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Rats are a reservoir of human- and livestock-associated methicillin-resistant Staphylococcus aureus (MRSA). However, the composition of the natural S. aureus population in wild and laboratory rats is largely unknown. Here, 144 nasal S. aureus isolates from free-living wild rats, captive wild rats and laboratory rats were genotyped and profiled for antibiotic resistances and human-specific virulence genes. The nasal S. aureus carriage rate was higher among wild rats (23.4%) than laboratory rats (12.3%). Free-living wild rats were primarily colonized with isolates of clonal complex (CC) 49 and CC130 and maintained these strains even in husbandry. Moreover, upon livestock contact, CC398 isolates were acquired. In contrast, laboratory rats were colonized with many different S. aureus lineages—many of which are commonly found in humans. Five captive wild rats were colonized with CC398-MRSA. Moreover, a single CC30-MRSA and two CC130-MRSA were detected in free-living or captive wild rats. Rat-derived S. aureus isolates rarely harbored the phage-carried immune evasion gene cluster or superantigen genes, suggesting long-term adaptation to their host. Taken together, our study revealed a natural S. aureus population in wild rats, as well as a colonization pressure on wild and laboratory rats by exposure to livestock- and human-associated S. aureus, respectively.
We present a new set of global and local sea‐level projections at example tide gauge locations under the RCP2.6, RCP4.5, and RCP8.5 emissions scenarios. Compared to the CMIP5‐based sea‐level projections presented in IPCC AR5, we introduce a number of methodological innovations, including (i) more comprehensive treatment of uncertainties, (ii) direct traceability between global and local projections, and (iii) exploratory extended projections to 2300 based on emulation of individual CMIP5 models. Combining the projections with observed tide gauge records, we explore the contribution to total variance that arises from sea‐level variability, different emissions scenarios, and model uncertainty. For the period out to 2300 we further breakdown the model uncertainty by sea‐level component and consider the dependence on geographic location, time horizon, and emissions scenario. Our analysis highlights the importance of local variability for sea‐level change in the coming decades and the potential value of annual‐to‐decadal predictions of local sea‐level change. Projections to 2300 show a substantial degree of committed sea‐level rise under all emissions scenarios considered and highlight the reduced future risk associated with RCP2.6 and RCP4.5 compared to RCP8.5. Tide gauge locations can show large ( > 50%) departures from the global average, in some cases even reversing the sign of the change. While uncertainty in projections of the future Antarctic ice dynamic response tends to dominate post‐2100, we see substantial differences in the breakdown of model variance as a function of location, time scale, and emissions scenario.
Monocytes and macrophages are key players in maintaining immune homeostasis. Identifying strategies to manipulate their functions via gene delivery is thus of great interest for immunological research and biomedical applications. We set out to establish conditions for mRNA transfection in hard-to-transfect primary human monocytes and monocyte-derived macrophages due to the great potential of gene expression from in vitro transcribed mRNA for modulating cell phenotypes. mRNA doses, nucleotide modifications, and different carriers were systematically explored in order to optimize high mRNA transfer rates while minimizing cell stress and immune activation. We selected three commercially available mRNA transfection reagents including liposome and polymer-based formulations, covering different application spectra. Our results demonstrate that liposomal reagents can particularly combine high gene transfer rates with only moderate immune cell activation. For the latter, use of specific nucleotide modifications proved essential. In addition to improving efficacy of gene transfer, our findings address discrete aspects of innate immune activation using cytokine and surface marker expression, as well as cell viability as key readouts to judge overall transfection efficiency. The impact of this study goes beyond optimizing transfection conditions for immune cells, by providing a framework for assessing new gene carrier systems for monocyte and macrophage, tailored to specific applications.
Background: Dietary protein restriction is emerging as an alternative approach to treat obesity and glucose intolerance because it markedly increases plasma fibroblast growth factor 21 (FGF21) concentrations. Similarly, dietary restriction of methionine is known to mimic metabolic effects of energy and protein restriction with FGF21 as a required mechanism. However, dietary protein has been shown to be required for normal bone growth, though there is conflicting evidence as to the influence of dietary protein restriction on bone remodeling. The purpose of the current study was to evaluate the effect of dietary protein and methionine restriction on bone in lean and obese mice, and clarify whether FGF21 and general control nonderepressible 2 (GCN2) kinase, that are part of a novel endocrine pathway implicated in the detection of protein restriction, influence the effect of dietary protein restriction on bone.
Methods: Adult wild-type (WT) or Fgf21 KO mice were fed a normal protein (18 kcal%; CON) or low protein (4 kcal%; LP) diet for 2 or 27 weeks. In addition, adult WT or Gcn2 KO mice were fed a CON or LP diet for 27 weeks. Young New Zealand obese (NZO) mice were placed on high-fat diets that provided protein at control (16 kcal%; CON), low levels (4 kcal%) in a high-carbohydrate (LP/HC) or high-fat (LP/HF) regimen, or on high-fat diets (protein, 16 kcal%) that provided methionine at control (0.86%; CON-MR) or low levels (0.17%; MR) for up to 9 weeks. Long bones from the hind limbs of these mice were collected and evaluated with micro-computed tomography (mu CT) for changes in trabecular and cortical architecture and mass.
Results: In WT mice the 27-week LP diet significantly reduced cortical bone, and this effect was enhanced by deletion of Fgf21 but not Gcn2. This decrease in bone did not appear after 2 weeks on the LP diet. In addition, Fgf21 KO mice had significantly less bone than their WT counterparts. In obese NZO mice dietary protein and methionine restriction altered bone architecture. The changes were mediated by FGF21 due to methionine restriction in the presence of cystine, which did not increase plasma FGF21 levels and did not affect bone architecture.
Conclusions: This study provides direct evidence of a reduction in bone following long-term dietary protein restriction in a mouse model, effects that appear to be mediated by FGF21.
We recently demonstrated that the sympathetic nervous system can be voluntarily activated following a training program consisting of cold exposure, breathing exercises, and meditation. This resulted in profound attenuation of the systemic inflammatory response elicited by lipopolysaccharide (LPS) administration. Herein, we assessed whether this training program affects the plasma metabolome and if these changes are linked to the immunomodulatory effects observed. A total of 224 metabolites were identified in plasma obtained from 24 healthy male volunteers at six timepoints, of which 98 were significantly altered following LPS administration. Effects of the training program were most prominent shortly after initiation of the acquired breathing exercises but prior to LPS administration, and point towards increased activation of the Cori cycle. Elevated concentrations of lactate and pyruvate in trained individuals correlated with enhanced levels of anti-inflammatory interleukin (IL)-10. In vitro validation experiments revealed that co-incubation with lactate and pyruvate enhances IL-10 production and attenuates the release of pro-inflammatory IL-1 beta and IL-6 by LPS-stimulated leukocytes. Our results demonstrate that practicing the breathing exercises acquired during the training program results in increased activity of the Cori cycle. Furthermore, this work uncovers an important role of lactate and pyruvate in the anti-inflammatory phenotype observed in trained subjects.
The prevalence of vitamin A deficiency in sub-Saharan Africa necessitates effective approaches to improve provitamin A content of major staple crops. Cassava holds much promise for food security in sub-Saharan Africa, but a negative correlation between beta-carotene, a provitamin A carotenoid, and dry matter content has been reported, which poses a challenge to cassava biofortification by conventional breeding. To identify suitable material for genetic transformation in tissue culture with the overall aim to increase beta-carotene and maintain starch content as well as better understand carotenoid composition, root and leaf tissues from thirteen field-grown cassava landraces were analyzed for agronomic traits, carotenoid, chlorophyll, and starch content. The expression of five genes related to carotenoid biosynthesis were determined in selected landraces. Analysis revealed a weak negative correlation between starch and beta-carotene content, whereas there was a strong positive correlation between root yield and many carotenoids including beta-carotene. Carotenoid synthesis genes were expressed in both white and yellow cassava roots, but phytoene synthase 2 (PSY2), lycopene-epsilon-cyclase (LCY epsilon), and beta-carotenoid hydroxylase (CHY beta) expression were generally higher in yellow roots. This study identified lines with reasonably high content of starch and beta-carotene that could be candidates for biofortification by further breeding or plant biotechnological means.
Fluorination of organic spacer impacts on the structural and optical response of 2D perovskites
(2020)
Low-dimensional hybrid perovskites have triggered significant research interest due to their intrinsically tunable optoelectronic properties and technologically relevant material stability. In particular, the role of the organic spacer on the inherent structural and optical features in two-dimensional (2D) perovskites is paramount for material optimization. To obtain a deeper understanding of the relationship between spacers and the corresponding 2D perovskite film properties, we explore the influence of the partial substitution of hydrogen atoms by fluorine in an alkylammonium organic cation, resulting in (Lc)(2)PbI4 and (Lf)(2)PbI4 2D perovskites, respectively. Consequently, optical analysis reveals a clear 0.2 eV blue-shift in the excitonic position at room temperature. This result can be mainly attributed to a band gap opening, with negligible effects on the exciton binding energy. According to Density Functional Theory (DFT) calculations, the band gap increases due to a larger distortion of the structure that decreases the atomic overlap of the wavefunctions and correspondingly bandwidth of the valence and conduction bands. In addition, fluorination impacts the structural rigidity of the 2D perovskite, resulting in a stable structure at room temperature and the absence of phase transitions at a low temperature, in contrast to the widely reported polymorphism in some non-fluorinated materials that exhibit such a phase transition. This indicates that a small perturbation in the material structure can strongly influence the overall structural stability and related phase transition of 2D perovskites, making them more robust to any phase change. This work provides key information on how the fluorine content in organic spacer influence the structural distortion of 2D perovskites and their optical properties which possess remarkable importance for future optoelectronic applications, for instance in the field of light-emitting devices or sensors.
In June 2019, more than a hundred plant researchers met in Cologne, Germany, for the 6th European Workshop on Plant Chromatin (EWPC). This conference brought together a highly dynamic community of researchers with the common aim to understand how chromatin organization controls gene expression, development, and plant responses to the environment. New evidence showing how epigenetic states are set, perpetuated, and inherited were presented, and novel data related to the three-dimensional organization of chromatin within the nucleus were discussed. At the level of the nucleosome, its composition by different histone variants and their specialized histone deposition complexes were addressed as well as the mechanisms involved in histone post-translational modifications and their role in gene expression. The keynote lecture on plant DNA methylation by Julie Law (SALK Institute) and the tribute session to Lars Hennig, honoring the memory of one of the founders of the EWPC who contributed to promote the plant chromatin and epigenetic field in Europe, added a very special note to this gathering. In this perspective article we summarize some of the most outstanding data and advances on plant chromatin research presented at this workshop.
New Zealand's Alpine Fault is a large, platebounding strike-slip fault, which ruptures in large (M-w > 8) earthquakes. We conducted field and laboratory analyses of fault rocks to assess its fault zone architecture. Results reveal that the Alpine Fault Zone has a complex geometry, comprising an anastomosing network of multiple slip planes that have accommodated different amounts of displacement. This contrasts with the previous perception of the Alpine Fault Zone, which assumes a single principal slip zone accommodated all displacement. This interpretation is supported by results of drilling projects and geophysical investigations. Furthermore, observations presented here show that the young, largely unconsolidated sediments that constitute the footwall at shallow depths have a significant influence on fault gouge rheological properties and structure.
In classical thermodynamic processes the unavoidable presence of irreversibility, quantified by the entropy production, carries two energetic footprints: the reduction of extractable work from the optimal, reversible case, and the generation of a surplus of heat that is irreversibly dissipated to the environment. Recently it has been shown that in the quantum regime an additional quantum irreversibility occurs that is linked to decoherence into the energy basis. Here we employ quantum trajectories to construct distributions for classical heat and quantum heat exchanges, and show that the heat footprint of quantum irreversibility differs markedly from the classical case. We also quantify how quantum irreversibility reduces the amount of work that can be extracted from a state with coherences. Our results show that decoherence leads to both entropic and energetic footprints which both play an important role in the optimization of controlled quantum operations at low temperature.
In classical thermodynamics irreversibility occurs whenever a non-thermal system is brought into contact with a thermal environment. Using quantum trajectories the authors here establish two energetic footprints of quantum irreversible processes, and find that while quantum irreversibility leads to the occurrence of a quantum heat and a reduction of work production, the two are not linked in the same manner as the classical laws of thermodynamics would dictate.
Estimating global mean sea-level rise and its uncertainties by 2100 and 2300 from an expert survey
(2020)
Sea-level rise projections and knowledge of their uncertainties are vital to make informed mitigation and adaptation decisions. To elicit projections from members of the scientific community regarding future global mean sea-level (GMSL) rise, we repeated a survey originally conducted five years ago. Under Representative Concentration Pathway (RCP) 2.6, 106 experts projected a likely (central 66% probability) GMSL rise of 0.30-0.65 m by 2100, and 0.54-2.15 m by 2300, relative to 1986-2005. Under RCP 8.5, the same experts projected a likely GMSL rise of 0.63-1.32 m by 2100, and 1.67-5.61 m by 2300. Expert projections for 2100 are similar to those from the original survey, although the projection for 2300 has extended tails and is higher than the original survey. Experts give a likelihood of 42% (original survey) and 45% (current survey) that under the high-emissions scenario GMSL rise will exceed the upper bound (0.98 m) of the likely range estimated by the Fifth Assessment Report of the Intergovernmental Panel on Climate Change, which is considered to have an exceedance likelihood of 17%. Responses to open-ended questions suggest that the increases in upper-end estimates and uncertainties arose from recent influential studies about the impact of marine ice cliff instability on the meltwater contribution to GMSL rise from the Antarctic Ice Sheet.
Landscapes in high northern latitudes are assumed to be highly sensitive to future global change, but the rates and long-term trajectories of changes are rather uncertain. In the boreal zone, fires are an important factor in climate-vegetation interactions and biogeochemical cycles. Fire regimes are characterized by small, frequent, low-intensity fires within summergreen boreal forests dominated by larch, whereas evergreen boreal forests dominated by spruce and pine burn large areas less frequently but at higher intensities. Here, we explore the potential of the monosaccharide anhydrides (MA) levoglucosan, mannosan and galactosan to serve as proxies of low-intensity biomass burning in glacial-to-interglacial lake sediments from the high northern latitudes. We use sediments from Lake El'gygytgyn (cores PG 1351 and ICDP 5011-1), located in the far north-east of Russia, and study glacial and interglacial samples of the last 430 kyr (marine isotope stages 5e, 6, 7e, 8, 11c and 12) that had different climate and biome configurations. Combined with pollen and non-pollen palynomorph records from the same samples, we assess how far the modern relationships between fire, climate and vegetation persisted during the past, on orbital to centennial timescales. We find that MAs attached to particulates were well-preserved in up to 430 kyr old sediments with higher influxes from low-intensity biomass burning in interglacials compared to glacials. MA influxes significantly increase when summergreen boreal forest spreads closer to the lake, whereas they decrease when tundra-steppe environments and, especially, Sphagnum peatlands spread. This suggests that low-temperature fires are a typical characteristic of Siberian larch forests also on long timescales. The results also suggest that low-intensity fires would be reduced by vegetation shifts towards very dry environments due to reduced biomass availability, as well as by shifts towards peatlands, which limits fuel dryness. In addition, we observed very low MA ratios, which we interpret as high contributions of galactosan and mannosan from biomass sources other than those currently monitored, such as the moss-lichen mats in the understorey of the summergreen boreal forest. Overall, sedimentary MAs can provide a powerful proxy for fire regime reconstructions and extend our knowledge of long-term natural fire-climate-vegetation feedbacks in the high northern latitudes.
Landscapes in high northern latitudes are assumed to be highly sensitive to future global change, but the rates and long-term trajectories of changes are rather uncertain. In the boreal zone, fires are an important factor in climate-vegetation interactions and biogeochemical cycles. Fire regimes are characterized by small, frequent, low-intensity fires within summergreen boreal forests dominated by larch, whereas evergreen boreal forests dominated by spruce and pine burn large areas less frequently but at higher intensities. Here, we explore the potential of the monosaccharide anhydrides (MA) levoglucosan, mannosan and galactosan to serve as proxies of low-intensity biomass burning in glacial-to-interglacial lake sediments from the high northern latitudes. We use sediments from Lake El'gygytgyn (cores PG 1351 and ICDP 5011-1), located in the far north-east of Russia, and study glacial and interglacial samples of the last 430 kyr (marine isotope stages 5e, 6, 7e, 8, 11c and 12) that had different climate and biome configurations. Combined with pollen and non-pollen palynomorph records from the same samples, we assess how far the modern relationships between fire, climate and vegetation persisted during the past, on orbital to centennial timescales. We find that MAs attached to particulates were well-preserved in up to 430 kyr old sediments with higher influxes from low-intensity biomass burning in interglacials compared to glacials. MA influxes significantly increase when summergreen boreal forest spreads closer to the lake, whereas they decrease when tundra-steppe environments and, especially, Sphagnum peatlands spread. This suggests that low-temperature fires are a typical characteristic of Siberian larch forests also on long timescales. The results also suggest that low-intensity fires would be reduced by vegetation shifts towards very dry environments due to reduced biomass availability, as well as by shifts towards peatlands, which limits fuel dryness. In addition, we observed very low MA ratios, which we interpret as high contributions of galactosan and mannosan from biomass sources other than those currently monitored, such as the moss-lichen mats in the understorey of the summergreen boreal forest. Overall, sedimentary MAs can provide a powerful proxy for fire regime reconstructions and extend our knowledge of long-term natural fire-climate-vegetation feedbacks in the high northern latitudes.
Identification of a super-functional Tfh-like subpopulation in murine lupus by pattern perception
(2020)
Dysregulated cytokine expression by T cells plays a pivotal role in the pathogenesis of autoimmune diseases. However, the identification of the corresponding pathogenic subpopulations is a challenge, since a distinction between physiological variation and a new quality in the expression of protein markers requires combinatorial evaluation. Here, we were able to identify a super-functional follicular helper T cell (Tfh)-like subpopulation in lupus-prone NZBxW mice with our binning approach "pattern recognition of immune cells (PRI)". PRI uncovered a subpopulation of IL-21(+) IFN-gamma(high) PD-1(low) CD40L(high) CXCR5(-) Bcl-6(-) T cells specifically expanded in diseased mice. In addition, these cells express high levels of TNF-alpha and IL-2, and provide B cell help for IgG production in an IL-21 and CD40L dependent manner. This super-functional T cell subset might be a superior driver of autoimmune processes due to a polyfunctional and high cytokine expression combined with Tfh-like properties.
We propose a novel way to measure and analyze networks of drainage divides from digital elevation models. We developed an algorithm that extracts drainage divides based on the drainage basin boundaries defined by a stream network. In contrast to streams, there is no straightforward approach to order and classify divides, although it is intuitive that some divides are more important than others. A meaningful way of ordering divides is the average distance one would have to travel down on either side of a divide to reach a common stream location. However, because measuring these distances is computationally expensive and prone to edge effects, we instead sort divide segments based on their tree-like network structure, starting from endpoints at river confluences. The sorted nature of the network allows for assigning distances to points along the divides, which can be shown to scale with the average distance downslope to the common stream location. Furthermore, because divide segments tend to have characteristic lengths, an ordering scheme in which divide orders increase by 1 at junctions mimics these distances. We applied our new algorithm to the Big Tujunga catchment in the San Gabriel Mountains of southern California and studied the morphology of the drainage divide network. Our results show that topographic metrics, like the downstream flow distance to a stream and hillslope relief, attain characteristic values that depend on the drainage area threshold used to derive the stream network. Portions along the divide network that have lower than average relief or are closer than average to streams are often distinctly asymmetric in shape, suggesting that these divides are unstable. Our new and automated approach thus helps to objectively extract and analyze divide networks from digital elevation models.
Xanthomonas phaseoli pv. manihotis (Xpm) is the causal agent of cassava bacterial blight, the most important bacterial disease in this crop. There is a paucity of knowledge about the metabolism of Xanthomonas and its relevance in the pathogenic process, with the exception of the elucidation of the xanthan biosynthesis route. Here we report the reconstruction of the genome-scale model of Xpm metabolism and the insights it provides into plant-pathogen interactions. The model, iXpm1556, displayed 1,556 reactions, 1,527 compounds, and 890 genes. Metabolic maps of central amino acid and carbohydrate metabolism, as well as xanthan biosynthesis of Xpm, were reconstructed using Escher (https://escher.github.io/) to guide the curation process and for further analyses. The model was constrained using the RNA-seq data of a mutant of Xpm for quorum sensing (QS), and these data were used to construct context-specific models (CSMs) of the metabolism of the two strains (wild type and QS mutant). The CSMs and flux balance analysis were used to get insights into pathogenicity, xanthan biosynthesis, and QS mechanisms. Between the CSMs, 653 reactions were shared; unique reactions belong to purine, pyrimidine, and amino acid metabolism. Alternative objective functions were used to demonstrate a trade-off between xanthan biosynthesis and growth and the re-allocation of resources in the process of biosynthesis. Important features altered by QS included carbohydrate metabolism, NAD(P)(+) balance, and fatty acid elongation. In this work, we modeled the xanthan biosynthesis and the QS process and their impact on the metabolism of the bacterium. This model will be useful for researchers studying host-pathogen interactions and will provide insights into the mechanisms of infection used by this and other Xanthomonas species.
The remarkable progress of metal halide perovskites in photovoltaics has led to the power conversion efficiency approaching 26%. However, practical applications of perovskite-based solar cells are challenged by the stability issues, of which the most critical one is photo-induced degradation. Bare CH3NH3PbI3 perovskite films are known to decompose rapidly, with methylammonium and iodine as volatile species and residual solid PbI2 and metallic Pb, under vacuum under white light illumination, on the timescale of minutes. We find, in agreement with previous work, that the degradation is non-uniform and proceeds predominantly from the surface, and that illumination under N-2 and ambient air (relative humidity 20%) does not induce substantial degradation even after several hours. Yet, in all cases the release of iodine from the perovskite surface is directly identified by X-ray photoelectron spectroscopy. This goes in hand with a loss of organic cations and the formation of metallic Pb. When CH3NH3PbI3 films are covered with a few nm thick organic capping layer, either charge selective or non-selective, the rapid photodecomposition process under ultrahigh vacuum is reduced by more than one order of magnitude, and becomes similar in timescale to that under N-2 or air. We conclude that the light-induced decomposition reaction of CH3NH3PbI3, leading to volatile methylammonium and iodine, is largely reversible as long as these products are restrained from leaving the surface. This is readily achieved by ambient atmospheric pressure, as well as a thin organic capping layer even under ultrahigh vacuum. In addition to explaining the impact of gas pressure on the stability of this perovskite, our results indicate that covalently "locking" the position of perovskite components at the surface or an interface should enhance the overall photostability.
Recent findings suggest a role of oxytocin on the tendency to spontaneously mimic the emotional facial expressions of others. Oxytocin-related increases of facial mimicry, however, seem to be dependent on contextual factors. Given previous literature showing that people preferentially mimic emotional expressions of individuals associated with high (vs. low) rewards, we examined whether the reward value of the mimicked agent is one factor influencing the oxytocin effects on facial mimicry. To test this hypothesis, 60 male adults received 24 IU of either intranasal oxytocin or placebo in a double-blind, between-subject experiment. Next, the value of male neutral faces was manipulated using an associative learning task with monetary rewards. After the reward associations were learned, participants watched videos of the same faces displaying happy and angry expressions. Facial reactions to the emotional expressions were measured with electromyography. We found that participants judged as more pleasant the face identities associated with high reward values than with low reward values. However, happy expressions by low rewarding faces were more spontaneously mimicked than high rewarding faces. Contrary to our expectations, we did not find a significant direct effect of intranasal oxytocin on facial mimicry, nor on the reward-driven modulation of mimicry. Our results support the notion that mimicry is a complex process that depends on contextual factors, but failed to provide conclusive evidence of a role of oxytocin on the modulation of facial mimicry.