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Year of publication
- 2020 (2525) (remove)
Document Type
- Article (1462)
- Doctoral Thesis (233)
- Part of Periodical (215)
- Preprint (173)
- Contribution to a Periodical (140)
- Working Paper (115)
- Book (88)
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- Bachelor Thesis (11)
- Master's Thesis (11)
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- English (1726)
- German (767)
- Portuguese (11)
- French (6)
- Spanish (4)
- Italian (3)
- Multiple languages (3)
- slo (3)
- Turkish (2)
Keywords
- Capital Markets Union (25)
- Financial Markets (25)
- Coronavirus (24)
- ECB (24)
- COVID-19 (23)
- inflammation (18)
- SARS-CoV-2 (15)
- coronavirus (15)
- Financial Institutions (13)
- Banking Regulation (12)
Institute
- Medizin (742)
- Präsidium (278)
- Physik (269)
- Wirtschaftswissenschaften (216)
- Sustainable Architecture for Finance in Europe (SAFE) (167)
- Biowissenschaften (159)
- Frankfurt Institute for Advanced Studies (FIAS) (152)
- Informatik (117)
- Biochemie, Chemie und Pharmazie (104)
- Neuere Philologien (95)
Rezensionen [2020]
(2020)
Kliewer, Heinz-Jürgen ; Franz, Kurt ; Henning-Mohr, Astrid ; Stierstorfer, Michael ; Planka, Sabine ; Führer, Carolin ; Blumesberger, Susanne ; Bäni Rigler, Petra ; Hoffmann, Lena ; Seibert, Ernst ; Ißler, Roland Alexander ; Kullmann, Thomas ; Paiska, Maike ; Dammers, Ben ; Bieker, Nadine ; Holzen, Aleta-Amirée von ; Kliewer, Annette ; Henning-Mohr, Astrid ; Fuchs, Sabine
Verzeichnis
Einzelrezensionen
148 Bäni Rigler, Petra: Bilderbuch – Lesebuch – Künstlerbuch. Elsa Beskows Ästhetik des Materiellen (Heinz-Jürgen Kliewer)
149 Barilaro, Christina/Oetken, Mareile(Hg.): Erzähl mir vom Tier. Tiere in der Kinderliteratur und in der Natur (Kurt Franz)
151 Bieker, Nadine: Erzählanfänge und Erzählschlüsse im Adoleszenzroman (Astrid Henning-Mohr)
153 Blumesberger, Susanne/Seibert, Ernst (Hg.): Kinderliteratur in Wien um 1800 (Michael Stierstorfer)
154 Brons, Patricia/Nickel, Artur /Nicolai, Matthias (Hg.): Kästneriaden zum 120. Geburtstag (Sabine Planka)
156 Dallmann, Christine/Hartung, Anja/Aigner, Alfons /Buchele, Kai-Thorsten (Hg.): Comics. Interdisziplinäre Perspektiven aus Theorie und Praxis auf ein Stiefkind der Medienpädagogik (Carolin Führer)
157 Darr, Yael: The Nation and the Child. Nation Building in Hebrew Children’s Literature, 1930–1970 (Susanne Blumesberger)
159 Dingelmaier, Theresia: Das Märchen vom Märchen. Eine kultur- und literaturwissenschaftliche Untersuchung des deutschsprachigen jüdischen Volks- und Kindermärchens (Kurt Franz)
161 Field, Hannah: Playing with the Book. Victorian Movable Picture Books and the Child Reader (Petra Bäni Rigler)
163 Gittinger, Kerstin/ Loidl, Sonja (Hg.): Unter Wölfen. Käthe Recheis – Literatur und Politik (Lena Hoffmann)
164 Giuriato, Davide/Hubmann, Philipp/Schildmann, Mareike (Hg.): Kindheit und Literatur. Konzepte – Poetik – Wissen (Ernst Seibert)
166 Glasenapp, Gabriele von/Pecher, Claudia Maria/Anker, Martin (Hg.): Martin Luther und die Reformation in der Kinder- und Jugendliteratur. Beiträge zur literarhistorischen und literarästhetischen Praxis (Roland Issler)
169 Gruner, Elizabeth Rose: Constructing the Adolescent Reader in Contemporary Young Adult Fiction (Thomas Kullmann)
171 Harde, Roxanne/Kokkola, Lydia (Hg.): The Embodied Child. Readings in Children’s Literature and Culture (Thomas Kullmann)
172 Holzen, Aleta-Amirée von: Maskierte Helden. Zur Doppelidentität in Pulp-Novels und Superheldencomics (Maike Paiska)
174 Hubli, Kathrin: Kunstprojekt (Mumin-)Buch. Tove Janssons prozessuale Ästhetik und materielle Transmission (Ben Dammers)
175 Jantzen, Christoph/ Josting, Petra/Ritter, Michael (Hg.): Ästhetik – Leserbezug – Wirkung. Ansprüche an Kinder- und Jugendliteratur im Wandel der Zeit (Nadine Bieker)
177 Jung, Britta C.: Komplexe Lebenswelten – multidirektionale Erinnerungsdiskurse. Jugendliteratur zum Nationalsozialismus, Zweiten Weltkrieg und Holocaust im Spiegel des postmemorialen Wandels (Susanne Blumesberger)
179 Meyer, Christina: Producing Mass Entertainment. The Serial Life of the Yellow Kid (Aleta-Amirée von Holzen)
181 Rox-Helmer, Monika: Der historische Jugendroman als geschichtskulturelle Gattung. Fiktionalisierung von Geschichte und ihr didaktisches Potential (Annette Kliewer)
182 Seidel, Nadine Maria: Adoleszenz, Geschlecht, Identität. Queere Konstruktionen in Romanen nach der Jahrtausendwende (Annette Kliewer)
184 Sonyem, Alain Belmond: Kinder- und Jugendliteratur als Gegendiskurs? Zu Afrikavorstellungen in neueren deutschen und deutschafrikanischen Kinder- und Jugendbüchern (Astrid Henning-Mohr)
186 Sprenger, Karoline: Bertolt Brechts Kinderlyrik. Hintergründe, Analysen und fachdidaktische Perspektiven (Kurt Franz)
188 Uhlig, Bettina/ Lieber, Gabriele/Pieper, Irene (Hg.): Erzählen zwischen Bild und Text (Heinz-Jürgen Kliewer) 190 Van Nahl, Ruth: Jugendkrimis im 21. Jahrhundert. Eine Typologie (Sabine Fuchs)
192 Wietersheim, Annegret von: »Später einmal werde ich es dir erzählen«. Leerstellen in der Kinder- und Jugendliteratur der 1950er Jahre (Susanne Blumesberger)
An Kinder- und Jugendliteratur (KJL) herrschte in der DDR, die ja bekanntlich in vielen Bereichen durch Mangelwirtschaft gekennzeichnet war, tatsächlich kein Mangel. Sie wurde vom Staat gefördert und unterstützt, weil sie als wichtiges Instrument der sozialistischen Erziehung von Kindern und Jugendlichen galt (vgl. Lüdecke 2002, S. 434). Insofern besaß die KJL in der DDR einen vergleichsweise höheren gesellschaftlichen, politischen und künstlerischen Stellenwert als in der alten Bundesrepublik. Auch war die Grenze zwischen AutorInnen, die für eine erwachsene und eine kindliche bzw. jugendliche Leserschaft schrieben, nicht so strikt gezogen, wie man dies aus der Bundesrepublik kannte...
In Ludwig Tiecks Die Elfen (1812) und E.T.A. Hoffmanns Das fremde Kind (1817) nehmen Naturräume eine zentrale Position ein. Insbesondere der Wald ist als ein Kindheitsraum besetzt, der ambivalent konnotiert ist. Im Wald können sich die kindlichen Figuren fernab der Eltern autonom bewegen, dennoch geht diese Raumaneignung auch mit bedrohlichen Erfahrungen einher, die die aufstörenden Ablösungsprozesse in der Kindheit verdeutlichen...
Tankstellen im Alltag sind grundsätzlich unauffällig. Überlandstraßen und Autobahnen saumend, eingefaltet in urbane Raume oder als Element suburbaner, industrieller Zonen nimmt man sie kaum wahr. Werden sie jedoch gebraucht, sei es zum Tanken, sei es zum Einkaufen abseits der üblichen Öffnungszeiten, rücken sie aus ihrer Latenz von einem Augenblick auf den anderen in den Vordergrund der Wahrnehmung und können für Reisende zu einer Obsession werden – rettende Oasen in der Wüste...
In der Antike und den überlieferten antiken Mythen spielen Visionen bzw. Prophezeiungen und Träume – wie sich beispielsweise am Status des Orakels von Delphi als Omphalos (Giebel 2001, S. 7 f.) oder am vom römischen Philosophen Lukrez beschriebenen Beruf des Traumdeuters (Naf 2004, S. 90 f.) erkennen lasst – eine wichtige Rolle und nehmen ebenfalls politischen Einfluss (Trampedach 2015). Es ist daher nicht verwunderlich, dass auch gegenwärtige Mythenadaptionen, allen voran Rick Riordans Percy Jackson-Reihe bzw. mittlerweile korrekter: Reihen, in denen Percy Jackson mitunter als Crossover-Figur auftritt, auf Orakel, Prophezeiungen, Visionen und Träume vermehrt zurückgreifen...
In Franz Hohlers Tschipo (1978), dem ersten Teil einer Trilogie, erlebt ein Schweizer Junge Abenteuer auf seltsamen Inseln. Und in Maggie Stiefvaters Serien The Raven Cycle (2012 – 2016) und The Dreamer Trilogy (2019 – ) bekämpft ein amerikanischer junger Erwachsener mit Namen Ronan Lynch magische Gefahren. Was haben Tschipo und Ronan gemeinsam? Eine seltsame Gabe: Von ihren Träumen bleibt am Morgen etwas zurück...
Dieses Buch ist so Mindfuck. [...] [D]ieses Buch lebt davon, dass man keinen Plan hat. Dass man, genau wie der Protagonist, keine Ahnung hat, was da eigentlich abgeht. [...] Wie der Protagonist hinterfragt man das, was man kennt, denkt sich zwischendurch »wtf« und ist sich einschließlich des Endes nie so ganz sicher, was jetzt eigentlich Sache ist. (Weltentraeumerin 2019)
Dieses Urteil der LovelyBooks-Rezensentin Weltentraeumerin über Patrick Ness’ Mehr als das (engl. EA More Than This) ist insofern repräsentativ, als fast alle der etwas ausführlicheren Rezensionen auf der Plattform hervorheben, dass die Lektüre dieses Buches mehr Fragen aufwirft als sie beantwortet...
Traumdarstellungen in Büchern und Filmen mit ›ambiguem‹ Ende sind in der Populärkultur seit den 1990er-Jahren beliebt. (Kuhn 2009, S. 141 f.) Man kann die Popularität solcher plot-Strukturen durchaus plausibel als Reaktion der Kunst auf die zunehmende Komplexität der Gesellschaft (Berndt / Koepnick 2018, S. 7) deuten. Diese Komplexitätssteigerung ergibt sich beispielsweise durch die Möglichkeiten digitaler Technologien, neben der wirklichen Welt auch virtuelle Welten, eine virtual, mixed oder augmented reality, zu kreieren, in denen sich die Grenze zwischen Realität und Fiktion verschiebt.
»Nun denkt der Traum hauptsächlich in Bildern« (Freud 2008, S. 51), stellt schon Sigmund Freud 1900 in seiner Traumdeutung fest. Träumen ist nach Freud eine visuelle Erfahrung, und als solche erscheint das Bilderbuch prädestiniert, Träume darzustellen. Was von dem Abgebildeten jedoch Traum ist und was nicht, lässt sich nicht immer eindeutig bestimmen...
Editorial [2020, english]
(2020)
Combining cultural history with the insights of psychoanalytic theory, this article examines Maurice Sendak's Caldecott-winning and controversial Where the Wild Things Are (1963), arguing that Sendak’s book represents picturebook psychology as it stood in the early 1960s but also radically recasts it, paving the way for a groundswell in applied picturebook psychology. The book can be understood as rewriting classical Freudian analysis, retaining some of its rigor and edge while making it more palatably American. Where the Wild Things Are has been embraced as a psychological primer, a story about anger and its management through fantasy; it is also a text in which echoes of Freud remain audible. It is read it here as a bedtime-story version of Freud’s Wolf Man case history of 1918, an updated and upbeat dream of the wolf boy. It is to Sendak what the Wolf Man case was to Freud, a career-making feral tale. Standing at the crossroads of Freudian tradition, child analysis, humanistic psychology, and bibliotherapy, the article reveals how the book both clarified and expanded the uses of picturebook enchantment.
Die Phänomene des Traums und Träumens als allnächtliche Konfrontation mit dem Fremden und Anderen des wachen (Er-)Lebens (vgl. Engel 2003, S. 153) wie auch der wachen Persönlichkeit üben eine nachhaltige Faszination aus, die maßgeblich auf ihre ambivalente Charakteristik zurückzuführen ist. Der/die Träumende befindet sich in einem Stadium jenseits der Realität, in einem Dazwischen von Leben und Tod, und ist »mit einer Erlebenswelt und einer Erlebensweise konfrontiert, die [Manfred Engel zufolge] auf ebenso evidente wie rätselhafte Weise anders sind als die des wachen Lebens« (ebd.)...
"Die Träume gehören zweifellos zur Wirklichkeit" : Traum-Erzählungen über Kindheit und für Kinder
(2020)
Theodor Storms Kindermärchen Der kleine Häwelmann, von dem Autor 1849 für seinen Sohn Hans verfasst und 1850 veröffentlicht, ist in seiner moralisch-komischen Form ein exemplarisches Exponat der Kinderliteratur des 19. Jahrhunderts. Gemäß der biedermeierlich gestimmten, belehrenden Funktion des Textes steht kindliche Allmachtsfantasie im Mittelpunkt des Geschehens. Die Haltung des ›Mehr-mehr‹ überschreitet indes die Grenzen der Moralerzählung. Entgegen der abschreckenden Funktion scheint vielmehr der kleine Häwelmann in der Verschränkung von Norm-Übertritt und Eskapismus ein ›modernes‹ Kind seiner Entstehungszeit zu sein und durchaus mit den Figuren des Struwwelpeters vergleichbar, die der Arzt und Kinderpsychiater Heinrich Hoffmann 1845 entworfen hat...
Editorial [2020, deutsch]
(2020)
Klingelhöfer, Doris ; Braun, Markus ; Seeger-Zybok, Rebekka ; Quarcoo, David ; Brüggmann, Dörthe ; Groneberg, Jan David Alexander
Background: Fabry disease (FD), the second most prevalent lysosomal storage disorder, is classified as a rare disease. It often leads to significant quality of life impairments and premature death. Many cases remain undiagnosed due to the rarity and heterogeneity. Further, costs related to treatment often constitute a substantial financial burden for patients and health systems. While its epidemiology is still unclear, newborn screenings suggest that its actual prevalence rate is significantly higher than previously suspected. Methods: Based on well-established methodologies, this study gives an overview about the background of the development of FD-related research and provides a critical view of future needs. Results: On the grounds of benchmarking findings, an increasing research activity on FD can be observed. Most publishing countries are the USA, some European countries, Japan, Taiwan, and South Korea. In general, high-income countries publish comparably more on FD than low- or middle-income economies. The countries' financial and infrastructural background are unveiled as crucial factors for the FD research activity. Conclusions: Overall, there is a need to foster FD research infrastructure in developing and emerging countries with focus on cost-intensive genetic research that is independent from economic interests of big pharmaceutical companies.
Lapa, Sriramya ; Claus, Inga ; Reitz, Sarah ; Quick-Weller, Johanna ; Sauer, Sonja ; Colbow, Sigrid ; Nasari, Christiane ; Dziewas, Rainer ; Kang, Jun-Suk ; Baudrexel, Simon ; Warnecke, Tobias
Objective: Deep brain stimulation (DBS) of the ventral intermediate nucleus (VIM) is a mainstay treatment for severe and drug-refractory essential tremor (ET). Although stimulation-induced dysarthria has been extensively described, possible impairment of swallowing has not been systematically investigated yet. Methods: Twelve patients with ET and bilateral VIM-DBS with self-reported dysphagia after VIM-DBS were included. Swallowing function was assessed clinically and using by flexible endoscopic evaluation of swallowing in the stim-ON and in the stim-OFF condition. Presence, severity, and improvement of dysphagia were recorded. Results: During stim-ON, the presence of dysphagia could be objectified in all patients, 42% showing mild, 42% moderate, and 16 % severe dysphagia. During stim-OFF, all patients experienced a statistically significant improvement of swallowing function. Interpretation: VIM-DBS may have an impact on swallowing physiology in ET-patients. Further studies to elucidate the prevalence and underlying pathophysiological mechanisms are warranted.
Global landscapes are changing due to human activities with consequences for both biodiversity and ecosystems. For single species, terrestrial mammal population densities have shown mixed responses to human pressure, with both increasing and decreasing densities reported in the literature. How the impacts of human activities on mammal populations translates into altered global density patterns remains unclear. Here we aim to disentangle the effect of human impacts on large-scale patterns of mammal population densities using a global dataset of 6729 population density estimates for 468 mammal species (representing 59% and 44% of mammalian orders and families). We fitted a mixed effect model to explain the variation in density based on a 1-degree resolution as a function of the human footprint index (HFI), a global proxy of direct and indirect human disturbances, while accounting for body mass, trophic level and primary productivity (normalized vegetation index; NDVI). We found a significant positive relationship between population density and HFI, where population densities were higher in areas with a higher HFI (e.g. agricultural or suburban areas – no populations were located in very high HFI urban areas) compared to areas with a low HFI (e.g. wilderness areas). We also tested the effect of the individual components of the HFI and still found a consistent positive effect. The relationships remained positive even across populations of the same species, although variability among species was high. Our results indicate shifts in mammal population densities in human modified landscapes, which is due to the combined effect of species filtering, increased resources and a possible reduction in competition and predation. Our study provides further evidence that macroecological patterns are being altered by human activities, where some species will benefit from these activities, while others will be negatively impacted or even extirpated.
Strack, Elisabeth ; Rolfe, P. Alexander ; Fink, Annika ; Bankov, Katrin ; Schmid, Tobias ; Solbach, Christine ; Savai, Rajkumar ; Sha, Weixiao ; Pradel, Leon ; Hartmann, Sylvia ; Brüne, Bernhard ; Weigert, Andreas
Background: Breast cancer is the leading cause of cancer-related deaths in women, demanding new treatment options. With the advent of immune checkpoint blockade, immunotherapy emerged as a treatment option. In addition to lymphocytes, tumor-associated macrophages exert a significant, albeit controversial, impact on tumor development. Pro-inflammatory macrophages are thought to hinder, whereas anti-inflammatory macrophages promote tumor growth. However, molecular markers to identify prognostic macrophage populations remain elusive. Methods: We isolated two macrophage subsets, from 48 primary human breast tumors, distinguished by the expression of CD206. Their transcriptomes were analyzed via RNA-Seq, and potential prognostic macrophage markers were validated by PhenOptics in tissue microarrays of patients with invasive breast cancer. Results: Normal human breast tissue contained mainly CD206+ macrophages, while increased relative amounts of CD206− macrophages were observed in tumors. The presence of CD206+ macrophages correlated with a pronounced lymphocyte infiltrate and subsets of CD206+ macrophages, expressing SERPINH1 and collagen 1, or MORC4, were unexpectedly associated with improved survival of breast cancer patients. In contrast, MHCIIhi CD206− macrophages were linked with a poor survival prognosis. Conclusion: Our data highlight the heterogeneity of tumor-infiltrating macrophages and suggest the use of multiple phenotypic markers to predict the impact of macrophage subpopulations on cancer prognosis. We identified novel macrophage markers that correlate with the survival of patients with invasive mammary carcinoma.
Hoffmann, Jedrzej ; Mas-Peiro, Silvia ; Berkowitsch, Alexander ; Böckling, Felicitas Juana ; Rasper, Tina ; Pieszko, Konrad ; De Rosa, Roberta ; Hiczkiewicz, Jarosław ; Burchardt, Paweł ; Fichtlscherer, Stephan ; Zeiher, Andreas M. ; Dimmeler, Stefanie ; Vasa-Nicotera, Mariuca
Aims: Systemic inflammatory response, identified by increased total leucocyte counts, was shown to be a strong predictor of mortality after transcatheter aortic valve implantation (TAVI). Yet the mechanisms of inflammation-associated poor outcome after TAVI are unclear. Therefore, the present study aimed at investigating individual inflammatory signatures and functional heterogeneity of circulating myeloid and T-lymphocyte subsets and their impact on 1 year survival in a single-centre cohort of patients with severe aortic stenosis undergoing TAVI. Methods and results: One hundred twenty-nine consecutive patients with severe symptomatic aortic stenosis admitted for transfemoral TAVI were included. Blood samples were obtained at baseline, immediately after, and 24 h and 3 days after TAVI, and these were analysed for inflammatory and cardiac biomarkers. Myeloid and T-lymphocyte subsets were measured using flow cytometry. The inflammatory parameters were first analysed as continuous variables; and in case of association with outcome and area under receiver operating characteristic (ROC) curve (AUC) ≥ 0.6, the values were dichotomized using optimal cut-off points. Several baseline inflammatory parameters, including high-sensitivity C-reactive protein (hsCRP; HR = 1.37, 95% CI: 1.15–1.63; P < 0.0001) and IL-6 (HR = 1.02, 95% CI: 1.01–1.03; P = 0.003), lower counts of Th2 (HR = 0.95, 95% CI: 0.91–0.99; P = 0.009), and increased percentages of Th17 cells (HR = 1.19, 95% CI: 1.02–1.38; P = 0.024) were associated with 12 month all-cause mortality. Among postprocedural parameters, only increased post-TAVI counts of non-classical monocytes immediately after TAVI were predictive of outcome (HR = 1.03, 95% CI: 1.01–1.05; P = 0.003). The occurrence of SIRS criteria within 48 h post-TAVI showed no significant association with 12 month mortality (HR = 0.57, 95% CI: 0.13–2.43, P = 0.45). In multivariate analysis of discrete or dichotomized clinical and inflammatory variables, the presence of diabetes mellitus (HR = 3.50; 95% CI: 1.42–8.62; P = 0.006), low left ventricular (LV) ejection fraction (HR = 3.16; 95% CI: 1.35–7.39; P = 0.008), increased baseline hsCRP (HR = 5.22; 95% CI: 2.09–13.01; P < 0.0001), and low baseline Th2 cell counts (HR = 8.83; 95% CI: 3.02–25.80) were significant predictors of death. The prognostic value of the linear prediction score calculated of these parameters was superior to the Society of Thoracic Surgeons score (AUC: 0.88; 95% CI: 0.78–0.99 vs. 0.75; 95% CI: 0.64–0.86, respectively; P = 0.036). Finally, when analysing LV remodelling outcomes, ROC curve analysis revealed that low numbers of Tregs (P = 0.017; AUC: 0.69) and increased Th17/Treg ratio (P = 0.012; AUC: 0.70) were predictive of adverse remodelling after TAVI. Conclusions: Our findings demonstrate an association of specific pre-existing inflammatory phenotypes with increased mortality and adverse LV remodelling after TAVI. Distinct monocyte and T-cell signatures might provide additive biomarkers to improve pre-procedural risk stratification in patients referred to TAVI for severe aortic stenosis.
In der vorliegenden Studie wurden Patienten mit struktureller Epilepsie bedingt durch eine fokale kortikale Dysplasie (FCD) mittels moderner Magnetresonanztomographie (MRT)-Verfahren untersucht.
Bei FCDs handelt es sich um Fehlbildungen der Großhirnrinde, die mit einer hohen epileptogenen Aktivität vergesellschaftet sind. Einige dieser Patienten unterziehen sich einer epilepsiechirurgischen Resektion, sind jedoch hiernach hinsichtlich ihrer Anfallsfrequenz dennoch nicht ausreichend kontrollierbar, weshalb Grund zur Annahme besteht, dass es neben der fokalen kortikalen Dysplasie andere Faktoren geben könnte, die epileptische Anfälle verursachen.
Basierend auf dieser Überlegung wurde mittels T2-Relaxometrie untersucht, ob bei Patienten mit FCDs mikrostrukturelle Veränderungen in Teilen des Kortex vorhanden sind, die mittels konventioneller MRT-Verfahren normal bzw. gesund erscheinen. Es wird angenommen, dass bei diesen Patienten auch außerhalb der FCD mikrostrukturelle Veränderungen, beispielsweise bedingt durch Schädigung im Rahmen von Anfällen oder durch Therapieeffekte, vorzufinden sind.
Für die Studie wurden 16 Patienten mit einer neuroradiologisch gesicherten FCD und 16 hinsichtlich des Alters und des Geschlechts gematchte gesunde Probanden rekrutiert.
Die Daten wurden an einem 3 Tesla (T) MRT-Scanner erhoben. Um die T2-Relaxationszeit zu messen, wurden Spin-Echo Datensätze mit verschiedenen Echozeiten (TE) aufgezeichnet. Zur Erfassung der Ausdehnung der FCD wurden konventionelle fluid-attenuated inversion recovery (FLAIR)-Datensätze akquiriert. Zur Segmentierung des Gewebes wurden synthetische T1-gewichtete magnetization-prepared rapid acquisition of gradient echos (MP-RAGE)-Datensätze aus quantitativen T1-Karten berechnet. Der Kortex und dessen Grenzflächen wurden mittels FreeSurfer anhand der MP-RAGE-Datensätze identifiziert und die kortikale Dicke wurde gemessen. Die FCD-Areale wurden in den FLAIR-Datensätzen manuell markiert und aus den T2-Karten exkludiert, um die FCD-assoziierten Veränderungen nicht in die Analyse einzubeziehen.
Anschließend wurden kortikale T2-Werte ausgelesen und in Oberflächendatensätzen gespeichert, um dann durchschnittliche kortikale T2-Werte für jeden Probanden zu ermitteln und mittels ungepaartem t-Test zwischen den Gruppen zu vergleichen. Zudem wurde der Pearson-Korrelationskoeffizient zwischen den kortikalen T2 Werten und klinischen Parametern berechnet. Außerdem wurde eine oberflächenbasierte Gruppenanalyse kortikaler T2-Werte und der kortikalen Dicke durchgeführt. Hierbei wurden Permutationssimulationen durchgeführt, um kortikale Cluster zu erkennen, die fokale Gruppenunterschiede anzeigen, und um für Mehrfachvergleiche zu korrigieren.
Die Analyse ergab, dass die durchschnittlichen kortikalen T2-Werte außerhalb der FCD in der Patientenkohorte im Vergleich zu den gesunden Probanden signifikant erhöht waren. Diese T2-Veränderungen zeigten weder eine signifikante Korrelation mit der Anzahl der Anfälle der letzten drei Monate, noch mit der Anzahl der jemals eingenommenen antiepileptischen Medikamente. Insbesondere wurden T2-Erhöhungen in den frontalen, parietalen und manchen temporalen Regionen festgestellt. Die oberflächenbasierte Analyse der Kortexdicke zeigte keine signifikanten Gruppenunterschiede.
Mittels T2-Relaxometrie und oberflächenbasierten Analyse-Techniken wurden demnach T2-Veränderungen des mittels konventioneller MRT-Bildgebung unauffällig erscheinenden zerebralen Kortex bei Patienten mit FCD und Epilepsie festgestellt.
Die Ergebnisse deuten auf das Vorhandensein von mikrostrukturellen Veränderungen hin, die sich mit konventionellen MRT-Verfahren nicht erfassen lassen. Potentielle Ursachen dieser Veränderungen sind neben Effekten der antikonvulsiven Medikation möglicherweise auch gliotischer Gewebeumbau bedingt durch stattgehabte epileptische Anfälle. Die Studie legt nahe, dass strukturelle Epilepsien mehr als ein Symptom bedingt durch eine fokale Läsion sind und stattdessen das Gehirn als Ganzes betreffen.
Spahr, Dominik ; Stękiel, Michał ; Zimmer, Dominik ; Bayarjargal, Lkhamsuren ; Bunk, Katja ; Morgenroth, Wolfgang ; Milman, Victor ; Refson, Keith ; Jochym, Dominik ; Byrne, Peter J. P. ; Winkler, Björn
High-pressure single-crystal to 20 GPa and powder diffraction measurements to 50 GPa, show that the structure of Pb2SnO4 strongly distorts on compression with an elongation of one axis. A structural phase transition occurs between 10 GPa and 12 GPa, with a change of space group from Pbam to Pnam. The resistivity decreases by more than six orders of magnitude when pressure is increased from ambient conditions to 50 GPa. This insulator-to-semiconductor transition is accompanied by a reversible appearance change from transparent to opaque. Density functional theory-based calculations show that at ambient conditions the channels in the structure host the stereochemically-active Pb 6s2 lone electron pairs. On compression the lone electron pairs form bonds between Pb2+ ions. Also provided is an assignment of irreducible representations to the experimentally observed Raman bands.
Meier, Sylvia ; Petzel-Witt, Silvana ; Schubert-Zsilavecz, Manfred ; Perna, Elizabeth B. de Sousa Fernandes ; Theunissen, Eef L. ; Ramaekers, Johannes G. ; Tönnes, Stefan W.
Cerumen was found to be a promising alternative specimen for the detection of drugs. In a pilot study, drugs of abuse were identified at a higher detection rate and a longer detection window in cerumen than in urine. In this study, cerumen from subjects was analyzed after they ingested the designer stimulant 4-fluoroamphetamine (4-FA) in a controlled manner. Methods: Twelve subjects ingested placebo and 100 mg of 4-FA. Five of them were also given 150 mg of 4-FA in 150 mL Royal Club bitter lemon drink at least after 7 days. Cerumen was sampled using cotton swabs at baseline, 1 h after the ingestion of the drug and at the end of the study day (12 h). After extraction with ethyl acetate followed by solid-phase extraction, the extracts were analyzed using liquid chromatography coupled with tandem mass spectrometry (LC–MS/MS). Results and discussion: In the cerumen of all 12 subjects, 4-FA was detected 12 h after its ingestion; in most subjects, cerumen was detected after 1 h of ingestion, ranging from 0.06 to 13.90 (median 1.52) ng per swab. The detection of 4-FA in cerumen sampled 7 days or more after the first dose suggested a long detection window of cerumen. Conclusions: Cerumen can be successfully used to detect a single drug ingestion even immediately after the ingestion when a sufficient amount of cerumen is used.
Super-resolution optical fluctuation imaging (SOFI) is a super-resolution microscopy technique that overcomes the diffraction limit by analyzing intensity fluctuations of statistically independent emitters in a time series of images. The final images are background-free and show confocality and enhanced spatial resolution (super-resolution). Fluorophore photobleaching, however, is a key limitation for recording long time series of images that will allow for the calculation of higher order SOFI results with correspondingly increased resolution. Here, we demonstrate that photobleaching can be circumvented by using fluorophore labels that reversibly and transiently bind to a target, and which are being replenished from a buffer which serves as a reservoir. Using fluorophore-labeled short DNA oligonucleotides, we labeled cellular structures with target-specific antibodies that contain complementary DNA sequences and record the fluctuation events caused by transient emitter binding. We show that this concept bypasses extensive photobleaching and facilitates two-color imaging of cellular structures with SOFI.
Brunst, Steffen ; Kramer, Jan S. ; Kilu, Whitney ; Heering, Jan Peter ; Pollinger, Julius Carl ; Hiesinger, Kerstin ; George, Sven ; Steinhilber, Dieter ; Merk, Daniel ; Proschak, Ewgenij
Designed multitarget ligands are a popular approach to generating efficient and safe drugs, and fragment-based strategies have been postulated as a versatile avenue to discover multitarget ligand leads. To systematically probe the potential of fragment-based multiple ligand discovery, we have employed a large fragment library for comprehensive screening on five targets chosen from proteins for which multitarget ligands have been successfully developed previously (soluble epoxide hydrolase, leukotriene A4 hydrolase, 5-lipoxygenase, retinoid X receptor, farnesoid X receptor). Differential scanning fluorimetry served as primary screening method before fragments hitting at least two targets were validated in orthogonal assays. Thereby, we obtained valuable fragment leads with dual-target engagement for six out of ten target combinations. Our results demonstrate the applicability of fragment-based approaches to identify starting points for polypharmacological compound development with certain limitations.
This article investigates the roles of psychological biases for deviations between subjective survival beliefs (SSBs) and objective survival probabilities. We model these deviations through age-dependent inverse S-shaped probability weighting functions. Our estimates suggest that implied measures for cognitive weakness increase and relative optimism decrease with age. Direct measures of cognitive weakness and optimism share these trends. Our regression analyses confirm that these factors play strong quantitative roles in the formation of SSBs. Our main finding is that cognitive weakness instead of optimism becomes with age an increasingly important contributor to the well-documented overestimation of survival chances in old age.
Mezhyrova, Julija ; Martin, Janosch ; Peetz, Oliver ; Dötsch, Volker ; Morgner, Nina ; Ma, Yi ; Bernhard, Frank
The bacteriophage ΦX174 causes large pore formation in Escherichia coli and related bacteria. Lysis is mediated by the small membrane-bound toxin ΦX174-E, which is composed of a transmembrane domain and a soluble domain. The toxin requires activation by the bacterial chaperone SlyD and inhibits the cell wall precursor forming enzyme MraY. Bacterial cell wall biosynthesis is an important target for antibiotics; therefore, knowledge of molecular details in the ΦX174-E lysis pathway could help to identify new mechanisms and sites of action. In this study, cell-free expression and nanoparticle technology were combined to avoid toxic effects upon ΦX174-E synthesis, resulting in the efficient production of a functional full-length toxin and engineered derivatives. Pre-assembled nanodiscs were used to study ΦX174-E function in defined lipid environments and to analyze its membrane insertion mechanisms. The conformation of the soluble domain of ΦX174-E was identified as a central trigger for membrane insertion, as well as for the oligomeric assembly of the toxin. Stable complex formation of the soluble domain with SlyD is essential to keep nascent ΦX174-E in a conformation competent for membrane insertion. Once inserted into the membrane, ΦX174-E assembles into high-order complexes via its transmembrane domain and oligomerization depends on the presence of an essential proline residue at position 21. The data presented here support a model where an initial contact of the nascent ΦX174-E transmembrane domain with the peptidyl-prolyl isomerase domain of SlyD is essential to allow a subsequent stable interaction of SlyD with the ΦX174-E soluble domain for the generation of a membrane insertion competent toxin.
Certain electron-rich 1,4-diborabenzene derivatives efficiently activate single, double, and triple bonds and thereby increasingly compete with transition metals in homogeneous catalysis. This review compares the activation of three model substrates (H2, H2C=CH2, CO2) by (i) 9,10-dihydro-9,10-diboraanthracene dianions, (ii) their neutral carbene-stabilized congeners, (iii) 1,3,2,5-diazadiborinines, and (iv) 1,4,2,5-diazadiborinines. Distinct structure-properties relationships become apparent, the most influential factors being (i) the steric demands of the B-bonded substituents, (ii) the charges on the B-doped (hetero)arenes, (iii) charge polarization as a result of additional N-doping, and (iv) the energies and nodal structures of the frontier orbitals. The observed reactions are explained by a transition metal-like activation mechanism. If the two boron atoms are chemically inequivalent, contributions of a B(+I)/B(+III) mixed-valence state determine the observed regioselectivities when polar substrates are added. The lessons learned from the conversions of the model substrates are subsequently used to rationalize the behavior of the B2 heterocycles also toward more sophisticated substrate molecules. Finally, catalytic cycles based on H2- and H−-transfers, hydroboration reactions, and CO2 reductions will be covered.
Neef, Vanessa ; Meisenzahl, David ; Kessler, Paul ; Raimann, Florian ; Piekarski, Florian ; Choorapoikayil, Suma ; Fleege, Christoph ; Zacharowski, Kai ; Meybohm, Patrick ; Meurer, Andrea
Background: Approximately one in three patients suffers from preoperative anaemia. Even though haemoglobin is measured before surgery, anaemia management is not implemented in every hospital. Objective: Here, we demonstrate the implementation of an anaemia walk-in clinic at an Orthopedic University Hospital. To improve the diagnosis of iron deficiency (ID), we examined whether reticulocyte haemoglobin (Ret-He) could be a useful additional parameter. Material and Methods: In August 2019, an anaemia walk-in clinic was established. Between September and December 2019, major orthopaedic surgical patients were screened for preoperative anaemia. The primary endpoint was the incidence of preoperative anaemia. Secondary endpoints included Ret-He level, red blood cell (RBC) transfusion rate, in-hospital length of stay and anaemia at hospital discharge. Results: A total of 104 patients were screened for anaemia. Preoperative anaemia rate was 20.6%. Intravenous iron was supplemented in 23 patients. Transfusion of RBC units per patient (1.7 ± 1.2 vs. 0.2 ± 0.9; p = 0.004) and hospital length of stay (13.1 ± 4.8 days vs. 10.6 ± 5.1 days; p = 0.068) was increased in anaemic patients compared to non-anaemic patients. Ret-He values were significantly lower in patients with ID anaemia (33.3 pg [28.6–40.2 pg]) compared to patients with ID (35.3 pg [28.9–38.6 pg]; p = 0.015) or patients without anaemia (35.4 pg [30.2–39.4 pg]; p = 0.001). Conclusion: Preoperative anaemia is common in orthopaedic patients. Our results proved the feasibility of an anaemia walk-in clinic to manage preoperative anaemia. Furthermore, our analysis supports the use of Ret-He as an additional parameter for the diagnosis of ID in surgical patients.
USP22 controls necroptosis by regulating receptor-interacting protein kinase 3 ubiquitination
(2020)
Rödig, Jens ; Kowald, Lisa ; Juretschke, Thomas ; Karlowitz, Rebekka ; Abhari, Behnaz ; Rödig, Heiko ; Fulda, Simone ; Beli, Petra ; Wijk, Sjoerd van
Dynamic control of ubiquitination by deubiquitinating enzymes is essential for almost all biological processes. Ubiquitin-specific peptidase 22 (USP22) is part of the SAGA complex and catalyzes the removal of mono-ubiquitination from histones H2A and H2B, thereby regulating gene transcription. However, novel roles for USP22 have emerged recently, such as tumor development and cell death. Apart from apoptosis, the relevance of USP22 in other programmed cell death pathways still remains unclear. Here, we describe a novel role for USP22 in controlling necroptotic cell death in human tumor cell lines. Loss of USP22 expression significantly delays TNFα/Smac mimetic/zVAD.fmk (TBZ)-induced necroptosis, without affecting TNFα-mediated NF-κB activation or extrinsic apoptosis. Ubiquitin remnant profiling identified receptor-interacting protein kinase 3 (RIPK3) lysines 42, 351, and 518 as novel, USP22-regulated ubiquitination sites during necroptosis. Importantly, mutation of RIPK3 K518 reduced necroptosis-associated RIPK3 ubiquitination and amplified necrosome formation and necroptotic cell death. In conclusion, we identify a novel role of USP22 in necroptosis and further elucidate the relevance of RIPK3 ubiquitination as crucial regulator of necroptotic cell death.
Ketter, Sophie ; Gopinath, Aathira ; Rogozhnikova, Olga ; Trukhin, Dmitrii ; Tormyshev, Victor M. ; Bagryanskaya, Elena ; Joseph, Benesh
In situ investigation of membrane proteins is a challenging task. Previously we demonstrated that nitroxide labels combined with pulsed ESR spectroscopy is a promising tool for this purpose. However, the nitroxide labels suffer from poor stability, high background labeling, and low sensitivity. Here we show that Finland (FTAM) and OX063 based labels enable labeling of the cobalamin transporter BtuB and BamA, the central component of the β-barrel assembly machinery (BAM) complex, in E coli. Compared to the methanethiosulfonate spin label (MTSL), trityl labels eliminated the background signals and enabled specific in situ labeling of the proteins with high efficiency. The OX063 labels show a long phase memory time (TM) of ≈5 μs. All the trityls enabled distance measurements between BtuB and an orthogonally labeled substrate with high selectivity and sensitivity down to a few μm concentration. Our data corroborate the BtuB and BamA conformations in the cellular environment of E. coli.
Friedauer, Lucie ; Rezny-Kasprzak, Beata ; Steinmetz, Helmuth ; Du Mesnil de Rochemont, Richard Klaus Frieder ; Förch, Christian
Background and purpose: Superficial siderosis of the central nervous system is a sporadic finding in magnetic resonance imaging, resulting from recurrent bleedings into the subarachnoid space. This study aimed to determine the frequency of spinal dural cerebrospinal fluid (CSF) leaks amongst patients with a symmetric infratentorial siderosis pattern. Methods: In all, 97,733 magnetic resonance images performed between 2007 and 2018 in our neurocenter were screened by a keyword search for “hemosiderosis” and “superficial siderosis.” Siderosis patterns on brain imaging were classified according to a previously published algorithm. Potential causative intracranial bleeding events were also assessed. Patients with a symmetric infratentorial siderosis pattern but without causative intracranial bleeding events in history were prospectively evaluated for spinal pathologies. Results: Forty-two patients with isolated supratentorial siderosis, 30 with symmetric infratentorial siderosis and 21 with limited (non-symmetric) infratentorial siderosis were identified. Amyloid angiopathy and subarachnoid hemorrhage were causes for isolated supratentorial siderosis. In all four patients with a symmetric infratentorial siderosis pattern but without a causative intracranial bleeding event in history, spinal dural abnormalities were detected. Dural leaks were searched for in patients with symmetric infratentorial siderosis and a history of intracranial bleeding event without known bleeding etiology, considering that spinal dural CSF leaks themselves may also cause intracranial hemorrhage, for example by inducing venous thrombosis due to low CSF pressure. Thereby, one additional spinal dural leak was detected. Conclusions: Persisting spinal dural CSF leaks can frequently be identified in patients with a symmetric infratentorial siderosis pattern. Diagnostic workup in these cases should include magnetic resonance imaging of the whole spine.
Linking epigenetic signature and metabolic phenotype in IDH mutant and IDH wildtype diffuse glioma
(2020)
Braun, Yannick ; Filipski, Katharina Johanna ; Bernatz, Simon ; Baumgarten, Peter ; Roller, Bastian ; Zinke, Jenny ; Zeiner, Pia Susan ; Ilina, Elena ; Senft, Christian ; Ronellenfitsch, Michael Wilfried ; Plate, Karl ; Bähr, Roy Oliver ; Hattingen, Elke ; Steinbach, Joachim Peter ; Mittelbronn, Michel Guy André ; Harter, Patrick Nikolaus
Aims: Changes in metabolism are known to contribute to tumour phenotypes. If and how metabolic alterations in brain tumours contribute to patient outcome is still poorly understood. Epigenetics impact metabolism and mitochondrial function. The aim of this study is a characterisation of metabolic features in molecular subgroups of isocitrate dehydrogenase mutant (IDHmut) and isocitrate dehydrogenase wildtype (IDHwt) gliomas. Methods: We employed DNA methylation pattern analyses with a special focus on metabolic genes, large-scale metabolism panel immunohistochemistry (IHC), qPCR-based determination of mitochondrial DNA copy number and immune cell content using IHC and deconvolution of DNA methylation data. We analysed molecularly characterised gliomas (n = 57) for in depth DNA methylation, a cohort of primary and recurrent gliomas (n = 22) for mitochondrial copy number and validated these results in a large glioma cohort (n = 293). Finally, we investigated the potential of metabolic markers in Bevacizumab (Bev)-treated gliomas (n = 29). Results: DNA methylation patterns of metabolic genes successfully distinguished the molecular subtypes of IDHmut and IDHwt gliomas. Promoter methylation of lactate dehydrogenase A negatively correlated with protein expression and was associated with IDHmut gliomas. Mitochondrial DNA copy number was increased in IDHmut tumours and did not change in recurrent tumours. Hierarchical clustering based on metabolism panel IHC revealed distinct subclasses of IDHmut and IDHwt gliomas with an impact on patient outcome. Further quantification of these markers allowed for the prediction of survival under anti-angiogenic therapy. Conclusion: A mitochondrial signature was associated with increased survival in all analyses, which could indicate tumour subgroups with specific metabolic vulnerabilities.
Culturally adapted cognitive behavioral therapy (CA-CBT) is a well-evaluated, transdiagnostic group intervention for refugees that uses psychoeducation, meditation, and stretching exercises. In the current study, we added problem-solving training to CA-CBT and evaluated this treatment (i.e., CA-CBT+) in a randomized controlled pilot trial with a sample of Farsi-speaking refugees. Participants (N = 24) were male refugees diagnosed with DSM-5 PTSD, major depressive disorder, and anxiety disorders who were randomly assigned to either a treatment or waitlist control (WLC) condition. Treatment components were adapted both to the specific cultural background and the current social problems of asylum seekers. Assessments were performed pretreatment, 12-weeks posttreatment, and 1-year follow-up. The primary treatment outcome was the General Health Questionnaire (GHQ-28); secondary outcome measures included the Posttraumatic Stress Disorder Checklist, Patient Health Questionnaire, Somatic Symptom Scale, World Health Organization Quality of Life, and Emotion Regulation Scale. Eleven of 12 participants were randomized to CA-CBT+ completed treatment. Based on intent-to-treat data, large between-group effect sizes were seen at posttreatment in the GHQ-28, d = 3.0, and for most secondary outcome measures. Improvements for individuals in the treatment group decreased at 1-year follow-up, but effect sizes demonstrated continued large improvements on all measures as compared to pretreatment levels. In summary, CA-CBT+ led to large improvements in general psychopathological distress and quality of life, which were maintained in the long term. In addition, the dropout rate was very low, with delivery in group format. Thus, problem-solving training appears to be a promising addition to CA-CBT.
This article presents the findings from systematically reviewing 26 empirical research studies published from 2005 to 2014 on the use of GIS for learning and teaching. By employing methods of narrative synthesis and qualitative content analysis, the study gives evidence about the state of knowledge of competence-based GIS education. The results explain what factors and variables effect GIS learning in terms of technology use, major subject contents, learning contexts, and didactic and pedagogical aspects. They also show what facets of knowledge, process skills, and affect the research literature has investigated. The analysis of the type and quality of the methods used indicates that current GIS education research is a heterogeneous field that needs a systematic research framework for future efforts, according to empirical education research.
This paper explores the many interesting implications for oscillator design, with optimized phase-noise performance, deriving from a newly proposed model based on the concept of oscillator conjugacy. For the case of 2-D (planar) oscillators, the model prominently predicts that only circuits producing a perfectly symmetric steady-state can have zero amplitude-to-phase (AM-PM) noise conversion, a so-called zero-state. Simulations on standard industry oscillator circuits verify all model predictions and, however, also show that these circuit classes cannot attain zero-states except in special limit-cases which are not practically relevant. Guided by the newly acquired design rules, we describe the synthesis of a novel 2-D reduced-order LC oscillator circuit which achieves several zero-states while operating at realistic output power levels. The potential future application of this developed theoretical framework for implementation of numerical algorithms aimed at optimizing oscillator phase-noise performance is briefly discussed.
Broft, Patrizia ; Dzatko, Simon ; Krafcikova, Michaela ; Wacker, Anna ; Hänsel-Hertsch, Robert ; Dötsch, Volker ; Trantirek, Lukáš ; Schwalbe, Harald
We report here the in-cell NMR-spectroscopic observation of the binding of the cognate ligand 2′-deoxyguanosine to the aptamer domain of the bacterial 2′-deoxyguanosine-sensing riboswitch in eukaryotic cells, namely Xenopus laevis oocytes and in human HeLa cells. The riboswitch is sufficiently stable in both cell types to allow for detection of binding of the ligand to the riboswitch. Most importantly, we show that the binding mode established by in vitro characterization of this prokaryotic riboswitch is maintained in eukaryotic cellular environment. Our data also bring important methodological insights: Thus far, in-cell NMR studies on RNA in mammalian cells have been limited to investigations of short (<15 nt) RNA fragments that were extensively modified by protecting groups to limit their degradation in the intracellular space. Here, we show that the in-cell NMR setup can be adjusted for characterization of much larger (≈70 nt) functional and chemically non-modified RNA.
Becker, Yvonne ; Roth, Sina ; Scheurer, Maximilian ; Jakob, Andreas ; Gacek, Daniel A. ; Walla, Peter Jomo ; Dreuw, Andreas ; Wachtveitl, Josef ; Heckel, Alexander
We developed three bathochromic, green-light activatable, photolabile protecting groups based on a nitrodibenzofuran (NDBF) core with D-π-A push–pull structures. Variation of donor substituents (D) at the favored ring position enabled us to observe their impact on the photolysis quantum yields. Comparing our new azetidinyl-NDBF (Az-NDBF) photolabile protecting group with our earlier published DMA-NDBF, we obtained insight into its excitation-specific photochemistry. While the “two-photon-only” cage DMA-NDBF was inert against one-photon excitation (1PE) in the visible spectral range, we were able to efficiently release glutamic acid from azetidinyl-NDBF with irradiation at 420 and 530 nm. Thus, a minimal change (a cyclization adding only one carbon atom) resulted in a drastically changed photochemical behavior, which enables photolysis in the green part of the spectrum.