48674 research outputs found
Sort by
Evolution of the IgE response to the house dust mite allergen Der p 23 from birth to the age of 20 years and its clinical implications
No full textHintergrund: Hausstaubmilben, insbesondere Dermatophagoides pteronyssinus (D.pt.)
und Dermatophagoides farinae, stellen eine der häufigsten Ursachen für ganzjährige
respiratorische allergische Erkrankungen dar. Innerhalb der Spezies D.pt. wurde vor
einigen Jahren das Molekül Der p 23 identifiziert und nachfolgend als Majorallergen
klassifiziert. In Querschnittsstudien konnte bereits eine Assoziation des Moleküls zu
allergischen Erkrankungen aufgezeigt werden.
Zielsetzung: Ziel dieser Arbeit ist die detaillierte Untersuchung der IgE-vermittelten
Sensibilisierung gegen Der p 23 in Hinblick auf die zeitliche Entwicklung, potenzielle
Risikofaktoren und die Assoziation zu klinischen allergischen Erkrankungen (Asthma,
Allergische Rhinitis, Atopische Dermatitis) in einer longitudinalen Studie.
Methodik: Im Rahmen der Multizentrischen Allergiestudie (MAS) wurden über einen
Zeitraum von 20 Jahren, beginnend ab Geburt, Daten innerhalb einer prospektiven
Geburtskohorte ermittelt. In die aktuelle Arbeit wurden 191 Proband*innen mit
Sensibilisierung gegen D.pt.-Extrakt eingeschlossen. Nachfolgend wurden alle
Serumproben mit positivem sIgE gegen Der p 23 in einem semiquantitativen Microarray
(ImmunoCAP ISAC) mittels quantitativem Singleplex-Assay auf Der p 23-sIgE
untersucht (ImmunoCAP 100). Für die statistischen Berechnungen wurden zusätzlich
Daten aus der MAS-Datenbank genutzt.
Ergebnisse: 51% der 191 Proband*innen mit Milbensensibilisierung wiesen eine
Sensibilisierung gegen Der p 23 auf. Eine hohe frühkindliche Milbenexposition sowie
Atopische Dermatitis im Kleinkindalter schienen als Risikofaktoren eine Rolle zu
spielen. In 46% begann die Sensibilisierung gegen Der p 23 bereits vor dem Alter von
10 Jahren, wo sie ein Maximum erreichte und unabhängig vom Zeitpunkt der initialen
Sensibilisierung mit zunehmendem Alter abnahm. Bei 11 Proband*innen konnte
innerhalb der Spezies D.pt. eine monomolekulare Sensibilisierung gegen Der p 23
beobachtet werden. Diese Proband*innen wiesen im Vergleich zu den Proband*innen
mit polymolekularer Milbensensibilisierung deutlich geringere IgE-Konzentrationen
gegen das Milbenextrakt bei hohen Der p 23-sIgE-Konzentrationen auf. Die Prävalenz
respiratorischer allergischer Erkrankungen war signifikant erhöht in der Gruppe mit Der
p 23-Sensibilisierung, dabei stieg die Prävalenz von Asthma nach initialer Der p 23-
Sensibilisierung deutlich an.
Schlussfolgerung: Der p 23 ist ein bedeutendes Milbenallergen mit Assoziation zu
allergischen Erkrankungen wie Asthma und Allergischer Rhinitis, dessen
Sensibilisierung durch frühkindliche Milbenexposition oder Atopische Dermatitis
begünstigt werden kann. In Milbenextrakten scheint das Molekül unterrepräsentiert zu
sein. Bei Verdacht auf eine Milbenallergie trotz negativer sIgE-Antworten gegen das
Milbenextrakt oder die beiden anderen Majorallergene Der p 1 und Der p 2 sollte an
eine Der p 23-Monosensibilisierung gedacht und die Diagnostik entsprechend erweitert
werden.Background: House dust mites, especially Dermatophagoides pteronyssinus (D.pt.) and Dermatophagoides farinae, represent one of the most common causes of perennial respiratory allergic diseases. Within the species D.pt, the molecule Der p 23 was identified several years ago and subsequently classified as a major allergen. An association of the molecule to allergic diseases has been shown in cross-sectional studies.
Objective: The aim of this longitudinal study is the detailed investigation of the IgE-mediated sensitisation to Der p 23 regarding its evolution over time, potential risk factors and association with allergic diseases, such as asthma, allergic rhinitis and atopic dermatitis.
Methods: Within the German Multicentre Allergy Study (MAS), clinical and serological data were collected within a birth cohort over a period of 20 years, from birth onwards. In the current work, 191 subjects with sensitisation to mite extract were included. Subsequently, all serum samples with positive sIgE against Der p 23 in a semiquantitative microarray (ImmunoCAP ISAC) were analysed for Der p 23-sIgE with a quantitative singleplex assay (ImmunoCAP 100). Additional data from the MAS database was used for statistical calculations.
Results: 51% of the 191 subjects with mite sensitisation were sensitised to Der p 23. High exposure to mites and atopic dermatitis in infancy seemed to play a role as risk factors. Sensitisation to Der p 23 started in 46% before the age of 10, when it reached a maximum and decreased to minimal values at 20 years, independent of the time of initial sensitisation. In 11 subjects, monomolecular sensitisation against Der p 23 (within the species D.pt.) was observed. Compared to the subjects with polymolecular mite sensitisation, these subjects showed significantly lower IgE concentrations to the mite extract, yet had high Der p 23-sIgE concentrations. The prevalence of respiratory allergic diseases was significantly increased in the group with Der p 23 sensitisation, with a significant increase in the prevalence of asthma after initial Der p 23 sensitisation.
Conclusion: Der p 23 is a major mite allergen associated with allergic diseases such as asthma and allergic rhinitis. Its sensitisation may be promoted by early childhood mite exposure and atopic dermatitis. The molecule appears to be underrepresented in mite extracts. Therefore, if mite allergy is suspected despite negative sIgE responses to the mite extract or the other two major allergens Der p 1 and Der p 2, monomolecular sensitisation to Der p 23 should be considered and the diagnostic algorithm should be extended accordingly
Deep learning, deeper relief: pipeline toward tailored analgesia for experimental animal models
No full textEffective pain management in animal models is crucial for maintaining ethical and scientific integrity. However, commonly used analgesics may affect immune responses and disturb signaling pathways, thereby potentially confounding the experimental outcomes. In mouse colitis models, opioids and non-steroidal anti-inflammatory drugs have been shown to interfere with the immune response and the activation of the central regulator of inflammation, the transcription factor nuclear factor kappa B (NF-κB). Here, we propose a tailored pipeline for the identification and the validation of analgesics with minimal off-target effects. This approach combines protein-centered relation extraction using deep language models and distant supervision via the Protein-Centered Association Extraction with Deep Language (PEDL + ) together with an in vivo experimental validation with a NF-κB reporter mouse model that enables unambiguous visualization of direct NF-κB activity across different tissues. Our findings indicate that commonly used analgesics, such as tramadol and acetaminophen, not only interfere with immune cell recruitment and NF-κB activation but also skew the differentiation of epithelial stem cells into goblet cells, affecting epithelial functions even after short exposures. Conversely, the analgesics selected by our PEDL + -based workflow, such as piritramide, demonstrated no significant interference with NF-κB signaling. To validate our findings in vivo , we treated our NF-κB reporter mice with the analgesics selected by our computational pipeline. Amantadine demonstrated the least impact on the inflammatory responses and NF-κB activation. We then predicted and identified the signaling pathways that are impacted by amantadine treatment. In summary, our proposed pipeline facilitates a shift from one-size-fits-all analgesics to a precision medicine approach that considers the unique molecular interactions associated with each model
Brain tumors induce widespread disruption of calvarial bone and alteration of skull marrow immune landscape
No full textThe skull marrow niche has recently been identified as a reservoir that supplies the brain with monocytes and neutrophils in the context of disease and injury, but its role in brain cancers remains unknown. Here we show that glioblastoma, the most malignant type of brain tumor, induces calvarial bone abnormalities in murine models and patients with glioblastoma, altering osteoclast activities and increasing the number of skull channels in mice. Single-cell RNA sequencing revealed glioblastoma-mediated alterations in the immune landscape of skull marrow and femoral bone marrow, including expansion of neutrophils and deterioration of various B cell subsets. In vivo inhibition of bone resorption reduced bone abnormalities, but promoted tumor progression in mesenchymal subtype tumors. This also abolished the survival benefit of the checkpoint inhibitor anti-PD-L1, by reducing activated T cell and increasing inflammatory neutrophil numbers. Together, these data provide insight into how brain tumors affect skull bone and the immune environment
Kritische und superkritische singuläre S(P)DGs: Ein probabilistischer Ansatz
No full textThis thesis studies singular stochastic (partial) differential equations in particular in the
scaling-critical and -supercritical regime.
In the first chapter, we show well-posedness of energy solutions to stochastic differential equations (SDEs) driven by Brownian motion and supercritical distributional drifts, both in the periodic setting and on the full space. Energy solutions are certain martingale problems which describe singular stochastic partial differential equations (SPDEs) and we employ this theory in the finite-dimensional setting to show existence of solutions. We further analyze the corresponding Kolmogorov backward equation (KBE) via PDE and semigroup techniques and use an interplay between the regularities of the KBE and the process to establish Markov duality between these two objects and thus well-posedness. In this way, we also extend the theory of energy solutions by generalizing the structure of the underlying equation in several directions and by weakening the notion of solution. Moreover, we show more properties on -or related to- energy solutions: We prove resolvent bounds for the generator, derive weak convergence rates for approximations and analyze the regularity of the occupation time measure of the solution.
In the second chapter we develop a well-posedness framework for solutions to certain
critical singular SPDEs. We first analyze the regularity of KBEs in an abstract Hilbert
space setting from the PDE and semigroup perspective. Then, we introduce the martingale problem for cylinder functions, which is closely related to energy solutions, in a slightly less abstract setting and provide a general uniqueness result. We apply this theory to show well-posedness of such solutions to fractional stochastic surface quasi-geostrophic equations and fractional stochastic Burgers equations, both in the critical and full subcritical regimes and we analyze certain infinite-dimensional SDEs with infinite interaction. Also in the SPDE case we generalize the usual equational structure and setting of energy solutions. Moreover, we derive further interesting properties such as the non-Gaussianity of solutions at stationarity, certain regularity of the law of the solution and the resolvent coming from scaling-invariance and existence of Markovian solutions in the supercritical regime. In a rather independent part of the chapter we also provide a partially alternative proof of a recent weak coupling result for the anisotropic Kardar-Parisi-Zhang equation in two dimensions.Diese Arbeit untersucht singuläre stochastische (partielle) Differentialgleichungen, ins-
besondere im skalen-kritischen und -superkritischen Regime.
Im ersten Kapitel zeigen wir Wohlgestelltheit von Energie-Lösungen stochastischer
Differentialgleichungen (SDG), die von Brownscher Bewegung und superkritischen distributionellen Driften getrieben werden, sowohl im periodischen Fall, als auch auf dem ganzen Raum. Energie-Lösungen sind gewisse Martingallösungen, welche singuläre stochastische partielle Differentialgleichungen (SPDGs) beschreiben und wir wenden die entsprechende Theorie im endlichdimensionalen Fall an, um Existenz von Lösungen zu zeigen. Darüber hinaus analysieren wir die zugehörige Kolmogorov Rückwärtsgleichung (KRG) aus dem Blickwinkel der Theorie der partiellen Differentialgleichungen (PDG) und der Halbgruppentheorie und nutzen ein Zusammenspiel der Regularitäten der KRG und des Prozesses um Markov-Dualität dieser beiden Objekte und somit Wohlgestelltheit zu etablieren. Auf diese Weise erweitern wir auch die Theorie der Energielösungen, indem wir die Struktur der zugrundeliegenden Gleichung in verschiedene Richtungen verallgemeinern und den Lösungsbegriff abschwächen. Ausserdem zeigen wir weitere Eigenschaften von - oder mit Bezug auf - Energielösungen: Wir zeigen Resolventenschranken für den Generator, leiten schwache Konvergenzraten für Näherungen her und analysieren die Regularität des Besetzungszeitmasses der Lösung.
Im zweiten Kapitel entwickeln wir ein Rahmenwerk für Wohlgestelltheit von Lösungen
gewisser kritischer singulärer SPDGs. Wir analysieren zuerst die Regularität von KRGs
in abstrakten Hilberträumen aus dem Blickwinkel der PDG- und der Halbgruppentheorie. Dann führen wir ein etwas weniger abstrakt formuliertes Martingalproblem für Zylinderfunktionen ein und zeigen ein allgemeines Eindeutigkeitsresultat. Wir wenden diese Theorie an, um Wohlgestelltheit solcher Lösungen für fraktionale stochastische quasigeostrophische Gleichungen und fraktionale stochastische Burgers Gleichungen im kritischen und subkritischen Fall zu zeigen und wir analysieren unendlichdimensionale SDGs mit gewissen unendlichen Interaktionstermen. Auch im SPDG-Fall verallgemeinern wir die übliche Gleichungsstruktur und das Szenario der Energielösungen. Darüber hinaus leiten wir weitere interessante Eigenschaften her wie etwa gewisse Regularitätseigenschaften der Verteilung der Lösung und der Resolvente ausgehend von der Skaleninvarianz des Systems, die Existenz Markovscher Lösungen im superkritischen Regime und wir zeigen, dass stationäre Lösungen im Allgemeinen keine Gaussschen Prozesse sind. In einem etwas unabhängigen Teil des Kapitels geben wir auch einen teilweise eigenständigen Beweis eines kürzlich bewiesenen schwachen Kopplungsresultats für die anisotrope Kardar-Parisi-Zhang Gleichung in zwei Dimensionen
Status and trends of Germany’s urban biodiversity: A nationwide assessment and identified knowledge gaps
No full textKnowledge on the status and trends of biodiversity in urban areas is scattered and biased towards a few taxonomic groups, despite the fact that cities are where most humans get in touch with nature today. As part of the German Biodiversity Assessment (‘Faktencheck Artenvielfalt’), we conducted a nationwide review of published studies that recorded species occurrences in urban areas in Germany. We found that urban areas can host a large proportion of all plant, animal, and fungal species found in Germany, thus contributing to the nationwide conservation of biodiversity. However, compared to other habitat types outside of cities, the number of studies analysing the status and trends of urban biodiversity is relatively small. We could not identify a general trend over time for species diversity in German cities, based on the available studies. Even within individual species groups, there are combinations of declining, positive, and/or neutral trends. Information on population trends remains limited. Similarly, evidence of whether urbanisation promotes the homogenisation or differentiation of species groups is weak, with those groups investigated more thoroughly showing mixed patterns. With regard to biodiversity promotion, preserving the environmental heterogeneity that contributes to biodiversity is important, such as the maintenance of various habitat types (forests, parks, gardens, ponds, streams, etc.) that offer various food and nesting resources. Hence, the proportion of built-up impervious areas must remain limited, i.e. must not increase, and additional measures to promote biodiversity must be implemented. However, local authorities are largely ill-equipped to systematically monitor species occurrence across the variety of habitat types, or elements of green-blue infrastructure and taxonomic groups in cities. We discuss these findings, considering international urban biodiversity assessments and suggest key attributes of an effective national monitoring system to support urban biodiversity conservation and enhancement
Beauty in/of mathematics: tessellations and their formulas
No full textTessellations of the Euclidean plane and a circle, a model of the hyperbolic plane, impress by their beauty, elegance and balance equally mathematical amateurs as mathematicians. Besides its impressive figures, esthetic and elegance of related basic formulas affect scientists. The parqueting-reflection method provides besides the tiling related fundamental solutions to complex partial differential equations in the domains of the tessellation
Prevention and control of avian influenza virus: Recent advances in diagnostic technologies and surveillance strategies
No full textThe natural host for avian influenza virus (AIV) is waterfowl. However, certain subtypes have breached species barriers, causing epizootics in many avian and mammalian species with occasional zoonotic infections in humans. The ongoing spread of highly pathogenic avian influenza (HPAI) A(H5N1) poses a significant and growing public health threat. Here, we discuss recent advances in viral detection and characterization technologies and their integration into the diagnostics and surveillance of AIV within a “One Health” framework
The Forgotten Hungarian Jewish Correspondence to Stockholm, Summer 1943
No full textNearly 2,000 forgotten letters from Hungarian Jews, sent to a Jewish aid organization in
Stockholm during the summer of 1943, were uncovered in the Swedish National Archive by
Elena Medvedev during her initial research into the personal micro-archive of historian Paul A.
Levine. The discovered artefacts sought information about Jewish men conscripted into
Hungary’s Jewish labor battalions under an increasingly repressive regime. The survival and
decades-long neglect of this correspondence is both astonishing and revealing. Now housed for
starting scholarly examination at the Osteuropa-Institut at Freie Universität Berlin, the letters
will be studied through both quantitative and qualitative methods—initially analyzing socio-
demographic variables and narrative content to explore patterns of assumed selective
repression. Were intellectuals and cosmopolitan figures especially targeted? What mechanisms
allowed these letters to bypass censorship? More than historical documents, the letters supposed
to display logic that guided the regime’s repressive choices; they challenge us to claim the
Holocaust details left in silence
How to control synaptic autophagy from the neuronal soma
No full textAutophagy dysregulation at the neural synapse is a hallmark of Parkinson’s disease and has diverse molecular origins. New research in The EMBO Journal investigates the role of Drosophila Rab39, and uncovers a system for compartmentalized regulation of synaptic autophagy, with implications for our understanding of dysregulated synaptic proteostasis as observed in neurodegenerative diseases