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Here, we describe a new immersion-based clearing method suitable for optical clearing of thick adult human brain samples while preserving its lipids and lipophilic labels such as 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate (DiI). This clearing procedure is simple, easy to implement, and allowed for clearing of 5 mm thick human brain tissue samples within 12 days. Furthermore, we show for the first time the advantageous effect of the Periodate-Lysine-Paraformaldehyde (PLP) fixation as compared to the more commonly used 4% paraformaldehyde (PFA) on clearing performance.
Aging is a one-way process associated with profound structural and functional changes in the organism. Indeed, the neuromuscular system undergoes a wide remodeling, which involves muscles, fascia, and the central and peripheral nervous systems. As a result, intrinsic features of tissues, as well as their functional and structural coupling, are affected and a decline in overall physical performance occurs. Evidence from the scientific literature demonstrates that senescence is associated with increased stiffness and reduced elasticity of fascia, as well as loss of skeletal muscle mass, strength, and regenerative potential. The interaction between muscular and fascial structures is also weakened. As for the nervous system, aging leads to motor cortex atrophy, reduced motor cortical excitability, and plasticity, thus leading to accumulation of denervated muscle fibers. As a result, the magnitude of force generated by the neuromuscular apparatus, its transmission along the myofascial chain, joint mobility, and movement coordination are impaired. In this review, we summarize the evidence about the deleterious effect of aging on skeletal muscle, fascial tissue, and the nervous system. In particular, we address the structural and functional changes occurring within and between these tissues and discuss the effect of inflammation in aging. From the clinical perspective, this article outlines promising approaches for analyzing the composition and the viscoelastic properties of skeletal muscle, such as ultrasonography and elastography, which could be applied for a better understanding of musculoskeletal modifications occurring with aging. Moreover, we describe the use of tissue manipulation techniques, such as massage, traction, mobilization as well as acupuncture, dry needling, and nerve block, to enhance fascial repair.
Most fungal fatty acid synthases assemble from two multidomain subunits, α and β, into a heterododecameric FAS complex. It has been recently shown that the complex assembly occurs in a cotranslational manner and is initiated by an interaction between the termini of α and β subunits. This initial engagement of subunits may be the rate-limiting phase of the assembly and subject to cellular regulation. Therefore, we hypothesized that bypassing this step by genetically fusing the subunits could be beneficial for biotechnological production of fatty acids. To test the concept, we expressed fused FAS subunits engineered for production of octanoic acid in Saccharomyces cerevisiae. Collectively, our data indicate that FAS activity is a limiting factor of fatty acid production and that FAS fusion proteins show a superior performance compared to their split counterparts. This strategy is likely a generalizable approach to optimize the production of fatty acids and derived compounds in microbial chassis organisms.
Sphingosine 1-phosphate (S1P), derived from membrane sphingolipids, is a pleiotropic bioactive lipid mediator capable of evoking complex immune phenomena. Studies have highlighted its importance regarding intracellular signaling cascades as well as membrane-bound S1P receptor (S1PR) engagement in various clinical conditions. In neurological disorders, the S1P–S1PR axis is acknowledged in neurodegenerative, neuroinflammatory, and cerebrovascular disorders. Modulators of S1P signaling have enabled an immense insight into fundamental pathological pathways, which were pivotal in identifying and improving the treatment of human diseases. However, its intricate molecular signaling pathways initiated upon receptor ligation are still poorly elucidated. In this review, the authors highlight the current evidence for S1P signaling in neurodegenerative and neuroinflammatory disorders as well as stroke and present an array of drugs targeting the S1P signaling pathway, which are being tested in clinical trials. Further insights on how the S1P–S1PR axis orchestrates disease initiation, progression, and recovery may hold a remarkable potential regarding therapeutic options in these neurological disorders.
Deradicalization has become a priority agenda of Islamic education studies in the last few decades. This study aims to comprehensively understand the efforts to deradicalize Islamic Education conducted by the Annuqayah Islamic boarding school in Madura, East Java, Indonesia. Researchers used qualitative methods with a case study. Data collection was done through in-depth interviews, documentation studies, and observations. The results of this study found ten efforts at deradicalization conducted by Annuqayah Islamic boarding school, i.e. (1) Reactualization of learning resources; (2) Strengthening anti-radicalism; (3) Increasing literacy and discussion skills; (4) Strengthening the spirits of nationalism; (5) Promoting the principle of wasathiyah (moderatism); (6) Applying the theological concept of Ahlus-Sunnah wal Jama’ah (the group who perform the sunnah); (7) Initiating anti-radicalism curriculum; (8) Implementing progressive manhaj; (9) Formulating halaqa (meetings) with ulama; and (10) Empowering friendship and brotherhood. The implications of this research provided considerations in evaluating the curriculum, teaching materials, and teaching and learning process to support the creation of Islamic education institutions that promote peace, non-violence, and rahmatan lil alamin.
Ziel des Lehr-Lern-Projektes war die Schaffung einer kollegialen Arbeitsgemeinschaft zwischen Lehramtsstudierenden der hochschulischen Ausbildungsphase und bereits im Beruf etablierten Lehrkräften im Fachbereich Geschichte. Traditionell hierarchische Strukturen wurden aufgebrochen, um die jeweiligen Kompetenzen der Teilnehmenden für beide Seiten gewinnbringend zu vereinen. Anders als in den hochschulischen Praktika treten Lehramtsstudierende den Lehrkräften mit Expertise gegenüber: Der Austausch ist daher weniger einseitig als vielmehr von doppelseitigem Nutzen. Dieses Konzept bietet im Sinne einer community of practice nicht nur den Lehramtsstudierenden die Chance, ihr theoretisch erworbenes Wissen praxisorientiert anzuwenden und zu reflektieren, sondern ermöglicht auch den Lehrkräften, an den aktuellen geschichtsdidaktischen Forschungen und Entwicklungen an den Hochschulen teilzuhaben und mithilfe der Studierenden in der eigenen Schulpraxis zu reflektieren und gegebenenfalls anzuwenden. Anliegen des Lehr-Lern-Projektes ist ein Plädoyer, das Potenzial der Hochschulen über die eigenen Studierenden im Fortbildungsbereich der Lehrkräfte gewinnbringend zu nutzen, die schulische Reichweite von fachdidaktischer For-schung auszuschöpfen und den Lehramtsstudierenden zugleich eine weitere Möglichkeit einer schulpraktischen Erfahrung zu bieten. Nicht zuletzt: Die Verzahnung von Ausbildungs- und Weiterbildungsphase ist eine weitere gewinnbringende Möglichkeit, Akteur*innen der Lehrer*innenbildung in einen gewinnbringenden und praxisnahen Dialog zu bringen.
Does the Polish development concern us — the European citizens and the European institutions we have set up? There is a functional and a normative argument to state that it does. The normative argument is that the European Union organizes a community of states that profess allegiance to a set of fundamental values—among others, democracy, the rule of law, and human rights. The functional reason is that the European legal space presupposes mutual trust. European law operates on the presumption that all institutions are law-abiding. Otherwise, the legal edifice crumbles.
Background: A growing number of studies are questioning the validity of current DSM diagnoses, either as "discrete" or distinct mental disorders and/or as phenotypically homogeneous syndromes. In this study, we investigated how symptom domains in patients with a main diagnosis of obsessive-compulsive disorder (OCD), panic disorder (PD) and social anxiety disorder (SAD) coaggregate. We predicted that symptom domains would be unrelated to DSM diagnostic categories and less likely to cluster with each other as severity increases.
Methods: One-hundred eight treatment seeking patients with a main diagnosis of OCD, SAD or PD were assessed with the Dimensional Obsessive-Compulsive Scale (DOCS), the Social Phobia Inventory (SPIN), the Panic and Agoraphobia Scale (PAS), the Anxiety Sensitivity Index-Revised (ASI-R), and the Beck Depression and Anxiety Inventories (BDI and BAI, respectively). Subscores generated by each scale (herein termed "symptom domains") were used to categorize individuals into mild, moderate and severe subgroups through K-means clusterization and subsequently analysed by means of multiple correspondence analysis.
Results: Broadly, we observed that symptom domains of OCD, SAD or PD tend to cluster on the basis of their severities rather than their DSM diagnostic labels. In particular, symptom domains and disorders were grouped into (1) a single mild "neurotic" syndrome characterized by multiple, closely related and co-occurring mild symptom domains; (2) two moderate (complicated and uncomplicated) "neurotic" syndromes (the former associated with panic disorder); and (3) severe but dispersed "neurotic" symptom domains.
Conlusion: Our findings suggest that symptoms domains of treatment seeking patients with OCD and anxiety disorders tend to be better conceptualized in terms of severity rather than rigid diagnostic boundaries.
The application of the EU Commission’s Rule of Law Framework in the current Polish case is a step in the right direction. It seems a good instance to develop the Framework as an EU mechanism to protect European constitutional values in a European legal space which is rife with constitutional crises, but short of instruments to address them. Its pertinence appears even more clearly in comparison to the Council’s (in)activity under its own rule-of-law mechanism, hastily put forward after the Commission’s Framework. The activation of the Framework has shown its potential to mobilize European public opinion and orient public discourses to the current condition of EU values