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Sonstige beteiligte Institutionen
- VolkswagenStiftung (24)
- Johns Hopkins School of Medicine (18)
- Fraunhofer-Institut für Silicatforschung ISC (8)
- IZKF Nachwuchsgruppe Geweberegeneration für muskuloskelettale Erkrankungen (7)
- Akademie der Wissenschaften und der Literatur, Mainz (6)
- DFG Forschungsgruppe 2757 / Lokale Selbstregelungen im Kontext schwacher Staatlichkeit in Antike und Moderne (LoSAM) (6)
- Clinical Trial Center (CTC) / Zentrale für Klinische Studien Würzburg (ZKSW) (5)
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- D-1221-2009 (1)
- D-1250-2010 (1)
- D-3057-2014 (1)
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- J-8841-2015 (1)
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Besides their central role in haemostasis and thrombosis, platelets are increasingly recognised as versatile effector cells in inflammation, the innate and adaptive immune response, extracellular matrix reorganisation and fibrosis, maintenance of barrier and organ integrity, and host response to pathogens. These platelet functions, referred to as thrombo-inflammation and immunothrombosis, have gained major attention in the COVID-19 pandemic, where patients develop an inflammatory disease state with severe and life-threatening thromboembolic complications. In the CRC/TR 240, a highly interdisciplinary team of basic, translational and clinical scientists explored these emerging roles of platelets with the aim to develop novel treatment concepts for cardiovascular disorders and beyond. We have i) unravelled mechanisms leading to life-threatening thromboembolic complica-tions following vaccination against SARS-CoV-2 with adenoviral vector-based vaccines, ii) identified unrecognised functions of platelet receptors and their regulation, offering new potential targets for pharmacological intervention and iii) developed new methodology to study the biology of megakar-yocytes (MKs), the precursor cells of platelets in the bone marrow, which lay the foundation for the modulation of platelet biogenesis and function. The projects of the CRC/TR 240 built on the unique expertise of our research network and focussed on the following complementary fields: (A) Cell bi-ology of megakaryocytes and platelets and (B) Platelets as regulators and effectors in disease. To achieve this aim, we followed a comprehensive approach starting out from in vitro systems and animal models to clinical research with large prospective patient cohorts and data-/biobanking. Despite the comparably short funding period the CRC/TR 240 discovered basic new mechanisms of platelet biogenesis, signal transduction and effector function and identified potential MK/platelet-specific molecular targets for diagnosis and therapy of thrombotic, haemorrhagic and thrombo-inflammatory disease states.
Humans actively interact with the world through a wide range of body movements. To understand human cognition in its natural state, we need to incorporate ecologically relevant body movement into our account. One fundamental body movement during daily life is natural walking. Despite its ubiquity, the impact of natural walking on brain activity and cognition has remained a realm underexplored.
In electrophysiology, previous studies have shown a robust reduction of ongoing alpha power in the parieto-occipital cortex during body movements. However, what causes the reduction of ongoing alpha, namely whether this is due to body movement or prevalent sensory input changes, was unknown. To clarify this, study 1 was performed to test if the alpha reduction is dependent on visual input. I compared the resting state alpha power during natural walking and standing, in both light and darkness. The results showed that natural walking led to decreased alpha activity over the occipital cortex compared to standing, regardless of the lighting condition. This suggests that the movement-induced modulation of occipital alpha activity is not driven by visual input changes during walking. I argue that the observed alpha power reduction reflects a change in the state of the subject based on disinhibition induced by walking. Accordingly, natural walking might enhance visual processing and other cognitive processes that involve occipital cortical activity.
I first tested this hypothesis in vision. Study 2 was performed to examine the possible effects of natural walking across visual processing stages by assessing various neural markers during different movement states. The findings revealed an amplified early visual response, while a later visual response remain unaffected. A follow-up study 3 replicated the walking-induced enhancement of the early visual evoked potential and showed that the enhancement was dependent on specific stimulus-related parameters (eccentricity, laterality, distractor presence). Importantly, the results provided evidence that the enhanced early visual responses are indeed linked to the modulation of ongoing occipital alpha power. Walking also modulated the stimulus-induced alpha power. Specifically, it showed that when the target appeared in the fovea area without a distractor, walking exhibited a significantly reduced modulation of alpha power, and showed the largest difference to standing condition. This effect of eccentricity indicates that during later visual processing stages, the visual input in the fovea area is less processed than in peripheral areas while walking.
The two visual studies showed that walking leads to an enhancement in temporally early visual processes which can be predicted by the walking-induced change in ongoing alpha oscillation likely marking disinhibition. However, while walking affects neural markers of early sensory processes, it does not necessarily lead to a change in the behavioural outcome of a sensory task. The two visual studies suggested that the behavioural outcome seems to be mainly based on later processing stages.
To test the effects of walking outside the visual domain, I turned to audition in study 4. I investigated the influence of walking in a particular path vs. simply stepping on auditory processing. Specifically, the study tested whether enhanced processing due to natural walking can be found in primary auditory brain activity and whether the processing preferences are dependent on the walking path. In addition, I tested whether the changed spatial processing that was reported in previous visual studies can be seen in the auditory domain. The results showed enhanced sensory processing due to walking in the auditory domain, which was again linked to the modulation of occipital alpha oscillation. The auditory processing was further dependent on the walking path. Additionally, enhanced peripheral sensory processing, as found in vision, was also present in audition.
The findings outside vision supported the idea of natural walking affecting cognition in a rather general way. Therefore in my study 5, I examined the effect of natural walking on higher cognitive processing, namely divergent thinking, and its correlation with the modulation of ongoing alpha oscillation. I analyzed alpha oscillations and behavioural performance during restricted and unrestricted movement conditions while subjects completed a Guilford's alternate uses test. The results showed that natural walking, as well as missing body restriction, reduces the occipital alpha ongoing power independent of the task phase which goes along with higher test scores. The occipital alpha power reduction can therefore be an indicator of a changed state that allows improved higher cognitive processes.
In summary, the research presented in this thesis highlights that natural walking can change different processes in the visual and auditory domain as well as higher cognitive processes. The effect can be attributed to the movement of natural walking itself rather than to changes in sensory input during walking. The results further indicate that the walking-induced modulation of ongoing occipital alpha oscillations drives the cognitive effects. We therefore suggest that walking changes the inhibitory state which can influence awareness and attention. Such a mechanism could facilitate an adaptive enhancement in cognitive processes and thereby optimize movement-related behaviour such as navigation.
Metaphors, Dead and Alive
(2023)
This paper examins how the medieval distinction between proper and improper signification can give a plausible explanation of both metaphorical use and the usual transformations a language can undergo. I will show how Thomas Aquinas distinguishes between ordinary ambiguous terms and metaphors, whereas William of Ockham and Walter Burley do not leave room for this distinction. I will argue that Ockham’s conception of transfer of sense through subsequent institution of words is best thought of as an explanation of how ordinary usage can contain ambiguities, whereas Burley’s conception of transfer of sense without new imposition is more plausible when it comes to explaining metaphors. If metaphorical use is lumped together with equivocation, the account of how they work cannot do full justice to either, an insight that we already find in Peter Abelard, if not in Boethius.
In diesem Beitrag wird zunächst das Konzept des digital storytelling mit dem Tablet im frühen Fremdsprachenunterricht methodisch-didaktisch gerahmt (Kapitel 1). Daran anschließend wird die Bedeutung lernunterstützender Maßnahmen in einem solchen digital gestützten und potenziell kreativitätsfördernden Unterrichtssetting erläutert (Kapitel 2). In Kapitel 3 folgt die Vorstellung der Unterrichtsreihe „It’s storytime – Let’s create our own digital fairy tale“. Im Verlauf dieser Unterrichtsreihe, die auch als Projektwoche angelegt werden kann, rezipieren die Schüler:innen zunächst eigenständig Märchen in englischer Sprache, die aus dem deutschen und angloamerikanischen Sprachraum bekannt sind. Die Märchen liegen für das Tablet multimedial aufbereitet vor. Anschließend entwickeln die Lernenden auf Grundlage des erarbeiteten gattungsspezifischen Wortschatzes ein eigenes multimediales Märchen. Alle für die Unterrichtsreihe benötigten digitalen und analogen Materialien stehen als Download zur Verfügung und können für den eigenen Unterricht genutzt und adaptiert werden.
Maihoff, Fabienne ; Sahler, Simone ; Schoger, Simon ; Brenzinger, Kristof ; Kallnik, Katharina ; Sauer, Nikki ; Bofinger, Lukas ; Schmitt, Thomas ; Nooten, Sabine S. ; Classen, Alice
Alpine bumble bees are the most important pollinators in temperate mountain ecosystems. Although they are used to encounter small-scale successions of very different climates in the mountains, many species respond sensitively to climatic changes, reflected in spatial range shifts and declining populations worldwide. Cuticular hydrocarbons (CHCs) mediate climate adaptation in some insects. However, whether they predict the elevational niche of bumble bees or their responses to climatic changes remains poorly understood. Here, we used three different approaches to study the role of bumble bees’ CHCs in the context of climate adaptation: using a 1,300 m elevational gradient, we first investigated whether the overall composition of CHCs, and two potentially climate-associated chemical traits (proportion of saturated components, mean chain length) on the cuticle of six bumble bee species were linked to the species’ elevational niches. We then analyzed intraspecific variation in CHCs of Bombus pascuorum along the elevational gradient and tested whether these traits respond to temperature. Finally, we used a field translocation experiment to test whether CHCs of Bombus lucorum workers change, when translocated from the foothill of a cool and wet mountain region to (a) higher elevations, and (b) a warm and dry region. Overall, the six species showed distinctive, species-specific CHC profiles. We found inter- and intraspecific variation in the composition of CHCs and in chemical traits along the elevational gradient, but no link to the elevational distribution of species and individuals. According to our expectations, bumble bees translocated to a warm and dry region tended to express longer CHC chains than bumble bees translocated to cool and wet foothills, which could reflect an acclimatization to regional climate. However, chain lengths did not further decrease systematically along the elevational gradient, suggesting that other factors than temperature also shape chain lengths in CHC profiles. We conclude that in alpine bumble bees, CHC profiles and traits respond at best secondarily to the climate conditions tested in this study. While the functional role of species-specific CHC profiles in bumble bees remains elusive, limited plasticity in this trait could restrict species’ ability to adapt to climatic changes.
Introduction: Grasslands cover one third of the agricultural area in Germany and are mainly used for fodder production. However, grasslands fulfill many other ecosystem functions, like carbon storage, water filtration and the provision of habitats. In Germany, grasslands are mown and/or grazed multiple times during the year. The type and timing of management activities and the use intensity vary strongly, however co-determine grassland functions. Large-scale spatial information on grassland activities and use intensity in Germany is limited and not openly provided. In addition, the cause for patterns of varying mowing intensity are usually not known on a spatial scale as data on the incentives of farmers behind grassland management decisions is not available.
Methods: We applied an algorithm based on a thresholding approach utilizing Sentinel-2 time series to detect grassland mowing events to investigate mowing dynamics in Germany in 2018–2021. The detected mowing events were validated with an independent dataset based on the examination of public webcam images. We analyzed spatial and temporal patterns of the mowing dynamics and relationships to climatic, topographic, soil or socio-political conditions.
Results: We found that most intensively used grasslands can be found in southern/south-eastern Germany, followed by areas in northern Germany. This pattern stays the same among the investigated years, but we found variations on smaller scales. The mowing event detection shows higher accuracies in 2019 and 2020 (F1 = 0.64 and 0.63) compared to 2018 and 2021 (F1 = 0.52 and 0.50). We found a significant but weak (R2 of 0–0.13) relationship for a spatial correlation of mowing frequency and climate as well as topographic variables for the grassland areas in Germany. Further results indicate a clear value range of topographic and climatic conditions, characteristic for intensive grassland use. Extensive grassland use takes place everywhere in Germany and on the entire spectrum of topographic and climatic conditions in Germany. Natura 2000 grasslands are used less intensive but this pattern is not consistent among all sites.
Discussion: Our findings on mowing dynamics and relationships to abiotic and socio-political conditions in Germany reveal important aspects of grassland management, including incentives of farmers.
Liu, Ruiqi ; Friedrich, Mike ; Hemmen, Katherina ; Jansen, Kerstin ; Adolfi, Mateus C. ; Schartl, Manfred ; Heinze, Katrin G.
Xiphophorus fish exhibit a clear phenotypic polymorphism in puberty onset and reproductive strategies of males. In X. nigrensis and X. multilineatus, puberty onset is genetically determined and linked to a melanocortin 4 receptor (Mc4r) polymorphism of wild-type and mutant alleles on the sex chromosomes. We hypothesized that Mc4r mutant alleles act on wild-type alleles by a dominant negative effect through receptor dimerization, leading to differential intracellular signaling and effector gene activation. Depending on signaling strength, the onset of puberty either occurs early or is delayed. Here, we show by Förster Resonance Energy Transfer (FRET) that wild-type Xiphophorus Mc4r monomers can form homodimers, but also heterodimers with mutant receptors resulting in compromised signaling which explains the reduced Mc4r signaling in large males. Thus, hetero- vs. homo- dimerization seems to be the key molecular mechanism for the polymorphism in puberty onset and body size in male fish.
Remde, Hanna ; Kranz, Stefanie ; Morell, Sarah Maria ; Altieri, Barbara ; Kroiss, Matthias ; Detomas, Mario ; Fassnacht, Martin ; Deutschbein, Timo
Background
Adrenal incidentalomas with cortisol autonomy are associated with increased cardiovascular morbidity and mortality. Specific data on the clinical and biochemical course of affected patients are lacking.
Methods
Retrospective study from a tertiary referral centre in Germany. After exclusion of overt hormone excess, malignancy and glucocorticoid medication, patients with adrenal incidentalomas were stratified according to serum cortisol after 1 mg dexamethasone: autonomous cortisol secretion (ACS), >5.0; possible ACS (PACS), 1.9-5.0; non-functioning adenomas (NFA), ≤1.8 µg/dl.
Results
A total of 260 patients were enrolled (147 women (56.5%), median follow-up 8.8 (2.0-20.8) years). At initial diagnosis, median age was 59.5 (20-82) years, and median tumour size was 27 (10-116) mm. Bilateral tumours were more prevalent in ACS (30.0%) and PACS (21.9%) than in NFA (8.1%). Over time, 40/124 (32.3%) patients had a shift of their hormonal secretion pattern (NFA to PACS/ACS, n=15/53; PACS to ACS, n=6/47; ACS to PACS, n=11/24; PACS to NFA, n=8/47). However, none of the patients developed overt Cushing’s syndrome. Sixty-one patients underwent adrenalectomy (NFA, 17.9%; PACS, 24.0%; ACS, 39.0%). When non-operated patients with NFA were compared to PACS and ACS at last follow-up, arterial hypertension (65.3% vs. 81.9% and 92.0%; p<0.05), diabetes (23.8% vs. 35.6% and 40.0%; p<0.01), and thromboembolic events (PACS: HR 3.43, 95%-CI 0.89-13.29; ACS: HR 5.96, 95%-CI 1.33-26.63; p<0.05) were significantly less frequent, along with a trend towards a higher rate of cardiovascular events in case of cortisol autonomy (PACS: HR 2.23, 95%-CI 0.94-5.32; ACS: HR 2.60, 95%-CI 0.87-7.79; p=0.1). Twenty-five (12.6%) of the non-operated patients died, with higher overall mortality in PACS (HR 2.6, 95%-CI 1.0-4.7; p=0.083) and ACS (HR 4.7, 95%-CI 1.6-13.3; p<0.005) compared to NFA. In operated patients, prevalence of arterial hypertension decreased significantly (77.0% at diagnosis to 61.7% at last follow-up; p<0.05). The prevalence of cardiovascular events and mortality did not differ significantly between operated and non-operated patients, whereas thromboembolic events were significantly less frequent in the surgical treatment group.
Conclusion
Our study confirms relevant cardiovascular morbidity in patients with adrenal incidentalomas (especially those with cortisol autonomy). These patients should therefore be monitored carefully, including adequate treatment of typical cardiovascular risk factors. Adrenalectomy was associated with a significantly decreased prevalence of hypertension. However, more than 30% of patients required reclassification according to repeated dexamethasone suppression tests. Thus, cortisol autonomy should ideally be confirmed before making any relevant treatment decision (e.g. adrenalectomy).
The transition to school is a key juncture in an individual’s educational trajectory, with far-reaching effects on the development of children and their families. Successful transitions require flexibility in the design of the transition process, addressing the needs of the persons involved in an adaptive manner. Adaptivity is also considered crucial for the success of inclusive transitions. However, a systematic breakdown of the aspects that characterize the concept of adaptivity in the context of inclusive school entry is not available at this point. This article therefore provides a conceptualization of adaptivity in the inclusive transition to school as well as a review of the current literature focusing this topic. The goal is to develop a model that structures the various aspects of adaptivity at school entry and offers an overview of the way these aspects are important to design the transition successfully according to current findings of empirical research. Building on a concept of transitions informed by ecological systems theory, we are guided by the assumption that adaptivity at transition to school may occur in three forms: as a feature of the persons involved in the transition; as a feature of the processes that moderate the course of the transition; and as a feature of the structures that frame the transition. Based on this distinction, we develop a model that presents adaptivity in the inclusive transition to school.
Providing adaptive, independence-preserving and theory-guided support to students in dealing with real-world problems in mathematics lessons is a major challenge for teachers in their professional practice. This paper examines this challenge in the context of simulations and mathematical modelling with digital tools: in addition to mathematical difficulties when autonomously working out individual solutions, students may also experience challenges when using digital tools. These challenges need to be closely examined and diagnosed, and might – if necessary – have to be overcome by intervention in such a way that the students can subsequently continue working independently. Thus, if a difficulty arises in the working process, two knowledge dimensions are necessary in order to provide adapted support to students. For teaching simulations and mathematical modelling with digital tools, more specifically, these knowledge dimensions are: pedagogical content knowledge about simulation and modelling processes supported by digital tools (this includes knowledge about phases and difficulties in the working process) and pedagogical content knowledge about interventions during the mentioned processes (focussing on characteristics of suitable interventions as well as their implementation and effects on the students’ working process). The two knowledge dimensions represent cognitive dispositions as the basis for the conceptualisation and operationalisation of a so-called adaptive intervention competence for teaching simulations and mathematical modelling with digital tools. In our article, we present a domain-specific process model and distinguish different types of teacher interventions. Then we describe the design and content of a university course at two German universities aiming to promote this domain-specific professional adaptive intervention competence, among others. In a study using a quasi-experimental pre-post design (N = 146), we confirm that the structure of cognitive dispositions of adaptive intervention competence for teaching simulations and mathematical modelling with digital tools can be described empirically by a two-dimensional model. In addition, the effectiveness of the course is examined and confirmed quantitatively. Finally, the results are discussed, especially against the background of the sample and the research design, and conclusions are derived for possibilities of promoting professional adaptive intervention competence in university courses.