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"Diachrone Interkulturalität". Tagung der Universität Luxemburg, 17.-19. November 2016
Ziel der Tagung "Diachrone Interkulturalität" war einerseits eine stärkere Anbindung der interkulturellen Forschung an ästhetische und literaturwissenschaftliche Fragestellungen, andererseits auch die Erweiterung eines bislang vorwiegend gegenwartszentrierten Theoriediskurses um die diachrone Betrachtungsweise: "Im aktuellen Theoriediskurs wird jedoch inzwischen häufiger darauf hingewiesen, dass eine Beschränkung der Interkulturalitätsforschung auf Globalisierungsphänomene zu kurz gegriffen ist und die Notwendigkeit einer Historisierung besteht. In diesem Sinne intendiert die Tagung eine Erweiterung des Forschungsfeldes im Zeichen des Diachron-Geschichtlichen und damit auch eine Komplexitätssteigerung eines häufig undifferenziert gedachten Interkulturalitätsbegriffes."
"Globale - Festival für grenzüberschreitende Literatur" in Bremen, 25. Oktober - 15. November 2016
(2016)
"Globale - Festival für grenzüberschreitende Literatur" in Bremen, 25. Oktober - 15. November 2016
Das Festival für grenzüberschreitende Literatur verwandelte auch dieses Jahr die Stadt Bremen drei wochenlang in einen Begegnungs- und Diskussionsort für alle literarisch Interessierten mit einem vielfältigen Programmangebot an Lesungen von Autoren und Autorinnen, die die Grenzüberschreitung verbindet. Denn die Intention des Festivals ist, wie die diesjährige Festivalleitung Prof. Dr. Elisabeth Arend und Libuše Černá im Vorwort des umfangreichen Programmhefts betonen, eine Literatur vorzustellen, die sich mit "den Federn fremder Herkünfte" schmückt, "viele Zungen" spricht und "dabei deutsch" ist.
"Vielfältige Konzepte - Konzepte der Vielfalt: Interkulturalität(en) weltweit". Internationale Tagung der Gesellschaft für interkulturelle Germanistik e.V. (GiG) in Ústí nad Labem und Prag, 04.-09. Oktober 2016
Vom 4. bis 9. Oktober 2016 fand in Ústí nad Labem und in Prag die Jahrestagung der GiG in Zusammenarbeit mit dem Tschechischen Germanistenverband unter der Schirmherrschaft des Kulturministers der Tschechischen Republik Mgr. Daniel Herman, des Regionspräsidenten von Ústí nad Labem Herrn Oldřich Bubeníček, des Rektors der J. E. Purkyně-Universität in Ústí nad Labem doc. RNDr. Martin Balej, Ph.D., der Oberbürgermeisterin der Stadt Ústí nad Labem Frau Ing. Věra Nechybová und der Stadträtin der Hauptstadt Prag Ing. Irena Ropková statt. Die wissenschaftliche Leitung hatten Dr. habil. Renata Cornejo (Ústí nad Labem), Prof. Dr. Manfred Weinberg (Prag) und Prof. Dr. Gesine Lenore Schiewer (Bayreuth) inne.
"Gewalt und Sprache". Internationale SUNG-Tagung an der Comenius-Universität in Bratislava, 30. Juni - 2. Juli 2016
Anlässlich des 25. Jahrestages seiner Gründung veranstaltete der Verband der Deutschlehrer und Germanisten der Slowakei (SUNG) eine Konferenz, die sich thematisch auf das Verhältnis von Gewalt und Sprache konzentrierte. Veranstaltungsort war die Philosophische Fakultät der Comenius-Universität, Mitveranstalter der dortige Lehrstuhl für Germanistik, Nederlandistik und Skandinavistik. Die Konferenz stellte zugleich die zwölfte Tagung des Verbandes dar.
Linguistik- und Literaturtage "Sprachen verbinden". 24. internationale GeSuS-Fachtagung an der Masaryk-Universität in Brno, 22.-24. Juni 2016
Die 24. internationale Fachtagung der Gesellschaft für Sprache und Sprachen (GeSuS) fand vom 22. bis 24. Juni 2016 statt. Als Ort wurde diesmal die Pädagogische Fakultät der Masaryk-Universität in Brno gewählt, die nicht nur einen Großteil der Organisation übernahm, sondern damit gleichzeitig auch ihr 70. Gründungsjubiläum feierte. Die internationale Tagung setzte sich zum Ziel, eine Plattform zur Präsentation neuer Forschungsergebnisse im Bereich der Germanistik zu schaffen und das Knüpfen neuer Kontakte zu ermöglichen.
"Grenzüberschreitungen: Migration und Literatur aus der Perspektive der Literatursoziologie". Tagung der Österreichischen Akademie der Wissenschaften in Wien, 20.-21. Juni 2016
Die zeitgenössische Literaturproduktion reagiert seit Längerem auf Thematiken wie Kulturkonflikte, Fremdheit, Einwanderung und Migration. Das Forschungsprojekt Literature on the Move untersuchte die Migration von Autor(inn)en nach Österreich und deren Möglichkeiten bzw. Schwierigkeiten beim Eintritt in das Feld der österreichischen Literatur. Es wurde der Versuch unternommen, die Rahmenbedingungen, die Struktur und die Konsequenzen literarischer Produktion miteinander in Beziehung zu bringen und mit Hinblick auf die literarischen Texte zu analysieren.
"Zentrum und Peripherie". Internationale Konferenz des Germanistenverbandes der Tschechischen Republik an der Schlesischen Universität in Opava, 25.-27. Mai 2016
Die internationale Tagung Zentrum und Peripherie wurde vom Germanistenverband der Tschechischen Republik und der Abteilung für Germanistik am Institut für Fremdsprachen der Schlesischen Universität in Opava veranstaltet. Das Organisationsteam aus Opava bestand aus Dr. habil. Gabriela Rykalová, Dr. habil. Veronika Kotůlková und Dr. Miroslav Urbanec. Fast hundert FachteilnehmerInnen aus der Tschechischen Republik, Deutschland, Österreich, Polen, der Slowakei, Spanien, der Türkei und Ungarn konnten in Opava begrüßt werden, außerdem VertreterInnen des DAAD, der Deutschen Welle, des Österreichischen Kulturforums Prag sowie Germanistikstudierende verschiedener Universitäten. Im Rahmen der Konferenz fand auch die Mitgliederversammlung des Germanistenverbands der Tschechischen Republik statt.
"Marie von Ebner-Eschenbach. Básnířka tří staletí / Dichterin dreier Jahrhunderte 1830 - 1916 - 2016". Internationale Tagung in Brno, 21.-23. April 2016
Über Fächer-, Sprach- und Landesgrenzen hinweg wurde bei der Konferenz Marie von Ebner-Eschenbach. Básnířka tři staletí/ Dichterin dreier Jahrhunderte (1830 - 1916 - 2016) in Brno (Brünn) vom 21. bis zum 23. April 2016 das Leben und Werk der in Mähren geborenen österreichischen Schriftstellerin beleuchtet. Vom sozialhistorischen Ansatz über die Werkanalyse bis hin zur Präsentation der Tagebücher war die Konferenz eine vielfältige Demonstration des regen Interesses an dem Forschungsgegenstand.
"Sinn - Unsinn - Wahnsinn. Beispiele zur österreichischen Kulturgeschichte". Tagung der Franz Werfel-Stipendiat(inn)en in Wien, 18.-19. März 2016
Das Franz Werfel-Stipendium des Österreichischen akademischen Austauschdienstes (OeAD) wendet sich an junge Germanist(inn)en und UniversitätslehrerInnen, die sich an ihren Heimatuniversitäten in der ganzen Welt schwerpunktmäßig mit der österreichischen Literatur beschäftigen. Als Plattform der ehemaligen sowie aktuellen Franz Werfel-Stipendiat(inn)en an den österreichischen Universitäten wird die alljährliche Franz Werfel-Tagung veranstaltet, die sich jeweils einem Thema aus der österreichischen Literatur widmet. Die Konferenz findet unter der Betreuung der Wiener Germanistin Konstanze Fliedl statt.
"Österreich - USA: Künstlerischer und interkultureller Dialog". Konferenz der Austrian Studies Association (ASA) an der Universität Wien, 14.-17. März 2016
Zum zweiten Mal seit Bestehen der 1961 ins Leben gerufenen Austrian Studies Association (ASA) fand die jährliche ASA-Konferenz in Europa, und zwar wieder in Wien, statt. Organisiert wurde sie von Pia Janke (Forschungsplattform Elfriede Jelinek, Universität Wien), Maria-Regina Kecht (Rice University) und Teresa Kovacs (Forschungsplattform Elfriede Jelinek, Universität Wien). Die Veranstaltung vernetzte durch ein vielfältiges Programm an wissenschaftlichen Vorträgen und künstlerischen Programmpunkten die Universität Wien mit anderen in Wien beheimateten Institutionen, die als Kooperationspartner fungierten, namentlich mit dem Wien Museum, dem Österreichischen Filmmuseum und dem Amerika-Haus.
"Raum Gefühl Heimat - Literarische Repräsentationen nach 1945". Internationale Tagung an der Universität des Baskenlandes in Vitoria-Gasteiz, 23.-25. September 2015
Nach einem einleitenden Vortrag von Thomas Anz (Marburg) über literarische Techniken der Emotionalisierung in der Repräsentation protoypischer Räume und Szenarien widmeten sich die Vortragenden aufbauend auf den theoretischen Grundlagen des Spatial und Emotional Turns aus verschiedenen Perspektiven und mit verschiedenen Foki dem Tagungsthema.
Für die deutsche Minderheit spielte die deutschsprachige Presse immer eine bedeutende Rolle. Über sie bewahrte man die deutsche Sprache und wurde es möglich, Informationen in der Muttersprache zu bekommen. Für die tschechoslowakischen Deutschen übernahmen diese Rolle seit 1951 zuerst die Blätter Aufbau und Frieden und seit 1964 die Prager Volkszeitung. Der vorliegende Aufsatz behandelt die Rolle der Prager Volkszeitung für die Identitätsbildung der deutschen Minderheit. Er befasst sich mit der historischen Entwicklung dieser Zeitung bis zu ihrer Einstellung im Jahr 2005 und verfolgt, wie in den einzelnen geschichtlichen Abschnitten, vor allem in jenem bis 1968, dann von 1968 bis 1989 und schließlich seit 1989 das genannte Blatt die Existenz der Deutschen beeinflusst bzw. widergespiegelt hat.
Zeit ihres Lebens bewegte sich Marie Luise Kaschnitz zwischen den Kulturen: denen des Nordens und des Südens, subtiler auch zwischen der deutschen (ihres familiären Ursprungs) und der österreichischen (ihres Ehemannes). In dem gefeierten lyrischen Prosatext Beschreibung eines Dorfes gelingt ihr gleichsam von der Peripherie aus, dem badischen Ort Bollschweil, ein durchaus interkultureller Weltentwurf. Seine tragende Mitte, das Haus Nr. 84, bleibt zwar weitgehend ausgespart, dennoch offenbart sich, welche Energien diese unbeschriebene Mitte des peripheren Dorfes in sich bündelt.
Ausgehend von der Verschränkung der aktuellen Diskurse von Spatial Turn und Emotional Turn wird in dem Beitrag der Frage nachgegangen, inwiefern der Begriff 'Heimat' als Raum des sozialen und symbolischen Handelns des Menschen bzw. dessen Emotionen in den Werken deutschsprachiger Gegenwartsautor(inn)en tschechischer Herkunft konstruiert wird. Während im Roman Die Fassade (Libuše Moníková) der Heimat eine symbolische Funktion eines externen Gedächtnisses zugesprochen wird, rückt in dem Roman Georgs Sorgen um die Vergangenheit… (Jan Faktor) die räumliche Komponente in den Vordergrund. Die Hauptfigur in Novemberfäden (Katja Fusek) konstruiert dagegen ihren Heimatbegriff aus der eigenen emotionsbeladenen Erinnerung heraus, wobei dessen Revision eine notwendige Voraussetzung für die eigene Identitätsbildung auf Grund der Konfrontation von 'Fiktion' und 'Realität' darstellt.
Der Beitrag versucht die Lektüre einer wenig bekannten Erzählung Oskar Panizzas unter machttheoretischen Aspekten. Mit ihrer Fokussierung auf Panizzas Kritik an der Hegemonie des wilhelminischen Kaiserreiches reproduziert die Panizza-Forschung ein Machtverständnis, das Macht als Besitz der Herrschenden konzipiert. Ein solches Verständnis verstellt den Blick auf die produktive Qualität und die performative Wirkung von Panizzas Texten. In Anlehnung an Michel Foucaults Konzept von Macht als produktivem Netz von Kräfteverhältnissen zeigt mein Beitrag, wie sich das Verhältnis zwischen Norm und Abweichung nicht in der zentralen Ausübung einer einzelnen Machtinstanz, sondern in dem dezentralen und produktiven Spiel der Kräfteverhältnisse beschreiben lässt. Vermittels literarischer Techniken inszeniert Panizzas Erzählung Ein scandalöser Fall ein solch dynamisches Machtverständnis und macht dabei die prekäre Beschaffenheit hegemonialer Konstellationen sichtbar.
"… die ehernen Blöcke männlichen Schaffens umkreisen" - Elfriede Jelinek queert Lessing und Goethe
(2016)
Der Beitrag verschränkt kommunikations-, informations-, kulturwissenschaftliche sowie philosophische Ansätze zur Störung mit gender- und queer theory, um Elfriede Jelineks 'Gattung' des Sekundärdramas analytisch zu beschreiben. Jelinek verfasst ihre Sekundärdramen zu kanonisierten Dramen des deutschsprachigen Raums und stellt über ihr typisches, intertextuelles Verfahren Bezug zu den Stücken her, fordert gleichzeitig aber auch die Kombination der Sekundärdramen mit ihren Bezugstexten im Moment der Inszenierung und geht damit über ihr bisheriges Verfahren hinaus. Ausgehend von der Feststellung, dass Jelineks Sekundärdramen in den Umsetzungen am Theater meist als weibliche Gegenschreibung interpretiert werden, will der vorliegende Beitrag zeigen, dass die Sekundärdramen vielmehr an einer Auflösung der Kategorien von 'Weiblichkeit' und 'Männlichkeit' arbeiten. Ein besonderes Augenmerk liegt dabei auf der Thematisierung des Inzests, der mit Judith Butler als vorhandene Ordnungen und Relationen verschiebendes Element gelesen werden kann.
Der Beitrag untersucht anhand von Amazon-Kundenrezensionen zu Werken Judith Hermanns die Beweggründe für deren Verwendung. Dabei wird ersichtlich, dass eine Abgrenzung zur professionellen Literaturkritik vorhanden ist und durch mindestens sechs folgende Gründe ergänzt werden muss: (1.) virtuelle Hilfsbereitschaft, (2.) Nacherzählung des Inhalts, (3.) Wertung und Kaufempfehlung, (4.) Beschreibung des Lektüreprozesses mit Empfehlung für Art und Weise des Lesens, (5.) Kommunikationsmittel zwischen Kunden und Autorin sowie (6.) vernichtender Umgang mit Hörbüchern.
Hinter dem kritischen und kommerziellen Erfolg literarischer Texte stehen nicht selten Autor(inn)en, verstanden als mächtige Akteure des literarischen Feldes sowie als Marken, die beim Publikum bestimmte Erwartungen erwecken und zur Gestaltung von entsprechenden Wertungsstrategien beitragen. Derartige Wertungen überschreiten nicht immer nationale Grenzen. Am Beispiel der polnischen Rezeption der deutschsprachigen Literatur kann bewiesen werden, dass die Macht der genannten Akteure kulturgeographisch begrenzt ist und dass sie im Kulturtransfer stereotypisiert werden. So lassen sich einzelne Rezeptionsfälle in Figuren ausdrücken: Metapher (Allgegenwart) - Günter Grass, Metonymie (Repräsentation) - Elfriede Jelinek, Litotes (Abwesenheit) - Daniel Kehlmann und Wolf Haas im polnischen Feld.
Das literarische Feld Deutschlands wurde lange durch eine Spaltung zwischen West und Ost geprägt, die man nun zu überwinden versucht. Seit der Wende wird nämlich an Mechanismen gearbeitet, die zu einer friedlichen Wiedervereinigung des Literaturbetriebs beitragen können, wie z. B. die Einführung zweier neuer Literaturpreise, und zwar des Deutschen Buchpreises und des Preises der Leipziger Buchmesse. Die beiden haben sich von Anfang an dank des Publikumserfolgs der ausgezeichneten Werke als kanonbildende Instanzen durchgesetzt, die die Richtlinien sowohl des Buchmarktes, als auch der Literaturkritik, stark beeinflussen. Es wird im folgenden Beitrag versucht, durch eine gründliche Analyse der Mechanismen dieser Preise, ihre Rolle als politisch-ökonomische Vorrichtungen, nämlich als 'agent in the cultural economy' (ENGLISH 2005), zu untersuchen. Darüber hinaus wird auch erforscht, wie diese zwei Ehrungen, die Aufnahme einzelner Werke in den herrschenden Kanon ermöglichen oder wesentlich erleichtern, indem sie als materielles Mittel eines 'invisible-hand Phänomens' (WINKO 2002) fungieren, und wie sie zur Produktion von Texten, die als 'Klassiker von heute' bezeichnet werden könnten, beitragen.
Dieser Beitrag versteht sich als Fallstudie zu den Aspekten der Macht und Aufmerksamkeit im literarischen Feld und untersucht beide im Kontext des Deutschen Buchpreises. Dieser Preis wurde während der letzten zehn Jahre zu einem mächtigen Marketingtool im deutschsprachigen Raum. Die Initiatoren und Organisatoren des Deutschen Buchpreises haben die Bedeutung von Aufmerksamkeit im literarischen Feld erkannt und versuchen, möglichst viele Akteure des Feldes an der durch den Preis generierten Aufmerksamkeit partizipieren zu lassen: Verlage, Autor(inn)en, den Buchhandel, den Börsenverein selbst, die Literaturkritik in ihren vielfältigen Erscheinungsformen. Problematisch dabei ist, dass diese Aufmerksamkeitsmaximierung im Rahmen von bestimmten Machtstrukturen erfolgt. Wer lenkt bei diesem Prozess die Aufmerksamkeit worauf und wie passiert das? Wer hat im Rahmen der Hierarchien des Feldes die Möglichkeit, diese Aufmerksamkeit zu nutzen bzw. daran zu partizipieren?
This paper presents an imaging radar system for structural health monitoring (SHM) of wind turbine blades. The imaging radar system developed here is based on two frequency modulated continuous wave (FMCW) radar sensors with a high output power of 30 dBm. They have been developed for the frequency bands of 24,05 GHz-24,25 GHz and 33.4 GHz-36.0 GHz, respectively. Following the successful proof of damage detection and localization in laboratory conditions, we present here the installation of the sensor system at the tower of a 2 MW wind energy plant at 95 m above ground. The realization of the SHM-system will be introduced including the sensor system, the data acquisition framework and the signal processing procedures. We have achieved an imaging of the rotor blades using inverse synthetic aperture radar techniques under changing environmental and operational condition. On top of that, it was demonstrated that the front wall and back wall radar echo can be extracted from the measured signals demonstrating the full penetration of wind turbine blades during operation.
Dysregulation of blood sphingolipids is an emerging topic in clinical science. The objective of this study was to determine preanalytical biases that typically occur in clinical and translational studies and that influence measured blood sphingolipid levels. Therefore, we collected blood samples from four healthy male volunteers to investigate the effect of storage conditions (time, temperature, long-term storage, freeze–thaw cycles), blood drawing (venous or arterial sampling, prolonged venous compression), and sample preparation (centrifugation, freezing) on sphingolipid levels measured by LC-MS/MS. Our data show that sphingosine 1-phosphate (S1P) and sphinganine 1-phosphate (SA1P) were upregulated in whole blood samples in a time- and temperature-dependent manner. Increased centrifugation at higher speeds led to lower amounts of S1P and SA1P. All other preanalytical biases did not significantly alter the amounts of S1P and SA1P. Further, in almost all settings, we did not detect differences in (dihydro)ceramide levels. In summary, besides time-, temperature-, and centrifugation-dependent changes in S1P and SA1P levels, sphingolipids in blood remained stable under practically relevant preanalytical conditions.
Innerhalb der Gentrifizierungsforschung analysiert die Rent‑Gap‑Theorie, wie kleinräumige Differenzen zwischen gegenwärtigen Verwertungsbedingungen einerseits sowie Erwartungen auf zukünftig steigende Mieten andererseits Verdrängungsprozesse antreiben. Dementgegen hat Eric Clark (2014) jüngst eingefordert, dass die Stadtforschung den Blick verstärkt darauf richten müsse, wie Verdrängung verhindert werden kann. Diesen Appell aufgreifend, zeigen wir bezogen auf den deutschen Kontext, inwiefern mietrechtliche Regularien, stadtplanerische Entscheidungen und die jeweilige Eigentümerstruktur wesentlich darüber entscheiden, ob sich ein immobilienwirtschaftlicher Verwertungsdruck auch tatsächlich in Verdrängungsprozesse übersetzt. Illustriert wird dies am Wandel der Eigentümerstruktur im Frankfurter Gallus seit den 1970er Jahren. Deutlich wird dabei, dass Gentrifizierung kein Naturgesetz darstellt, sondern ein zutiefst politischer Prozess ist, der sich effektiv verhindern lässt.
Far outside the surface of slabs, the exact exchange (EXX) potential vx falls off as −1/z , if z denotes the direction perpendicular to the surface and the slab is localized around z=0 . Similarly, the EXX energy density ex behaves as −n/(2z) , where n is the electron density. Here, an alternative proof of these relations is given, in which the Coulomb singularity in the EXX energy is treated in a particularly careful fashion. This new approach allows the derivation of the next-to-leading order contributions to the asymptotic vx and ex . It turns out that in both cases, the corrections are proportional to 1/z2 in general.
Acute graft-versus-host disease (GvHD) is still a major cause of treatment-related mortality after allogeneic stem cell transplantation. Allo-antigen recognition of donor T cells after transplantation account for the onset and persistence of this disease. MicroRNAs (miRNAs) are molecular regulators involved in numerous processes during T-cell development, homeostasis, and activation. Thus, miRNAs also contribute to pathological T-cell function during GvHD. Given their capacity of fine-tuning T-cell function, miRNAs have emerged as promising therapeutic targets to curtail acute GvHD, but simultaneously maintain T-cell-mediated graft-versus-tumor effects. Here, we review the role of key miRNAs contributing to the pathophysiology of GvHD. We focus on those miRNAs acting in T cells and for which a role in GvHD has been established in preclinical models. Finally, we provide an outlook for clinical application of this new therapeutic target for GvHD prevention and treatment.
Background: Bradykinin-mediated angioedema (Bk-AE) can be life-threatening and requires specific targeted therapies. Knowledge of its epidemiology may help optimize its management.
Methods: We systematically searched the medical literature to identify abstracts of interest indexed between 1948 and March, 2016. We used published national survey data on the proportion of the population treated with angiotensin-converting enzyme inhibitors (ACEI) to derive estimates of the population prevalence of ACEI-AE in the USA, Germany and France. For hereditary angioedema (C1-INH-HAE) and C1-inhibitor related acquired angioedema (C1-INH-AAE), publications had to contain original epidemiologic data collection within a defined geographical area. Hereditary angioedema with normal C1-INH was not included in the analysis due to lack of clearly defined criteria.
Results: We identified 4 relevant publications on the prevalence of ACEI-AE, 6 on the prevalence of C1-INH-HAE, and 1 on the prevalence of C1-INH-AAE. The 1st year cumulative incidence of ACEI-AE was estimated to vary between 0.12 (population-based analyses) and 0.30 (meta-analyses of clinical trials) per 100 patient-years. The population prevalence of ACEI-AE was modeled to vary between 7 and 26 in 100,000. The prevalence of C1-INH-HAE was estimated to vary between 1.1 and 1.6 per 100,000. The prevalence of C1-INH-AAE was estimated to be 0.15 per 100,000 in one epidemiological investigation of AAE in Denmark.
Conclusions: Epidemiological evidence on Bk-AE is limited to North America and Europe. ACEI-AE is more common than C1-INH-HAE (~ 10:1), which is more common than C1-INH-AAE (~ 10:1). More studies are needed to comprehensively assess the epidemiological burden of Bk-AE.
The bile acid activated transcription factor farnesoid X receptor (FXR) regulates numerous metabolic processes and is a rising target for the treatment of hepatic and metabolic disorders. FXR agonists have revealed efficacy in treating non-alcoholic steatohepatitis (NASH), diabetes and dyslipidemia. Here we characterize imatinib as first-in-class allosteric FXR modulator and report the development of an optimized descendant that markedly promotes agonist induced FXR activation in a reporter gene assay and FXR target gene expression in HepG2 cells. Differential effects of imatinib on agonist-induced bile salt export protein and small heterodimer partner expression suggest that allosteric FXR modulation could open a new avenue to gene-selective FXR modulators.
An empirical study of the per capita yield of science Nobel prizes : is the US era coming to an end?
(2018)
We point out that the Nobel prize production of the USA, the UK, Germany and France has been in numbers that are large enough to allow for a reliable analysis of the long-term historical developments. Nobel prizes are often split, such that up to three awardees receive a corresponding fractional prize. The historical trends for the fractional number of Nobelists per population are surprisingly robust, indicating in particular that the maximum Nobel productivity peaked in the 1970s for the USA and around 1900 for both France and Germany. The yearly success rates of these three countries are to date of the order of 0.2–0.3 physics, chemistry and medicine laureates per 100 million inhabitants, with the US value being a factor of 2.4 down from the maximum attained in the 1970s. The UK in contrast managed to retain during most of the last century a rate of 0.9–1.0 science Nobel prizes per year and per 100 million inhabitants. For the USA, one finds that the entire history of science Noble prizes is described on a per capita basis to an astonishing accuracy by a single large productivity boost decaying at a continuously accelerating rate since its peak in 1972.
The theory and practice of urban governance in recent years has undergone both a collaborative and participatory turn. The strong connection between collaboration and participation has meant that citizen participation in urban governance has been conceived in a very particular way: as varying levels of partnership between state actors and citizens. This over-focus on collaboration has led to: 1) a dearth of proposals in theory and practice for citizens to engage oppositionally with institutions; 2) the miscasting of agonistic opportunities for participation as forms of collaboration; 3) an inability to recognise the irruption of agonistic practices into participatory procedures. This article attempts to expand the conception of participatory urban governance by adapting Rosanvallon’s (2008) three democratic counter-powers—prevention, oversight and judgement—to consider options for institutionalising agonistic participatory practices. It argues that these counter-governance processes would more fully realise the inclusion agenda that underpins the participatory governance project.
By the fabrication of periodically arranged nanomagnetic systems it is possible to engineer novel physical properties by realizing artificial lattice geometries that are not accessible via natural crystallization or chemical synthesis. This has been accomplished with great success in two dimensions in the fields of artificial spin ice and magnetic logic devices, to name just two. Although first proposals have been made to advance into three dimensions (3D), established nanofabrication pathways based on electron beam lithography have not been adapted to obtain free-form 3D nanostructures. Here we demonstrate the direct-write fabrication of freestanding ferromagnetic 3D nano-architectures. By employing micro-Hall sensing, we have determined the magnetic stray field generated by our free-form structures in an externally applied magnetic field and we have performed micromagnetic and macro-spin simulations to deduce the spatial magnetization profiles in the structures and analyze their switching behavior. Furthermore we show that the magnetic 3D elements can be combined with other 3D elements of different chemical composition and intrinsic material properties.
Fluctuation spectroscopy measurements of quasi-two-dimensional organic charge-transfer salts (BEDT-TTF) 2 X are reviewed. In the past decade, the method has served as a new approach for studying the low-frequency dynamics of strongly correlated charge carriers in these materials. We review some basic aspects of electronic fluctuations in solids, and give an overview of selected problems where the analysis of 1/f -type fluctuations and the corresponding slow dynamics provide a better understanding of the underlying physics. These examples are related to (1) an inhomogeneous current distribution due to phase separation and/or a percolative transition; (2) slow dynamics due to a glassy freezing either of structural degrees of freedom coupling to the electronic properties or (3) of the electrons themselves, e.g., when residing on a highly-frustrated crystal lattice, where slow and heterogeneous dynamics are key experimental properties for the vitrification process of a supercooled charge-liquid. Another example is (4), the near divergence and critical slowing down of charge carrier fluctuations at the finite-temperature critical endpoint of the Mott metal-insulator transition. Here also indications for a glassy freezing and temporal and spatial correlated dynamics are found. Mapping out the region of ergodicity breaking and understanding the influence of disorder on the temporal and spatial correlated fluctuations will be an important realm of future studies, as well as the fluctuation properties deep in the Mott or charge-ordered insulating states providing a connection to relaxor or ordered ferroelectric states studied by dielectric spectroscopy.
Single nucleotide polymorphism (SNP) rs738409 C>G in the patatin‐like phospholipase domain containing 3 (PNPLA3) gene results in an amino acid exchange from isoleucin to methionine at position I148M of PNPLA3. The expression of this loss‐of‐function mutation leads to impaired hepatocellular triglyceride hydrolysis and is associated with the development of liver steatosis, fibrosis, and hepatocellular carcinoma. In contrast to these well‐established associations, the relationship of the PNPLA3 rs738409 variant with other metabolic traits is incompletely understood. We therefore assessed the association of the PNPLA3 rs738409 genotype with relevant metabolic traits in a prospective study of patients at high risk for cardiovascular events, i.e., patients undergoing coronary angiography. In a total of 270 patients, known associations of the PNPLA3 rs738409 GG genotype with nonalcoholic steatohepatitis and liver fibrosis were confirmed. In addition, we found an association of the PNPLA3 rs738409 G allele with the presence of diabetes (22% versus 28% versus 58% for CC versus CG versus GG genotype, respectively; P = 0.02). In contrast to its association with nonalcoholic fatty liver disease, liver fibrosis, and diabetes, the minor G allele of PNPLA3 rs738409 was inversely associated with total serum cholesterol and low‐density lipoprotein serum levels (P = 0.003 and P = 0.02, respectively). Finally, there was a trend toward an inverse association between the presence of the PNPLA3 rs738409 G allele and significant coronary heart disease. Comparable trends were observed for the transmembrane 6 superfamily member 2 (TM6SF2) 167 K variant, but the sample size was too small to evaluate this rarer variant. Conclusion: The PNPLA3 rs738409 G allele is associated with liver disease but also with a relatively benign cardiovascular risk profile.
The prediction of protein–ligand interactions and their corresponding binding free energy is a challenging task in structure-based drug design and related applications. Docking and scoring is broadly used to propose the binding mode and underlying interactions as well as to provide a measure for ligand affinity or differentiate between active and inactive ligands. Various studies have revealed that most docking software packages reliably predict the binding mode, although scoring remains a challenge. Here, a diverse benchmark data set of 99 matched molecular pairs (3D-MMPs) with experimentally determined X-ray structures and corresponding binding affinities is introduced. This data set was used to study the predictive power of 13 commonly used scoring functions to demonstrate the applicability of the 3D-MMP data set as a valuable tool for benchmarking scoring functions.
Background: Immigration has a strong impact on the development of health systems, medicine and science worldwide. Therefore, this article provides a descriptive study on the overall research output.
Methods: Utilizing the scientific database Web of Science, data research was performed. The gathered bibliometric data was analyzed using the established platform NewQIS, a benchmarking system to visualize research quantity and quality indices.
Findings: Between 1900 and 2016 a total of 6763 articles on immigration were retrieved and analyzed. 86 different countries participated in the publications. Quantitatively the United States followed by Canada and Spain were prominent regarding the article numbers. On comparing by additionally taking the population size into account, Israel followed by Sweden and Norway showed the highest performance. The main releasing journals are the Public Health Reports, the Journal of Immigrant and Minority Health and Social Science & Medicine. Over the decades, an increasing number of Public, Environmental & Occupational Health articles can be recognized which finally forms the mainly used subject area.
Conclusion: Considerably increasing scientific work on immigration cannot only be explained by the general increase of scientific work but is also owed to the latest development with increased mobility, worldwide crises and the need of flight and migration. Especially countries with a good economic situation are highly affected by immigrants and prominent in their publication output on immigration, since the countries’ publication effort is connected with the appointed expenditures for research and development. Remarkable numbers of immigrants throughout Europe compel medical professionals to consider neglected diseases, requires the public health system to restructure itself and finally promotes science.
Background: Cancer research is critically dependent on a continuous recruitment of junior research staff that devotes its academic life not only to clinical duties but also to basic and translational research. The present study aims to elucidate the success concerning gender equality in cancer research in the last decade (from 2008 to 2016) with lung cancer as the target parameter.
Materials and Methods: On the basis of the Gendermetrics Platform, a total of 19,724 articles related to lung cancer research were analyzed. The key method was the combined analysis of the proportion of female authorships and the female-to-male odds ratio for first, co- and last authorships. The distribution of prestigious authorships was measured by the Prestige Index.
Results: 31.3% of all authorships and 35.2% of the first, 32.2% of the co- and 22.1% of the last authorships were held by women. The corresponding female-to-male odds ratio is 1.22 (CI: 1.18–1.27) for first, 1.19 (CI: 1.16–1.23) for co- and 0.59 (CI: 0.57–0.61) for last authorships. Women are underrepresented at prestigious authorships compared to men (Prestige Index = −0.22). The female underrepresentation accentuates in articles with many authors that attract the highest citation rates.
Conclusions: While the current system promotes early career promotion of women, men still outnumber women in leadership positions. However, this male-female career dichotomy has been narrowed in the last decade and will likely be further reduced in the next decade.
The HCV NS5A protein plays multiple roles during viral replication, including viral genome replication and virus particle assembly. The crystal structures of the NS5A N-terminal domain indicated the potential existence of the NS5A dimers formed via at least two or more distinct dimeric interfaces. However, it is unknown whether these different forms of NS5A dimers are involved in its numerous functions. To address this question, we mutated the residues lining the two different NS5A dimer interfaces and determined their effects on NS5A self-interaction, NS5A-cyclophilin A (CypA) interaction, HCV RNA replication and infectious virus production. We found that the mutations targeting either of two dimeric interfaces disrupted the NS5A self-interaction in cells. The NS5A dimer-interrupting mutations also inhibited both viral RNA replication and infectious virus production with some genotypic differences. We also determined that reduced NS5A self-interaction was associated with altered NS5A-CypA interaction, NS5A hyperphosphorylation and NS5A subcellular localization, providing the mechanistic bases for the role of NS5A self-interaction in multiple steps of HCV replication. The NS5A oligomers formed via different interfaces are likely its functional form, since the residues at two different dimeric interfaces played similar roles in different aspects of NS5A functions and, consequently, HCV replication. In conclusion, this study provides novel insight into the functional significance of NS5A self-interaction in different steps of the HCV replication, potentially, in the form of oligomers formed via multiple dimeric interfaces.
The NF-κB-like velvet domain protein VosA (viability of spores) binds to more than 1,500 promoter sequences in the filamentous fungus Aspergillus nidulans. VosA inhibits premature induction of the developmental activator gene brlA, which promotes asexual spore formation in response to environmental cues as light. VosA represses a novel genetic network controlled by the sclB gene. Bfunction is antagonistic to VosA, because it induces the expression of early activator genes of asexual differentiation as flbC and flbD as well as brlA. The SclB controlled network promotes asexual development and spore viability, but is independent of the fungal light control. SclB interactions with the RcoA transcriptional repressor subunit suggest additional inhibitory functions on transcription. SclB links asexual spore formation to the synthesis of secondary metabolites including emericellamides, austinol as well as dehydroaustinol and activates the oxidative stress response of the fungus. The fungal VosA-SclB regulatory system of transcription includes a VosA control of the sclB promoter, common and opposite VosA and SclB control functions of fungal development and several additional regulatory genes. The relationship between VosA and SclB illustrates the presence of a convoluted surveillance apparatus of transcriptional control, which is required for accurate fungal development and the linkage to the appropriate secondary metabolism.
Five new species belonging to Hermatomyces (Hermatomycetaceae, Pleosporales) are described based on morphological investigations of specimens collected on rotten twigs and stems of various plants in Panama as well as phylogenetic analyses of sequence data of nuclear ribosomal and protein coding genes (EF1-α, RPB2, β-TUB). The new species are described as: Hermatomyces bifurcatus, H. constrictus, H. megasporus, H. sphaericoides, and H. verrucosus spp. nov. Previously described species such as H. sphaericus and H. tucumanensis were identified among the studied specimens. The new combination, H. reticulatus, is made for Subicularium reticulatum based on examination of the holotype and fresh collections. Hermatomyces subiculosus, originally described from Thailand, is reduced to synonymy with H. reticulatus; H. tectonae is synonymized under H. sphaericus based on morphological and molecular evidence; and H. chiangmaiensis and H. thailandicus are considered later synonyms of H. krabiensis and H. indicus, respectively. The type material of Scyphostroma mirum was found to be conspecific with H. tucumanensis and, therefore, the generic name Hermatomyces should be conserved or protected against the older name Scyphostroma and the binomial H. tucumanensis against S. mirum. Sixteen species of Hermatomyces are recognized, their distinctive characteristics are highlighted in line drawings and a key is provided for their identification. The peculiar morphology and consistent phylogeny of new and previously known Hermatomyces species supports the recognition of the recently introduced monotypic family Hermatomycetaceae as a well delimited monophyletic taxon within the order Pleosporales.
Leaf-stripe smuts on grasses are a highly polyphyletic group within Ustilaginomycotina, occurring in three genera, Tilletia, Urocystis, and Ustilago. Currently more than 12 Ustilago species inciting stripe smuts are recognised. The majority belong to the Ustilago striiformis-complex, with about 30 different taxa described from 165 different plant species. This study aims to assess whether host distinct-lineages can be observed amongst the Ustilago leaf-stripe smuts using nine different loci on a representative set. Phylogenetic reconstructions supported the monophyly of the Ustilago striiformis-complex that causes leaf-stripe and the polyphyly of other leaf-stripe smuts within Ustilago. Furthermore, smut specimens from the same host genus generally clustered together in well-supported clades that often had available species names for these lineages. In addition to already-named lineages, three new lineages were observed, and described as new species on the basis of host specificity and molecular differences: namely Ustilago jagei sp. nov. on Agrostis stolonifera, U. kummeri sp. nov. on Bromus inermis, and U. neocopinata sp. nov. on Dactylis glomerata.
Background: Recent epidemics have entailed global discussions on revamping epidemic control and prevention approaches. A general consensus is that all sources of data should be embraced to improve epidemic preparedness. As a disease transmission is inherently governed by individual-level responses, pathogen dynamics within infected hosts posit high potentials to inform population-level phenomena. We propose a multiscale approach showing that individual dynamics were able to reproduce population-level observations.
Methods: Using experimental data, we formulated mathematical models of pathogen infection dynamics from which we simulated mechanistically its transmission parameters. The models were then embedded in our implementation of an age-specific contact network that allows to express individual differences relevant to the transmission processes. This approach is illustrated with an example of Ebola virus (EBOV).
Results: The results showed that a within-host infection model can reproduce EBOV’s transmission parameters obtained from population data. At the same time, population age-structure, contact distribution and patterns can be expressed using network generating algorithm. This framework opens a vast opportunity to investigate individual roles of factors involved in the epidemic processes. Estimating EBOV’s reproduction number revealed a heterogeneous pattern among age-groups, prompting cautions on estimates unadjusted for contact pattern. Assessments of mass vaccination strategies showed that vaccination conducted in a time window from five months before to one week after the start of an epidemic appeared to strongly reduce epidemic size. Noticeably, compared to a non-intervention scenario, a low critical vaccination coverage of 33% cannot ensure epidemic extinction but could reduce the number of cases by ten to hundred times as well as lessen the case-fatality rate.
Conclusions: Experimental data on the within-host infection have been able to capture upfront key transmission parameters of a pathogen; the applications of this approach will give us more time to prepare for potential epidemics. The population of interest in epidemic assessments could be modelled with an age-specific contact network without exhaustive amount of data. Further assessments and adaptations for different pathogens and scenarios to explore multilevel aspects in infectious diseases epidemics are underway.
In several tumor entities, transketolase-like protein 1 (TKTL1) has been suggested to promote the nonoxidative part of the pentose phosphate pathway (PPP) and thereby to contribute to a malignant phenotype. However, its role in glioma biology has only been sparsely documented. In the present in vitro study using LNT-229 glioma cells, we analyzed the impact of TKTL1 gene suppression on basic metabolic parameters and on survival following oxygen restriction and ionizing radiation. TKTL1 was induced by hypoxia and by hypoxia-inducible factor-1α (HIF-1α). Knockdown of TKTL1 via shRNA increased the cells’ demand for glucose, decreased flux through the PPP and promoted cell death under hypoxic conditions. Following irradiation, suppression of TKTL1 expression resulted in elevated levels of reactive oxygen species (ROS) and reduced clonogenic survival. In summary, our results indicate a role of TKTL1 in the adaptation of tumor cells to oxygen deprivation and in the acquisition of radioresistance. Further studies are necessary to examine whether strategies that antagonize TKTL1 function will be able to restore the sensitivity of glioma cells towards irradiation and antiangiogenic therapies in the more complex in vivo environment.
Background: Although mortality after cardiac surgery has significantly decreased in the last decade, patients still experience clinically relevant postoperative complications. Among others, atrial fibrillation (AF) is a common consequence of cardiac surgery, which is associated with prolonged hospitalization and increased mortality.
Methods: We retrospectively analyzed data from patients who underwent coronary artery bypass grafting, valve surgery or a combination of both at the University Hospital Muenster between April 2014 and July 2015. We evaluated the incidence of new onset and intermittent/permanent AF (patients with pre- and postoperative AF). Furthermore, we investigated the impact of postoperative AF on clinical outcomes and evaluated potential risk factors.
Results: In total, 999 patients were included in the analysis. New onset AF occurred in 24.9% of the patients and the incidence of intermittent/permanent AF was 59.5%. Both types of postoperative AF were associated with prolonged ICU length of stay (median increase approx. 2 days) and duration of mechanical ventilation (median increase 1 h). Additionally, new onset AF patients had a higher rate of dialysis and hospital mortality and more positive fluid balance on the day of surgery and postoperative days 1 and 2. In a multiple logistic regression model, advanced age (odds ratio (OR) = 1.448 per decade increase, p < 0.0001), a combination of CABG and valve surgery (OR = 1.711, p = 0.047), higher C-reactive protein (OR = 1.06 per unit increase, p < 0.0001) and creatinine plasma concentration (OR = 1.287 per unit increase, p = 0.032) significantly predicted new onset AF. Higher Horowitz index values were associated with a reduced risk (OR = 0.996 per unit increase, p = 0.012). In a separate model, higher plasma creatinine concentration (OR = 2.125 per unit increase, p = 0.022) was a significant risk factor for intermittent/permanent AF whereas higher plasma phosphate concentration (OR = 0.522 per unit increase, p = 0.003) indicated reduced occurrence of this arrhythmia.
Conclusions: New onset and intermittent/permanent AF are associated with adverse clinical outcomes of elective cardiac surgery patients. Different risk factors implicated in postoperative AF suggest different mechanisms might be involved in its pathogenesis. Customized clinical management protocols seem to be warranted for a higher success rate of prevention and treatment of postoperative AF.
Cardiac sarcoidosis is a rare immunologic disease causing heart involvement in 5% of patients. Cardiac sarcoidosis may manifest clinically as a cardiomyopathy with impaired left ventricular (LV) function or as tachyarrhythmias or bradyarrhythmias. On autopsy, cardiac granulomas can be found in approximately 25% of patients. The most common location for granulomas and scars is the LV free wall, followed by the intraventricular septum, often with involvement of the conduction system. ...
Temperature- and field-dependent 1H-, 19F-, and 79,81Br-NMR measurements together with zero - field 79,81Br-NQR measurements on polycrystalline samples of barlowite, Cu4(OH)6FBr are conducted to study the magnetism and possible structural distortions on a microscopic level. The temperature dependence of the 79,81Br-NMR spin-lattice relaxation rates 1/T1 indicate a phase transition at TN ≃ 15 K which is of magnetic origin, but with an unusually weak slowing down of fluctuations below TN. Moreover, 1/T1T scales linear with the bulk susceptibility which indicates persisting spin fluctuations down to 2 K. Quadupolare resonance (NQR) studies reveal a pair of zero-field NQR- lines associated with the two isotopes of Br with the nuclear spins of I = 3/2. Quadrupole coupling constants of vQ ≃ 28.5 MHz and 24.7 MHz for 79Br- and 81Br-nuclei are determined from Br-NMR and the asymmetry parameter of the electric field gradient was estimated to η ≃ 0.2. The Br-NQR lines are consistent with our findings from Br-NMR and they are relatively broad, even above TN. This broadening and the relative large η value suggests a symmetry reduction at the Br- site reflecting the presence of a local distortion in the lattice. Our density-functional calculations show that the displacements of Cu2 atoms located between the kagome planes do not account for this relatively large η. On the other hand, full structural relaxation, including the deformation of kagome planes, leads to a better agreement with the experiment.
Tubulogenesis is essential for the formation and function of internal organs. One such organ is the trachea, which allows gas exchange between the external environment and the lungs. However, the cellular and molecular mechanisms underlying tracheal tube development remain poorly understood. Here, we show that the potassium channel KCNJ13 is a critical modulator of tracheal tubulogenesis. We identify Kcnj13 in an ethylnitrosourea forward genetic screen for regulators of mouse respiratory organ development. Kcnj13 mutants exhibit a shorter trachea as well as defective smooth muscle (SM) cell alignment and polarity. KCNJ13 is essential to maintain ion homeostasis in tracheal SM cells, which is required for actin polymerization. This process appears to be mediated, at least in part, through activation of the actin regulator AKT, as pharmacological increase of AKT phosphorylation ameliorates the Kcnj13-mutant trachea phenotypes. These results provide insight into the role of ion homeostasis in cytoskeletal organization during tubulogenesis.
Background: Most smokers start smoking during their early adolescence, often with the idea that smoking is glamorous. Interventions that harness the broad availability of mobile phones as well as adolescents' interest in their appearance may be a novel way to improve school-based prevention. A recent study conducted in Germany showed promising results. However, the transfer to other cultural contexts, effects on different genders, and implementability remains unknown.
Objective: In this observational study, we aimed to test the perception and implementability of facial-aging apps to prevent smoking in secondary schools in Brazil in accordance with the theory of planned behavior and with respect to different genders.
Methods: We used a free facial-aging mobile phone app ("Smokerface") in three Brazilian secondary schools via a novel method called mirroring. The students’ altered three-dimensional selfies on mobile phones or tablets and images were "mirrored" via a projector in front of their whole grade. Using an anonymous questionnaire, we then measured on a 5-point Likert scale the perceptions of the intervention among 306 Brazilian secondary school students of both genders in the seventh grade (average age 12.97 years). A second questionnaire captured perceptions of medical students who conducted the intervention and its conduction per protocol.
Results: The majority of students perceived the intervention as fun (304/306, 99.3%), claimed the intervention motivated them not to smoke (289/306, 94.4%), and stated that they learned new benefits of not smoking (300/306, 98.0%). Only a minority of students disagreed or fully disagreed that they learned new benefits of nonsmoking (4/306, 1.3%) or that they themselves were motivated not to smoke (5/306, 1.6%). All of the protocol was delivered by volunteer medical students.
Conclusions: Our data indicate the potential for facial-aging interventions to reduce smoking prevalence in Brazilian secondary schools in accordance with the theory of planned behavior. Volunteer medical students enjoyed the intervention and are capable of complete implementation per protocol.
Background: Health care accessibility is known to differ geographically. With this study we focused on analysing accessibility of general and specialized obstetric units in England and Germany with regard to urbanity, area deprivation and neonatal outcome using routine data.
Methods: We used a floating catchment area method to measure obstetric care accessibility, the degree of urbanization (DEGURBA) to measure urbanity and the index of multiple deprivation to measure area deprivation.
Results: Accessibility of general obstetric units was significantly higher in Germany compared to England (accessibility index of 16.2 vs. 11.6; p < 0.001), whereas accessibility of specialized obstetric units was higher in England (accessibility index for highest level of care of 0.235 vs. 0.002; p < 0.001). We further demonstrated higher obstetric accessibility for people living in less deprived areas in Germany (r = − 0.31; p < 0.001) whereas no correlation was present in England. There were also urban–rural disparities present, with higher accessibility in urban areas in both countries (r = 0.37–0.39; p < 0.001). The analysis did not show that accessibility affected neonatal outcomes. Finally, our computer generated model for obstetric care provider demand in terms of birth counts showed a very strong correlation with actual birth counts at obstetric units (r = 0.91–0.95; p < 0.001).
Conclusion: In Germany the focus of obstetric care seemed to be put on general obstetric units leading to higher accessibility compared to England. Regarding specialized obstetric care the focus in Germany was put on high level units whereas in England obstetric care seems to be more balanced between the different levels of care with larger units on average leading to higher accessibility.
The identification of inhibitors of eukaryotic protein biosynthesis, which are targeting single translation factors, is highly demanded. Here we report on a small molecule inhibitor, gephyronic acid, isolated from the myxobacterium Archangium gephyra that inhibits growth of transformed mammalian cell lines in the nM range. In direct comparison, primary human fibroblasts were shown to be less sensitive to toxic effects of gephyronic acid than cancer-derived cells. Gephyronic acid is targeting the protein translation system. Experiments with IRES dual luciferase reporter assays identified it as an inhibitor of the translation initiation. DARTs approaches, co-localization studies and pull-down assays indicate that the binding partner could be the eukaryotic initiation factor 2 subunit alpha (eIF2α). Gephyronic acid seems to have a different mode of action than the structurally related polyketides tedanolide, myriaporone, and pederin and is a valuable tool for investigating the eukaryotic translation system. Because cancer derived cells were found to be especially sensitive, gephyronic acid could potentially find use as a drug candidate.
TEMPO spin labels protected with 2-nitrobenzyloxymethyl groups were attached to the amino residues of three different nucleosides: deoxycytidine, deoxyadenosine, and adenosine. The corresponding phosphoramidites could be incorporated by unmodified standard procedures into four different self-complementary DNA and two RNA oligonucleotides. After photochemical removal of the protective group, elimination of formic aldehyde and spontaneous air oxidation, the nitroxide radicals were regenerated in high yield. The resulting spin-labeled palindromic duplexes could be directly investigated by PELDOR spectroscopy without further purification steps. Spin–spin distances measured by PELDOR correspond well to the values obtained from molecular models.
Tight regulation of inflammation is very important to guarantee a balanced immune response without developing chronic inflammation. One of the major mediators of the resolution of inflammation is the transcription factor: the nuclear factor erythroid 2-like 2 (Nrf2). Stabilized following oxidative stress, Nrf2 induces the expression of antioxidants as well as cytoprotective genes, which provoke an anti-inflammatory expression profile, and is crucial for the initiation of healing. In view of this fundamental modulatory role, it is clear that both hyper- or hypoactivation of Nrf2 contribute to the onset of chronic diseases. Understanding the tight regulation of Nrf2 expression/activation and its interaction with signaling pathways, known to affect inflammatory processes, will facilitate development of therapeutic approaches to prevent Nrf2 dysregulation and ameliorate chronic inflammatory diseases. We discuss in this review the principle mechanisms of Nrf2 regulation with a focus on inflammation and autophagy, extending the role of dysregulated Nrf2 to chronic diseases and tumor development.