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Metagenomic sequencing has revolutionised our knowledge of virus diversity, with new virus sequences being reported faster than ever before. However, virus discovery from metagenomic sequencing usually depends on detectable homology: without a sufficiently close relative, so-called ‘dark’ virus sequences remain unrecognisable. An alternative approach is to use virus-identification methods that do not depend on detecting homology, such as virus recognition by host antiviral immunity. For example, virus-derived small RNAs have previously been used to propose ‘dark’ virus sequences associated with the Drosophilidae (Diptera). Here, we combine published Drosophila data with a comprehensive search of transcriptomic sequences and selected meta-transcriptomic datasets to identify a completely new lineage of segmented positive-sense single-stranded RNA viruses that we provisionally refer to as the Quenyaviruses. Each of the five segments contains a single open reading frame, with most encoding proteins showing no detectable similarity to characterised viruses, and one sharing a small number of residues with the RNA-dependent RNA polymerases of single- and double-stranded RNA viruses. Using these sequences, we identify close relatives in approximately 20 arthropods, including insects, crustaceans, spiders, and a myriapod. Using a more conserved sequence from the putative polymerase, we further identify relatives in meta-transcriptomic datasets from gut, gill, and lung tissues of vertebrates, reflecting infections of vertebrates or of their associated parasites. Our data illustrate the utility of small RNAs to detect viruses with limited sequence conservation, and provide robust evidence for a new deeply divergent and phylogenetically distinct RNA virus lineage.
Quantifying the extremeness of heavy precipitation allows for the comparison of events. Conventional quantitative indices, however, typically neglect the spatial extent or the duration, while both are important to understand potential impacts. In 2014, the weather extremity index (WEI) was suggested to quantify the extremeness of an event and to identify the spatial and temporal scale at which the event was most extreme. However, the WEI does not account for the fact that one event can be extreme at various spatial and temporal scales. To better understand and detect the compound nature of precipitation events, we suggest complementing the original WEI with a “cross-scale weather extremity index” (xWEI), which integrates extremeness over relevant scales instead of determining its maximum.
Based on a set of 101 extreme precipitation events in Germany, we outline and demonstrate the computation of both WEI and xWEI. We find that the choice of the index can lead to considerable differences in the assessment of past events but that the most extreme events are ranked consistently, independently of the index. Even then, the xWEI can reveal cross-scale properties which would otherwise remain hidden. This also applies to the disastrous event from July 2021, which clearly outranks all other analyzed events with regard to both WEI and xWEI.
While demonstrating the added value of xWEI, we also identify various methodological challenges along the required computational workflow: these include the parameter estimation for the extreme value distributions, the definition of maximum spatial extent and temporal duration, and the weighting of extremeness at different scales. These challenges, however, also represent opportunities to adjust the retrieval of WEI and xWEI to specific user requirements and application scenarios.
Background
Teleost fishes comprise more than half of the vertebrate species. Within teleosts, most phylogenies consider the split between Osteoglossomorpha and Euteleosteomorpha/Otomorpha as basal, preceded only by the derivation of the most primitive group of teleosts, the Elopomorpha. While Osteoglossomorpha are generally species poor, the taxon contains the African weakly electric fish (Mormyroidei), which have radiated into numerous species. Within the mormyrids, the genus Campylomormyrus is mostly endemic to the Congo Basin. Campylomormyrus serves as a model to understand mechanisms of adaptive radiation and ecological speciation, especially with regard to its highly diverse species-specific electric organ discharges (EOD). Currently, there are few well-annotated genomes available for electric fish in general and mormyrids in particular. Our study aims at producing a high-quality genome assembly and to use this to examine genome evolution in relation to other teleosts. This will facilitate further understanding of the evolution of the osteoglossomorpha fish in general and of electric fish in particular.
Results
A high-quality weakly electric fish (C. compressirostris) genome was produced from a single individual with a genome size of 862 Mb, consisting of 1,497 contigs with an N50 of 1,399 kb and a GC-content of 43.69%. Gene predictions identified 34,492 protein-coding genes, which is a higher number than in the two other available Osteoglossomorpha genomes of Paramormyrops kingsleyae and Scleropages formosus. A Computational Analysis of gene Family Evolution (CAFE5) comparing 33 teleost fish genomes suggests an overall faster gene family turnover rate in Osteoglossomorpha than in Otomorpha and Euteleosteomorpha. Moreover, the ratios of expanded/contracted gene family numbers in Osteoglossomorpha are significantly higher than in the other two taxa, except for species that had undergone an additional genome duplication (Cyprinus carpio and Oncorhynchus mykiss). As potassium channel proteins are hypothesized to play a key role in EOD diversity among species, we put a special focus on them, and manually curated 16 Kv1 genes. We identified a tandem duplication in the KCNA7a gene in the genome of C. compressirostris.
Conclusions
We present the fourth genome of an electric fish and the third well-annotated genome for Osteoglossomorpha, enabling us to compare gene family evolution among major teleost lineages. Osteoglossomorpha appear to exhibit rapid gene family evolution, with more gene family expansions than contractions. The curated Kv1 gene family showed seven gene clusters, which is more than in other analyzed fish genomes outside Osteoglossomorpha. The KCNA7a, encoding for a potassium channel central for EOD production and modulation, is tandemly duplicated which may related to the diverse EOD observed among Campylomormyrus species.
A new evidence-based diet score to capture associations of food consumption and chronic disease risk
(2022)
Previously, the attempt to compile German dietary guidelines into a diet score was predominantly not successful with regards to preventing chronic diseases in the EPIC-Potsdam study. Current guidelines were supplemented by the latest evidence from systematic reviews and expert papers published between 2010 and 2020 on the prevention potential of food groups on chronic diseases such as type 2 diabetes, cardiovascular diseases and cancer. A diet score was developed by scoring the food groups according to a recommended low, moderate or high intake. The relative validity and reliability of the diet score, assessed by a food frequency questionnaire, was investigated. The consideration of current evidence resulted in 10 key food groups being preventive of the chronic diseases of interest. They served as components in the diet score and were scored from 0 to 1 point, depending on their recommended intake, resulting in a maximum of 10 points. Both the reliability (r = 0.53) and relative validity (r = 0.43) were deemed sufficient to consider the diet score as a stable construct in future investigations. This new diet score can be a promising tool to investigate dietary intake in etiological research by concentrating on 10 key dietary determinants with evidence-based prevention potential for chronic diseases.
Anthropogenic changes in climate, land use, and disturbance regimes, as well as introductions of non-native species can lead to the transformation of many ecosystems. The resulting novel ecosystems are usually characterized by species assemblages that have not occurred previously in a given area. Quantifying the ecological novelty of communities (i.e., biotic novelty) would enhance the understanding of environmental change. However, quantification remains challenging since current novelty metrics, such as the number and/or proportion of non-native species in a community, fall short of considering both functional and evolutionary aspects of biotic novelty. Here, we propose the Biotic Novelty Index (BNI), an intuitive and flexible multidimensional measure that combines (a) functional differences between native and non-native introduced species with (b) temporal dynamics of species introductions. We show that the BNI is an additive partition of Rao's quadratic entropy, capturing the novel interaction component of the community's functional diversity. Simulations show that the index varies predictably with the relative amount of functional novelty added by recently arrived species, and they illustrate the need to provide an additional standardized version of the index. We present a detailed R code and two applications of the BNI by (a) measuring changes of biotic novelty of dry grassland plant communities along an urbanization gradient in a metropolitan region and (b) determining the biotic novelty of plant species assemblages at a national scale. The results illustrate the applicability of the index across scales and its flexibility in the use of data of different quality. Both case studies revealed strong connections between biotic novelty and increasing urbanization, a measure of abiotic novelty. We conclude that the BNI framework may help building a basis for better understanding the ecological and evolutionary consequences of global change.
A multidimensional and analytical perspective on Open Educational Practices in the 21st century
(2022)
Participatory approaches to teaching and learning are experiencing a new lease on life in the 21st century as a result of the rapid technology development. Knowledge, practices, and tools can be shared across spatial and temporal boundaries in higher education by means of Open Educational Resources, Massive Open Online Courses, and open-source technologies. In this context, the Open Education Movement calls for new didactic approaches that encourage greater learner participation in formal higher education. Based on a representative literature review and focus group research, in this study an analytical framework was developed that enables researchers and practitioners to assess the form of participation in formal, collaborative teaching and learning practices. The analytical framework is focused on the micro-level of higher education, in particular on the interaction between students and lecturers when organizing the curriculum. For this purpose, the research reflects anew on the concept of participation, taking into account existing stage models for participation in the educational context. These are then brought together with the dimensions of teaching and learning processes, such as methods, objectives and content, etc. This paper aims to make a valuable contribution to the opening up of learning and teaching, and expands the discourse around possibilities for interpreting Open Educational Practices.
Investigation of processes that contribute to the maintenance of genomic stability is one crucial factor in the attempt to understand mechanisms that facilitate ageing. The DNA damage response (DDR) and DNA repair mechanisms are crucial to safeguard the integrity of DNA and to prevent accumulation of persistent DNA damage. Among them, base excision repair (BER) plays a decisive role. BER is the major repair pathway for small oxidative base modifications and apurinic/apyrimidinic (AP) sites. We established a highly sensitive non-radioactive assay to measure BER incision activity in murine liver samples. Incision activity can be assessed towards the three DNA lesions 8-oxo-2’-deoxyguanosine (8-oxodG), 5-hydroxy-2’-deoxyuracil (5-OHdU), and an AP site analogue. We applied the established assay to murine livers of adult and old mice of both sexes. Furthermore, poly(ADP-ribosyl)ation (PARylation) was assessed, which is an important determinant in DDR and BER. Additionally, DNA damage levels were measured to examine the overall damage levels. No impact of ageing on the investigated endpoints in liver tissue were found. However, animal sex seems to be a significant impact factor, as evident by sex-dependent alterations in all endpoints investigated. Moreover, our results revealed interrelationships between the investigated endpoints indicative for the synergetic mode of action of the cellular DNA integrity maintaining machinery.
In an attempt to pave the way for more extensive Computer Science Education (CSE) coverage in K-12, this research developed and made a preliminary evaluation of a blended-learning Introduction to CS program based on an academic MOOC. Using an academic MOOC that is pedagogically effective and engaging, such a program may provide teachers with disciplinary scaffolds and allow them to focus their attention on enhancing students’ learning experience and nurturing critical 21st-century skills such as self-regulated learning. As we demonstrate, this enabled us to introduce an academic level course to middle-school students. In this research, we developed the principals and initial version of such a program, targeting ninth-graders in science-track classes who learn CS as part of their standard curriculum. We found that the middle-schoolers who participated in the program achieved academic results on par with undergraduate students taking this MOOC for academic credit. Participating students also developed a more accurate perception of the essence of CS as a scientific discipline. The unplanned school closure due to the COVID19 pandemic outbreak challenged the research but underlined the advantages of such a MOOCbased blended learning program above classic pedagogy in times of global or local crises that lead to school closure. While most of the science track classes seem to stop learning CS almost entirely, and the end-of-year MoE exam was discarded, the program’s classes smoothly moved to remote learning mode, and students continued to study at a pace similar to that experienced before the school shut down.
We consider a sequential cascade of molecular first-reaction events towards a terminal reaction centre in which each reaction step is controlled by diffusive motion of the particles. The model studied here represents a typical reaction setting encountered in diverse molecular biology systems, in which, e.g. a signal transduction proceeds via a series of consecutive 'messengers': the first messenger has to find its respective immobile target site triggering a launch of the second messenger, the second messenger seeks its own target site and provokes a launch of the third messenger and so on, resembling a relay race in human competitions. For such a molecular relay race taking place in infinite one-, two- and three-dimensional systems, we find exact expressions for the probability density function of the time instant of the terminal reaction event, conditioned on preceding successful reaction events on an ordered array of target sites. The obtained expressions pertain to the most general conditions: number of intermediate stages and the corresponding diffusion coefficients, the sizes of the target sites, the distances between them, as well as their reactivities are arbitrary.
In this paper, we investigate the continuous version of modified iterative Runge–Kutta-type methods for nonlinear inverse ill-posed problems proposed in a previous work. The convergence analysis is proved under the tangential cone condition, a modified discrepancy principle, i.e., the stopping time T is a solution of ∥𝐹(𝑥𝛿(𝑇))−𝑦𝛿∥=𝜏𝛿+ for some 𝛿+>𝛿, and an appropriate source condition. We yield the optimal rate of convergence.
In this study, we model a sequence of a confined and a full eruption, employing the relaxed end state of the confined eruption of a kink-unstable flux rope as the initial condition for the ejective one. The full eruption, a model of a coronal mass ejection, develops as a result of converging motions imposed at the photospheric boundary, which drive flux cancellation. In this process, parts of the positive and negative external flux converge toward the polarity inversion line, reconnect, and cancel each other. Flux of the same amount as the canceled flux transfers to a flux rope, increasing the free magnetic energy of the coronal field. With sustained flux cancellation and the associated progressive weakening of the magnetic tension of the overlying flux, we find that a flux reduction of approximate to 11% initiates the torus instability of the flux rope, which leads to a full eruption. These results demonstrate that a homologous full eruption, following a confined one, can be driven by flux cancellation.
Atmospheric water vapour content is a key variable that controls the development of deep convective storms and rainfall extremes over the central Andes. Direct measurements of water vapour are challenging; however, recent developments in microwave processing allow the use of phase delays from L-band radar to measure the water vapour content throughout the atmosphere: Global Navigation Satellite System (GNSS)-based integrated water vapour (IWV) monitoring shows promising results to measure vertically integrated water vapour at high temporal resolutions. Previous works also identified convective available potential energy (CAPE) as a key climatic variable for the formation of deep convective storms and rainfall in the central Andes. Our analysis relies on GNSS data from the Argentine Continuous Satellite Monitoring Network, Red Argentina de Monitoreo Satelital Continuo (RAMSAC) network from 1999 to 2013. CAPE is derived from version 2.0 of the ECMWF’s (European Centre for Medium-Range Weather Forecasts) Re-Analysis (ERA-interim) and rainfall from the TRMM (Tropical Rainfall Measuring Mission) product. In this study, we first analyse the rainfall characteristics of two GNSS-IWV stations by comparing their complementary cumulative distribution function (CCDF). Second, we separately derive the relation between rainfall vs. CAPE and GNSS-IWV. Based on our distribution fitting analysis, we observe an exponential relation of rainfall to GNSS-IWV. In contrast, we report a power-law relationship between the daily mean value of rainfall and CAPE at the GNSS-IWV station locations in the eastern central Andes that is close to the theoretical relationship based on parcel theory. Third, we generate a joint regression model through a multivariable regression analysis using CAPE and GNSS-IWV to explain the contribution of both variables in the presence of each other to extreme rainfall during the austral summer season. We found that rainfall can be characterised with a higher statistical significance for higher rainfall quantiles, e.g., the 0.9 quantile based on goodness-of-fit criterion for quantile regression. We observed different contributions of CAPE and GNSS-IWV to rainfall for each station for the 0.9 quantile. Fourth, we identify the temporal relation between extreme rainfall (the 90th, 95th, and 99th percentiles) and both GNSS-IWV and CAPE at 6 h time steps. We observed an increase before the rainfall event and at the time of peak rainfall—both for GNSS-integrated water vapour and CAPE. We show higher values of CAPE and GNSS-IWV for higher rainfall percentiles (99th and 95th percentiles) compared to the 90th percentile at a 6-h temporal scale. Based on our correlation analyses and the dynamics of the time series, we show that both GNSS-IWV and CAPE had comparable magnitudes, and we argue to consider both climatic variables when investigating their effect on rainfall extremes.
The MOOChub is a joined web-based catalog of all relevant German and Austrian MOOC platforms that lists well over 750 Massive Open Online Courses (MOOCs). Automatically building such a catalog requires that all partners describe and publicly offer the metadata of their courses in the same way. The paper at hand presents the genesis of the idea to establish a common metadata standard and the story of its subsequent development. The result of this effort is, first, an open-licensed de-facto-standard, which is based on existing commonly used standards and second, a first prototypical platform that is using this standard: the MOOChub, which lists all courses of the involved partners. This catalog is searchable and provides a more comprehensive overview of basically all MOOCs that are offered by German and Austrian MOOC platforms. Finally, the upcoming developments to further optimize the catalog and the metadata standard are reported.
A Metabarcoding Analysis of the Mycobiome of Wheat Ears Across a Topographically Heterogeneous Field
(2019)
Author summary <br /> The use of orally inhaled drugs for treating lung diseases is appealing since they have the potential for lung selectivity, i.e. high exposure at the site of action -the lung- without excessive side effects. However, the degree of lung selectivity depends on a large number of factors, including physiochemical properties of drug molecules, patient disease state, and inhalation devices. To predict the impact of these factors on drug exposure and thereby to understand the characteristics of an optimal drug for inhalation, we develop a predictive mathematical framework (a "pharmacokinetic model"). In contrast to previous approaches, our model allows combining knowledge from different sources appropriately and its predictions were able to adequately predict different sets of clinical data. Finally, we compare the impact of different factors and find that the most important factors are the size of the inhaled particles, the affinity of the drug to the lung tissue, as well as the rate of drug dissolution in the lung. In contrast to the common belief, the solubility of a drug in the lining fluids is not found to be relevant. These findings are important to understand how inhaled drugs should be designed to achieve best treatment results in patients. <br /> The fate of orally inhaled drugs is determined by pulmonary pharmacokinetic processes such as particle deposition, pulmonary drug dissolution, and mucociliary clearance. Even though each single process has been systematically investigated, a quantitative understanding on the interaction of processes remains limited and therefore identifying optimal drug and formulation characteristics for orally inhaled drugs is still challenging. To investigate this complex interplay, the pulmonary processes can be integrated into mathematical models. However, existing modeling attempts considerably simplify these processes or are not systematically evaluated against (clinical) data. In this work, we developed a mathematical framework based on physiologically-structured population equations to integrate all relevant pulmonary processes mechanistically. A tailored numerical resolution strategy was chosen and the mechanistic model was evaluated systematically against data from different clinical studies. Without adapting the mechanistic model or estimating kinetic parameters based on individual study data, the developed model was able to predict simultaneously (i) lung retention profiles of inhaled insoluble particles, (ii) particle size-dependent pharmacokinetics of inhaled monodisperse particles, (iii) pharmacokinetic differences between inhaled fluticasone propionate and budesonide, as well as (iv) pharmacokinetic differences between healthy volunteers and asthmatic patients. Finally, to identify the most impactful optimization criteria for orally inhaled drugs, the developed mechanistic model was applied to investigate the impact of input parameters on both the pulmonary and systemic exposure. Interestingly, the solubility of the inhaled drug did not have any relevant impact on the local and systemic pharmacokinetics. Instead, the pulmonary dissolution rate, the particle size, the tissue affinity, and the systemic clearance were the most impactful potential optimization parameters. In the future, the developed prediction framework should be considered a powerful tool for identifying optimal drug and formulation characteristics.
Author summary <br /> Switching between local and global attention is a general strategy in human information processing. We investigate whether this strategy is a viable approach to model sequences of fixations generated by a human observer in a free viewing task with natural scenes. Variants of the basic model are used to predict the experimental data based on Bayesian inference. Results indicate a high predictive power for both aggregated data and individual differences across observers. The combination of a novel model with state-of-the-art Bayesian methods lends support to our two-state model using local and global internal attention states for controlling eye movements. <br /> Understanding the decision process underlying gaze control is an important question in cognitive neuroscience with applications in diverse fields ranging from psychology to computer vision. The decision for choosing an upcoming saccade target can be framed as a selection process between two states: Should the observer further inspect the information near the current gaze position (local attention) or continue with exploration of other patches of the given scene (global attention)? Here we propose and investigate a mathematical model motivated by switching between these two attentional states during scene viewing. The model is derived from a minimal set of assumptions that generates realistic eye movement behavior. We implemented a Bayesian approach for model parameter inference based on the model's likelihood function. In order to simplify the inference, we applied data augmentation methods that allowed the use of conjugate priors and the construction of an efficient Gibbs sampler. This approach turned out to be numerically efficient and permitted fitting interindividual differences in saccade statistics. Thus, the main contribution of our modeling approach is two-fold; first, we propose a new model for saccade generation in scene viewing. Second, we demonstrate the use of novel methods from Bayesian inference in the field of scan path modeling.
Aging in speech production is a multidimensional process. Biological, cognitive, social, and communicative factors can change over time, stay relatively stable, or may even compensate for each other. In this longitudinal work, we focus on stability and change at the laryngeal and supralaryngeal levels in the discourse particle euh produced by 10 older French-speaking females at two times, 10 years apart. Recognizing the multiple discourse roles of euh, we divided out occurrences according to utterance position. We quantified the frequency of euh, and evaluated acoustic changes in formants, fundamental frequency, and voice quality across time and utterance position. Results showed that euh frequency was stable with age. The only acoustic measure that revealed an age effect was harmonics-to-noise ratio, showing less noise at older ages. Other measures mostly varied with utterance position, sometimes in interaction with age. Some voice quality changes could reflect laryngeal adjustments that provide for airflow conservation utterance-finally. The data suggest that aging effects may be evident in some prosodic positions (e.g., utterance-final position), but not others (utterance-initial position). Thus, it is essential to consider the interactions among these factors in future work and not assume that vocal aging is evident throughout the signal.
Older adults with amnestic mild cognitive impairment (aMCI) who in addition to their memory deficits also suffer from frontal-executive dysfunctions have a higher risk of developing dementia later in their lives than older adults with aMCI without executive deficits and older adults with non-amnestic MCI (naMCI). Handgrip strength (HGS) is also correlated with the risk of cognitive decline in the elderly. Hence, the current study aimed to investigate the associations between HGS and executive functioning in individuals with aMCI, naMCI and healthy controls. Older, right-handed adults with amnestic MCI (aMCI), non-amnestic MCI (naMCI), and healthy controls (HC) conducted a handgrip strength measurement via a handheld dynamometer. Executive functions were assessed with the Trail Making Test (TMT A&B). Normalized handgrip strength (nHGS, normalized to Body Mass Index (BMI)) was calculated and its associations with executive functions (operationalized through z-scores of TMT B/A ratio) were investigated through partial correlation analyses (i.e., accounting for age, sex, and severity of depressive symptoms). A positive and low-to-moderate correlation between right nHGS (rp (22) = 0.364; p = 0.063) and left nHGS (rp (22) = 0.420; p = 0.037) and executive functioning in older adults with aMCI but not in naMCI or HC was observed. Our results suggest that higher levels of nHGS are linked to better executive functioning in aMCI but not naMCI and HC. This relationship is perhaps driven by alterations in the integrity of the hippocampal-prefrontal network occurring in older adults with aMCI. Further research is needed to provide empirical evidence for this assumption.
A few months before his death, A. v. Humboldt attended the celebration in honor of the 127th birthday of George Washington at the US legation in Berlin. A letter to the American Envoy, Joseph A. Wright (1810 – 1867), underlines Humboldt’s admiration for the fi rst president of the United States. At the same time Humboldt asked the diplomat to mail a letter to the German-American Bernard Moses (1832 – 1897) in Clinton, Louisiana, who had named his son Alexander Humboldt Moses (grave on the Hebrew Rest Cemetery #2 in New Orleans, burial plot A, 12, 5). It appears to be possible that the Moses family still owns Humboldt’s letter.
Although the use of stable transformation technology has led to great insight into gene function, its application in high-throughput studies remains arduous. Agro-infiltration have been widely used in species such as Nicotiana benthamiana for the rapid detection of gene expression and protein interaction analysis, but this technique does not work efficiently in other plant species, including Arabidopsis thaliana. As an efficient high-throughput transient expression system is currently lacking in the model plant species A. thaliana, we developed a method that is characterized by high efficiency, reproducibility, and suitability for transient expression of a variety of functional proteins in A. thaliana and 7 other plant species, including Brassica oleracea, Capsella rubella, Thellungiella salsuginea, Thellungiella halophila, Solanum tuberosum, Capsicum annuum, and N. benthamiana. Efficiency of this method was independently verified in three independent research facilities, pointing to the robustness of this technique. Furthermore, in addition to demonstrating the utility of this technique in a range of species, we also present a case study employing this method to assess protein-protein interactions in the sucrose biosynthesis pathway in Arabidopsis.