lateral dissolved organic matter (DOM) fluxes. Whereas riverine DOM fluxes of the large Arctic rivers are well assessed, knowledge is limited with regard to small catchments that cover more than 40% of the Arctic drainage basin. Here, we use absorption measurements to characterize changes in DOM quantity and quality in a low Arctic (Herschel Island, Yukon, Canada) and a high Arctic (Cape Bounty, Melville Island, Nunavut, Canada) setting with regard to geographical differences, impacts of permafrost degradation, and rainfall events. We find that DOM quantity and quality is controlled by differences in vegetation cover and soil organic carbon content (SOCC). The low Arctic site has higher SOCC and greater abundance of plant material resulting in higher chromophoric dissolved organic matter (cDOM) and dissolved organic carbon (DOC) than in the high Arctic. DOC concentration and cDOM in surface waters at both sites show strong linear relationships similar to the one for the great Arctic rivers. We used the optical characteristics of DOM such as cDOM absorption, specific ultraviolet absorbance (SUVA), ultraviolet (UV) spectral slopes (S275-295), and slope ratio (SR) for assessing quality changes downstream, at base flow and storm flow conditions, and in relation to permafrost disturbance. DOM in streams at both sites demonstrated optical signatures indicative of photodegradation downstream processes, even over short distances of 2000 m. Flow pathways and the connected hydrological residence time control DOM quality. Deeper flow pathways allow the export of permafrost-derived DOM (i.e. from deeper in the active layer), whereas shallow pathways with shorter residence times lead to the export of fresh surface- and near-surface-derived DOM. Compared to the large Arctic rivers, DOM quality exported from the small catchments studied here is much fresher and therefore prone to degradation. Assessing optical properties of DOM and linking them to catchment properties will be a useful tool for understanding changing DOM fluxes and quality at a pan-Arctic scale.
Um auch die unbeabsichtigten Folgen ihrer Politik zu ermitteln, unternehmen Regierungen umfassende Gesetzesfolgenabschätzungen. Immer häufiger lassen sie sich dabei von unabhängigen Expertengremien kontrollieren. Doch: Wie erzielen diese Gremien Einfluss? Und welche Rolle spielen sie als Politikberater für Bürokratieabbau und bessere Rechtsetzung? Das Buch eröffnet neue Einblicke in die Entwicklungshistorie und Handlungsrealität der drei erfahrensten Normenkontrollräte in Europa. Vor dem Hintergrund unterschiedlicher Verwaltungskulturen werden die Ratstypen „Wachhund“, „Torwächter“ und „Kritischer Freund“ herausgearbeitet. Die Ergebnisse schärfen die politische und wissenschaftliche Debatte um die Leistungsfähigkeit von Normenkontrollräten.
The synthesis of chiral nanoporous carbons based on chiral ionic liquids (CILs) of amino acids as precursors is described. Such unique precursors for the carbonization of CILs yield chiral carbonaceous materials with high surface area (approximate to 620 m(2) g(-1)). The enantioselectivities of the porous carbons are examined by advanced techniques such as selective adsorption of enantiomers using cyclic voltammetry, isothermal titration calorimetry, and mass spectrometry. These techniques demonstrate the chiral nature and high enantioselectivity of the chiral carbon materials. Overall, we believe that the novel approach presented here can contribute significantly to the development of new chiral carbon materials that will find important applications in chiral chemistry, such as in chiral catalysis and separation and in chiral sensors. From a scientific point of view, the approach and results reported here can significantly deepen our understanding of chirality at the nanoscale and of the structure and nature of chiral nonporous materials and surfaces.
Eine Gruppe, gar eine innerlich verbundene Gemeinschaft, können Intellektuelle im Normalfall nur bilden, soweit sie von gleichem Denken und Wollen bewegt werden […]. Wo dagegen die von den Intellektuellen vertretenen Ansichten weit divergieren, da kann es nur unter sehr kritischen Umständen geschehen, daß die verschieden gearteten (sozialen, politischen, rechtlichen, kulturellen, religiösen) Standpunkte und Anliegen – auf Zeit – sich zusammenfinden […]. Das polemische Element, das kritischen Intellektuellen ja wesensmäßig zu eigen ist, bringt am ehesten eine gemeinsame Front zwischen ihnen zustande.
Deformation associated with plate convergence at subduction zones is accommodated by a complex system involving fault slip and viscoelastic flow. These processes have proven difficult to disentangle. The 2010 M-w 8.8 Maule earthquake occurred close to the Chilean coast within a dense network of continuously recording Global Positioning System stations, which provide a comprehensive history of surface strain. We use these data to assemble a detailed picture of a structurally controlled megathrust fault frictional patchwork and the three-dimensional rheological and time-dependent viscosity structure of the lower crust and upper mantle, all of which control the relative importance of afterslip and viscoelastic relaxation during postseismic deformation. These results enhance our understanding of subduction dynamics including the interplay of localized and distributed deformation during the subduction zone earthquake cycle.
The most severe flood events in Turkey were determined for the period 1960–2014 by considering the number of fatalities, the number of affected people, and the total economic losses as indicators. The potential triggering mechanisms (i.e., atmospheric circulations and precipitation amounts) and aggravating pathways (i.e., topographic features, catchment size, land use types, and soil properties) of these 25 events were analyzed. On this basis, a new approach was developed to identify the main influencing factor per event and to provide additional information for determining the dominant flood occurrence pathways for severe floods. The events were then classified through hierarchical cluster analysis. As a result, six different clusters were found and characterized. Cluster 1 comprised flood events that were mainly influenced by drainage characteristics (e.g., catchment size and shape); Cluster 2 comprised events aggravated predominantly by urbanization; steep topography was identified to be the dominant factor for Cluster 3; extreme rainfall was determined as the main triggering factor for Cluster 4; saturated soil conditions were found to be the dominant factor for Cluster 5; and orographic effects of mountain ranges characterized Cluster 6. This study determined pathway patterns of the severe floods in Turkey with regard to their main causal or aggravating mechanisms. Accordingly, geomorphological properties are of major importance in large catchments in eastern and northeastern Anatolia. In addition, in small catchments, the share of urbanized area seems to be an important factor for the extent of flood impacts. This paper presents an outcome that could be used for future urban planning and flood risk prevention studies to understand the flood mechanisms in different regions of Turkey.
In this report, we illustrate the considerable impact of researcher degrees of freedom with respect to exclusion of participants in paradigms with a learning element. We illustrate this empirically through case examples from human fear conditioning research, in which the exclusion of ‘non-learners’ and ‘non-responders’ is common – despite a lack of consensus on how to define these groups. We illustrate the substantial heterogeneity in exclusion criteria identified in a systematic literature search and highlight the potential problems and pitfalls of different definitions through case examples based on re-analyses of existing data sets. On the basis of these studies, we propose a consensus on evidence-based rather than idiosyncratic criteria, including clear guidelines on reporting details. Taken together, we illustrate how flexibility in data collection and analysis can be avoided, which will benefit the robustness and replicability of research findings and can be expected to be applicable to other fields of research that involve a learning element.