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Health-related quality of life (HRQL) among migrant populations can be associated with acculturation (i.e., the process of adopting, acquiring and adjusting to a new cultural environment). Since there is a lack of longitudinal studies, we aimed to describe HRQL changes among adults of Turkish descent living in Berlin and Essen, Germany, and their association with acculturation. Participants of a population-based study were recruited in 2012–2013 and reinvited six years later to complete a questionnaire. Acculturation was assessed at baseline using the Frankfurt acculturation scale (integration, assimilation, separation and marginalization). HRQL was assessed at baseline (SF-8) and at follow-up (SF-12) resulting in a physical (PCS) and mental (MCS) sum score. Associations with acculturation and HRQL were analyzed with linear regression models using a time-by-acculturation status interaction term. In the study 330 persons were included (65% women, mean age ± standard deviation 43.3 ± 11.8 years). Over the 6 years, MCS decreased, while PCS remained stable. While cross-sectional analyses showed associations of acculturation status with both MCS and PCS, temporal changes including the time interaction term did not reveal associations of baseline acculturation status with HRQL. When investigating HRQL in acculturation, more longitudinal studies are needed to take changes in both HRQL and acculturation status into account.
Dieser Artikel schildert die Neukonzeption eines Kurses für Erstsemesterstudierende der Medizin an der Universitätsbibliothek Würzburg unter Einbeziehung des Frameworks for Information Literacy for Higher Education (im Folgenden Framework genannt). Nach einleitenden Bemerkungen zur Theorie der Schwellenkonzepte und zum Framework selbst steht der Kursinhalt mit den dazugehörigen Frames, Knowledge Practices und Dispositions im Fokus. Die Auswertung der Evaluation und ein Ausblick auf die Umsetzung des Kurses in der coronabedingten digitalen Lehre bilden den Schluss.
Die Arbeitsgruppe Informationskompetenz im Bibliotheksverbund Bayern (AGIK Bay) veröffentlichte im Oktober 2020 das interaktive E-Tutorial S.P.U.T.N.I.K. zur Förderung der Informationskompetenz von Schüler*innen der Oberstufe, das sich inhaltlich am Framework for Information Literacy for Higher Education orientiert. Der Artikel zeichnet die Entstehung des Tutorials in Kooperation mit Studierenden des Fachbereichs Archiv- und Bibliothekswesen der Hochschule für den öffentlichen Dienst in Bayern nach und skizziert die Herausforderungen bei der finalen Umsetzung durch die Universitätsbibliothek Würzburg. Das Tutorial ist als Moodle- und Ilias-kompatibles SCORM-Lernpaket mit vielen interaktiven Quizelementen konzipiert und in fünf Modulen aufgebaut. Es ist online zugänglich und steht zur Nachnutzung innerhalb der DACH-Bibliothekscommunity unter einer Creative Commons Lizenz bereit.
Dynamic point cloud compression based on projections, surface reconstruction and video compression
(2021)
In this paper we will present a new dynamic point cloud compression based on different projection types and bit depth, combined with the surface reconstruction algorithm and video compression for obtained geometry and texture maps. Texture maps have been compressed after creating Voronoi diagrams. Used video compression is specific for geometry (FFV1) and texture (H.265/HEVC). Decompressed point clouds are reconstructed using a Poisson surface reconstruction algorithm. Comparison with the original point clouds was performed using point-to-point and point-to-plane measures. Comprehensive experiments show better performance for some projection maps: cylindrical, Miller and Mercator projections.
Fragestellung: In Bayern leben etwa 10 % aller jungen Menschen mit Intelligenzminderung in Heimeinrichtungen. 2016 wurde in Presseberichten der Vorwurf unzulässiger freiheitsentziehender Maßnahmen formuliert. Im Rahmen des Projekts REDUGIA wurde in bayerischen Heimeinrichtungen eine repräsentative Erhebung zu freiheitsentziehenden Maßnahmen (FeM), herausforderndem Verhalten (hfV) und der Mitarbeiterbelastung (MaB) durchgeführt. Methodik: 65 Einrichtungen für junge Menschen mit Intelligenzminderung in Bayern wurde ein Fragebogen zu strukturellen Gegebenheiten sowie MaB, hfV und FeM zugesendet. Neben deskriptiven Auswertungen wurden korrelative Analysen bzw. Regressionsanalysen zum Zusammenhang zwischen hfV, FeM und MaB durchgeführt. Ergebnisse: Es wurden Daten zu 1839 Personen in 61 Einrichtungen erhoben. 84.3 % der Einrichtungen berichteten geringe Raten an hfV und FeM, während 15.7 % ein gehäuftes Vorkommen von hfV und FeM angaben. Auf n = 1809 Vollzeitäquivalente kam es innerhalb von 14 Tagen zu 639 körperlichen Angriffen durch Bewohner_innen. In 12 Monaten wurden problemverhaltensassoziiert 85 Krankmeldungen sowie 33 Versetzungsanträge/Kündigungen berichtet. Es zeigte sich ein signifikant positiver Zusammenhang zwischen hfV und FeM (R² = .307, F = 21.719, p < .001). Die Mitarbeiterbelastung korrelierte positiv mit hfV (r = .507, p < .001). Schlussfolgerungen: Die Studienbefunde weisen darauf hin, dass hfV sowie FeM bei jungen Menschen mit Intelligenzminderung kein flächendeckendes Phänomen darstellen, sondern sich auf wenige spezialisierte Einrichtungen fokussieren. Mögliche Maßnahmen zur Prävention von Problemverhalten und Freiheitsentzug werden diskutiert.
Effects of Acrophobic Fear and Trait Anxiety on Human Behavior in a Virtual Elevated Plus-Maze
(2021)
The Elevated Plus-Maze (EPM) is a well-established apparatus to measure anxiety in rodents, i.e., animals exhibiting an increased relative time spent in the closed vs. the open arms are considered anxious. To examine whether such anxiety-modulated behaviors are conserved in humans, we re-translated this paradigm to a human setting using virtual reality in a Cave Automatic Virtual Environment (CAVE) system. In two studies, we examined whether the EPM exploration behavior of humans is modulated by their trait anxiety and also assessed the individuals’ levels of acrophobia (fear of height), claustrophobia (fear of confined spaces), sensation seeking, and the reported anxiety when on the maze. First, we constructed an exact virtual copy of the animal EPM adjusted to human proportions. In analogy to animal EPM studies, participants (N = 30) freely explored the EPM for 5 min. In the second study (N = 61), we redesigned the EPM to make it more human-adapted and to differentiate influences of trait anxiety and acrophobia by introducing various floor textures and lower walls of closed arms to the height of standard handrails. In the first experiment, hierarchical regression analyses of exploration behavior revealed the expected association between open arm avoidance and Trait Anxiety, an even stronger association with acrophobic fear. In the second study, results revealed that acrophobia was associated with avoidance of open arms with mesh-floor texture, whereas for trait anxiety, claustrophobia, and sensation seeking, no effect was detected. Also, subjects’ fear rating was moderated by all psychometrics but trait anxiety. In sum, both studies consistently indicate that humans show no general open arm avoidance analogous to rodents and that human EPM behavior is modulated strongest by acrophobic fear, whereas trait anxiety plays a subordinate role. Thus, we conclude that the criteria for cross-species validity are met insufficiently in this case. Despite the exploratory nature, our studies provide in-depth insights into human exploration behavior on the virtual EPM.
The design and evaluation of assisting technologies to support behavior change processes have become an essential topic within the field of human-computer interaction research in general and the field of immersive intervention technologies in particular. The mechanisms and success of behavior change techniques and interventions are broadly investigated in the field of psychology. However, it is not always easy to adapt these psychological findings to the context of immersive technologies. The lack of theoretical foundation also leads to a lack of explanation as to why and how immersive interventions support behavior change processes. The Behavioral Framework for immersive Technologies (BehaveFIT) addresses this lack by 1) presenting an intelligible categorization and condensation of psychological barriers and immersive features, by 2) suggesting a mapping that shows why and how immersive technologies can help to overcome barriers and finally by 3) proposing a generic prediction path that enables a structured, theory-based approach to the development and evaluation of immersive interventions. These three steps explain how BehaveFIT can be used, and include guiding questions for each step. Further, two use cases illustrate the usage of BehaveFIT. Thus, the present paper contributes to guidance for immersive intervention design and evaluation, showing that immersive interventions support behavior change processes and explain and predict 'why' and 'how' immersive interventions can bridge the intention-behavior-gap.
Companies increasingly seek to use gay protagonists in audio-visual commercials to attract a new affluent target group. There is also growing demand for the diversity present in society to be reflected in media formats such as advertising. Studies have shown, however, that heterosexual consumers (especially men), who may be part of the company's loyal consumer base, tend to react negatively to gay-themed advertising campaigns. Searching for an instrument to mitigate this unwanted effect, the present study investigated whether carefully selected background music can shape the perceived gender of gay male advertising protagonists. In a 2 × 2 between-subjects online experiment (musical connotation × gender of the participant), 218 heterosexual participants watched a commercial promoting engagement rings that featured gay male protagonists, scored with feminine- or masculine-connoted background music. As expected, women generally reacted more positively than men to the advertising. Men exposed to the masculine-connoted background music rated the promoted brand more positively, and masculine music also enhanced (at least in the short term) these men's acceptance of gay men in general (low and medium effect sizes) more than was the case for feminine background music. Carefully selected background music affecting the perceived gender of gay male advertising protagonists may prevent negative reactions from heterosexual audiences and, therefore, motivate companies to use gay protagonists in television commercials on a more regular basis.
The ubiquity of mobile devices fosters the combined use of ecological momentary assessments (EMA) and mobile crowdsensing (MCS) in the field of healthcare. This combination not only allows researchers to collect ecologically valid data, but also to use smartphone sensors to capture the context in which these data are collected. The TrackYourTinnitus (TYT) platform uses EMA to track users' individual subjective tinnitus perception and MCS to capture an objective environmental sound level while the EMA questionnaire is filled in. However, the sound level data cannot be used directly among the different smartphones used by TYT users, since uncalibrated raw values are stored. This work describes an approach towards making these values comparable. In the described setting, the evaluation of sensor measurements from different smartphone users becomes increasingly prevalent. Therefore, the shown approach can be also considered as a more general solution as it not only shows how it helped to interpret TYT sound level data, but may also stimulate other researchers, especially those who need to interpret sensor data in a similar setting. Altogether, the approach will show that measuring sound levels with mobile devices is possible in healthcare scenarios, but there are many challenges to ensuring that the measured values are interpretable.
Sensitivity analysis for interpretation of machine learning based segmentation models in cardiac MRI
(2021)
Background
Image segmentation is a common task in medical imaging e.g., for volumetry analysis in cardiac MRI. Artificial neural networks are used to automate this task with performance similar to manual operators. However, this performance is only achieved in the narrow tasks networks are trained on. Performance drops dramatically when data characteristics differ from the training set properties. Moreover, neural networks are commonly considered black boxes, because it is hard to understand how they make decisions and why they fail. Therefore, it is also hard to predict whether they will generalize and work well with new data. Here we present a generic method for segmentation model interpretation. Sensitivity analysis is an approach where model input is modified in a controlled manner and the effect of these modifications on the model output is evaluated. This method yields insights into the sensitivity of the model to these alterations and therefore to the importance of certain features on segmentation performance.
Results
We present an open-source Python library (misas), that facilitates the use of sensitivity analysis with arbitrary data and models. We show that this method is a suitable approach to answer practical questions regarding use and functionality of segmentation models. We demonstrate this in two case studies on cardiac magnetic resonance imaging. The first case study explores the suitability of a published network for use on a public dataset the network has not been trained on. The second case study demonstrates how sensitivity analysis can be used to evaluate the robustness of a newly trained model.
Conclusions
Sensitivity analysis is a useful tool for deep learning developers as well as users such as clinicians. It extends their toolbox, enabling and improving interpretability of segmentation models. Enhancing our understanding of neural networks through sensitivity analysis also assists in decision making. Although demonstrated only on cardiac magnetic resonance images this approach and software are much more broadly applicable.
At the end of the first larval stage, the nematode Caenorhabditis elegans developing in harsh environmental conditions is able to choose an alternative developmental path called the dauer diapause. Dauer larvae exhibit different physiology and behaviors from non-dauer larvae. Using focused ion beam-scanning electron microscopy (FIB-SEM), we volumetrically reconstructed the anterior sensory apparatus of C. elegans dauer larvae with unprecedented precision. We provide a detailed description of some neurons, focusing on structural details that were unknown or unresolved by previously published studies. They include the following: (1) dauer-specific branches of the IL2 sensory neurons project into the periphery of anterior sensilla and motor or putative sensory neurons at the sub-lateral cords; (2) ciliated endings of URX sensory neurons are supported by both ILso and AMso socket cells near the amphid openings; (3) variability in amphid sensory dendrites among dauers; and (4) somatic RIP interneurons maintain their projection into the pharyngeal nervous system. Our results support the notion that dauer larvae structurally expand their sensory system to facilitate searching for more favorable environments.
Revealing the molecular organization of anatomically precisely defined brain regions is necessary for refined understanding of synaptic plasticity. Although three-dimensional (3D) single-molecule localization microscopy can provide the required resolution, imaging more than a few micrometers deep into tissue remains challenging. To quantify presynaptic active zones (AZ) of entire, large, conditional detonator hippocampal mossy fiber (MF) boutons with diameters as large as 10 mu m, we developed a method for targeted volumetric direct stochastic optical reconstruction microscopy (dSTORM). An optimized protocol for fast repeated axial scanning and efficient sequential labeling of the AZ scaffold Bassoon and membrane bound GFP with Alexa Fluor 647 enabled 3D-dSTORM imaging of 25 mu m thick mouse brain sections and assignment of AZs to specific neuronal substructures. Quantitative data analysis revealed large differences in Bassoon cluster size and density for distinct hippocampal regions with largest clusters in MF boutons. Pauli et al. develop targeted volumetric dSTORM in order to image large hippocampal mossy fiber boutons (MFBs) in brain slices. They can identify synaptic targets of individual MFBs and measured size and density of Bassoon clusters within individual untruncated MFBs at nanoscopic resolution.
Individual-based models are doubly complex: as well as representing complex ecological systems, the software that implements them is complex in itself. Both forms of complexity must be managed to create reliable models. However, the ecological modelling literature to date has focussed almost exclusively on the biological complexity. Here, we discuss methods for containing software complexity.
Strategies for containing complexity include avoiding, subdividing, documenting and reviewing it. Computer science has long-established techniques for all of these strategies. We present some of these techniques and set them in the context of IBM development, giving examples from published models.
Techniques for avoiding software complexity are following best practices for coding style, choosing suitable programming languages and file formats and setting up an automated workflow. Complex software systems can be made more tractable by encapsulating individual subsystems. Good documentation needs to take into account the perspectives of scientists, users and developers. Code reviews are an effective way to check for errors, and can be used together with manual or automated unit and integration tests.
Ecological modellers can learn from computer scientists how to deal with complex software systems. Many techniques are readily available, but must be disseminated among modellers. There is a need for further work to adapt software development techniques to the requirements of academic research groups and individual-based modelling.
Oxidative precipitation is a facile synthesis method to obtain ferromagnetic iron oxide nanoparticles from ferrous salts—with unexplored potential. The concentration of base and oxidant alone strongly affects the particle's structure and thus their magnetic properties despite the same material, magnetite (Fe\(_{3}\)O\(_{4}\)), is obtained when precipitated with potassium hydroxide (KOH) from ferrous sulfate (FeSO\(_{4}\)) and treated with potassium nitrate (KNO\(_{3}\)) at appropriate temperature. Depending on the potassium hydroxide and potassium nitrate concentrations, it is possible to obtain a series of different types of either single crystals or mesocrystals. The time‐dependent mesocrystal evolution can be revealed via electron microscopy and provides insights into the process of oriented attachment, yielding faceted particles, showing a facet‐dependent reactivity. It is found that it is the nitrate and hydroxide concentration that influences the ligand exchange process and thus the crystallization pathways. The presence of sulfate ions contributes to the mesocrystal evolution as well, as sulfate apparently hinders further crystal fusion, as revealed via infrared spectroscopy. Finally, it is found that nitrite, as one possible and ecologically highly relevant reduction product occurring in nature in context with iron, only evolves if the reaction is quantitative.
In the course of a screen designed to produce antibodies (ABs) with affinity to proteins in the honey bee brain we found an interesting AB that detects a highly specific epitope predominantly in the nuclei of Kenyon cells (KCs). The observed staining pattern is unique, and its unfamiliarity indicates a novel previously unseen nuclear structure that does not colocalize with the cytoskeletal protein f-actin. A single rod-like assembly, 3.7-4.1 mu m long, is present in each nucleus of KCs in adult brains of worker bees and drones with the strongest immuno-labelling found in foraging bees. In brains of young queens, the labelling is more sporadic, and the rod-like structure appears to be shorter (similar to 2.1 mu m). No immunostaining is detectable in worker larvae. In pupal stage 5 during a peak of brain development only some occasional staining was identified. Although the cellular function of this unexpected structure has not been determined, the unusual distinctiveness of the revealed pattern suggests an unknown and potentially important protein assembly. One possibility is that this nuclear assembly is part of the KCs plasticity underlying the brain maturation in adult honey bees. Because no labelling with this AB is detectable in brains of the fly Drosophila melanogaster and the ant Camponotus floridanus, we tentatively named this antibody AmBNSab (Apis mellifera Brain Neurons Specific antibody). Here we report our results to make them accessible to a broader community and invite further research to unravel the biological role of this curious nuclear structure in the honey bee central brain.
We consider the Bathnagar–Gross–Krook (BGK) model, an approximation of the Boltzmann equation, describing the time evolution of a single momoatomic rarefied gas and satisfying the same two main properties (conservation properties and entropy inequality). However, in practical applications, one often has to deal with two additional physical issues. First, a gas often does not consist of only one species, but it consists of a mixture of different species. Second, the particles can store energy not only in translational degrees of freedom but also in internal degrees of freedom such as rotations or vibrations (polyatomic molecules). Therefore, here, we will present recent BGK models for gas mixtures for mono- and polyatomic particles and the existing mathematical theory for these models.
We describe a system for the analysis of an important unicellular eukaryotic flagellate in a confining and crowded environment. The parasite Trypanosoma brucei is arguably one of the most versatile microswimmers known. It has unique properties as a single microswimmer and shows remarkable adaptations (not only in motility, but prominently so), to its environment during a complex developmental cycle involving two different hosts. Specific life cycle stages show fascinating collective behaviour, as millions of cells can be forced to move together in extreme confinement. Our goal is to examine such motile behaviour directly in the context of the relevant environments. Therefore, for the first time, we analyse the motility behaviour of trypanosomes directly in a widely used assay, which aims to evaluate the parasites behaviour in collectives, in response to as yet unknown parameters. In a step towards understanding whether, or what type of, swarming behaviour of trypanosomes exists, we customised the assay for quantitative tracking analysis of motile behaviour on the single-cell level. We show that the migration speed of cell groups does not directly depend on single-cell velocity and that the system remains to be simplified further, before hypotheses about collective motility can be advanced.
The macromolecular SMN complex facilitates the formation of Sm-class ribonucleoproteins involved in mRNA processing (UsnRNPs). While biochemical studies have revealed key activities of the SMN complex, its structural investigation is lagging behind. Here we report on the identification and structural determination of the SMN complex from the lower eukaryote Schizosaccharomyces pombe, consisting of SMN, Gemin2, 6, 7, 8 and Sm proteins. The core of the SMN complex is formed by several copies of SMN tethered through its C-terminal alpha-helices arranged with alternating polarity. This creates a central platform onto which Gemin8 binds and recruits Gemins 6 and 7. The N-terminal parts of the SMN molecules extrude via flexible linkers from the core and enable binding of Gemin2 and Sm proteins. Our data identify the SMN complex as a multivalent hub where Sm proteins are collected in its periphery to allow their joining with UsnRNA.
Impaired decision-making leads to the inability to distinguish between advantageous and disadvantageous choices. The impairment of a person’s decision-making is a common goal of gambling games. Given the recent trend of gambling using immersive Virtual Reality it is crucial to investigate the effects of both immersion and the virtual environment (VE) on decision-making. In a novel user study, we measured decision-making using three virtual versions of the Iowa Gambling Task (IGT). The versions differed with regard to the degree of immersion and design of the virtual environment. While emotions affect decision-making, we further measured the positive and negative affect of participants. A higher visual angle on a stimulus leads to an increased emotional response. Thus, we kept the visual angle on the Iowa Gambling Task the same between our conditions. Our results revealed no significant impact of immersion or the VE on the IGT. We further found no significant difference between the conditions with regard to positive and negative affect. This suggests that neither the medium used nor the design of the VE causes an impairment of decision-making. However, in combination with a recent study, we provide first evidence that a higher visual angle on the IGT leads to an effect of impairment.
Aspergillus fumigatus causes life-threatening opportunistic infections in immunocompromised patients. As therapeutic outcomes of invasive aspergillosis (IA) are often unsatisfactory, the development of targeted immunotherapy remains an important goal. Linking the innate and adaptive immune system, dendritic cells are pivotal in anti-Aspergillus defense and have generated interest as a potential immunotherapeutic approach in IA. While monocyte-derived dendritic cells (moDCs) require ex vivo differentiation, antigen-pulsed primary myeloid dendritic cells (mDCs) may present a more immediate platform for immunotherapy. To that end, we compared the response patterns and cellular interactions of human primary mDCs and moDCs pulsed with an A. fumigatus lysate and two A. fumigatus proteins (CcpA and Shm2) in a serum-free, GMP-compliant medium. CcpA and Shm2 triggered significant upregulation of maturation markers in mDCs and, to a lesser extent, moDCs. Furthermore, both A. fumigatus proteins elicited the release of an array of key pro-inflammatory cytokines including TNF-α, IL-1β, IL-6, IL-8, and CCL3 from both DC populations. Compared to moDCs, CcpA- and Shm2-pulsed mDCs exhibited greater expression of MHC class II antigens and stimulated stronger proliferation and IFN-γ secretion from autologous CD4\(^+\) and CD8\(^+\) T-cells. Moreover, supernatants of CcpA- and Shm2-pulsed mDCs significantly enhanced the oxidative burst in allogeneic neutrophils co-cultured with A. fumigatus germ tubes. Taken together, our in vitro data suggest that ex vivo CcpA- and Shm2-pulsed primary mDCs have the potential to be developed into an immunotherapeutic approach to tackle IA.
Receptor tyrosine kinases (RTK) are rarely mutated in cutaneous melanoma, but the expression and activation of several RTK family members are associated with a proinvasive phenotype and therapy resistance. Epidermal growth factor receptor (EGFR) is a member of the RTK family and is only expressed in a subgroup of melanomas with poor prognosis. The insight into regulators of EGFR expression and activation is important for the understanding of the development of this malignant melanoma phenotype. Here, we describe that the transcription factor NRF2, the master regulator of the oxidative and electrophilic stress response, mediates the expression and activation of EGFR in melanoma by elevating the levels of EGFR as well as its ligands EGF and TGFα. ChIP sequencing data show that NRF2 directly binds to the promoter of EGF, which contains a canonical antioxidant response element. Accordingly, EGF is induced by oxidative stress and is also increased in lung adenocarcinoma and head and neck carcinoma with mutationally activated NRF2. In contrast, regulation of EGFR and TGFA occurs by an indirect mechanism, which is enabled by the ability of NRF2 to block the activity of the melanocytic lineage factor MITF in melanoma. MITF effectively suppresses EGFR and TGFA expression and therefore serves as link between NRF2 and EGFR. As EGFR was previously described to stimulate NRF2 activity, the mutual activation of NRF2 and EGFR pathways was investigated. The presence of NRF2 was necessary for full EGFR pathway activation, as NRF2-knockout cells showed reduced AKT activation in response to EGF stimulation compared to controls. Conversely, EGF led to the nuclear localization and activation of NRF2, thereby demonstrating that NRF2 and EGFR are connected in a positive feedback loop in melanoma. In summary, our data show that the EGFR-positive melanoma phenotype is strongly supported by NRF2, thus revealing a novel maintenance mechanism for this clinically challenging melanoma subpopulation.
Key elements of sacred landscapes of the Nile Delta were lakes, canals and artificial basins connected to temples, which were built on elevated terrain. In the case of temples of goddesses of an ambivalent, even dangerous, nature, i.e. lioness goddesses and all female deities who could appear as such, the purpose of sacred lakes and canals exceeded their function as a water resource for basic practical and religious needs. Their pleasing coolness was believed to calm the goddess' fiery nature, and during important religious festivals, the barques of the goddesses were rowed on those waters. As archaeological evidence was very rare in the past, the study of those sacred waters was mainly confined to textual sources. Recently applied geoarchaeological methods, however, have changed this situation dramatically: they allow in-depth investigations and reconstructions of these deltaic sacred landscapes. Exploring these newly available data, the paper presented here focuses on the sites of Buto, Sais and Bubastis, by investigating the characteristics of their sacred lakes, canals and marshes with respect to their hydrogeographical and geomorphological context and to their role in ancient Egyptian religion and mythology as well.
Staphylococcus aureus is a major human pathogen, which can invade and survive in non-professional and professional phagocytes. Uptake by host cells is thought to contribute to pathogenicity and persistence of the bacterium. Upon internalization by epithelial cells, cytotoxic S. aureus strains can escape from the phagosome, replicate in the cytosol and induce host cell death. Here, we identified a staphylococcal cysteine protease to induce cell death after translocation of intracellular S. aureus into the host cell cytoplasm. We demonstrated that loss of staphopain A function leads to delayed onset of host cell death and prolonged intracellular replication of S. aureus in epithelial cells. Overexpression of staphopain A in a non-cytotoxic strain facilitated intracellular killing of the host cell even in the absence of detectable intracellular replication. Moreover, staphopain A contributed to efficient colonization of the lung in a mouse pneumonia model. In phagocytic cells, where intracellular S. aureus is exclusively localized in the phagosome, staphopain A did not contribute to cytotoxicity. Our study suggests that staphopain A is utilized by S. aureus to exit the epithelial host cell and thus contributes to tissue destruction and dissemination of infection.
Author summary Staphylococcus aureus is an antibiotic-resistant pathogen that emerges in hospital and community settings and can cause a variety of diseases ranging from skin abscesses to lung inflammation and blood poisoning. The bacterium can asymptomatically colonize the upper respiratory tract and skin of humans and take advantage of opportune conditions, like immunodeficiency or breached barriers, to cause infection. Although S. aureus was not regarded as intracellular bacterium, it can be internalized by human cells and subsequently exit the host cells by induction of cell death, which is considered to cause tissue destruction and spread of infection. The bacterial virulence factors and underlying molecular mechanisms involved in the intracellular lifestyle of S. aureus remain largely unknown. We identified a bacterial cysteine protease to contribute to host cell death of epithelial cells mediated by intracellular S. aureus. Staphopain A induced killing of the host cell after translocation of the pathogen into the cell cytosol, while bacterial proliferation was not required. Further, the protease enhanced survival of the pathogen during lung infection. These findings reveal a novel, intracellular role for the bacterial protease staphopain A.
The Gram-negative rod-shaped bacterium Pseudomonas aeruginosa is not only a major cause of nosocomial infections but also serves as a model species of bacterial RNA biology. While its transcriptome architecture and posttranscriptional regulation through the RNA-binding proteins Hfq, RsmA, and RsmN have been studied in detail, global information about stable RNA-protein complexes in this human pathogen is currently lacking. Here, we implement gradient profiling by sequencing (Grad-seq) in exponentially growing P. aeruginosa cells to comprehensively predict RNA and protein complexes, based on glycerol gradient sedimentation profiles of >73% of all transcripts and ∼40% of all proteins. As to benchmarking, our global profiles readily reported complexes of stable RNAs of P. aeruginosa, including 6S RNA with RNA polymerase and associated product RNAs (pRNAs). We observe specific clusters of noncoding RNAs, which correlate with Hfq and RsmA/N, and provide a first hint that P. aeruginosa expresses a ProQ-like FinO domain-containing RNA-binding protein. To understand how biological stress may perturb cellular RNA/protein complexes, we performed Grad-seq after infection by the bacteriophage ΦKZ. This model phage, which has a well-defined transcription profile during host takeover, displayed efficient translational utilization of phage mRNAs and tRNAs, as evident from their increased cosedimentation with ribosomal subunits. Additionally, Grad-seq experimentally determines previously overlooked phage-encoded noncoding RNAs. Taken together, the Pseudomonas protein and RNA complex data provided here will pave the way to a better understanding of RNA-protein interactions during viral predation of the bacterial cell.
IMPORTANCE Stable complexes by cellular proteins and RNA molecules lie at the heart of gene regulation and physiology in any bacterium of interest. It is therefore crucial to globally determine these complexes in order to identify and characterize new molecular players and regulation mechanisms. Pseudomonads harbor some of the largest genomes known in bacteria, encoding ∼5,500 different proteins. Here, we provide a first glimpse on which proteins and cellular transcripts form stable complexes in the human pathogen Pseudomonas aeruginosa. We additionally performed this analysis with bacteria subjected to the important and frequently encountered biological stress of a bacteriophage infection. We identified several molecules with established roles in a variety of cellular pathways, which were affected by the phage and can now be explored for their role during phage infection. Most importantly, we observed strong colocalization of phage transcripts and host ribosomes, indicating the existence of specialized translation mechanisms during phage infection. All data are publicly available in an interactive and easy to use browser.
Chronic respiratory diseases are among the leading causes of death worldwide, but only symptomatic therapies are available for terminal illness. This in part reflects a lack of biomimetic in vitro models that can imitate the complex environment and physiology of the lung. Here, a copolymeric membrane consisting of poly(ε‐)caprolactone and gelatin with tunable properties, resembling the main characteristics of the alveolar basement membrane is introduced. The thin bioinspired membrane (≤5 μm) is stretchable (up to 25% linear strain) with appropriate surface wettability and porosity for culturing lung epithelial cells under air–liquid interface conditions. The unique biphasic concept of this membrane provides optimum characteristics for initial cell growth (phase I) and then switch to biomimetic properties for cyclic cell‐stretch experiments (phase II). It is showed that physiologic cyclic mechanical stretch improves formation of F‐actin cytoskeleton filaments and tight junctions while non‐physiologic over‐stretch induces cell apoptosis, activates inflammatory response (IL‐8), and impairs epithelial barrier integrity. It is also demonstrated that cyclic physiologic stretch can enhance the cellular uptake of nanoparticles. Since this membrane offers considerable advantages over currently used membranes, it may lead the way to more biomimetic in vitro models of the lung for translation of in vitro response studies into clinical outcome.
Supplement-free induction of cellular differentiation and polarization solely through the topography of materials is an auspicious strategy but has so far significantly lagged behind the efficiency and intensity of media-supplementation-based protocols. Consistent with the idea that 3D structural motifs in the extracellular matrix possess immunomodulatory capacity as part of the natural healing process, it is found in this study that human-monocyte-derived macrophages show a strong M2a-like prohealing polarization when cultured on type I rat-tail collagen fibers but not on collagen I films. Therefore, it is hypothesized that highly aligned nanofibrils also of synthetic polymers, if packed into larger bundles in 3D topographical biomimetic similarity to native collagen I, would induce a localized macrophage polarization. For the automated fabrication of such bundles in a 3D printing manner, the strategy of “melt electrofibrillation” is pioneered by the integration of flow-directed polymer phase separation into melt electrowriting and subsequent selective dissolution of the matrix polymer postprocessing. This process yields nanofiber bundles with a remarkable structural similarity to native collagen I fibers, particularly for medical-grade poly(ε-caprolactone). These biomimetic fibrillar structures indeed induce a pronounced elongation of human-monocyte-derived macrophages and unprecedentedly trigger their M2-like polarization similar in efficacy as interleukin-4 treatment.
The present study explored the origin of perceptual changes repeatedly observed in the context of actions. In Experiment 1, participants tried to hit a circular target with a stylus movement under restricted feedback conditions. We measured the perception of target size during action planning and observed larger estimates for larger movement distances. In Experiment 2, we then tested the hypothesis that this action specific influence on perception is due to changes in the allocation of spatial attention. For this purpose, we replaced the hitting task by conditions of focused and distributed attention and measured the perception of the former target stimulus. The results revealed changes in the perceived stimulus size very similar to those observed in Experiment 1. These results indicate that action's effects on perception root in changes of spatial attention.
SMART (Simple Modular Architecture Research Tool) is a web resource (https://smart.embl.de) for the identification and annotation of protein domains and the analysis of protein domain architectures. SMART version 9 contains manually curatedmodels formore than 1300 protein domains, with a topical set of 68 new models added since our last update article (1). All the new models are for diverse recombinase families and subfamilies and as a set they provide a comprehensive overview of mobile element recombinases namely transposase, integrase, relaxase, resolvase, cas1 casposase and Xer like cellular recombinase. Further updates include the synchronization of the underlying protein databases with UniProt (2), Ensembl (3) and STRING (4), greatly increasing the total number of annotated domains and other protein features available in architecture analysis mode. Furthermore, SMART's vector-based protein display engine has been extended and updated to use the latest web technologies and the domain architecture analysis components have been optimized to handle the increased number of protein features available.
A new Ru oligomer of formula {[Ru-\(^{II}\)(bda-\(\kappa\)-N\(^2\)O\(^2\))(4,4'-bpy)]\(_{10}\)(4,4'-bpy)}, 10 (bda is [2,2'-bipyridine]-6,6'-dicarbox-ylate and 4,4'-bpy is 4,4'-bipyridine), was synthesized and thoroughly characterized with spectroscopic, X-ray, and electrochemical techniques. This oligomer exhibits strong affinity for graphitic materials through CH-\(\pi\) interactions and thus easily anchors on multiwalled carbon nanotubes (CNT), generating the molecular hybrid material 10@CNT. The latter acts as a water oxidation catalyst and converts to a new species, 10'(H\(_2\)O)\(_2\)@CNT, during the electrochemical oxygen evolution process involving solvation and ligand reorganization facilitated by the interactions of molecular Ru catalyst and the surface. This heterogeneous system has been shown to be a powerful and robust molecular hybrid anode for electrocatalytic water oxidation into molecular oxygen, achieving current densities in the range of 200 mA/cm\(^2\) at pH 7 under an applied potential of 1.45 V vs NHE. The remarkable long-term stability of this hybrid material during turnover is rationalized based on the supramolecular interaction of the catalyst with the graphitic surface.