Immunological responses of hibernating mammals are suppressed at low body temperatures, a possible explanation for the devastating effect of the white-nose syndrome on hibernating North American bats. However, European bats seem to cope well with the fungal causative agent of the disease. To better understand the immune response of hibernating bats, especially against fungal pathogens, we challenged European greater mouse-eared bats (Myotis myotis) by inoculating the fungal antigen zymosan. We monitored torpor patterns, immune gene expressions, different aspects of the acute phase response and plasma oxidative status markers, and compared them with sham-injected control animals at 30 min, 48 h and 96 h after inoculation. Torpor patterns, body temperatures, body masses, white blood cell counts, expression of immune genes, reactive oxygen metabolites and non-enzymatic antioxidant capacity did not differ between groups during the experiment. However, zymosan injected bats had significantly higher levels of haptoglobin than the control animals. Our results indicate that hibernating greater mouse-eared bats mount an inflammatory response to a fungal challenge, with only mild to negligible consequences for the energy budget of hibernation. Our study gives a first hint that hibernating European bats may have evolved a hibernation-adjusted immune response in order to balance the trade-off between competent pathogen elimination and a prudent energy-saving regime.

Negative interactions have been suggested as a major barrier for species arriving in a new habitat. More recently, positive interactions drew attention from community assembly theory and invasion science. The invasional meltdown hypothesis (IMH) introduced the idea that positive interactions among non-native species could facilitate one another’s invasion, even increasing their impact upon the native community. Many studies have addressed IMH, but with contrasting results, reflecting various types of evidence on a multitude of scales. Here we use the hierarchy-of-hypotheses (HoH) approach to differentiate key aspects of IMH, organizing and linking empirical studies to sub-hypotheses of IMH. We also assess the level of empirical support for each sub-hypothesis based on the evidence reported in the studies. We identified 150 studies addressing IMH. The majority of studies support IMH, but the evidence comes from studies with different aims and questions. Supporting studies at the community or ecosystem level are currently rare. Evidence is scarce for marine habitats and vertebrates. Few sub-hypotheses are questioned by more than 50% of the evaluated studies, indicating that non-native species do not affect each other’s survival, growth, reproduction, abundance, density or biomass in reciprocal A ↔ B interactions. With the HoH for IMH presented here, we can monitor progress in empirical tests and evidences of IMH. For instance, more tests at the community and ecosystem level are needed, as these are necessary to address the core of this hypothesis.

Climate change and biological invasions are threatening biodiversity and ecosystem services worldwide. It has now been widely acknowledged that climate change will affect biological invasions. A large number of studies have investigated predicted shifts and other changes in the geographic ranges of invasive alien species related to climate change using modeling approaches. Yet these studies have provided contradictory evidence, and no consensus has been reached. We conducted a systematic review of 423 modeling case studies included in 71 publications that have examined the predicted effects of climate change on those species. We differentiate the approaches used in these studies and synthesize their main results. Our results reaffirm the major role of climate change as a driver of invasive alien species distribution in the future. We found biases in the literature both regarding the taxa, toward plants and invertebrates, and the areas of the planet investigated. Despite these biases, we found for the plants and vertebrates studied that climate change will more frequently contribute to a decrease in species range size than an increase in the overall area occupied. This is largely due to oceans preventing terrestrial invaders from spreading poleward. In contrast, we found that the ranges of invertebrates and pathogens studied are more likely to increase following climate change. An important caveat to these findings is that researchers have rarely considered the effects of climate change on transport, introduction success, or the resulting impacts. We recommend closing these research gaps, and propose additional avenues for future investigations, as well as opportunities and challenges for managing invasions under climate change.

Background The Asian bush mosquito Aedes japonicus japonicus is an invasive species native to East Asia and has become established in North America and Europe. On both continents, the species has spread over wide areas. Since it is a potential vector of human and livestock pathogens, distribution and dissemination maps are urgently needed to implement targeted surveillance and control in case of disease outbreaks. Previous distribution models for Europe and Germany in particular focused on climate data. Until now, effects of other environmental variables such as land use and wind remained unconsidered.

Results In order to better explain the distribution pattern of Ae. j. japonicus in Germany at a regional level, we have developed a nested approach that allows for the combination of data derived from (i) a climate model based on a machine-learning approach; (ii) a landscape model developed by means of ecological expert knowledge; and (iii) wind speed data. The approach is based on the fuzzy modelling technique that enables to precisely define the interactions between the three factors and additionally considers uncertainties with regard to the acceptance of certain environmental conditions. The model combines different spatial resolutions of data for Germany and achieves a much higher degree of accuracy than previous published distribution models. Our results reveal that a well-suited landscape structure can even facilitate the occurrence of Ae. j. japonicus in a climatically unsuitable region. Vice versa, unsuitable land use types such as agricultural landscapes and coniferous forests reduce the occurrence probability in climatically suitable regions.

Conclusions The approach has significantly improved existing distribution models of Ae. j. japonicus for the area of Germany. We generated distribution maps with a resolution of 100 × 100 m that can serve as a basis for the design of control measures. All model input data and scripts are open source and freely available, so that the model can easily be applied to other countries or, more generally, to other species.

Mucins and mucin-like molecules are highly O-glycosylated proteins present on the cell surface of mammals and other organisms. These glycoproteins are highly diverse in the apoprotein and glycan cores and play a central role in many biological processes and diseases. Mucins are the most abundant macromolecules in mucus and are responsible for its biochemical and biophysical properties. Mucin-like molecules cover various protozoan parasites, fungi and viruses. In humans, modifications in mucin glycosylation are associated with tumors in epithelial tissue. These modifications allow the distinction between normal and abnormal cell conditions and represent important targets for vaccine development against some cancers. Mucins and mucin-like molecules derived from pathogens are potential diagnostic markers and targets for therapeutic agents. In this review, we summarize the distribution, structure, role as immunomodulators, and the correlation of human mucins with diseases and perform a comparative analysis of mucins with mucin-like molecules present in human pathogens. Furthermore, we review the methods to produce pathogenic and human mucins using chemical synthesis and expression systems. Finally, we present applications of mucin-like molecules in diagnosis and prevention of relevant human diseases.

Standardized tools are needed to identify and prioritize the most harmful non-native species (NNS). A plethora of assessment protocols have been developed to evaluate the current and potential impacts of non-native species, but consistency among them has received limited attention. To estimate the consistency across impact assessment protocols, 89 specialists in biological invasions used 11 protocols to screen 57 NNS (2614 assessments). We tested if the consistency in the impact scoring across assessors, quantified as the coefficient of variation (CV), was dependent on the characteristics of the protocol, the taxonomic group and the expertise of the assessor. Mean CV across assessors was 40%, with a maximum of 223%. CV was lower for protocols with a low number of score levels, which demanded high levels of expertise, and when the assessors had greater expertise on the assessed species. The similarity among protocols with respect to the final scores was higher when the protocols considered the same impact types. We conclude that all protocols led to considerable inconsistency among assessors. In order to improve consistency, we highlight the importance of selecting assessors with high expertise, providing clear guidelines and adequate training but also deriving final decisions collaboratively by consensus.

Invasive mosquito species and the pathogens they transmit represent a serious health risk to both humans and animals. Thus, predictions on their potential geographic distribution are urgently needed. In the case of a recently invaded region, only a small number of occurrence data is typically available for analysis, and absence data are not reliable. To overcome this problem, we have tested whether it is possible to determine the climatic ecological niche of an invasive mosquito species by using both the occurrence data of other, native species and machine learning. The approach is based on a support vector machine and in this scenario applied to the Asian bush mosquito (Aedes japonicus japonicus) in Germany. Presence data for this species (recorded in the Germany since 2008) as well as for three native mosquito species were used to model the potential distribution of the invasive species. We trained the model with data collected from 2011 to 2014 and compared our predicted occurrence probabilities for 2015 with observations found in the field throughout 2015 to evaluate our approach. The prediction map showed a high degree of concordance with the field data. We applied the model to medium climate conditions at an early stage of the invasion (2011–2015), and developed an explanation for declining population densities in an area in northern Germany. In addition to the already known distribution areas, our model also indicates a possible spread to Saarland, southwestern Rhineland-Palatinate and in 2015 to southern Bavaria, where the species is now being increasingly detected. However, there is also evidence that the possible distribution area under the mean climate conditions was underestimated.

Introduction:

Antigen processing and loading of peptides onto MHC class II molecules is a multistep process that involves vesicular transport of the MHCII molecules along the secretory pathway, where they eventually merge with antigen-containing endocytic vesicles or phagosomes (1). It is within these late endosomal or lysosomal compartments that protein antigens become degraded by proteases, most prominently by cathepsins, and where catalyzed peptide exchange by HLA-DM fulfills its role in the efficient replacement of the invariant chain-derived peptide CLIP by high-affinity pathogen- or host cell-derived peptides. Protease action may be limited by protein antigen abundance and redox conditions, while HLA-DM is regulated at several stages, including by expression levels, pH, or the co-expression of the competitive inhibitor HLA-DO. HLA-DM activity leads to significant changes in the immunopeptidome of antigen-presenting cells, thereby tailoring T cell responses and often shifting antigenicity toward high-affinity immunodominant epitopes (2). Control of DM activity by DO has been described to be of prime importance in thymic epithelial cells, in a subset of dendritic cells, and in B cells when entering the germinal centers for affinity maturation and class switching (3, 4). In all of these cases, the switch from a broader, self-peptide (CLIP) dominated immunopeptidome to a more focused repertoire is necessitated by the requirement for more stringent antigen presentation, often preceding more intense T cell reactivity and proliferation. Here, we review data on this cellular switch in the functionality of antigen presentation and propose that it is promoted by an as yet poorly understood molecular switch. Acknowledging that general biophysical parameters such as pH and redox are important for antigen processing in general, an elusive DM-DO switch is postulated that would allow rapid and strong shifts in immunopeptidomes. We capitalize on theoretical considerations to back our opinion that a regulatable switch would have the advantage of allowing for a rapid and possibly signal-dependent change in the peptide selection process, as might be required in the context of rapidly changing immunological conditions.

This article attempts to place the emergence of probabilistic numerics as a mathematical–statistical research field within its historical context and to explore how its gradual development can be related both to applications and to a modern formal treatment. We highlight in particular the parallel contributions of Sul′din and Larkin in the 1960s and how their pioneering early ideas have reached a degree of maturity in the intervening period, mediated by paradigms such as average-case analysis and information-based complexity. We provide a subjective assessment of the state of research in probabilistic numerics and highlight some difficulties to be addressed by future works.

SmartLipids are the latest generation of dermal lipid nanoparticles with solid particle matrix. Their characteristic properties resulting from the “chaotic” and disordered particle matrix structure are reviewed. These properties are high loading and firm inclusion of active agents, physical stability of the particle matrix lipid modification (primarily α, β′), and related to these three properties the improved chemical stabilization of labile active agents. Exemplarily data for these effects are shown and underlying mechanisms are discussed. Further, general properties of lipid nanoparticles, which are also exhibited by the SmartLipids, are reviewed. These include the restauration of the protective lipid skin barrier (anti-pollution effect), penetration enhancement by occlusion (invisible patch effect) and the option to control the release of active agents for optimized biological effect and reduction of side effects (e.g., skin irritation through sensitizing active agents), which improves the skin tolerability. Regulatory aspects, such as submicron particle status, excipients, and certifications, are also discussed.

The mammalian Staufen proteins (Stau1 and Stau2) mediate degradation of mRNA containing complex secondary structures in their 3’-untranslated region (UTR) through a pathway known as Staufen-mediated mRNA decay (SMD). This pathway also involves the RNA helicase UPF1, which is best known for its role in the nonsense-mediated mRNA decay (NMD) pathway. Here we present a biochemical reconstitution of the recruitment and activation of UPF1 in context of the SMD pathway. We demonstrate the involvement of UPF2, a core NMD factor and a known activator of UPF1, in SMD. UPF2 acts as an adaptor between Stau1 and UPF1, stimulates the catalytic activity of UPF1 and plays a central role in the formation of an SMD-competent mRNP. Our study elucidates the molecular mechanisms of SMD and points towards extensive cross-talk between UPF1-mediated mRNA decay pathways in cells.

Soil carbon is essential for soil and ecosystem functioning. Its turnover and storage in soil are multifaceted processes that involve microbial activity in complex physical matrices. Biological litter, which include plants, animals, and microorganisms, is decomposed in soil stimulating soil biota (archaea, bacteria, fungi, protists, and animals) activity and yielding soil organic matter (SOM). Such decomposition processes are influenced by local physico-chemical characteristics including the spatial distribution of aggregates and pores. More refined analytical tools are needed to better understand these processes, especially considering the spatial 3D structure of soil matrices. Using synchrotron radiation (X-ray) micro computerized tomography (SR-μCT), we tested different contrast agents (staining methods) based on silver (Ag), eosin (Br based), and liquid and gaseous iodine (I) in order to spatially image biological material and SOM in soil samples. We also performed K-edge SR-μCT for the Ag and I2 treatments and conventional μCT for additional soil samples applying the I2 treatment. Our results indicated that I2 was the most efficient contrast method for SR-μCT imaging of soil samples. I2 qualitatively improved the images, but mainly, by using the K-edge SR-μCT, this method provided a powerful tool to determine the spatial location of SOM. We acknowledge that the use of SR-μCT is an expensive technique to study soil samples, which comes with bottlenecks in terms of access to facilities and measurement time. Nevertheless, we show that the I2 treatment improved soil images also using standard μCT. In conventional μCT the I2 treatment improved the visualization of biological material and consequently improved the qualitative analysis of fine plants roots and micro-fauna (Collembola). This improvement may have a positive implication in soil biology, by improving a non-destructive method to detect fungi (SR-μCT), soil fauna (conventional μCT) and roots in undisturbed soil samples. An unexpected finding was that the I2 treatment also stained the plastic sample containers (nylon and polyimide), indicating the potential for the I2 staining procedure to be applied for the detection of plastic pollution in soil samples.

In this study, a new detector for multiwavelength emission analytical ultracentrifugation (MWE-AUC) is presented, which allows measuring size- or composition-dependent fluorescence properties of nanoparticle ensembles. Validation of the new setup is carried out via comparison to a benchtop photoluminescence spectrometer and the established extinction-based multiwavelength analytical ultracentrifuge (MWL-AUC). The results on fluorescent proteins and silica particles demonstrate that the new device not only correctly reproduces sedimentation and diffusion coefficients of the particles but provides also meaningful fluorescence spectra. As an application example for a sample exhibiting a broad particle size distribution, spectra and size of graphene oxide nanoplatelets are extracted simultaneously. Narrowly distributed CdSe/ZnS quantum dots showing size- and structure-dependent shifts of their fluorescence spectra are analyzed as well. The combination of MWE- and MWL-AUC provides a comprehensive framework for the optical characterization for nanoparticles and macromolecules in terms of their extinction and emission properties.

In low‐stakes assessments, test performance has few or no consequences for examinees themselves, so that examinees may not be fully engaged when answering the items. Instead of engaging in solution behaviour, disengaged examinees might randomly guess or generate no response at all. When ignored, examinee disengagement poses a severe threat to the validity of results obtained from low‐stakes assessments. Statistical modelling approaches in educational measurement have been proposed that account for non‐response or for guessing, but do not consider both types of disengaged behaviour simultaneously. We bring together research on modelling examinee engagement and research on missing values and present a hierarchical latent response model for identifying and modelling the processes associated with examinee disengagement jointly with the processes associated with engaged responses. To that end, we employ a mixture model that identifies disengagement at the item‐by‐examinee level by assuming different data‐generating processes underlying item responses and omissions, respectively, as well as response times associated with engaged and disengaged behaviour. By modelling examinee engagement with a latent response framework, the model allows assessing how examinee engagement relates to ability and speed as well as to identify items that are likely to evoke disengaged test‐taking behaviour. An illustration of the model by means of an application to real data is presented.

A reliable synthesis of unstable and highly reactive BrO2F is reported. This compound can be converted into BrO2+SbF6−, BrO2+AsF6−, and BrO2+AsF6−⋅2 BrO2F. The latter decomposes into mixed‐valent Br3O4⋅Br2+AsF6− with five‐, three‐, one‐, and zero‐valent bromine. BrO2+ H(SO3CF3)2− is formed with HSO3CF3. Excess BrO2F yields mixed‐valent Br3O6+OSO3CF3− with five‐ and three‐valent bromine. Reactions of BrO2F and MoF5 in SO2ClF or CH2ClF result in Cl2BrO6+Mo3O3F13−. The reaction of BrO2F with (CF3CO)2O and NO2 produces O2Br‐O‐CO‐CF3 and the known NO2+Br(ONO2)2−. All of these compounds are thermodynamically unstable.

Are they still electrifying? Electrochemically switchable rotaxanes are well known for their ability to efficiently undergo changes of (co-)conformation and properties under redox-control. Thus, these mechanically interlocked assemblies represent an auspicious liaison between the fields of molecular switches and molecular electronics. Since the first reported example of a redox-switchable molecular shuttle in 1994, improved tools of organic and supramolecular synthesis have enabled sophisticated new architectures, which provide precise control over properties and function. This perspective covers recent advances in the area of electrochemically active rotaxanes including novel molecular switches and machines, metal-containing rotaxanes, non-equilibrium systems and potential applications.

Cancer cells interrelate with the bordering host microenvironment that encompasses the extracellular matrix and a nontumour cellular component comprising fibroblasts and immune-competent cells. The tumour microenvironment modulates cancer onset and progression, but the molecular factors managing this interaction are not fully understood. Malignant transformation of a benign tumour is among the first crucial events in colorectal carcinogenesis. The role of tumour stroma fibroblasts is well-described in cancer, but less well-characterized in benign tumours. In the current work we utilized fibroblasts isolated from tubulovillous adenoma, which has high risk for malignant transformation, to study the interaction between benign tumour stroma and the circadian clock machinery. We explored the role of the biological clock in this interplay taking advantage of an experimental model, represented by the co-culture of colon cancer cells with normal fibroblasts or tumour-associated fibroblasts, isolated from human colorectal tumour specimens. When co-cultured with tumour-associated fibroblasts, colon cancer cells showed alterations in their circadian and metabolic parameters, with decreased apoptosis, increased colon cancer cell viability, and increased resistance to chemotherapeutic agents. In conclusion, the interactions among colon cancer cells and tumour-associated fibroblasts affect the molecular clockwork and seem to aggravate malignant cell phenotypes, suggesting a detrimental effect of this interplay on cancer dynamics.

Sleep deprivation and disruption of the circadian rhythms could impair individual surgical performance and decision making. For this purpose, this study identified potential confounding factors on surgical renal transplant patient outcomes during day and night. Our retrospective cohort study of 215 adult renal cadaver transplant recipients, of which 132 recipients were allocated in the "day-time" group and 83 recipients in the "night-time" group, primarily stratified the patients into two cohorts, depending on the start time. Within a 24 h operational system, "day-time" was considered as being from 8 a.m. to 8 p.m. and "night-time" from 8 p.m. to 8 a.m.. Primary outcomes examined patient and graft survival after three months and one year. Secondary outcomes included the presence of acute rejection (AR) and delayed graft function (DGF), as well as the rate of postoperative complications. In log-rank testing, "day-time" surgery was associated with a significantly higher risk of patient death (p = 0.003), whereas long-term graft survival was unaffected by the operative time of day. The mean cold ischemia time (CIT), which was 12.4 ± 5.3 h in the "night-time" group, was significantly longer compared to 10.7 ± 3.6 for those during the day (p = 0.01). We observed that "night-time" kidney recipients experienced more wound complications. From our single-centre data, we conclude that night-time kidney transplantation does not increase the risk of adverse events or predispose the patient to a worse outcome. Nevertheless, further research is required to explore the effect of fatigue on nocturnal surgical performance.

Open Science is a pivotal global movement to advance science and scholarship. It includes key elements such as Open Access to scientific publications, Open Data, Open Source, and Open Methodology (Kraker et al. 2011; McKiernan et al. 2016; Stodden et al. 2016), and therefore fosters reproducibility and verification of findings (Wilkinson et al. 2016). Scientific knowledge, the product of research, is a public good and should thus be made publicly available. The vast majority of researchers agree with the idea of Open Science (Dallmeier-Tiessen et al. 2011), yet many face challenges in implementing Open Science in practice.

Many navigating insects include the celestial polarization pattern as an additional visual cue to orient their travels. Spontaneous orientation responses of both walking and flying fruit flies (Drosophila melanogaster) to linearly polarized light have previously been demonstrated. Using newly designed modular flight arenas consisting entirely of off-the-shelf parts and 3D-printed components we present individual flying flies with a slow and continuous rotational change in the incident angle of linear polarization. Under such open-loop conditions, single flies choose arbitrary headings with respect to the angle of polarized light and show a clear tendency to maintain those chosen headings for several minutes, thereby adjusting their course to the slow rotation of the incident stimulus. Importantly, flies show the tendency to maintain a chosen heading even when two individual test periods under a linearly polarized stimulus are interrupted by an epoch of unpolarized light lasting several minutes. Finally, we show that these behavioral responses are wavelength-specific, existing under polarized UV stimulus while being absent under polarized green light. Taken together, these findings provide further evidence supporting Drosophila’s abilities to use celestial cues for visually guided navigation and course correction.