Refine
Year of publication
- 2019 (1063) (remove)
Document Type
- Journal article (506)
- Doctoral Thesis (415)
- Complete part of issue (51)
- Book article / Book chapter (33)
- Preprint (19)
- Book (13)
- Working Paper (8)
- Master Thesis (4)
- Report (3)
- Study Thesis (term paper) (3)
Language
- English (696)
- German (363)
- Multiple languages (2)
- Russian (1)
- Spanish (1)
Keywords
- Universität (47)
- Wuerzburg (47)
- Würzburg (47)
- University (46)
- Wurzburg (46)
- Animal Studies (24)
- Cultural Animal Studies (24)
- Cultural Studies (24)
- Ecocriticism (24)
- Environmental Humanities (24)
Institute
- Theodor-Boveri-Institut für Biowissenschaften (105)
- Graduate School of Life Sciences (69)
- Physikalisches Institut (52)
- Universität - Fakultätsübergreifend (46)
- Medizinische Klinik und Poliklinik II (44)
- Institut für deutsche Philologie (39)
- Institut für Anorganische Chemie (38)
- Institut für Organische Chemie (35)
- Medizinische Klinik und Poliklinik I (35)
- Institut für Psychologie (34)
Schriftenreihe
Sonstige beteiligte Institutionen
- VolkswagenStiftung (24)
- DFG Forschungsgruppe 2757 / Lokale Selbstregelungen im Kontext schwacher Staatlichkeit in Antike und Moderne (LoSAM) (2)
- Deutsches Archäologisches Institut (2)
- Johns Hopkins School of Medicine (2)
- Universität Bayreuth (2)
- Universität Leipzig (2)
- Akademie der Wissenschaften und der Literatur, Mainz (1)
- Bio-Imaging Center Würzburg (1)
- CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - the development agency of the Brazilian Federal Government (1)
- Center for Nanosystems Chemistry (CNC), Universität Würzburg (1)
- DAAD - Deutscher Akademischer Austauschdienst (1)
- DFG (1)
- Department of Hematology and Oncology, Sana Hospital Hof, Hof, Germany (1)
- Department of Laboratory Medicine and Medicine Huddinge, Karolinska Institutet and University Hospital, Stockholm, Sweden (1)
- Department of Medicine A, University Hospital of Münster, Münster, Germany (1)
- Deutsches Zentrum für Herzinsuffizienz (1)
- Ernst Strüngmann Institute for Neuroscience in Cooperation with Max Planck Society (ESI) (1)
- Fraunhofer Institut für Integrierte Schaltungen (IIS) (1)
- Fraunhofer-Institut für Chemische Technologie (ICT) (1)
- Fraunhofer-Institut für Silicatforschung ISC (1)
- IZKF Nachwuchsgruppe Geweberegeneration für muskuloskelettale Erkrankungen (1)
- Institut für Medizinische Lehre und Ausbildungsforschung, Universität Würzburg (1)
- Institut für Medizintechnik Schweinfurt (IMeS) (1)
- Institut für Ur- und Frühgeschichtiche Archäologie und Vorderasiatische Archäologie der Universität Heidelberg (1)
- Institute for Biochemistry I, University of Cologne (1)
- Institute of Physics and Center for Nanotechnology, University of Münster (1)
- Interdisciplinary Center for Clinical Research (1)
- Joslin Diabetes Center (Harvard Medical School) (1)
- Klinik für Kinder- und Jugendmedizin des Caritas-Krankenhauses Bad Mergentheim (1)
- Klinikum Fulda (1)
- Klinikum Würzburg Mitte (Akademisches Lehrkrankenhaus der Uni Würzburg) (1)
- König-Ludwig-Haus Würzburg (1)
- LIDYL, CEA, CNRS, Université Paris-Saclay, CEA Saclay 91191 Gif-sur-Yvette France (1)
- Lehrkrankenhaus II. Medizinische Klinik Klinikum Coburg (1)
- Lehrstuhl für BioMolekulare Optik, Ludwig-Maximilians-Universität München (1)
- Medizinische Klinik und Poliklinik 1, Abteilung Kardiologie (1)
- Medizinische Klinik und Poliklinik 1, Abteilung Nephrologie (1)
- Medizinische Universität Innsbruck (1)
- NanoOptics & Biophotonics Group, Experimental Physics 5, Universität Würzburg (1)
- Orthopädische Klinik König-Ludwig-Haus (1)
- Queensland University of Technology (1)
- Rhön-Klinikum Campus Bad Neustadt (1)
- Rudolf-Virchow-Zentrum für Experimentelle Biomedizin der Universität Würzburg (1)
- Technische Hochschule Nürnberg Georg Simon Ohm (1)
- University of Bari Medical School, Bari, Italy (1)
- Universitätsklinikum Würzburg (1)
- Universitätsklinkium Magdeburg (1)
- Zentrum für Luft- und Raumfahrtmedizin der Luftwaffe (1)
- Zentrum für Telematik e.V. (1)
- Zentrum für experimentelle und molekulare Medizin (Würzburg) (1)
ResearcherID
- B-4606-2017 (1)
Background
Autologous hematopoietic stem cell transplantation (aHSCT) is performed in patients with aggressive forms of systemic sclerosis (SSc). The profile of B cell reconstitution after aHSCT is not fully understood. The aim of this study was to investigate changes of B cell subsets and cytokine production of B cells in patients with SSc after aHSCT.
Methods
Peripheral blood of six patients with SSc was collected at defined intervals up to 16 months after aHSCT. Immunophenotyping was performed, and B cell function was determined by measuring cytokine secretion in supernatants of stimulated B cell cultures.
Results
Within 1 month after aHSCT, a peak in the percentage of CD38\(^{++}\)/CD10\(^+\)/IgD\(^+\) transitional B cells and CD38\(^{++}\)/CD27\(^{++}\)/IgD\(^−\) plasmablasts was detected. Long-term changes persisted up to 14 months after aHSCT and showed an increased percentage of total B cells; the absolute B cell number did not change significantly. Within the B cell compartment, an increased CD27/IgD\(^+\) naïve B cell percentage was found whereas decreased percentages of CD27\(^+\)/IgD\(^+\) pre-switched memory, CD27\(^+\)/IgD\(^−\) post-switched memory, and CD27\(^−\) /IgD\(^−\) double-negative B cells were seen after aHSCT. Cytokine secretion in B cell cultures showed significantly increased IL-10 concentrations 13 to 16 months after aHSCT.
Conclusion
A changed composition of the B cell compartment is present for up to 14 months after aHSCT indicating positive persisting effects of aHSCT on B cell homeostasis. The cytokine secretion profile of B cells changes in the long term and shows an increased production of the immune regulatory cytokine IL-10 after aHSCT. These findings might promote the clinical improvements after aHSCT in SSc patients.
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and its death receptors TRAILR1/death receptor 4 (DR4) and TRAILR2/DR5 trigger cell death in many cancer cells but rarely exert cytotoxic activity on non-transformed cells. Against this background, a variety of recombinant TRAIL variants and anti-TRAIL death receptor antibodies have been developed and tested in preclinical and clinical studies. Despite promising results from mice tumor models, TRAIL death receptor targeting has failed so far in clinical studies to show satisfying anti-tumor efficacy. These disappointing results can largely be explained by two issues: First, tumor cells can acquire TRAIL resistance by several mechanisms defining a need for combination therapies with appropriate sensitizing drugs. Second, there is now growing preclinical evidence that soluble TRAIL variants but also bivalent anti-TRAIL death receptor antibodies typically require oligomerization or plasma membrane anchoring to achieve maximum activity. This review discusses the need for oligomerization and plasma membrane attachment for the activity of TRAIL death receptor agonists in view of what is known about the molecular mechanisms of how TRAIL death receptors trigger intracellular cell death signaling. In particular, it will be highlighted which consequences this has for the development of next generation TRAIL death receptor agonists and their potential clinical application.
Der Harz ist eine Mittelgebirgsregion, die in Deutschland und Mitteleuropa auf faszinierende Weise hervorsticht: Kaum eine andere deutsche Landschaft kann mit einer solchen Vielfalt an Gesteinen und Erzen aufwarten. Diese Besonderheit wurzelt tief in der geologischen Entstehung der Region. Ihrer Geschichte will nun der Katalog auf die Spur kommen – anhand von ausgewählten Exponaten einer einzigartigen Sammlung.
Aufgebaut wurde die umfangreiche Sammlung von Peter C. Ruppert. Der Kunstsammler und Würzburger Ehrenbürger sammelte über Jahrzehnte hinweg außergewöhnliche Mineralien und Gesteine aus den historischen Erzlagerstätten des Harzes. Seit Januar 2014 zeigt das Mineralogische Museum der Universität Würzburg die wertvollen Exponate – und widmet der Sammlung diesen Katalog.
Animals, just like humans, can freely move. They do so for various important reasons, such as finding food and escaping predators. Observing these behaviors can inform us about the underlying cognitive processes. In addition, while humans can convey complicated information easily through speaking, animals need to move their bodies to communicate. This has prompted many creative solutions by animal neuroscientists to enable studying the brain during movement. In this review, we first summarize how animal researchers record from the brain while an animal is moving, by describing the most common neural recording techniques in animals and how they were adapted to record during movement. We further discuss the challenge of controlling or monitoring sensory input during free movement.
However, not only is free movement a necessity to reflect the outcome of certain internal cognitive processes in animals, it is also a fascinating field of research since certain crucial behavioral patterns can only be observed and studied during free movement. Therefore, in a second part of the review, we focus on some key findings in animal research that specifically address the interaction between free movement and brain activity. First, focusing on walking as a fundamental form of free movement, we discuss how important such intentional movements are for understanding processes as diverse as spatial navigation, active sensing, and complex motor planning. Second, we propose the idea of regarding free movement as the expression of a behavioral state. This view can help to understand the general influence of movement on brain function.
Together, the technological advancements towards recording from the brain during movement, and the scientific questions asked about the brain engaged in movement, make animal research highly valuable to research into the human “moving brain”.
The transcription factor 12 (tcf12) is a basic Helix-Loop-Helix protein (bHLH) of the E-protein family, proven to play an important role in developmental processes like neurogenesis, mesoderm formation, and cranial vault development. In humans, mutations in TCF12 lead to craniosynostosis, a congenital birth disorder characterized by the premature fusion of one or several of the cranial sutures. Current research has been primarily focused on functional studies of TCF12, hence the cellular expression profile of this gene during embryonic development and early stages of ossification remains poorly understood. Here we present the establishment and detailed analysis of two transgenic tcf12:EGFP fluorescent zebrafish (Danio rerio) reporter lines. Using these transgenic lines, we analyzed the general spatiotemporal expression pattern of tcf12 during different developmental stages and put emphasis on skeletal development and cranial suture patterning. We identified robust tcf12 promoter-driven EGFP expression in the central nervous system (CNS), the heart, the pronephros, and the somites of zebrafish embryos. Additionally, expression was observed inside the muscles and bones of the viscerocranium in juvenile and adult fish. During cranial vault development, the transgenic fish show a high amount of tcf12 expressing cells at the growth fronts of the ossifying frontal and parietal bones and inside the emerging cranial sutures. Subsequently, we tested the transcriptional activity of three evolutionary conserved non-coding elements (CNEs) located in the tcf12 locus by transient transgenic assays and compared their in vivo activity to the expression pattern determined in the transgenic tcf12:EGFP lines. We could validate two of them as tcf12 enhancer elements driving specific gene expression in the CNS during embryogenesis. Our newly established transgenic lines enhance the understanding of tcf12 gene regulation and open up the possibilities for further functional investigation of these novel tcf12 enhancer elements in zebrafish.
Fin development and regeneration are complex biological processes that are highly relevant in teleost fish. They share genetic factors, signaling pathways and cellular properties to coordinate formation of regularly shaped extremities. Especially correct tissue structure defined by extracellular matrix (ECM) formation is essential. Gene expression and protein localization studies demonstrated expression of fndc3a (fibronectin domain containing protein 3a) in both developing and regenerating caudal fins of zebrafish (Danio rerio). We established a hypomorphic fndc3a mutant line (fndc3a\(^{wue1/wue1}\)) via CRISPR/Cas9, exhibiting phenotypic malformations and changed gene expression patterns during early stages of median fin fold development. These developmental effects are mostly temporary, but result in a fraction of adults with permanent tail fin deformations. In addition, caudal fin regeneration in adult fndc3a\(^{wue1/wue1}\) mutants is hampered by interference with actinotrichia formation and epidermal cell organization. Investigation of the ECM implies that loss of epidermal tissue structure is a common cause for both of the observed defects. Our results thereby provide a molecular link between these developmental processes and foreshadow Fndc3a as a novel temporal regulator of epidermal cell properties during extremity development and regeneration in zebrafish.
Als „ewiger Patient“ des deutschen Gesetzgebers steht die Umweltverbandsklage seit über vierzig Jahren in der rechtswissenschaftlichen Diskussion. Neuen Schwung erlangte die Debatte durch die völkerrechtlichen Vorgaben der im Jahr 1998 beschlossenen Aarhus-Konvention sowie deren unionsrechtliche Umsetzung in der Öffentlichkeitsbeteiligungsrichtlinie (RL 2003/35/EG). Für den deutschen Gesetzgeber entstand dadurch erheblicher Anpassungsbedarf des nationalen Rechts, dem er zuerst im Jahr 2006 mit dem Erlass des Umwelt-Rechtsbehelfsgesetzes (UmwRG) nachkam. Dieses warf allerdings von Beginn an Fragen im Hinblick auf die Beachtung der völker- und unionsrechtlichen Vorgaben auf und wurde schließlich im Jahr 2011 vom EuGH für partiell unionswidrig erklärt. Der deutsche Gesetzgeber hat daraufhin mehrere Novellierungsversuche unternommen, die alle nicht frei von Kritik blieben. Daher folgten wenig überraschend im Jahr 2013 sowie 2015 erneute Rügen durch den EuGH. Im April 2016 startete der Gesetzgeber schließlich einen erneuten Vorstoß zur Schaffung eines völker- und unionsrechtskonformen UmwRG, welcher in die bislang umfassendste und grundlegendste Novelle des UmwRG vom 02.06.2017 mündete.
This article focuses on selected Latin American female rap artists (Anita Tijoux, Rebeca Lane, and the duo Krudas Cubensi), and the way they perform feminism, autobiography and testimony through their lyrics and performances. The analysis concentrates on the synergies between the texts themselves, the official music videos shared on YouTube and the background music. It aims to demonstrate that only such a synergistic approach to rap allows a profound understanding of its particularities and its contributions to feminist discourses and spaces for feminist testimony in the current rise of both right-wing politics and feminist movements on the continent.
This article is dedicated to the analysis of the body, which is staged as sick and painful. El último cuerpo de Úrsula by Peruvian author Patricia de Souza is characterized by the connection between body, pain perception and eroticism. Illness and paralysis play a fundamental role in the narrative because they cause the recomposition of the ego, which leads the protagonist, Úrsula Res, to perceive and reflect the fragmentation of her identity and the increasing distance from her body. Through approaches to pain and disability, the expressiveness of the narrativized eroticism of this text, based on an obedient relationship to the body, is revealed.
Previous research has demonstrated that humans are able to match unfamiliar voices to corresponding faces and vice versa. It has been suggested that this matching ability might be based on common underlying factors that have a characteristic impact on both faces and voices. Some researchers have additionally assumed that dynamic facial information might be especially relevant to successfully match faces to voices. In the present study, static and dynamic face-voice matching ability was compared in a simultaneous presentation paradigm. Additionally, a procedure (matching additionally supported by incidental association learning) was implemented which allowed for reliably excluding participants that did not pay sufficient attention to the task. A comparison of performance between static and dynamic face-voice matching suggested a lack of substantial differences in matching ability, suggesting that dynamic (as opposed to mere static) facial information does not contribute meaningfully to face-voice matching performance. Importantly, this conclusion was not merely derived from the lack of a statistically significant group difference in matching performance (which could principally be explained by assuming low statistical power), but from a Bayesian analysis as well as from an analysis of the 95% confidence interval (CI) of the actual effect size. The extreme border of this CI suggested a maximally plausible dynamic face advantage of less than four percentage points, which was considered way too low to indicate any theoretically meaningful dynamic face advantage. Implications regarding the underlying mechanisms of face-voice matching are discussed.
Die Europäische Union (EU) sieht sich gegenwärtig einem Prozess der Politisierung ausgesetzt, der durch die Polykrise der letzten Jahre verstärkt wurde. Der „permissive consensus“ (Lindberg/Scheingold 1970), welcher schon seit dem „post-Maastricht Blues“ (Eichen-berg/Dalton 2007) bröckelte, wird durch eine Reihe ablehnender Referenden zu europapolitischen Themen weiter in Frage gestellt. Die seit langem spürbaren Desintegrationstendenzen und Zentrifugalkräfte kulminierten im Brexit-Referendum vom Juni 2016. Vor diesem Hintergrund ist mehr denn je zu konstatieren, dass die Öffentlichkeit, die UnionsbürgerInnen eine zentrale, den Integrationsprozess mindestens beeinflussende, bisweilen limitierende Rolle einnehmen.
Diese Studie stellt die Frage, inwiefern die Theorien der europäischen Integration diesen wichtigen, den Integrationsprozess immer deutlicher (mit-)bestimmenden Faktor der Öffentlichkeit erfassen. Der Beitrag liefert zum einen eine komprimierte Übersicht der einschlägigen theoretischen Ansätze, die seit den 1950er-Jahren bis heute zur Beschreibung und Erklärung von Prozess und Zustand der europäischen Integration verwendet wurden und werden. Dabei wird zum zweiten die jeweilige Rolle der Öffentlichkeit in den Ansätzen ausgewählter ReferenztheoretikerInnen retrospektiv und aktuell durchgesehen. Mit dieser integrationstheoretischen Rundumschau unter dem Filter der Öffentlichkeit liefert die vorliegende Analyse Anknüpfungspunkte für theoriegeleitete Europaforschung, die den Politisierungsprozess der EU einordnend, analysierend, erklärend, verstehend und bei Bedarf kritisch begleiten kann.
Due to the complexityof research objects, theoretical concepts, and stimuli in media research, researchers in psychology and communications presumably need sophisticated measures beyond self-report scales to answer research questions on media use processes. The present study evaluates stimulus-dependent structure in spontaneous eye-blink behavior as an objective, corroborative measure for the media use phenomenon of spatial presence. To this end, a mixed methods approach is used in an experimental setting to collect, combine, analyze, and interpret data from standardized participant self-report, observation of participant behavior, and content analysis of the media stimulus. T-pattern detection is used to analyze stimulus-dependent blinking behavior, and this structural data is then contrasted with self-report data. The combined results show that behavioral indicators yield the predicted results, while self-report data shows unpredicted results that are not predicted by the underlying theory. The use of a mixed methods approach offered insights that support further theory development and theory testing beyond a traditional, mono-method experimental approach.
WUEMoCA is an operational scientific webmapping tool for the regional monitoring of land and water use efficiency in the irrigated croplands of the transboundary Aral Sea Basin that is shared by Kazakhstan, Kyrgyzstan, Tajikistan, Turkmenistan, Uzbekistan, and Afghanistan. Satellite data on land use, crop pro-duction and water consumption is integrated with hydrological and economic information to provide of a set indicators. The tool is useful for large-scale decisions on water distribution or land use, and may be seen as demonstrator for numerous applications in practice, that require independent area-wide spatial information.
This article explores the construction of Catalan masculinity and Catalan identity in literature on the Spanish-Moroccan War of 1859/60. During the war, an immense amount of patriotic literature in Catalan language was published in Catalonia, in which the authors glorified the deeds of the Catalan general Joan Prim i Prats and of the Catalan volunteers who fought in the war. The article aims to illustrate, on the basis of the analysis of poems, theatre plays, patriotic songs, reports and chronicles written by Catalan authors, the importance of the First Spanish-Moroccan War for the development of Catalan identity. It attempts as well to demonstrate that the authors used the literature about the war to diffuse a specific Catalan ideal of masculinity and to stylize General Prim and the volunteers into national heroes, who embodied the strength of the Catalan cultural nation, since the Catalan community needed new idols after a long time of political and cultural decline caused by the centralist policies of the Spanish state. The Catalan ideal of masculinity was utilized to differentiate the Catalans from the other Spaniards whose masculinity was considered to be in decadence by the other European nations.
This contribution deals with the phonetic heterogeneity of spoken Spanish in Andalusia in the sector of public auditory media, specifically in the program ¡Anda Levanta! of Canal Fiesta Radio. First, we take into consideration Article 10 of the Statute of the Autonomy of Andalusia, which enhances the protection, promotion, study, and prestige of the Andalusian modalities and its respective variety (cf. Parlamento de Andalucía 2007: 13). Second, we refer to the Libro de Estilo, a mandatory guide for presenters of public audiovisual media in Andalusia since 2014. The results of the qualitative analysis indicate divergences between the presenters and their audience with regard to their use of phonetic characteristics typical of the Andalusian varieties: where the presenters tend to avoid the salient aspects of the varieties, the audience employs a range of phonetic characteristics typical for Andalusian varieties, including some of the characteristics that are considered less prestigious.
This paper provides a critical analysis of the subadditivity axiom, which is the key condition for coherent risk measures. Contrary to the subadditivity assumption, bank mergers can create extra risk. We begin with an analysis how a merger affects depositors, junior or senior bank creditors, and bank owners. Next it is shown that bank mergers can result in higher payouts having to be made by the deposit insurance scheme. Finally, we demonstrate that if banks are interconnected via interbank loans, a bank merger could lead to additional contagion risks. We conclude that the subadditivity assumption should be rejected, since a subadditive risk measure, by definition, cannot account for such increased risks.
Purpose The purpose of this paper is to enhance consistent partial least squares (PLSc) to yield consistent parameter estimates for population models whose indicator blocks contain a subset of correlated measurement errors. Design/methodology/approach Correction for attenuation as originally applied by PLSc is modified to include a priori assumptions on the structure of the measurement error correlations within blocks of indicators. To assess the efficacy of the modification, a Monte Carlo simulation is conducted. Findings In the presence of population measurement error correlation, estimated parameter bias is generally small for original and modified PLSc, with the latter outperforming the former for large sample sizes. In terms of the root mean squared error, the results are virtually identical for both original and modified PLSc. Only for relatively large sample sizes, high population measurement error correlation, and low population composite reliability are the increased standard errors associated with the modification outweighed by a smaller bias. These findings are regarded as initial evidence that original PLSc is comparatively robust with respect to misspecification of the structure of measurement error correlations within blocks of indicators. Originality/value Introducing and investigating a new approach to address measurement error correlation within blocks of indicators in PLSc, this paper contributes to the ongoing development and assessment of recent advancements in partial least squares path modeling.
Schutzfaktoren bei Kindern vor dem Übergang in die Sekundarstufe – Ergebnisse aus der STRESSStudie
(2019)
Der Übergang in die Sekundarstufe stellt für Kinder ein normativ kritisches Lebensereignis dar, das unterschiedlich bewertet und bewältigt wird. Der vorliegende Beitrag befasst sich mit der Frage, welche Schutzfaktoren dazu beitragen, dass Kinder dem Übergang mit Gefühlen der Vorfreude begegnen und sie dieses Ereignis problemorientiert bewältigen. Untersucht werden 596 ViertklässlerInnen aus Bayern und Hessen vor dem Übergang in die Sekundarstufe. In Anlehnung an die kognitiv-transaktionale Theorie von Lazarus und Folkman (1984) werden die Zusammenhänge von primärer Bewertung als Herausforderung und problemorientierter Stressbewältigung unter Berücksichtigung von personalen (akademisches Selbstkonzept, Selbstwirksamkeit) und sozialen Schutzfaktoren (Familienzusammenhalt, allgemeines förderndes Elternverhalten) analysiert. Mithilfe von Strukturgleichungsmodellen lassen sich Mediationseffekte der Schutzfaktoren nachweisen. Insbesondere das akademische Selbstkonzept und ein förderliches Familienumfeld erweisen sich als bedeutsame protektive Faktoren in der Phase vor dem Übergang.
The central nervous system (CNS) barriers are highly specialized cellular barriers that promote brain homeostasis while restricting pathogen and toxin entry. The primary cellular constituent regulating pathogen entry in most of these brain barriers is the brain endothelial cell (BEC) that exhibits properties that allow for tight regulation of CNS entry. Bacterial meningoencephalitis is a serious infection of the CNS and occurs when bacteria can cross specialized brain barriers and cause inflammation. Models have been developed to understand the bacterial – BEC interaction that lead to pathogen crossing into the CNS, however, these have been met with challenges due to these highly specialized BEC phenotypes. This perspective provides a brief overview and outlook of the in vivo and in vitro models currently being used to study bacterial brain penetration, and opinion on improved models for the future.
The protein-bound uremic toxins para-cresyl sulfate (pCS) and indoxyl sulfate (IS) are associated with cardiovascular disease in chronic renal failure, but the effect of different dialysis procedures on their plasma levels over time is poorly studied. The present prospective, randomized, cross-over trial tested dialysis efficacy and monitored pre-treatment pCS and IS concentrations in 15 patients on low-flux and high-flux hemodialysis and high-convective volume postdilution hemodiafiltration over six weeks each. Although hemodiafiltration achieved by far the highest toxin removal, only the mean total IS level was decreased at week three (16.6 ± 12.1 mg/L) compared to baseline (18.9 ± 13.0 mg/L, p = 0.027) and to low-flux dialysis (20.0 ± 12.7 mg/L, p = 0.021). At week six, the total IS concentration in hemodiafiltration reached the initial values again. Concentrations of free IS and free and total pCS remained unaltered. Highest beta2-microglobulin elimination in hemodiafiltration (p < 0.001) led to a persistent decrease of the plasma levels at week three and six (each p < 0.001). In contrast, absent removal in low-flux dialysis resulted in rising beta2-microglobulin concentrations (p < 0.001). In conclusion, this trial demonstrated that even large differences in instantaneous protein-bound toxin removal by current extracorporeal dialysis techniques may have only limited impact on IS and pCS plasma levels in the longer term.
There is a specialized niche for the electrohydrodynamic jetting of melts, from biomedical products to filtration and soft matter applications. The next frontier includes optics, microfluidics, flexible electronic devices, and soft network composites in biomaterial science and soft robotics. The recent emphasis on reproducibly direct‐writing continual molten jets has enabled a spectrum of contemporary microscale 3D objects to be fabricated. One strong suit of melt processing is the capacity for the jet to solidify rapidly into a fiber, thus fixing a particular structure into position. The ability to direct‐write complex and multiscaled architectures and structures has greatly contributed to a large number of recent studies, explicitly, toward fiber–hydrogel composites and fugitive inks, and has expanded into several biomedical applications such as cartilage, skin, periosteum, and cardiovascular tissue engineering. Following the footsteps of a publication that summarized melt electrowriting literature up to 2015, the most recent literature from then until now is reviewed to provide a continuous and comprehensive timeline that demonstrates the latest advances as well as new perspectives for this emerging technology.
Protein-like enwrapped perylene bisimide chromophore as bright microcrystalline emitter material
(2019)
Strongly emissive solid‐state materials are mandatory components for many emerging optoelectronic technologies, but fluorescence is often quenched in the solid state owing to strong intermolecular interactions. The design of new organic pigments, which retain their optical properties despite their high tendency to crystallize, could overcome such limitations. Herein, we show a new material with monomer‐like absorption and emission profiles as well as fluorescence quantum yields over 90 % in its crystalline solid state. The material was synthesized by attaching two bulky tris(4‐tert‐butylphenyl)phenoxy substituents at the perylene bisimide bay positions. These substituents direct a packing arrangement with full enwrapping of the chromophore and unidirectional chromophore alignment within the crystal lattice to afford optical properties that resemble those of their natural pigment counterparts, in which chromophores are rigidly embedded in protein environments.
Two different chromophores, namely a dipolar and an octupolar system, were prepared and their linear and nonlinear optical properties as well as their bioimaging capabilities were compared. Both contain triphenylamine as the donor and a triarylborane as the acceptor, the latter modified with cationic trimethylammonio groups to provide solubility in aqueous media. The octupolar system exhibits a much higher two‐photon brightness, and also better cell viability and enhanced selectivity for lysosomes compared with the dipolar chromophore. Furthermore, both dyes were applied in two‐photon excited fluorescence (TPEF) live‐cell imaging.
Although usually asymptomatically colonizing the human nasopharynx, the Gram-negative bacterium Neisseria meningitidis (meningococcus) can spread to the blood stream and cause invasive disease. For survival in blood, N. meningitidis evades the complement system by expression of a polysaccharide capsule and surface proteins sequestering the complement regulator factor H (fH). Meningococcal strains belonging to the sequence type (ST-) 41/44 clonal complex (cc41/44) cause a major proportion of serogroup B meningococcal disease worldwide, but they are also common in asymptomatic carriers. Proteome analysis comparing cc41/44 isolates from invasive disease versus carriage revealed differential expression levels of the outer membrane protein NspA, which binds fH. Deletion of nspA reduced serum resistance and NspA expression correlated with fH sequestration. Expression levels of NspA depended on the length of a homopolymeric tract in the nspA promoter: A 5-adenosine tract dictated low NspA expression, whereas a 6-adenosine motif guided high NspA expression. Screening German cc41/44 strain collections revealed the 6-adenosine motif in 39% of disease isolates, but only in 3.4% of carriage isolates. Thus, high NspA expression is associated with disease, but not strictly required. The 6-adenosine nspA promoter is most common to the cc41/44, but is also found in other hypervirulent clonal complexes.
Human A3 adenosine receptor hA3AR has been implicated in gastrointestinal cancer, where its cellular expression has been found increased, thus suggesting its potential as a molecular target for novel anticancer compounds. Observation made in our previous work indicated the importance of the carbonyl group of amide in the indolylpyrimidylpiperazine (IPP) for its human A2A adenosine receptor (hA2AAR) subtype binding selectivity over the other AR subtypes. Taking this observation into account, we structurally modified an indolylpyrimidylpiperazine (IPP) scaffold, 1 (a non-selective adenosine receptors’ ligand) into a modified IPP (mIPP) scaffold by switching the position of the carbonyl group, resulting in the formation of both ketone and tertiary amine groups in the new scaffold. Results showed that such modification diminished the A2A activity and instead conferred hA3AR agonistic activity. Among the new mIPP derivatives (3–6), compound 4 showed potential as a hA3AR partial agonist, with an Emax of 30% and EC50 of 2.89 ± 0.55 μM. In the cytotoxicity assays, compound 4 also exhibited higher cytotoxicity against both colorectal and liver cancer cells as compared to normal cells. Overall, this new series of compounds provide a promising starting point for further development of potent and selective hA3AR partial agonists for the treatment of gastrointestinal cancers.
The East Himalaya is one of the world’s most biodiverse ecosystems. However, very little is known about the abundance and distribution of many plant and animal taxa in this region. Bumble bees are a group of cold-adapted and high elevation insects that fulfil an important ecological and economical function as pollinators of wild and agricultural flowering plants and crops. The Himalayan mountain range provides ample suitable habitats for bumble bees. Systematic study of Himalayan bumble bees began a few decades ago and the main focus has centred on the western region, while the eastern part of the mountain range has received little attention and only a few species have been verified. During a three-year survey, more than 700 bumble bee specimens of 21 species were collected in Arunachal Pradesh, the largest of the north-eastern states of India. The material included a range of species that were previously known from a limited number of collected specimens, which highlights the unique character of the East Himalayan ecosystem. Our results are an important first step towards a future assessment of species distribution, threat, and conservation. Clear elevation patterns of species diversity were observed, which raise important questions about the functional adaptations that allow bumble bees to thrive in this particularly moist region in the East Himalaya.
"MUS-IC-ON! Klang der Antike" ist der Begleitband zur gleichnamigen Sonderausstellung im Martin von Wagner-Museum Würzburg (10. Dezember 2019 bis 12. Juli 2020). Die eigene Musik zu verstehen verlangt auch, nach Klängen und Musik der Vergangenheit zu fragen. So offenbart der Blick auf antike Musikkulturen – des Vorderen Orients, Ägyptens, Griechenlands und Roms – dem Betrachter kulturelle Konstanten, deren Vermächtnis sich in unserer abendländischen Musik erhält. Ziel des Begleitbands zur Ausstellung "MUS-IC-ON! Klang der Antike" ist es, die Relevanz musikhistorischer und –archäologischer Forschung für das Verständnis der eigenen Musikkultur aufzuzeigen. An vier Schwerpunkten werden die Inhalte, Methoden und der Stand der Erforschung antiker Musik von international namhaften Wissenschaftler*innen in einer umfassenden und dennoch allgemein verständlichen Weise vorgestellt. Der reichhaltig bebilderte Band ist damit als ein einführendes und informatives Handbuch konzipiert, das über die Ausstellung hinaus von fachfremden Wissenschaftlern, Studierenden und interessierten Laien konsultiert wird.
1. Vom archäologischen Artefakt zum klingenden Instrument: Grundlage jedweder Erforschung antiker Musik ist die Rekonstruktion seiner Klangvielfalt. Unzählige Funde originaler Musikinstrumente, darunter vorderasiatische Kastenleiern, altägyptische Trompeten aus dem Grab des Tutanchamun oder die griechisch-römische Hydraulis, eröffnen einen Weg, den Klängen antiker Musik nachzugehen. Insgesamt sechs Beiträge mit einem historischen Rahmen, der von der Steinzeit bis in die römische Kaiserzeit reicht, stellen die Vorgehensweise aber auch die Herausforderungen bei der Bergung, Erforschung und dem Nachbau antiker Musikinstrumente vor.
2. Musik und Klang in Bild und Text: Ein umfassendes Bild vom Einsatz, der Spielweise, der Verbreitung und Entwicklung antiker Musikinstrumente liefern antike Bilder und Texte. Trotz der Vielfalt an Objekten, darunter griechische Vasen, assyrische Reliefbilder oder römische Mosaike, bedarf es einer analytischen und kritischen Herangehensweise bei der Analyse und Auswertung solcher Daten. Vorgestellt werden in diesem Themenschwerpunkt auch antike Notationsformen und Stimmungssysteme, die sich auf Papyri und Keilschrifttafeln erhalten haben, sowie die Schwierigkeiten ihrer Entzifferung.
3. Musikleben in der Antike: Wesentlich für das Verständnis antiker Musik ist die Kenntnis ihres Einsatzes und ihres Umfeldes. Getrennt nach den verschiedenen Kulturkreisen stellen in diesem Kapitel insgesamt neun Autoren unterschiedliche Bereiche und Funktionen des Musizierens vor. Herausragend ist hier die Rolle von Musik im täglichen Tempelkult, über die sich die in der Antike vorgestellte Macht von Musik aufzeigen lässt, die sogar auf die Gemüter der Götter Einfluss zu nehmen vermag. Zusätzlich aufschlussreich ist das Wissen von Ausbildung und Aufstieg auch namentlich bekannter Musiker, zumeist Hofmusiker, die den Ruhm ihres Königs verkünden, aber auch regelrechte Virtuosen, die sich beispielsweise in antiken Wettstreiten hervortun, den musischen Agonen.
4. Kontinuität und Interkulturalität antiker Musikkulturen: Dieser Teil widmet sich Spuren, die antike Musikkulturen in der abendländischen sowie in orientalischen Kulturräumen hinterlassen haben. So geht unser modernes Tonsystem auf griechische, ja sogar auf babylonische Tonleitern zurück. Vorläufer der europäischen Kirchenorgel ist die Hydraulis, eine griechische Erfindung aus dem 3. vorchristlichen Jahrhundert. Viele vor über 4500 Jahren zwischen Euphrat und Tigris entwickelte Musikinstrumente werden noch heute im arabischen und afrikanischen Kulturkreis, ja selbst in nord- und osteuropäischen Ländern gespielt. Hervorgehoben werden außerdem historische Momente, die einen wesentlichen Einfluss auf die Entwicklung moderner Musiksysteme ausgeübt haben.
Die Autoren:
Benedetta Bellucci (Vorderasiatische Archäologie, Mainz), Arndt A. Both (Altamerikanistik, Musikarchäologie, DAI Berlin), Ricardo Eichmann (Vorderasiatische Archäologie, DAI Berlin), Uri Gabbay (Altorientalistik, Jerusalem), Ralf Gehler (Instrumentenbauer, Schwerin), Carolin Goll (Martin von Wagner-Museum, Würzburg), Jochen Griesbach (Martin von Wagner-Museum, Klassische Archäologie, Würzburg), Stefan Hagel (Klassische Philologie, ÖAW Wien), Katharina Hepp (Ägyptologie, Würzburg), Peter Holmes (Instrumentenbauer, London), Marie Klein (Altorientalisik, Würzburg), Carola Koch Ägyptologie, Würzburg), Ulrich Konrad (Historische Musikwissenschaft, Würzburg), Eva Kurz (Ägyptologie Würzburg), Florian Leitmeir (Klassische Archäologie, Würzburg), Thomas Ludewig (Klassische Archäologie, Würzburg), Sam Mirelman (Altorientalistik, London), Daniel Schwemer (Altorientalistik, Würzburg), Dahlia Shehata (Altorientalisik, Würzburg), Martin Stadler (Ägyptologie, Würzburg), Olga Sutkowska (Kulturgeschicht der Antike, ÖAW Wien), Günther E. Thüry (Provinzialrömische Archäologie, Salzburg), Marc Wahl (Numismatik, Wien/Würzburg), Oliver Wiener (Historische Musikwissenschaft, Würzburg), Nele Ziegler (Altorientalistik, Paris)
Nationalparks sind das älteste und bekannteste flächenbezogene Naturschutzinstrument weltweit. Für den Erhalt einer nachhaltigen Lebensgrundlage und die Entwicklung der Biodiversität sowie für mehr Naturdynamik in der Landschaft haben sie eine sehr große Bedeutung, auch in unseren Breiten. Dennoch ist die Einstellung zu Nationalparks von Seiten der unmittelbaren Anwohner nicht immer unproblematisch. Entsprechend versucht die vorliegende wissenschaftliche Analyse neue Erkenntnisse bezüglich der Akzeptanz der Nationalparks Bayerischer Wald und Berchtesgaden, den ältesten Deutschlands, aufzuzeigen. Empirische Grundlagen für diese Studie sind eine bayernweite Online-Befragung, qualitative Experteninterviews und aufwändige repräsentative schriftliche Befragungen in den Nationalpark-Landkreisen Regen und Freyung-Grafenau bzw. Berchtesgadener Land im Jahr 2018. Auch die zeitliche Entwicklung der Akzeptanz wird auf Basis der Ergebnisse von Vorgängerstudien, soweit möglich, berücksichtigt. Dabei sind es ökonomische, emotionale, interpersonelle, soziokulturelle und nicht zuletzt für Geographen besonders interessante raumzeitliche Prädiktoren der Akzeptanz beider Nationalparks, die im Fokus der Untersuchungen stehen.
Dishevelled (DVL) is the key component of the Wnt signaling pathway. Currently, DVL conformational dynamics under native conditions is unknown. To overcome this limitation, we develop the Fluorescein Arsenical Hairpin Binder- (FlAsH-) based FRET in vivo approach to study DVL conformation in living cells. Using this single-cell FRET approach, we demonstrate that (i) Wnt ligands induce open DVL conformation, (ii) DVL variants that are predominantly open, show more even subcellular localization and more efficient membrane recruitment by Frizzled (FZD) and (iii) Casein kinase 1 ɛ (CK1ɛ) has a key regulatory function in DVL conformational dynamics. In silico modeling and in vitro biophysical methods explain how CK1ɛ-specific phosphorylation events control DVL conformations via modulation of the PDZ domain and its interaction with DVL C-terminus. In summary, our study describes an experimental tool for DVL conformational sampling in living cells and elucidates the essential regulatory role of CK1ɛ in DVL conformational dynamics.
Preclinical studies point to a pivotal role of the orexin 1 (OX1) receptor in arousal and fear learning and therefore suggest the HCRTR1 gene as a prime candidate in panic disorder (PD) with/without agoraphobia (AG), PD/AG treatment response, and PD/AG-related intermediate phenotypes. Here, a multilevel approach was applied to test the non-synonymous HCRTR1 C/T Ile408Val gene variant (rs2271933) for association with PD/AG in two independent case-control samples (total n = 613 cases, 1839 healthy subjects), as an outcome predictor of a six-weeks exposure-based cognitive behavioral therapy (CBT) in PD/AG patients (n = 189), as well as with respect to agoraphobic cognitions (ACQ) (n = 483 patients, n = 2382 healthy subjects), fMRI alerting network activation in healthy subjects (n = 94), and a behavioral avoidance task in PD/AG pre- and post-CBT (n = 271). The HCRTR1 rs2271933 T allele was associated with PD/AG in both samples independently, and in their meta-analysis (p = 4.2 × 10−7), particularly in the female subsample (p = 9.8 × 10−9). T allele carriers displayed a significantly poorer CBT outcome (e.g., Hamilton anxiety rating scale: p = 7.5 × 10−4). The T allele count was linked to higher ACQ sores in PD/AG and healthy subjects, decreased inferior frontal gyrus and increased locus coeruleus activation in the alerting network. Finally, the T allele count was associated with increased pre-CBT exposure avoidance and autonomic arousal as well as decreased post-CBT improvement. In sum, the present results provide converging evidence for an involvement of HCRTR1 gene variation in the etiology of PD/AG and PD/AG-related traits as well as treatment response to CBT, supporting future therapeutic approaches targeting the orexin-related arousal system.