Domänenspezifische Funktionen des Polaritätsproteins Stardust in der Embryonalentwicklung von Drosophila

In Drosophila ist das Adapter- Protein Stardust essentiell für die Stabilisierung des Polaritäts- Determinanten Crumbs in verschiedenen Epithelgeweben, wie der embryonalen Epidermis, dem Follikelepithel und Photorezeptorzellen des Auges. Seinerseits rekrutiert Stardust ein anderes Adapter- Protein, PATJ, in die subapikale Region, um die Bildung der Adherens- Junctions und verschiedene morphogenetische Effekte zu unterstützen. Darüber hinaus bindet Stardust an Lin-7, welches zwar in Epithelzellen zu vernachlässigen ist, jedoch in der postsynaptischen Fusion von Vesikeln eine wichtige Rolle spielt. Schließlich wurde auch herausgefunden, dass Sdt unmittelbar an PAR- 6 bindet und so den Crb- Sdt- PATJ- Komplex direkt mit dem aPKC/ Par-6- Komplex verbindet.PAR-6 und aPKC sind auch in der Lage, Bazooka direkt zu binden und so den PAR/ aPKC- Komplex zu formen, der in den meisten Epithelgeweben essentiell ist für die Etablierung einer apikal- basalen Polarität und die Ausbildung von Zell- Zell- Kontakten. Dennoch ist bisher wenig bekannt über die physiologische Bedeutung dieser Interaktionen in der embryonalen Epidermis von Drosophila in vivo. Folglich führten wir eine Struktur- Funktions- Analyse der erläuterten Domänen mit GFP- markiertem Stardust durch und beurteilten anschließend die Anordnung und Funktion der mutanten Proteine in Epithelzellen der embryonalen Epidermis. Die hier präsentierten Daten bestätigen die wesentliche Bedeutung der PDZ- Domäne bei der Bindung und Rekrutierung von Crb zur subapikalen Region. Allerdings kann die isolierte PDZ- Domäne nicht zum Kortex rekrutiert werden, da die SH-Domäne unbedingt notwendig ist, um die Bindung zu Crb zu unterstützen. Bemerkenswert ist, dass die embryonal konservierten, N- terminalen Regionen ECR-1 und ECR-2 nicht ausschlaggebend sind für die epitheliale Polarität. Schließlich spielt auch die GUK- Domäne eine wichtige Rolle für die Funktion des Proteins, welche jedoch nicht mit der Stabilisierung von Crb zusammenhängt. Die L27- N- Domäne ist darüber hinaus essentiell für die apikal- basale Polarität, unabhängig von der Rekrutierung von PATJ

Europäische Werberegulierungssysteme am Beispiel geschlechterdiskriminierender Wirtschaftswerbung

In the current debate on gender-appropriate and non-discriminatory commercial communication, this study takes a comparative legal look at the different legal and self-regulatory instruments of the European advertising regulation systems. With the inclusion of social science, cognitive psychology and communication theory, the study not only examines the existing national regulations in their respective cultural context, but also considers new European developments, social influencing factors and possible harmonization approaches in the highly controversial field of gender-discriminatory commercial advertising.PublishedVor dem Hintergrund der Debatte um eine gendergerechte und nichtdiskriminierende kommerzielle Kommunikation nimmt das Werk die unterschiedlichen gesetzlichen wie selbstregulativen Instrumentarien der europäischen Werberegulierungssysteme rechtsvergleichend in den Blick. Unter der Einbeziehung sozialwissenschaftlicher, kognitionspsychologischer und kommunikationstheoretischer Bezüge werden dabei nicht nur die bestehenden nationalen Vorgaben in ihrem jeweiligen kulturellen Umfeld untersucht, sondern auch neue europäische Entwicklungen, gesellschaftliche Einflussfaktoren und mögliche Harmonisierungsansätze des höchst kontrovers diskutierten Themenfeldes geschlechterdiskriminierender Wirtschaftswerbung berücksichtigt

Die Glasperlen des 8. und 7. Jhs. v. Chr. aus Verucchio (Emilia-Romagna, Italien).: Die monochromen Perlen und Augenperlen

The presentation of glass beads from Verucchio, especially from recent excavations, serves to improve our knowledge of an often neglected genre of archaeological finds of the Early Iron Age in Italy. Glass beads of the 1st millennium BC are frequently listed as evidence of long-distance contacts, but are rarely studied and classified in detail. Seeing them oneself or at least good photographic evidence is necessary for their correct evaluation. The impact of analytical chemistry on this archaeological material is clearly increasing, though without the archaeological analyses and resulting questions about the chemistry having been fully worked out. The first part of this study presents the monochrome beads and those decorated with dot or ring eyes. It then sets them in their comparative contexts both in Italy and beyond. Finally, the state of research on glass chemistry, especially the colouring possibilities of the respective glasses, is set out. Thus, it becomes clear that certain bead forms remain restricted to the Bologna-Verucchio region, while others are scattered across Italy as well as occurring in the north-eastern adjoining regions of central Europe and the Aegean. In another later contribution, the remaining bead types, their chronological occurrence and their purpose in the graves will be discussed.The presentation of glass beads from Verucchio, especially from recent excavations, serves to improve our knowledge of a often neglected genre of archaeological finds of the Early Iron Age in Italy. Glass beads of the 1st millennium B.C. are frequently listed as evidence of long-distance contacts, but are rarely studied and classified in detail. Autopsy or good photographic evidence is necessary for the correct evaluation of glass beads. Finally, the interest of analytical chemistry in this archaeological material is clearly increasing, without archaeological analyses and resulting questions to chemistry having been worked out. The present first part of the study, apart from presenting the monochrome beads and those decorated with dot or ring eyes, gives their comparative finding in Italy and beyond, and the state of research on glass chemistry, especially the colouring possibilities of the respective glasses. It becomes clear that certain bead forms remain restricted to the Bologna-Verucchio region, while others are scattered across Italy or also occur in the north-eastern adjoining central Europe. In a following contribution, the remaining bead types, their chronological occurrence and use in the graves will be discussed

Common symptoms during pregnancy to predict depression and health status 14 years post partum

Objective: To examine the prospective association between symptoms commonly experienced during pregnancy and the mental and general health status of women 14 years post partum. Methods: Data used were from the Mater-University of Queensland Study of Pregnancy, a community-based prospective birth cohort study begun in Brisbane, Australia, in 1981. Logistic regression analyses were conducted. Results: Data were available for 5118 women. Women who experienced a higher burden of symptoms during pregnancy were at greater risk of becoming depressed and reporting poorer health status 14 years post partum. Women who experienced major problems during pregnancy were 4 times more likely to be depressed and nearly 8 times more likely to report poorer health status 14 years after the index pregnancy compared with women who experienced few problems. Conclusions: Findings suggest that pregnant women who experience common symptoms during pregnancy are likely to experience poorer mental and self-reported general health 14 years after the pregnancy. (C) 2008 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved

Improving cooperation between general practitioners and dermatologists via telemedicine: study protocol of the cluster-randomized controlled TeleDerm study

Background: Internationally, teledermatology has proven to be a viable alternative to conventional physical referrals. Travel cost and referral times are reduced while patient safety is preserved. Especially patients from rural areas benefit from this healthcare innovation. Despite these established facts and positive experiences from EU neighboring countries like the Netherlands or the United Kingdom, Germany has not yet implemented store-and-forward teledermatology in routine care. Methods: The TeleDerm study will implement and evaluate store-and-forward teledermatology in 50 general practitioner (GP) practices as an alternative to conventional referrals. TeleDerm aims to confirm that the possibility of store-and-forward teledermatology in GP practices is going to lead to a 15% (n=260) reduction in referrals in the intervention arm. The study uses a cluster-randomized controlled trial design. Randomization is planned for the cluster county. The main observational unit is the GP practice. Poisson distribution of referrals is assumed. The evaluation of secondary outcomes like acceptance, enablers and barriers uses a mixed-methods design with questionnaires and interviews.Discussion: Due to the heterogeneity of GP practice organization, patient management software, information technology service providers, GP personal technical affinity and training, we expect several challenges in implementing teledermatology in German GP routine care. Therefore, we plan to recruit 30% more GPs than required by the power calculation. The implementation design and accompanying evaluation is expected to deliver vital insights into the specifics of implementing telemedicine in German routine care.Trial registration: German Clinical Trials Register, DRKS00012944. Registered prospectively on 31 August 2017

Para-infectious brain injury in COVID-19 persists at follow-up despite attenuated cytokine and autoantibody responses

To understand neurological complications of COVID-19 better both acutely and for recovery, we measured markers of brain injury, inflammatory mediators, and autoantibodies in 203 hospitalised participants; 111 with acute sera (1–11 days post-admission) and 92 convalescent sera (56 with COVID-19-associated neurological diagnoses). Here we show that compared to 60 uninfected controls, tTau, GFAP, NfL, and UCH-L1 are increased with COVID-19 infection at acute timepoints and NfL and GFAP are significantly higher in participants with neurological complications. Inflammatory mediators (IL-6, IL-12p40, HGF, M-CSF, CCL2, and IL-1RA) are associated with both altered consciousness and markers of brain injury. Autoantibodies are more common in COVID-19 than controls and some (including against MYL7, UCH-L1, and GRIN3B) are more frequent with altered consciousness. Additionally, convalescent participants with neurological complications show elevated GFAP and NfL, unrelated to attenuated systemic inflammatory mediators and to autoantibody responses. Overall, neurological complications of COVID-19 are associated with evidence of neuroglial injury in both acute and late disease and these correlate with dysregulated innate and adaptive immune responses acutely

Computer simulations of ordering effects and dislocation structures in high entropy alloys

High entropy alloys constitute a new class of materials, which recently have attracted considerable attention in the field of high-performance materials [1]. Such materials are distinguished by their structural stability, resistance to external loads and a considerable strength, while preserving a sufficient ductility even at high temperatures. It is therefore not surprising that, since the principle of atomic-scale composites was first presented in 1995 [2, 1], an increasing scientific community focus on structure formation and mechanical deformation mechanisms. The concept of high entropy alloys is based on the combination and interaction of several chemical elements, where the number, by definition, amounts to at least five different components. All principal elements occur in an equimolar or a near equimolar ratio such that a distinction between a solvent and a solute is hardly possible. The almost unlimited diversity of compositions enables to use high entropy alloys in different industries, involving lightweight metal combinations for transportation or refractory alloys for high temperature applications [1]. However, currently most research focuses on only a small number of possible alloy systems [3]. According to Hammond et al. [4], the driving force in the development of new materials is the achievement of “revolutionary–rather than evolutionary–advances”. But why should exactly these multimaterial cocktails [5] be revolutionary? The origin of outstanding properties, such as durability and load capacity, have been extensively studied by theoreticians as well as experimentalists. A number of researchers reported that the high entropy of mixing facilitates the formation of random solid solutions, while preventing the formation of brittle intermetallic phases with complex microstructures [6, 2]. In addition, the use of differently sized atom types may cause lattice distortions, which greatly influence the deformation behavior. For this reason several recent studies have focused on phase competitions, composition dependence of phase stability, mechanical and magnetic properties or temperature effects on deformation [7, 8, 9, 10, 11]. Nevertheless, there has been some debate about phase selection rules for high entropy alloy production. Although most work has concentrated on the influence of parameters such as mixing enthalpy, atomic-size differences or valence electron concentrations, a complete determination of phase diagrams is still missing. Whereas properties like density, melting temperature and lattice parameter may be derived from simple “rules of mixture” [4], the final microstructure strongly depends on “inter-elemental reactions” [12]. Since the understanding of atomic structures is essential in order to predict material behavior, the generation of basis structures seems to be one of the first steps in this field of research. These generated structures might serve as a basis for the implementation of simulation-based mechanical tests

First-principles study of the defect chemistry and conductivity in sodium bismuth titanate

The present thesis is an endeavor to understand the defect chemistry and conductivity in polymorphic sodium bismuth titanate (NBT) and NBT-based systems with the ultimate goal to design the next generation of ionic conductors for solid oxide fuel cells. Structural modifications such as non-stoichiometry and doping lead to unexpected high oxygen ionic conductivities in these A-site mixed perovskite structures. Particularly, the non-linear dependency of mobile oxygen vacancies on the defect concentration represents a challenge for scientists worldwide in terms of reliability and controllability. What are the fundamental mechanisms during oxygen vacancy migration and how can we use this knowledge to manipulate electric conductivities in our favor? These two central questions will guide us through the present thesis, where we will explore defect interaction, migration, and charge states in doped and undoped NBT. We discuss these results in the light of different chemical A-site orders, polar, and tilt distortions. For this purpose, we employ density functional theory calculations and focus our analysis on the following main aspects: Electrostatic, covalent, and elastic interactions between defects as well as their coupling to the host lattice. Such a comprehensive defect chemical understanding will allow deriving material properties of structurally and chemically more complex systems such as solid solutions. Furthermore, this knowledge is necessary to establish NBT in versatile industrial applications, ranging from low-loss piezoelectrics to high ionic conductors. After a broad overview of the present research and an introduction to the most relevant concepts in the field of ferroelectric perovskite oxides in the Chapters 1, 2, and 3, we introduce a macroscopic defect chemical model in Chapter 4. This approach is an over-simplification of the defect chemical complexity and neglects several degrees of freedom, for instance, displacement or electronic state occupation fluctuations. However, it illustrates how phase symmetries, dopant concentrations, and dopant types influence the conductivity in NBT. In Chapter 5, we present several novel material properties for the undoped and stoichiometric NBT structure, calculated mainly by density functional perturbation theory. These properties are necessary input parameters for all remaining chapters' calculations and serve as a benchmark of density functional theory approaches for A-site disordered perovskite oxides. A detailed comparison between a Mg-, Fe-, and Al-doping follows in the Chapters 6, 8, 9, and 10. In the former, we primarily deal with the electrostatic interaction between different defect types and local relaxation patterns. In the latter, we focus on charge transition states, elastic effects, and the covalent binding environments. All chapters show a delicate interplay between the electrostatic and the elastic interaction, leading to a reduction of the effective charge carrier concentration. The elastic contribution is particularly prevalent for small dopant types. We further identify the importance of polar and tilt distortions on the association energy between an oxygen vacancy and a neighboring B-site acceptor dopant. Especially in Chapter 6, we contrast our results to experimental impedance spectroscopy measurements. The formation of defect associates between an oxygen vacancy and an aluminium dopant in a ((Na,K)0.5Bi0.5)TiO3-BiAlO3 solid solution is addressed by a combination of nuclear magnetic resonance spectroscopy and ab-initio calculations. In the framework of Smarter Crystallography, we show that stable first-order defect associates only exist at small Al-dopant concentrations