We study the entanglement Hamiltonian for fermionic hopping models on rings and open chains and determine single-particle spectra, eigenfunctions and the form in real space. For the chain, we find a commuting operator as for the ring and compare with its properties in both cases. In particular, a scaling relation between the eigenvalues is found for large systems. We also show how the commutation property carries over to the critical transverse Ising model.View less
Fibro-adipogenic progenitors (FAPs) are resident mesenchymal progenitors in adult skeletal muscle that support muscle repair, but also give rise to fibrous and adipose infiltration in response to disease and chronic injury. FAPs are identified using cell surface markers that do not distinguish between quiescent FAPs and FAPs actively engaged in the regenerative process. We have shown previously that FAPs are derived from cells that express the transcription factor Osr1 during development. Here we show that adult FAPs express Osr1 at low levels and frequency, however upon acute injury FAPs reactivate Osr1 expression in the injured tissue. Osr1+ FAPs are enriched in proliferating and apoptotic cells demonstrating that Osr1 identifies activated FAPs. In vivo genetic lineage tracing shows that Osr1+ activated FAPs return to the resident FAP pool after regeneration as well as contribute to adipocytes after glycerol-induced fatty degeneration. In conclusion, reporter LacZ or eGFP-CreERt2 expression from the endogenous Osr1 locus serves as marker for FACS isolation and tamoxifen-induced manipulation of activated FAPs.View less
Terpenes constitute the largest and structurally most diverse natural product family. Most terpenoids exhibit a stereochemically complex macrocyclic core, which is generated by C–C bond forming of aliphatic oligo-prenyl precursors. This reaction is catalysed by terpene synthases (TPSs), which are capable of chaperoning highly reactive carbocation intermediates through an enzyme-specific reaction. Due to the instability of carbocation intermediates, the proteins’ structural dynamics and enzyme:substrate interactions during TPS catalysis remain elusive. Here, we present the structure of the diterpene synthase CotB2, in complex with an in crystallo cyclised abrupt reaction product and a substrate-derived diphosphate. We captured additional snapshots of the reaction to gain an overview of CotB2’s catalytic mechanism. To enhance insights into catalysis, structural information is augmented with multiscale molecular dynamic simulations. Our data represent fundamental TPS structure dynamics during catalysis, which ultimately enable rational engineering towards tailored terpene macrocycles that are inaccessible by conventional chemical synthesis.View less
Recently, infants younger than 2 years have been shown to display correct expectations of the actions of an agent with a false belief. The developmental trajectory of these early-developing abilities and their robustness, however, remain a matter of debate. Here, we tested children longitudinally from 2 to 4 years of age with an established anticipatory looking false belief task, and found a significant developmental change between the ages of 3 and 4 years. Children anticipated correctly only by the age of 4 years, and performed at chance at the ages of 2 and 3 years. Moreover, we found correct anticipation only when the agent falsely believed an object to be in its last rather than a previous location. These findings point towards the fragility of early belief-related action anticipation before the age of 4 years, when children start passing traditional false belief tasks.View less
We invented the first non-metallic, self-adhesive and dry biosignalling electrode. The PEDOT polymer electrode changes its aggregate state and conductivity by a light curing procedure. The electrode can be applied as a gel underneath hair without shaving. With the aid of blue light, the electrode can be hardened within a few seconds at the desired location on the scalp. The cured polymer electrode is highly conductive and can be applied on a very small location. Unlike other EEG electrodes, our electrode does not lose conductivity upon drying. Furthermore, our electrode strongly bonds to skin and does not require any additional adhesive. Short circuits due to an outflow of gel are prevented with this technique. Therefore, the PEDOT polymer electrode is extremely well suited for applications that, up to now, have been challenging, such as non-invasive EEG recordings from awake and freely moving animals, EEG recordings from preterm babies in the neonatal intensive care unit or long-term recordings in the case of sleep monitoring or epilepsy diagnostics. We addressed two technical questions in this work. First, is the EEG recorded with polymer electrodes comparable to a standard EEG? Second, is it possible to record full-band EEGs with our electrodes?View less
Obvious movements of plant organs have fascinated scientists for a long time. They have been studied extensively, but few behavioural studies to date have dealt with them, and hardly anything is known about their evolution. Here, we present a large experimental dataset on the stamen movement patterns found in the Loasaceae subfam. Loasoideae (Cornales). An evolutionary transition from autonomous-only to a combination of autonomous and thigmonastic stamen movement with increased complexity was experimentally demonstrated. We compare the stamen movement patterns with extensive pollinator observations and discuss it in the context of male mating behavior. Thigmonastic pollen presentation via stamen movements appears to be a crucial component of floral adaptation to pollinator behaviour, evolving in concert with complex adjustments of flower signal, reward and morphology. We hypothesize that rapid adjustments of pollen presentation timing may play a significant role in the diversification of this plant group, representing a striking example for the evolutionary significance of plant behaviour.View less
This article focuses on aspects of belonging the producers of reality TV programmes address in the staging of emotions. Based on interview statements by 12 experts from the field of national and international reality TV format production, we argue as follows: on the one hand, producers in reality TV shows address belonging as a perceived cultural proximity to trans-local meta-narratives of a longing for change, romantic love, competition and victory. The producers associate these trans-local meta-narratives with allegedly universal emotions. On the other hand, the producers address belonging as a perceived cultural proximity to local cultural discourses on beauty ideals and combine these with a specific local cultural performance of emotions. The results show that an emotional repertoire is developed and negotiated in the adaptation process of trans-local formats. It refers to universalistic understanding of emotional display and negotiates specific “feeling rules” accordingly.View less
The digestive tract plays a central role in nutrient acquisition and harbors a vast and intricate community of bacteria, fungi, viruses and parasites, collectively known as the microbiota. In recent years, there has been increasing recognition of the complex and highly contextual involvement of this microbiota in the induction and education of host innate and adaptive immune responses under homeostasis, during infection and inflammation. The gut passage and colonization by unicellular and multicellular parasite species present an immense challenge to the host immune system and to the microbial communities that provide vital support for its proper functioning. In mammals, parasitic nematodes induce distinct shifts in the intestinal microbial composition. Vice versa, the commensal microbiota has been shown to serve as a molecular adjuvant and immunomodulator during intestinal parasite infections. Moreover, similar interactions occur within insect vectors of deadly human pathogens. The gut microbiota has emerged as a crucial factor affecting vector competence in Anopheles mosquitoes, where it modulates outcomes of infections with malaria parasites. In this review, we discuss currently known involvements of the host microbiota in the instruction, support or suppression of host immune responses to gastrointestinal nematodes and protozoan parasites in mice, as well as in the malaria mosquito vector. A deeper understanding of the mechanisms underlying microbiota-dependent modulation of host and vector immunity against parasites in mammals and mosquitoes is key to a better understanding of the host-parasite relationships and the identification of more efficient approaches for intervention and treatment of parasite infections of both clinical and veterinary importance.View less
Background The zooplanktonic cladocerans Daphnia, present in a wide range of water bodies, are an important component of freshwater ecosystems. In contrast to their high dispersal capacity through diapausing eggs carried by waterfowl, Daphnia often exhibit strong population genetic differentiation. Here, to test for common patterns in the population genetic structure of a widespread Holarctic species, D. galeata, we genotyped two sets of populations collected from geographically distant areas: across 13 lakes in Eastern China and 14 lakes in Central Europe. The majority of these populations were genotyped at two types of markers: a mitochondrial gene (for 12S rRNA) and 15 nuclear microsatellite loci. Results Mitochondrial DNA demonstrated relatively shallow divergence within D. galeata, with distinct haplotype compositions in the two study regions but one widely distributed haplotype shared between several of the Chinese as well as European populations. At microsatellite markers, clear separation was observed at both large (between China and Europe) and small (within Europe) geographical scales, as demonstrated by Factorial Correspondence Analyses, Bayesian assignment and a clustering method based on genetic distances. Genetic diversity was comparable between the sets of Chinese and European D. galeata populations for both types of markers. Interestingly, we observed a significant association between genetic distance and geographical distance for D. galeata populations in China but not in Europe. Conclusions Our results indicate relatively recent spread of D. galeata across wide expanses of the Palaearctic, with one mtDNA lineage of D. galeata successfully establishing over large distances. Despite a clear differentiation of Chinese and European D. galeata at a nuclear level, the pattern of genetic variation is nevertheless similar between both regions. Overall, our findings provide insights into the genetic population structure of a cladoceran species with extremely wide geographical range.View less
Urea in diets of ruminants has been investigated to substitute expensive animal and vegetable protein sources for more than a century, and has been widely incorporated in diets of ruminants for many years. Urea is also recycled to the fermentative parts of the gastrointestinal (GI) tracts through saliva or direct secretory flux from blood depending upon the dietary situations. Within the GI tracts, urea is hydrolyzed to ammonia by urease enzymes produced by GI microorganisms and subsequent ammonia utilization serves the synthesis of microbial protein. In ruminants, excessive urease activity in the rumen may lead to urea/ammonia toxicity when high amounts of urea are fed to animals; and in non-ruminants, ammonia concentrations in the GI content and milieu may cause damage to the GI mucosa, resulting in impaired nutrient absorption, futile energy and protein spillage and decreased growth performance. Relatively little attention has been directed to this area by researchers. Therefore, the present review intends to discuss current knowledge in ureolytic bacterial populations, urease activities and factors affecting them, urea metabolism by microorganisms, and the application of inhibitors of urease activity in livestock animals. The information related to the ureolytic bacteria and urease activity could be useful for improving protein utilization efficiency in ruminants and for the reduction of the ammonia concentration in GI tracts of monogastric animals. Application of recent molecular methods can be expected to provide rationales for improved strategies to modulate urease and urea dynamics in the GI tract. This would lead to improved GI health, production performance and environmental compatibility of livestock production.View less
- The oomycete pathogen Hyaloperonospora arabidopsidis (Hpa) causes downy mildew disease on Arabidopsis. To colonize its host, Hpa translocates effector proteins that suppress plant immunity into infected host cells. Here, we investigate the relevance of the interaction between one of these effectors, HaRxL106, and Arabidopsis RADICAL‐INDUCED CELL DEATH1 (RCD1). - We use pathogen infection assays as well as molecular and biochemical analyses to test the hypothesis that HaRxL106 manipulates RCD1 to attenuate transcriptional activation of defense genes. - We report that HaRxL106 suppresses transcriptional activation of salicylic acid (SA)‐induced defense genes and alters plant growth responses to light. HaRxL106‐mediated suppression of immunity is abolished in RCD1 loss‐of‐function mutants. We report that RCD1‐type proteins are phosphorylated, and we identified Mut9‐like kinases (MLKs), which function as phosphoregulatory nodes at the level of photoreceptors, as RCD1‐interacting proteins. An mlk1,3,4 triple mutant exhibits stronger SA‐induced defense marker gene expression compared with wild‐type plants, suggesting that MLKs also affect transcriptional regulation of SA signaling. - Based on the combined evidence, we hypothesize that nuclear RCD1/MLK complexes act as signaling nodes that integrate information from environmental cues andView less
We propose the technique for a controllable manipulation of the transverse intensity distribution of an output beam by the temporal adjustment of a transverse gain profile in a laser amplifier. It was created by an independent manipulation of the output powers of each of the two pump diodes. The output beam of the laser amplifier is able to vary both the output power and the transverse intensity distribution. Additionally, it was shown experimentally that this technique is valid for the case of incoherent laser beam shaping.View less
Among 65 species belonging to the genus Cornus only two, Cornus mas L. and Cornus officinalis Sieb. et Zucc. (Cornaceae), have been traditionally used since ancient times. Cornus mas (cornelian cherry) is native to southern Europe and southwest Asia, whereas C. officinalis (Asiatic dogwood, cornel dogwood) is a deciduous tree distributed in eastern Asia, mainly in China, as well as Korea and Japan. Based on the different geographic distribution of the closely related species but clearly distinct taxa, the ethnopharmacological use of C. mas and C. officinalis seems to be independently originated. Many reports on the quality of C. mas fruits were performed due to their value as edible fruits, and few reports compared their physicochemical properties with other edible fruits. However, the detailed phytochemical profiles of C. mas and C. officinalis, in particular fruits, have never been compared. The aim of this review was highlighting the similarities and differences of phytochemicals found in fruits of C. mas and C. officinalis in relation to their biological effects as well as compare the therapeutic use of fruits from both traditional species. The fruits of C. mas and C. officinalis are characterized by the presence of secondary metabolites, in particular iridoids, anthocyanins, phenolic acids and flavonoids. However, much more not widely known iridoids, such as morroniside, as well as tannins were detected particularly in fruits of C. officinalis. The referred studies of biological activity of both species indicate their antidiabetic and hepatoprotective properties. Based on the available reports antihyperlipidemic and anticoagulant activity seems to be unique for extracts of C. mas fruits, whereas antiosteoporotic and immunomodulatory activities were assigned to preparations of C. officinalis fruits. In conclusion, the comparison of phytochemical composition of fruits from both species revealed a wide range of similarities as well as some constituents unique for cornelian cherry or Asiatic dogwood. Thus, these phytochemicals are considered the important factor determining the biological activity and justifying the use of C. mas and C. officinalis in the traditional European and Asiatic medicine.View less
The rise of multi-drug resistance in bacterial pathogens is one of the grand challenges facing medical science. A major concern is the speed of development of β-lactamase-mediated resistance in Gram-negative species, thus putting at risk the efficacy of the most recently approved antibiotics and inhibitors, including carbapenems and avibactam, respectively. New strategies to overcome resistance are urgently required, which will ultimately be facilitated by a deeper understanding of the mechanisms that regulate the function of β-lactamases such as the Klebsiella Pneumoniae carbapenemases (KPCs). Using enhanced sampling computational methods together with site-directed mutagenesis, we report the identification of two “hydrophobic networks” in the KPC-2 enzyme, the integrity of which has been found to be essential for protein stability and corresponding resistance. Present throughout the structure, these networks are responsible for the structural integrity and allosteric signaling. Disruption of the networks leads to a loss of the KPC-2 mediated resistance phenotype, resulting in restored susceptibility to different classes of β-lactam antibiotics including carbapenems and cephalosporins. The ”hydrophobic networks” were found to be highly conserved among class-A β-lactamases, which implies their suitability for exploitation as a potential target for therapeutic intervention.View less
The implementation of European emission abatement strategies has led to a significant reduction in the emissions of ozone precursors during the last decade. Ground-level ozone is also influenced by meteorological factors such as temperature, which exhibit interannual variability and are expected to change in the future. The impacts of climate change on air quality are usually investigated through air-quality models that simulate interactions between emissions, meteorology and chemistry. Within a multi-model assessment, this study aims to better understand how air-quality models represent the relationship between meteorological variables and surface ozone concentrations over Europe. A multiple linear regression (MLR) approach is applied to observed and modelled time series across 10 European regions in springtime and summertime for the period of 2000–2010 for both models and observations. Overall, the air-quality models are in better agreement with observations in summertime than in springtime and particularly in certain regions, such as France, central Europe or eastern Europe, where local meteorological variables show a strong influence on surface ozone concentrations. Larger discrepancies are found for the southern regions, such as the Balkans, the Iberian Peninsula and the Mediterranean basin, especially in springtime. We show that the air-quality models do not properly reproduce the sensitivity of surface ozone to some of the main meteorological drivers, such as maximum temperature, relative humidity and surface solar radiation. Specifically, all air-quality models show more limitations in capturing the strength of the ozone–relative-humidity relationship detected in the observed time series in most of the regions, for both seasons. Here, we speculate that dry-deposition schemes in the air-quality models might play an essential role in capturing this relationship. We further quantify the relationship between ozone and maximum temperature (mo3 − T, climate penalty) in observations and air-quality models. In summertime, most of the air-quality models are able to reproduce the observed climate penalty reasonably well in certain regions such as France, central Europe and northern Italy. However, larger discrepancies are found in springtime, where air-quality models tend to overestimate the magnitude of the observed climate penalty.View less
Equine herpesvirus type 1 (EHV-1) induces respiratory infection, abortion, and neurologic disease with significant impact. Virulence factors contributing to infection and immune evasion are of particular interest. A potential virulence factor of the neuropathogenic EHV-1 strain Ab4 is ORF2.
This study on 24 Icelandic horses, 2 to 4 years of age, describes the infection with EHV-1 Ab4, or its deletion mutant devoid of ORF2 (Ab4ΔORF2) compared to non-infected controls (each group n = 8). The horses’ clinical presentation, virus shedding, viremia, antibody and cellular immune responses were monitored over 260 days after experimental infection.
Infection with Ab4ΔORF2 reduced fever and minimized nasal virus shedding after infection compared to the parent virus strain Ab4, while Ab4ΔORF2 established viremia similar to Ab4. Concurrently with virus shedding, intranasal cytokine and interferon α (IFN-α) production increased in the Ab4 group, while horses infected with Ab4ΔORF2 expressed less IFN-α.
The antibody response to EHV-1 was evaluated by a bead-based multiplex assay and was similar in both infected groups, Ab4 and Ab4ΔORF2. EHV-1 specific immunoglobulin (Ig) G1 was induced 8 days after infection (d8 pi) with a peak on d10–12 pi. EHV-1 specific IgG4/7 increased starting on d10 pi, and remained elevated in serum until the end of the study. The intranasal antibody response to EHV-1 was dominated by the same IgG isotypes and remained elevated in both infected groups until d130 pi. In contrast to the distinct antibody response, no induction of EHV-1 specific T-cells was detectable by flow cytometry after ex vivo re-stimulation of peripheral blood mononuclear cells (PBMC) with EHV-1 in any group. The cellular immune response was characterized by increased secretion of IFN-γ and interleukin10 in response to ex vivo re-stimulation of PBMC with EHV-1. This response was present during the time of viremia (d5–10 pi) and was similar in both infected groups, Ab4 and Ab4ΔORF2.
ORF2 is a virulence factor of EHV-1 Ab4 with impact on pyrexia and virus shedding from the nasal mucosa. In contrast, ORF2 does not influence viremia. The immunogenicity of the Ab4ΔORF2 and parent Ab4 viruses are identical.View less
The Sumatran subduction zone exhibits strong seismic and tsunamogenic potential with the prominent examples of the 2004, 2005 and 2007 earthquakes. Here, we invert travel-time data of local earthquakes for vp and vp∕vs velocity models of the central Sumatran forearc. Data were acquired by an amphibious seismometer network consisting of 52 land stations and 10 ocean-bottom seismometers located on a segment of the Sumatran subduction zone that had not ruptured in a great earthquake since 1797 but witnessed recent ruptures to the north in 2005 (Nias earthquake, Mw = 8.7) and to the south in 2007 (Bengkulu earthquake, Mw = 8.5). The 2-D and 3-D vp velocity anomalies reveal the downgoing slab and the sedimentary basins. Although the seismicity pattern in the study area appears to be strongly influenced by the obliquely subducting Investigator Fracture Zone to at least 200km depth, the 3-D velocity model shows prevailing trench-parallel structures at depths of the plate interface. The tomographic model suggests a thinned crust below the basin east of the forearc islands (Nias, Pulau Batu, Siberut) at ∼ 180km distance to the trench. vp velocities beneath the magmatic arc and the Sumatran fault zone (SFZ) are around 5kms−1 at 10km depth and the vp∕vs ratios in the uppermost 10km are low, indicating the presence of felsic lithologies typical for continental crust. We find moderately elevated vp∕vs values of 1.85 at ∼ 150km distance to the trench in the region of the Mentawai Fault. vp∕vs ratios suggest an absence of large-scale alteration of the mantle wedge and might explain why the seismogenic plate interface (observed as a locked zone from geodetic data) extends below the continental forearc Moho in Sumatra. Reduced vp velocities beneath the forearc basin covering the region between the Mentawai Islands and the Sumatra mainland possibly reflect a reduced thickness of the overriding crust.View less
Time series of groundwater and stream water quality often exhibit substantial temporal and spatial variability, whereas typical existing monitoring data sets, e.g. from environmental agencies, are usually characterized by relatively low sampling frequency and irregular sampling in space and/or time. This complicates the differentiation between anthropogenic influence and natural variability as well as the detection of changes in water quality which indicate changes in single drivers. We suggest the new term "dominant changes" for changes in multivariate water quality data which concern (1) multiple variables, (2) multiple sites and (3) long-term patterns and present an exploratory framework for the detection of such dominant changes in data sets with irregular sampling in space and time. Firstly, a non-linear dimension-reduction technique was used to summarize the dominant spatiotemporal dynamics in the multivariate water quality data set in a few components. Those were used to derive hypotheses on the dominant drivers influencing water quality. Secondly, different sampling sites were compared with respect to median component values. Thirdly, time series of the components at single sites were analysed for long-term patterns. We tested the approach with a joint stream water and groundwater data set quality consisting of 1572 samples, each comprising sixteen variables, sampled with a spatially and temporally irregular sampling scheme at 29 sites in northeast Germany from 1998 to 2009. The first four components were interpreted as (1) an agriculturally induced enhancement of the natural background level of solute concentration, (2) a redox sequence from reducing conditions in deep groundwater to post-oxic conditions in shallow groundwater and oxic conditions in stream water, (3) a mixing ratio of deep and shallow groundwater to the streamflow and (4) sporadic events of slurry application in the agricultural practice. Dominant changes were observed for the first two components. The changing intensity of the first component was interpreted as response to the temporal variability of the thickness of the unsaturated zone. A steady increase in the second component at most stream water sites pointed towards progressing depletion of the denitrification capacity of the deep aquifer.View less
Signs and symbols relate to concepts and can be used to speak about objects, actions, and their features. Theories of semantic grounding address the question how the latter two, concepts and real‐world entities, come into play and interlink in symbol learning. Here, a neurobiological model is used to spell out concrete mechanisms of symbol grounding, which implicate the “association” of information about sign and referents and, at the same time, the extraction of semantic features and the formation of abstract representations best described as conjoined and disjoined feature sets that may or may not have a real‐life equivalent. The mechanistic semantic circuits carrying these feature sets are not static conceptual entries, but exhibit rich activation dynamics related to memory, prediction, and contextual modulation. Four key issues in specifying these activation dynamics will be highlighted: (a) the inner structure of semantic circuits, (b) mechanisms of semantic priming, (c) task specificity in semantic activation, and (d) context‐dependent semantic circuit activation in the processing of referential, existential, and universal statements. These linguistic‐semantic examples show that specific mechanisms are required to account for context‐dependent semantic function or conceptual “flexibility.” Static context‐independent concepts as such are insufficient to account for these different semantic functions. Whereas abstract amodal models of concepts did so far not spell out concrete mechanisms for context‐dependent semantic function, neuronal assembly mechanisms offer a workable perspective.View less
With the rise of artificial molecular machines, control of motion on the nanoscale has become a major contemporary research challenge. Tetrathiafulvalenes (TTFs) are one of the most versatile and widely used molecular redox switches to generate and control molecular motion. TTF can easily be implemented as functional unit into molecular and supramolecular structures and can be reversibly oxidized to a stable radical cation or dication. For over 20 years, TTFs have been key building blocks for the construction of redox-switchable mechanically interlocked molecules (MIMs) and their electrochemical operation has been thoroughly investigated. In this review, we provide an introduction into the field of TTF-based MIMs and their applications. A brief historical overview and a selection of important examples from the past until now are given. Furthermore, we will highlight our latest research on TTF-based rotaxanes.View less