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Das deutsche Open Science Festival geht in die dritte Runde und wird am 17. und 18. September 2024 an der Johannes Gutenberg-Universität Mainz stattfinden. In den Räumen der Musikhochschule bietet das Festival den Teilnehmenden die Gelegenheit, die Vielfalt und Bedeutung von Open Science zu entdecken und zu erleben.
Im Wintersemester 2022/23 wurde die dritte universitätsweite Studierendenbefragung durchgeführt, die für Studierende ein wichtiges Instrument der Partizipation an der Qualitätsentwicklung in Studium und Lehre ist. Aus diesem Grund gebührt den 7765 Studierenden, die den umfassenden Fragebogen mit 314 Basisfragen sowie zusätzlichen fachbereichsspezifischen Fragen beantwortet haben, besonderer Dank. Die Ergebnisse der Befragung können in den Berichten auf www.studierendenbefragung.uni-frankfurt.de nachgelesen werden.
Der unter der Ägide der Freunde und Förderer der Goethe-Universität von der Paul Ehrlich-Stiftung ausgelobte Paul Ehrlich-und-Ludwig Darmstaedter-Preis ist die renommierteste Auszeichnung, die in Deutschland für medizinische Forschung verliehen wird. Den mit 120.000 Euro dotierten Preis nahm in der Frankfurter Paulskirche in diesem Jahr der Arzt und Immunologe Prof. Dennis L. Kasper (81) von der Harvard Medical School entgegen. Er hat die ersten Wörter der biochemischen Sprache entdeckt, mit der Darmbakterien unserem Immunsystem zu einer gesunden Entwicklung verhelfen. Den mit 60.000 Euro dotierten Nachwuchspreis erhielt der Chemiker Dr. Johannes Karges (31) von der Ruhr-Universität Bochum für die Entwicklung eines Verfahrens zur ferngesteuerten Tumortherapie.
Das erziehungswissenschaftliche Projekt »InterCare« will erforschen, wie junge Menschen die Doppelbelastung von Ausbildung/Studium und Pflege bewältigen. Offizieller Start des Projekts, das über vier Jahre hinweg mit 1,2 Millionen Euro von der VolkswagenStiftung gefördert wird, ist im Oktober 2024. Die Soziologin und Altersforscherin Dr. Anna Wanka koordiniert InterCare und erläutert das Design des Projekts.
Über einen Schriftsteller und seinen Körper : Aris Fioretos wird neuer Frankfurter Poetikdozent
(2024)
Um den eigenen Beitrag zur sozial-ökologischen Transformation zu konkretisieren, entwickelt die Goethe-Universität in den kommenden Monaten eine Nachhaltigkeitsstrategie. Die Strategie soll klare Ziele, Maßnahmen und Verantwortlichkeiten definieren und das Bewusstsein für Nachhaltigkeit an der Universität, aber auch darüber hinaus, stärken.
Wie kommen Wissenschaft und Praxis zueinander? Unter dem Motto »Bridging the gap« stellte das Forschungsinstitut Gesellschaftlicher Zusammenhalt (FGZ) am 25. April auf einem Festival neue Formate der Wissenschaftskommunikation vor. Der UniReport sprach mit den FGZ-Referenten für Wissenstransfer Katja Maasch und Manuel Steinert.
Lifestyle factors—such as diet, physical activity (PA), smoking, and alcohol consumption—have a significant impact on mortality as well as healthcare costs. Moreover, they play a crucial role in the development of type 2 diabetes mellitus (DM2). There also seems to be a link between lifestyle behaviours and insulin resistance, which is often a precursor of DM2. This study uses an enhanced Healthy Living Index (HLI) integrating accelerometric data and an Ecological Momentary Assessment (EMA) to explore differences in lifestyle between insulin-sensitive (IS) and insulin-resistant (IR) individuals. Moreover, it explores the association between lifestyle behaviours and inflammation. Analysing data from 99 participants of the mPRIME study (57 women and 42 men; mean age 49.8 years), we calculated HLI scores—ranging from 0 to 4— based on adherence to specific low-risk lifestyle behaviours, including non-smoking, adhering to a healthy diet, maximally moderate alcohol consumption, and meeting World Health Organization (WHO) PA guidelines. Insulin sensitivity was assessed using a Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) and C-reactive protein (CRP) levels were used as a proxy for inflammation. Lifestyle behaviours, represented by HLI scores, were significantly different between IS and IR individuals (U = 1529.0; p = 0.023). The difference in the HLI score between IR and IS individuals was mainly driven by lower adherence to PA recommendations in the IR group. Moreover, reduced PA was linked to increased CRP levels in the IR group (r = −0.368, p = 0.014). Our findings suggest that enhancing PA, especially among individuals with impaired insulin resistance, holds significant promise as a preventive strategy.
leporello #21
(2024)
MicroRNAs (miRNAs) are critical post-transcriptional regulators in many biological processes. They act by guiding RNA-induced silencing complexes to miRNA response elements (MREs) in target mRNAs, inducing translational inhibition and/or mRNA degradation. Functional MREs are expected to predominantly occur in the 3’ untranslated region and involve perfect base-pairing of the miRNA seed. Here, we generate a high-resolution map of miR-181a/b-1 (miR-181) MREs to define the targeting rules of miR-181 in developing murine T-cells. By combining a multi-omics approach with computational high-resolution analyses, we uncover novel miR-181 targets and demonstrate that miR-181 acts predominantly through RNA destabilization. Importantly, we discover an alternative seed match and identify a distinct set of targets with repeat elements in the coding sequence which are targeted by miR-181 and mediate translational inhibition. In conclusion, deep profiling of MREs in primary cells is critical to expand physiologically relevant targetomes and establish context-dependent miRNA targeting rules.
Key Points:
* Deep profiling identifies novel targets of miR-181 associated with global gene regulation.
* miR-181 MREs in repeat elements in the coding sequence act through translational inhibition.
* High-resolution analysis reveals an alternative seed match in functional MREs.
Here, we introduce racoon_clip, a sustainable and fully automated pipeline for the complete processing of iCLIP and eCLIP data to extract RNA binding signal at single-nucleotide resolution. racoon_clip is easy to install and execute, with multiple pre-settings and fully customizable parameters, and outputs a conclusive summary report with visualizations and statistics for all analysis steps.
This paper examines the dynamic relationship between firm leverage and risktaking. We embed the traditional agency problem of asset substitution within a multi-period model, revealing a U-shaped relationship between leverage and risktaking, evident in data from both the U.S. and Europe. Firms with medium leverage avoid risk to preserve the option of issuing safe debt in the future. This option is valuable because safe debt does not incur the expected cost of bankruptcy, anticipated by debt-holders due to future risk-taking incentives. Our model offers new insights on the interaction between companies' debt financing and their risk profiles.
Cross-predictability denotes the fact that some assets can predict other assets' returns. I propose a novel performance-based measure that disentangles the economic value of cross-predictability into two components: the predictive power of one asset's signal for other assets' returns (cross-predictive signals) and the amount of an asset's return explained by other assets' signals (cross-predicted returns). Empirically, the latter component dominates the former in the overall cross-prediction effects. In the crosssection, cross-predictability gravitates towards small firms that are strongly mispriced and difficult to arbitrage, while it becomes more difficult to cross-predict returns when market capitalization and book-to-market ratio rise.
How can older adults participate equally in digitisation processes across Europe, and what inclusive research strategies are needed? This Zine summarizes findings from a “Research Innovation Lab on Ageing in a Digital Age”, funded by the VolkswagenStiftung, aiming to bring together 29 docs and postdocs anchored in 26 different disciplines coming from 11 countries, at all stages of their work, to address cutting edge questions relating to ageing in a digital age. Five groups worked together over five days in Frankfurt, Germany, in July 2023 in a creative and interactive hackathon, specific to developing non-technical solutions to social issues of this topic. Moreover, four distinguished experts presented keynote speeches and proposals from various conceptual, methodological and empirical perspectives.
Finanzielle Armut prägt Mobilitätspraktiken und kann dabei zum Prozess von mobilitätsbezogener sozialer Exklusion beitragen. Zu den Personen, deren Armutsrisiko besonders hoch ist, zählen in Deutschland Haushalte mit Kindern, insbesondere Alleinerziehende. Ältere Menschen haben nicht die höchste Armutsgefährdung, jedoch besteht bei ihnen das Risiko von Verharrung in Armut, da die Möglichkeiten, die finanzielle Situation aus eigener Kraft zu ändern mit zunehmendem Alter sinken.
Um ein tieferes Verständnis davon zu erhalten, wie finanzielle Armut die Mobilitätspraktiken und soziale Teilhabe von Haushalten mit Kindern sowie älteren Menschen prägt, wurden mit diesen beiden Personengruppen problemzentrierte Interviews in Ronnenberg (Region Hannover) geführt und analysiert. Die Ergebnisse belegen, dass, wenngleich alle Befragten mit ähnlich geringen finanziellen Ressourcen haushalten und Verzicht sowie Abwägungsprozesse notwendig sind, sich ihre Mobilitätspraktiken und Alltagsbewältigungsstrategien unterscheiden, was sich in zwei Typologien widerspiegelt. Erstens, eine Typologie der Mobilitätspraktiken von Haushalten mit Kindern: (i) autozentriert, (ii) autoreduziert, (iii) ÖPNV-orientiert und (iv) nichtmotorisiert. Zweitens, eine Typologie älterer Menschen anhand ihrer Mobilitätspraktiken: (i) aktive ältere Menschen mit vielseitigen sozialen Interaktionen, (ii) nachbarschaftsorientierte ältere Menschen mit lokalen Kontakten und (iii) ältere Menschen, die überwiegend zu Hause sind und wenig soziale Kontakte haben.
Um herauszufinden, inwiefern mobilitätsbezogene Barrieren der sozialen Teilhabe reduziert werden können, wurden fünf Maßnahmen bezüglich ihrer Wirkung auf die Mobilitätspraktiken einkommensarmer Haushalte mit Kindern untersucht: einerseits die Wirkung des 9-Euro-Tickets anhand von problemzentrierten Interviews mit einkommensarmen Haushalten mit Kindern, andererseits anhand von Expert:inneninterviews die Wirkung von Radlernkursen für Frauen mit Migrationshintergrund, eines Mietertickets, eines Quartierstickets und der Verbesserung der Nahraum- und Aufenthaltsqualität am Beispiel von Tempo 30. Die Ergebnisse zum 9-Euro-Ticket belegen, dass ein erschwingliches ÖPNV-Ticket erheblich zur Reduzierung mobilitätsbezogener Barrieren der sozialen Teilhabe im Armutskontext beiträgt. Die Expert:inneninterviews zeigen auf, dass eine Förderung des Umweltverbunds zielführend ist, um zu einer sozial-ökologischen Verkehrswende beizutragen und insbesondere Maßnahmenbündel Wirkung auf die Reduzierung von mobilitätsbezogenen Barrieren der sozialen Teilhabe entfalten.
Die Erkenntnisse dieser Dissertation ergänzen den wissenschaftlichen Forschungstand um ein tiefergehendes Verständnis der Wirkung von finanzieller Armut auf die Mobilitätspraktiken und soziale Teilhabe von Haushalten mit Kindern und älteren Menschen und helfen dabei, Maßnahmen zur Reduzierung mobilitätsbezogener Barrieren der sozialen Teilhabe zu konzipieren und umzusetzen.
Neurodevelopmental psychiatric disorders (NPDs) like attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and schizophrenia, affect millions of people worldwide. Despite recent progress in NPD research, much remains to be discovered about their underpinnings, therapeutic targets, effects of biological sex and age. Risk factors influencing brain development and signalling include prenatal inflammation and genetic variation. This dissertation aimed to build upon these findings by combining behavioural, molecular, and neuromorphological investigations in mouse models of such risk factors, i.e. maternal immune activation (MIA), neuron-specific overexpression (OE) of the cytoplasmatic isoforms of the RNA-binding protein RBFOX1, and neuronal deletion of the small Ras GTPase DIRAS2.
Maternal infections during pregnancy pose an increased risk for NPDs in the offspring. While viral-like MIA has been previously established elsewhere, this study was the first in our institution to implement the model. I validated NPD-relevant deficits in anxiety- and depression-like behaviours, as well as dose- and sex-specific social deficits in mouse offspring following MIA in early gestation. Proteomic analyses in embryonic and adult hippocampal (HPC) synaptoneurosomes highlighted novel and known targets affected by MIA. Analysis of the embryonic dataset implicated neurodevelopmental disruptions of the lipid, polysaccharide, and glycoprotein metabolism, important for proper membrane function, signalling, and myelination, for NPD-pertinent sequelae. In adulthood, the observed changes encompassed transmembrane trafficking and intracellular signalling, apoptosis, and cytoskeletal organisation pathways. Importantly, 50 proteins altered by MIA in embryonic and adult HPC were enriched in the NPD-relevant synaptic vesicle cycle. A persistently upregulated protein cluster formed a functional network involved in presynaptic signalling and proteins downregulated in embryos but upregulated in adults by MIA were correlated with observed social deficits. 49/50 genes encoding these proteins were significantly associated with NPD- and comorbidity-relevant traits in human phenome-wise association study data for psychiatric phenotypes. These findings highlight NPD-relevant targets for future study and early intervention in at-risk individuals. MIA-evoked changes in the neuroarchitecture of the NPD-relevant HPC and prefrontal cortex (PFC) of male and female mice highlighted sex- and region-specific alterations in dendritic and spine morphology, possibly underlining behavioural phenotypes.
To further investigate genetic risk factors of NPDs, I performed a study based on the implications of RBFOX1’s pleiotropic role in neuropsychiatric disorders and previous preclinical findings. Cytoplasmatic OE of RBFOX1, which affects the stability and translation of thousands of targets, was used to disseminate its role in morphology and behaviour. RBFOX1 OE affected dendritic length and branching in the male PFC and led to spine alterations in both PFC and HPC. Due to previously observed ASD-like endophenotypes in our Rbfox1 KO mice and the importance of gene × environment effects on NPD susceptibility, I probed the interaction of cytoplasmatic OE and a low-dose MIA on offspring. Both RBFOX1 OE alone and with MIA led to increased offspring loss during the perinatal period. Preliminary data suggested that RBFOX1 OE × MIA might increase anxiety- and anhedonia-like behaviours. Morphological changes in the adult male OE HPC and PFC suggested increased spine density and reduced dendritic complexity. A small post-mortem study in human dorsolateral PFC of older adults did not reveal significant effects of a common risk variant on RBFOX1 abundance.
To expand upon NPD genetic risks, I evaluated the effects of a homo- (KO) or heterozygous (HET) Diras2 deletion in a novel, neuron-specific mouse model. DIRAS2’s function is largely unknown, but it has been associated with ADHD in humans and neurodevelopment in vitro. In adult mice, there were subtle sex-specific effects on behaviour, i.e. more pronounced NPD-relevant deficits in males, in keeping with human data. KO mice had subtly improved cognitive performance, while HET mice exhibited behaviours in line with core ADHD symptoms, e.g. earning difficulties (females), response inhibition deficits and hyperactivity (males), suggesting Diras2 dose-sensitivity and sex-specificity. The morphological findings revealed multiple aberrations in dendritic and spine morphology in the adult PFC, HPC, and amygdala of HET males. KOs changes in spine and dendritic morphology were exclusively in the PFC and largely opposite to those in HETs and NPD-like phenotypes. Region- and genotype-specific expression changes in Diras2 and Diras1 were observed in six relevant brain regions of adult HET and KO females, also revealing differences in the survival and morphology regulator mTOR, which might underlie observed differences.
In conclusion, the effects of MIA and partial Diras2 knockdown resembled each other in core, NPD-associated behavioural and morphological phenotypes, while cytoplasmatic RBFOX1 OE and full Diras2 KO differed from those. My findings suggest complex dose- and sex-dependent relationships between these prenatal and genetic interventions, whose NPD-relevant influences might converge onto neurodevelopmental molecular pathways. An assessment of such putative overlap, based on available data from the MIA proteomic analyses of embryonic and adult HPC, suggested the three models might be linked via downstream targets, interactions, and upstream regulators. Future studies should disseminate both distinct and shared aspects of MIA, RBFOX1, and DIRAS2 relevant to NPDs and build upon these findings.
Research on the human and animal microbiome has become increasingly important in recent years. It is now widely accepted the gut microbiome is of crucial importance to health, as it is involved in a large number of physiological processes. The term ‘microbiome’ refers to the all living microorganisms including their genes and metabolites in a defined environment, while the specific composition of microorganisms consisting of bacteria, archaea and protozoa is referred to as the ‘microbiota’ (Lane-Petter, 1962; Lederberg and McCray, 2001).
In recent years, research has focused on various of these communities in the soil (Fierer, 2017), water (Sunagawa et al., 2015), air (Leung et al., 2014) and especially in the human gut. However, this topic is also becoming increasingly relevant for the conservation of endangered species. In the face of global mass extinctions and the listing of over 42,000 animal species as ‘critically endangered’, conservation breeding programmes are more important than ever (Díaz et al., 2019; IUCN, 2022). The responsibility for these tasks lies with zoological institutions, which are dedicated to animal conservation and the continuous monitoring of animal welfare. Microbiome research offers a non-invasive method to support species conservation. By analysing faecal samples, microbial markers can be identified that provide important information about the health status and reproductive cycle of animals (Weingrill et al., 2004; Antwis et al., 2019). Zoological facilities also provide an ideal research environment for comparing individuals from different habitats. In addition, all necessary metadata such as age, sex, kinship or medical treatment are documented and can be used for the analysis.
This is the starting point for this thesis. In order to identify such microbial markers, it is necessary to understand the microbiome of a variety of animal species. The first aim is therefore to characterise the faecal microbiota of 31 mammalian species, focusing on herbivores and carnivores. It could be shown that they differ significantly in terms of both microbial diversity and microbiota composition. Herbivorous species express a very diverse microbial composition, consisting mainly of cellulose-degrading taxa of the families Fibrobacteraceae or Spirochaetaceae. In contrast, the microbiota of carnivorous species is less diverse and is dominated by protein-degrading Fusobacteriaceae and Clostridiaceae. In addition, this thesis proves that the microbiota of herbivorous species is highly consistent, whereas the microbiota of carnivorous species is highly variable. The results of this study provide important insights for the sampling scheme of future projects. Especially when analysing carnivorous species, single samples are not sufficient to capture the full variability of the microbiome.
These results lead to the question of whether this variability can be explained by daily fluctuations in the individual microbiome and whether this can be used to distinguish between species or individuals. Using individual longitudinal data and a combined approach of clustering algorithms and dynamic time warping, it is shown that such a distinction is possible at the species and individual level. This was confirmed for both a carnivorous (Panthera tigris) and a herbivorous (Connochaetes taurinus) species. These results confirm the influence of the host individual on the faecal microbiota, in addition to the often described influence of diet (Ley et al., 2008a; Kartzinel et al., 2019).
Based on the knowledge gained from these studies, a methodology has been developed that will enable the conservation of species in the field to be supported by microbiome research in the future. The focus here lays on the identification of host-specific metadata based on the faecal microbiota. The developed regression model is able to distinguish between carnivorous, herbivorous and omnivorous hosts with up to 99% accuracy. In addition, a more accurate phylogenetic classification of the family (Canidae, Felidae, Ursidae, Herpestidae) can be made for carnivorous hosts. For herbivorous hosts, the model can predict the respective digestive system with up to 100% accuracy, distinguishing between ruminants, hindgut fermenters and a simple digestive system. The acquisition of host-specific metadata from an unknown faecal sample is an important step towards establishing microbiome research in species conservation. Field studies in particular will benefit from such new methods. Usually, costly microsatellite analysis and high-quality host DNA are required to obtain host-specific information from faecal samples. The newly developed method offers a less costly and labour-intensive alternative to conventional techniques and opens up a more accessible field for microbiome research in the field.