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This summary provides an overview of how new therapies or new aspects of established therapies relate to the latest findings. Neoadjuvant therapy, local therapy, new aspects of systemic therapy, and prognostic and predictive factors are presented. In the neoadjuvant setting, the association between pathological complete response (pCR) and prognosis is still of interest as is the identification of new molecular predictors for new therapies such as CDK4/6 inhibitors. As regards surgical treatment, the target is still to reduce the aggressiveness of surgery. To achieve this, a better understanding particularly of ductal carcinoma in situ is required. With regard to systemic therapy, more data on the best combinations and therapy sequences for existing therapies is available. Finally, the use of prognostic and predictive factors may help to avoid overtreatment and ensure that patients only receive therapies which have been shown to be effective for their specific condition and have fewer side effects.
In dieser Übersichtsarbeit wird dargestellt, wie neue Therapien oder neue Aspekte etablierter Therapien in Zusammenhang mit neuesten, aktuellen Erkenntnissen stehen. Neoadjuvanz, Lokaltherapie, neue Aspekte der Systemtherapie und Prognose- sowie Prädiktivfaktoren werden beleuchtet. In der Neoadjuvanz ist nach wie vor der Zusammenhang zwischen pCR und Prognose von Interesse, ebenso wie neue molekulare Prädiktoren für neue Therapien wie CDK4/6-Inhibitoren zu identifizieren. Bei der operativen Behandlung wird weiter nach einer Reduktion der Aggressivität gestrebt. Insbesondere das duktale Carcinoma in situ muss dafür noch besser verstanden werden. Bei den Systemtherapien wächst die Datenlage zum Verständnis der besten Kombinationen und Therapieabläufe für bestehende Therapieverfahren. Letztendlich muss mithilfe von Prognose- und Prädiktivfaktoren vermieden werden, dass Übertherapien stattfinden und nur die Patientin spezifische Therapien erhält, welche bei dieser individuellen Patientin eine nachgewiesene Wirksamkeit mit wenig Nebenwirkungen haben.
The article presents an interdisciplinary project that is focussed on an important cultural monument, namely a fortified hilltop settlement in the cadastre of Hradiště near Pilsen. This fortification is attested by five phases, which correspond to the main epochs of the erection of west Bohemian ramparts during the time span from the turn of the early to the Middle Bronze Age until the early medieval period. Geophysical prospection and trial excavations conducted there in 2012 and 2013 revealed important and new information on the stratigraphy and natural environment of the site. The project is particularly directed towards collaboration between archaeology and scientific studies. Geophysical and geochemical aspects of archaeological contexts, archaeobotanical and archaeozoological finds as well as geological composition of the materials from the fortification were analysed. Special attention was given to the problematic of the so-called vitrified walls (Schlackenwälle) associated with this site.
The Hultschin (Hlučín) region - now part of the Czech Republic - was annexed to the former Czechoslovakia in 1920. Throughout the centuries, its turbulent history has been shaped by various conflicting power interests, which have influenced the co-existence of the Czech and German communities which historically lived alongside each other. The Polish and Jewish communities had a relatively minor influence over the culture of this polylingual region, but the large German minority played a significant role. The influence of German language, culture and customs was not only visible in the political and economic life of the local population; it was also reflected in the various clubs and associations that were active in the region.
Im Bereich des Deutschen als Fremdsprache bietet etwa das Goethe-Institut Prüfungen auf allen Niveaus (A1-C2) an und entwickelt entsprechende Vorbereitungsmaterialien. Dazu gehören neben Modellprüfungen auch Wortlisten A1, A2 und B1 (vgl. z. B. Goethe-Institut 2016). Zur Arbeit mit den Wortlisten im DaF-Unterricht liegen nach Auskunft des Informationszentrums für Fremdsprachenforschung der Philipps-Universität Marburg vom 01.12.2017 weder wissenschaftliche Untersuchungen noch Praxisberichte vor. Mit der vorliegenden Arbeit soll versucht werden, zum Beheben dieses Desiderats beizutragen. Der Untersuchungsfokus liegt dabei auf den Erfahrungen der DaF-Studierenden mit dem Einsatz der Wortliste im Unterricht sowie ihren persönlichen Speicherstrategien beim Vokabellernen.
Der XIV. Internationale Türkische Germanistik-Kongress fand im Zeitraum vom 25. bis zum 27. Oktober 2018 unter dem Motto "Ex Oriente Lux: Orient in der deutschen Sprache, Literatur und Kultur" an der Atatürk Universität in Erzurum statt. Der Kongress wurde vom dortigen Institut für Deutsche Sprache und Literatur in Kooperation mit dem Türkischen Germanistenverband (GERDER) organisiert. [...] Auf dem Kongress wurden die Beiträge in fünf Parallelsitzungen zu den Fachbereichen Literaturwissenschaft, Sprachdidaktik (DaF), Linguistik und Translationswissenschaft vorgetragen.
Obwohl der Antisemitismus als Begriff im Jahre 1860 zum ersten Mal von dem österreichischen jüdischen Wissenschaftler Moritz Steinschneider benutzt und 1879 von Wilhelm Marr verbreitet wurde, beruht das Phänomen des Antisemitismus auf Tausenden von Jahren. Diese Feindseligkeit tauchte von Zeit zu Zeit mit zunehmender Stärke auf. Obwohl unter den Ursachen dieser Kräftigung die Auswirkung sozialer, wirtschaftlicher und politischer Faktoren ist, kann die Rolle der Literatur nicht bestritten werden. Ebenso gibt es literarische Werke gegen den Antisemitismus. Das Ziel dieser Arbeit ist, den Einfluss des Antisemitismus auf die Literatur zu bestimmen, die in Frankreich und Deutschland am Ende des 19. Jahrhunderts und zu Beginn des 20. Jahrhunderts entstanden ist. Man wird gleichzeitig versuchen, den Einfluss der Literatur auf den Antisemitismus zu bestimmen. Um dieses Ziel zu erreichen, wurde vor allem die Geschichte des Antisemitismus und die Entstehung des Antisemitismus-Konzeptes in Europa erforscht. Danach wurden die zwei Ereignisse, die den Antisemitismus am meisten in der Neuzeit anheizten, der Dreyfus-Fall und die Dolchstoßlegende, im literarischen Hintergrund erforscht. Eine reziproke Beziehung zwischen Literatur und Antisemitismus wurde in der Studie des Dokuments gefunden. Demnach entstehen gleichzeitig literarische Werke infolge der Judenfeindlichkeit, während die Judenfeindlichkeit infolge der Literatur entsteht. Einige dieser literarischen Werke - wie das berühmte Werk von Emile Zola, "J'accuse" - sind gegen die Judenfeindlichkeit entstanden. Es wird festgestellt, dass die Reaktion der beiden Gesellschaften auf Antisemitismus in dieser Hinsicht anders ist, wenn der politische Hintergrund berücksichtigt wird. Darüber hinaus kann man nach den Ergebnissen der durchgeführten Forschung feststellen, dass die Macht der literarischen Werke auch einer der Faktoren ist, der die Kräftigung oder den Rückgang des Phänomens Antisemitismus beeinflusst. Daher wird der Einfluss der Literatur auf die Gesellschaft betont.
A new monotypic genus of flatid planthoppers (Hemiptera: Fulgoromorpha: Flatidae), Medleria gen. nov., is described for Medleria caudata gen. et sp. nov. (type species) from the island of Socotra (Yemen). Habitus, male and female external and internal genital structures of the new species are illustrated and compared with similar taxa. Medleria caudata gen. et sp. nov. is probably endemic to Socotra where it is known to date from a small area of the Dixam mountain plateau only.
Der Lehrstuhl für Fremdsprachen der Philosophischen Fakultät der Universität Pardubice veranstaltete schon zum siebtem Mal seine traditionelle "bienale" internationale Konferenz "Interkulturelle und transkulturelle Dimension im linguistischen, kulturellen und historischen Kontext" zum aktuellen Thema Multikulturalismus in allen möglichen Erscheinungen, Dimensionen, Engpässen sowie Konsequenzen. In Bezug auf die Tradition der vorherigen erfolgreichen Begegnungen hat man ein großes Interesse von Akademikern an der aktiven Teilnahme auch im Jahre 2017 erwartet, und zwar nicht nur aus der Tschechischen Republik, sondern auch vor allem aus dem Ausland.
Der Lehrstuhl für Fremdsprachen der Philosophischen Fakultät der Universität Pardubice veranstaltete schon zum siebten Mal seine traditionelle "biennale" internationale Konferenz "Interkulturelle und transkulturelle Dimension im linguistischen, kulturellen und historischen Kontext" zum aktuellen Thema Multikulturalismus in allen möglichen Erscheinungen, Dimensionen, Engführungen sowie Konsequenzen.
Doğu Alman Yazar Franz Fühmann'ın çocuklar için yazdığı çok popüler (daha sonraki yıllarda çok sayıda baskı yapan) kitabı "Die dampfenden Hälse der Pferde im Turm von Babel" (Berlin: Kinderbuchverlag, 1978)'de karşımıza çıkan Türk figürün kişiliğinde Türk ve Türkçe imgesine dair ilginç değiniler görmekteyiz. Tipik Osmanlı kıyafetleri ve yüz hatlarıyla çizilen bu figürün adı Küslübürtün'dür. Uydurulmuş bir isim olduğu açık olan bu kişi, 1001 Gece Masalları'ından Alaaddinin Lambası'ından çıkan cin örneğine göre tasarlanmıştır, ama bir "dil cini" (Sprachgeist) olan Küslübürtün, çocukların dille ilgili sorularına yanıt verir, bu arada Arthur Schopenhauer ile ahbaplık eder. Türkçenin "ü" harfine fazlaca yer vermesine gönderme yapan "Küslübürtün" adı, bunun dışında Karacaoğlan'dan alıntılanan şiir parçası (Merhametin çoktur benden farıma/Beni görüp gül yüzünü bürüme) ve 1980'li yıllarda Batı Almanya'daki Türk imgesinin tersine tezahür eden olumlu alımlamanın araştırılması, eseri bir bildiri kapsamında ele almayı ilginç kılacak özelliklerindendir. Biyografisinden anlaşıldığı kadarıyla Franz Fühmann, Türkiye'ye gelmemiştir. İzi sadece Yunanistan'a kadar uzanan yazarın bu çocuk kitabında çizilen olumlu bir Türk imgesinin kontürlerini ortaya çıkarmak bildirimizin amacını oluşturacaktır.
FPP und GGPP sind Intermediate des Mevalonat-Weges und fungieren als post-translationale Modifikation kleiner GTPasen. Die Prenylierung kleiner GTPasen erfolgt katalysiert von spezifischen Prenyltransferasen und ist notwendig um die kleinen GTPasen in Membranen zu verankern, wo ihre Aktivierung stattfindet. Zu den intrazellulären Funktionen der GTPasen gehören unter anderem der Aufbau des Cytoskeletts, das neuronale Zellwachstum, die Leitung und Ausläuferbildung von Axonen, das Dendritenwachstum, die Synapsenformation, die synaptische Plastizität und die Apoptose. Diese Funktionen spielen in der Gehirnalterung sowie in neurodegenerativen Erkrankungen wie der Alzheimer Demenz (AD) und auch bei der Glioblastoma multiforme (GBM) eine wichtige Rolle.
Im Zuge einer in vivo Studie an C57BL/6 Mäusen konnten in der vorliegenden Arbeit altersbedingte Veränderungen der Lokalisation verschiedener Rho- und Rab-GTPasen in Membran- und Cytosol-Präparationen sowie der GGTase-I in Gehirnen gealterter Tiere gezeigt werden. Die zelluläre Lokalisation der Rho GTPasen Rac1, RhoA und Cdc42 verschiebt sich im Alter zu reduzierten Membran-gebundenen und erhöhten cytosolischen Gehalten. Dies ist mit einer Reduktion der Protein- und mRNA- Gehalte des Enzyms GGTase-Iβ assoziiert, der Untereinheit der GGTase-I, die die Bindung des Isoprenoids GGPP an die Rho-GTPasen reguliert. Diese wiederum korrelieren direkt mit der altersbedingten Reduktion der relativen GGTase-Aktivität. Die in vitro Inhibition der GGTase-I mittels GGTI-2133 an SH-SY5Y Zellen erwies sich als Modell, welches die gleichen Effekte wie die gealterten Gehirne in vivo zeigt.
7, 8-Dihydroxyflavon (7, 8-DHF) ist ein natürlich vorkommendes Flavon, welches als hoch affiner selektiver TrkB-Rezeptor-Agonist fungiert und hierdurch wie das Neurotrophin BDNF das Überleben von Neuronen, deren Differenzierung, synaptische Plastizität und Neurogenese vermittelt. In vivo verursacht die orale Gabe von 7, 8-Dihydroxyflavon in Gehirnen alter Tiere eine Abnahme des Isoprenoids GGPP, die Zunahme der prenylierten Membran-gebundenen GTPase Rac1 und eine Reduktion des Gehaltes an Membran-gebundenem Rab3A auf das Niveau der Gehalte in den Gehirnen der jungen Kontroll-Tiere. Das Neurotrophin BDNF interagiert mit dem TrkB-Rezeptor und ist in der Lage direkt an den Rac1-spezifischen GEF Tiam1 zu binden, wodurch dieser aktiviert wird und Veränderungen der zellulären Morphologie der betroffenen Neurone induziert. Während das Alter und die orale Gabe von 7, 8-Dihydroxyflavon in vivo keine Effekte auf die Proteingehalte von BDNF und TrkB in der Tierstudie aufzeigten, konnte eine alterbedingte Reduktion von Tiam1 im Hirngewebe detektiert werden, die wiederum durch 7, 8-Dihydroxyflavon aufgehoben werden konnte.
Die Isoprenoide FPP und GGPP, sowie die Regulation kleiner GTPasen spielen auch eine wichtige Rolle im Zusammenhang mit Veränderungen der APP-Prozessierung in der molekularen Pathogenese der AD. Bei der APP-Prozessierung sind die beiden Sekretasen β- und γ-Sekretase für die Bildung des β-Amyloid-Peptids verantwortlich. In vitro Studien mit dem β-Sekretase-Inhibitor IV und dem γ-Sekretase-Inhibitor DAPT an untransfizierten und APP-transfizierten HEK293 Zellen (HEK293-APP695wt und HEK293-APPsw Zellen) konnten zeigen, dass sowohl die β- als auch die γ-Sekretase an der Regulation der Isoprenoide FPP und GGPP beteiligt sind. FPP und GGPP liegen in APP-transfizierten HEK293 Zellen erhöht vor. Die Inhibition der β-Sekretase führt zur Reduktion von FPP und GGPP. Durch die Inhibition der γ-Sekretase wird ausschließlich FPP reduziert. Weiterhin liegen in APP-transfizierten HEK293 Zellen die Membran-gebundenen prenylierten Rho-GTPasen Rac1, Cdc42 und RhoA erhöht vor. Das Membran-gebundene prenylierte H-Ras kommt jedoch in APP-transfizierten Zellen im Vergleich zu untransfizierten HEK293 Zellen in deutlich niedrigeren Mengen vor. Die Inhibition der β-Sekretase bedingt die Reduktion von Membran-gebundenem prenylierten Rac1 und auch von Membran-gebundenem H-Ras in HEK293-APPsw Zellen.
Veränderungen von Signaltransduktionswegen, die durch kleine GTPasen vermittelt werden, haben sich auch bei der GBM als zentraler Teil der molekularen Pathogenese herausgestellt. Hierbei ist die Prenylierung durch FPP und GGPP die Voraussetzung für die Membran-Insertion und onkogenen Funktion der Ras- und Rho-Proteine über die Stimulierung des Ras-Raf-MEK-ERK Signalweges. In dieser Arbeit konnte gezeigt werden, dass der HMG-CoA-Reduktase Inhibitor Lovastatin die Bildung der beiden Isoprenoide FPP und GGPP in U87 und U343 Glioblastoma Zellen verringert und hierdurch die Isoprenylierung von H-Ras und Rac1 reduziert. Das natürlich vorkommende Monoterpen Perrilylalkohol hingegen inhibiert die Prenyltransferasen FTase und GGTase und verändert dadurch die post-translationale Prenylierung der GTPasen Rac1 und H-Ras in U87 und U343 Zellen ohne die Isoprenoide FPP und GGPP signifikant zu beeinflussen. Jedoch bewirkt Perillylalkohol in U343 Zellen eine Erhöhung des GGPPs. Beide Substanzen bewirkten die Reduktion der ERK-Phosphorylierung und der Migration, Invasion und Proliferation der untersuchten U87 und U343 Glioblastoma Zellen.
Die am Ende des 19. Jahrhunderts in Frankreich entstandene Décadence hatte einen wichtigen Einfluss auf europäische Literaturen. Charles Baudelaire, Paul Bourget, Hermann Bahr und Friedrich Nietzsche sind unter den Vertretern dieser literarischen Bewegung aufzuzählen. Die Wirkung der Décadence auf derzeitige türkische Literatur ist aus vielen Werken erkennbar. Yakup Kadris frühe Werke tragen auch klare Spuren der 'Décadence'. In seinem Roman 'Yaban' – obwohl es ein realistischer Roman ist – sind viele dekadente Eigenschaften zu betrachten. Der große Abgrund zwischen den türkischen Intellektuellen und den Dörfern ist ein wichtiges Thema des Werkes. Der Protagonist Ahmet Celâl beschließt nach dem Ersten Weltkrieg in einem kleinen Dorf Anatoliens zu leben. Durch seine Erfahrungen und Beziehungen mit den Dörflern treten zahlreiche dekadente Eigenschaften der Dörfler und des Protagonisten in Vordergrund. Ahmet Celâl konfrontiert die Einsamkeit, Krankheiten, Hilflosigkeit, Entfremdung und allerart soziokulturellen Verfall im Dorf, was die dekadente Seite des Dorfes zeigt. Andererseits sind seine dekadenten Haltungen wie Zurückgezogenheit, Übertreibung der Hässlichkeit und Schönheit, Widrigkeit, Verschönerung des Todes und Pessimismus im Werk zu sehen. In dieser Arbeit wird eine kurze Information über die Dekadenz und deren Vertreter vermittelt. Anhand der Décadence-Auffassungen von Nietzsche, Bourget und Bahr werden dekadente Motive in Yakup Kadris Roman Yaban dargestellt.
Önümüzdeki çalışma, Türkçe Çeviriler Bibliyografyası adlı çalışmada yer alan bilgiler ışığında Türkiye Cumhuriyeti’nin kuruluşundan 2016 yılına kadar Türkçeye çevrilmiş ve/ veya Türkiye’de yayımlanmış Alman edebi eserlerini raporlamayı amaçlamaktadır. Bu amaçla öncelikle, Türkçe Çeviriler Bibliyografyası kaynak kitabında da belirtildiği gibi çeşitli basılı ve elektronik kaynaklar (http://www.toplukatalog.gov.tr; https://kasif.mkutup.gov.tr ve http://koha.ekutuphane.gov.tr) taranarak bir veri tabanı oluşturulmuştur. Önümüzdeki çalışmada bu bilgilerden yola çıkılarak aşağıdaki soruların yanıtları aranmıştır: 1. Yıllara göre Almancadan Türkçeye çevrilen eserler belirlendiğinde karşımıza nasıl bir tablo çıkacaktır? 2. Her edebi türden toplam kaç kitap yayımlanmıştır? 3. En çok hangi yazarların eserleri Türkçeye çevrilmiştir? 4. Almancadan Türkçeye çevrilen eserler en çok hangi yayınevi tarafından basılmıştır? 5. En çok hangi çevirmenler Almancadan Türkçeye eserler kazandırmıştır? Bu soruların yanıtlarına istinaden niceliksel değerlere dayanan grafikler hazırlanmıştır. Daha sonra ise hazırlanan bu grafikler niteliksel olarak değerlendirilerek eserler Türkçeye çevrilirken hangi ölçütlerin esas alındığı, çeviri tercihlerinin- dönemine veya çevirmenine göre- nasıl yapıldığı tartışılmaktadır.
Çeviri faaliyeti, 18. yüzyılda Osmanlı Devleti'nin batılılaşması ve modernleşmesinde önemli bir yere sahipti. Bu amaca yönelik olarak çeviri eylemi, Osmanlı döneminde aydınlanma çağındaki fikirlerin yayılması ile birlikte siyasal ve bilimsel fikirlerin yerleşmesinde de çok etkili olmuştur. Bu durum Türkiye Cumhuriyeti'nin kuruluş yıllarında da devam etmiştir. Bu çeviri faaliyetini gerçekleştiren "gizli kahramanlar", yani çevirmenler, Türk diline ve edebiyatına yaptıkları katkılara nazaran pek tanınmazlar ve bilinmezler. Peki, bu çevirmenler kimlerdi? Kimlerin eserleri hangi dilden ve ne zaman çevrilip, hangi yayınevleri tarafından yayımlanmıştır? Türkçe Çevirmenler Sözlüğü'nde Türk edebiyatına katkıda bulunan ve Türk edebiyatının çeviri yoluyla zenginleşmesinde katkı sağlayan çevirmenlerin listelerini oluşturmak amaçlanmıştır. Ege Üniversitesi ile Johannes Gutenberg Üniversitesi Germersheim-Mainz (Almanya) mütercim tercümanlık bölümlerinin ortak yürüttükleri GIP (Germanistische Institutspartnerschaft) projesi bağlamında Türkçe Çeviriler Bibliyografyası kitap çalışması fikri de ortaya çıkmıştır. Uzun bir yöntem arayışından sonra başta Ege Üniversitesi Kütüphanesi, Hacettepe Üniversitesi Kütüphanesi, İstanbul Üniversitesi Kütüphanesi, Boğaziçi Üniversitesi Kütüphanesi ve Milli Kütüphane kayıtlarını barındıran ve T.C. Kültür ve Turizm Bakanlığı Kütüphaneler ve Yayımlar Genel Müdürlüğü ve TÜBİTAK ULAKBİM'in Ulusal Toplu Katalog veri tabanından yararlanılarak yabancı dilden Türkçeye aktarılan eserler ele alınmıştır. Çalışmada Cumhuriyetin ilk yıllarından 2016 yılına kadar Türkçeye aktarılan dil ve edebiyatların nesir, nazım ve tiyatro gibi edebi türlerine göre çevirileri incelenmiştir. Toplam 18.741 eser ve 6.006 çevirmen kaydına ulaşılmıştır.
Das Ziel dieses Beitrags besteht darin, am Beispiel der türkischen Germanistikstudenten an der Ege Universität die Merkmale und Entwicklung der pragmatisch-diskursiven Fähigkeit als eine Teilkompetenz der fremdsprachlichen Gesprächskompetenz zu untersuchen. Die Arbeit gliedert sich in zwei Abschnitte: Der erste Teil befasst sich mit der ausführlichen Beschreibung der Gesprächskompetenz als fremdsprachliche Kompetenz im Deutschen als Fremdsprache, der Bewertung der fremdsprachlichen Gesprächskompetenz als sprachproduktive Leistung und der Vorstellung von Subkategorien der pragmatisch-diskursiven Fähigkeit anhand der Beispiele aus dem Arbeitskorpus. Im zweiten Teil wird das Untersuchungsdesign und die Analyseergebnisse ausführlich dargestellt.
Reconstructing the evolution of baleen whales (Mysticeti) has been problematic because morphological and genetic analyses have produced different scenarios. This might be caused by genomic admixture that may have taken place among some rorquals. We present the genomes of six whales, including the blue whale (Balaenoptera musculus), to reconstruct a species tree of baleen whales and to identify phylogenetic conflicts. Evolutionary multilocus analyses of 34,192 genome fragments reveal a fast radiation of rorquals at 10.5 to 7.5 million years ago coinciding with oceanic circulation shifts. The evolutionarily enigmatic gray whale (Eschrichtius robustus) is placed among rorquals, and the blue whale genome shows a high degree of heterozygosity. The nearly equal frequency of conflicting gene trees suggests that speciation of rorqual evolution occurred under gene flow, which is best depicted by evolutionary networks. Especially in marine environments, sympatric speciation might be common; our results raise questions about how genetic divergence can be established.
Stress-induced cell surface expression of MHC class I-related glycoproteins of the MIC and ULBP families allows for immune recognition of dangerous “self cells” by human cytotoxic lymphocytes via the NKG2D receptor. With two MIC molecules (MICA and MICB) and six ULBP molecules (ULBP1–6), there are a total of eight human NKG2D ligands (NKG2DL). Since the discovery of the NKG2D–NKG2DL system, the cause for both redundancy and diversity of NKG2DL has been a major and ongoing matter of debate. NKG2DL diversity has been attributed, among others, to the selective pressure by viral immunoevasins, to diverse regulation of expression, to differential tissue expression as well as to variations in receptor interactions. Here, we critically review the current state of knowledge on the poorly studied human NKG2DL ULBP4. Summarizing available facts and previous studies, we picture ULBP4 as a peculiar ULBP family member distinct from other ULBP family members by various aspects. In addition, we provide novel experimental evidence suggesting that cellular processing gives rise to mature ULBP4 glycoproteins different to previous reports. Finally, we report on the proteolytic release of soluble ULBP4 and discuss these results in the light of known mechanisms for generation of soluble NKG2DL.
Social identification has been shown to be a protective resource for mental health. In this study, the relationships between social identification and emotional, as well as cognitive symptoms of test anxiety are investigated. Participants were university students diagnosed with test anxiety (N = 108). They completed questionnaires regarding a range of psychopathologic stress symptoms, and their social identification with fellow students and with their study program. Results reveal negative relations between social identification and almost all investigated emotional and cognitive symptoms of test anxiety. Based on this study, interventions could be developed that strengthen the social identity of university students.
Verblendungszusammenhang
(2018)
'Verblendungszusammenhang' ist kein Wort aus der Fremde. Aber das, was der Begriff ausdrücken möchte, seine Intention, muss dem souveränen, vernünftigen Subjekt gewissermaßen fremd bleiben. Jeder Bestandteil des Kompositums und die zugrundeliegenden Verben und Nomen - Verblendung, blenden, Blindheit, blind, Zusammenhang, zusammen, Hang, hängen - stammen aus dem Deutschen und haben für sich genommen eine alltägliche, nicht-fachsprachliche Bedeutung und Verwendung. Zusammengenommen jedoch und in der Bedeutung, die die Rede vom Verblendungszusammenhang bei Theodor W. Adorno erhält, könnte uns das Wort fremder nicht sein. Denn vielleicht kommt die Intransigenz der Kritischen Theorie, ihre Radikalität und all das, was auch heute noch an ihr provoziert und nicht selten zum Widerspruch oder gar zur affektiven Abwehr reizt, nirgends so sehr zum Ausdruck wie in diesem einen Wort: Verblendungszusammenhang.
In the insect brain, the mushroom body is a higher order brain area that is key to memory formation and sensory processing. Mushroom body (MB) extrinsic neurons leaving the output region of the MB, the lobes and the peduncle, are thought to be especially important in these processes. In the honeybee brain, a distinct class of MB extrinsic neurons, A3 neurons, are implicated in playing a role in learning. Their MB arborisations are either restricted to the lobes and the peduncle, here called A3 lobe connecting neurons, or they provide feedback information from the lobes to the input region of the MB, the calyces, here called A3 feedback neurons. In this study, we analyzed the morphology of individual A3 lobe connecting and feedback neurons using confocal imaging. A3 feedback neurons were previously assumed to innervate each lip compartment homogenously. We demonstrate here that A3 feedback neurons do not innervate whole subcompartments, but rather innervate zones of varying sizes in the MB lip, collar, and basal ring. We describe for the first time the anatomical details of A3 lobe connecting neurons and show that their connection pattern in the lobes resemble those of A3 feedback cells. Previous studies showed that A3 feedback neurons mostly connect zones of the vertical lobe that receive input from Kenyon cells of distinct calycal subcompartments with the corresponding subcompartments of the calyces. We can show that this also applies to the neck of the peduncle and the medial lobe, where both types of A3 neurons arborize only in corresponding zones in the calycal subcompartments. Some A3 lobe connecting neurons however connect multiple vertical lobe areas. Contrarily, in the medial lobe, the A3 neurons only innervate one division. We found evidence for both input and output areas in the vertical lobe. Thus, A3 neurons are more diverse than previously thought. The understanding of their detailed anatomy might enable us to derive circuit models for learning and memory and test physiological data.
GTP cyclohydrolase (GCH1) governs de novo synthesis of the enzyme cofactor, tetrahydrobiopterin (BH4), which is essential for biogenic amine production, bioactive lipid metabolism and redox coupling of nitric oxide synthases. Overproduction of BH4 via upregulation of GCH1 in sensory neurons is associated with nociceptive hypersensitivity in rodents, and neuron‐specific GCH1 deletion normalizes nociception. The translational relevance is revealed by protective polymorphisms of GCH1 in humans, which are associated with a reduced chronic pain. Because myeloid cells constitute a major non‐neuronal source of BH4 that may contribute to BH4‐dependent phenotypes, we studied here the contribution of myeloid‐derived BH4 to pain and itch in lysozyme M Cre‐mediated GCH1 knockout (LysM‐GCH1−/−) and overexpressing mice (LysM‐GCH1‐HA). Unexpectedly, knockout or overexpression in myeloid cells had no effect on nociceptive behaviour, but LysM‐driven GCH1 knockout reduced, and its overexpression increased the scratching response in Compound 48/80 and hydroxychloroquine‐evoked itch models, which involve histamine and non‐histamine dependent signalling pathways. Mechanistically, GCH1 overexpression increased BH4, nitric oxide and hydrogen peroxide, and these changes were associated with increased release of histamine and serotonin and degranulation of mast cells. LysM‐driven GCH1 knockout had opposite effects, and pharmacologic inhibition of GCH1 provided even stronger itch suppression. Inversely, intradermal BH4 provoked scratching behaviour in vivo and BH4 evoked an influx of calcium in sensory neurons. Together, these loss‐ and gain‐of‐function experiments suggest that itch in mice is contributed by BH4 release plus BH4‐driven mediator release from myeloid immune cells, which leads to activation of itch‐responsive sensory neurons.
The genus Raveniola Zonstein, 1987 is found to be represented in Western Asia by 16 species: ♂♀ R. adjarica sp. nov. (Georgia), ♂ R. anadolu sp. nov. (Turkey), ♂ R. arthuri Kunt & Yağmur, 2010 (Turkey), ♂ R. birecikensis sp. nov. (Turkey), ♂♀ R. dunini sp. nov. (Armenia, Azerbaijan, Iran), ♂♀ R. hyrcanica Dunin, 1988 (Azerbaijan), ♂ R. marusiki sp. nov. (Iran), ♂ R. mazandaranica Marusik, Zamani & Mirshamsi, 2014 (Iran), ♂♀ R. micropa (Ausserer, 1871) (Turkey), ♀ R. nana sp. nov. (Turkey), ♂♀ R. niedermeyeri (Brignoli, 1972) (Iran), ♂♀ R. pontica (Spassky, 1937) (Russia, Georgia), ♀ R. sinani sp. nov. (Turkey), ♂♀ R. turcica sp. nov. (Turkey), ♂♀ R. vonwicki Zonstein, 2000 (Iran) and ♂♀ R. zaitzevi (Charitonov, 1948) (Azerbaijan, Georgia) = ♀ Brachythele recki Mcheidze, 1983, syn. nov. Eight species are described as new; others are redescribed from types and/or conspecific material. Males of R. micropa and R. zaitzevi, hitherto unknown, are described for the first time. Data on the variability, relationships, distribution and ecology of all considered species are also provided.
The Central Asian spider genus Anemesia Pocock, 1895 is rediagnosed and revised. The genus was found to contain 14 species: ♂♀ A. andreevae sp. nov. (Uzbekistan, Tajikistan); ♂♀ A. birulai (Spassky, 1937) (Turkmenistan); ♂♀ A. castanea sp. nov.; ♂♀ A. incana Zonstein, 2001, ♂♀ A. infumata sp. nov.; ♂♀ A. infuscata sp. nov.; ♂♀ A. karatauvi (Andreeva, 1968) (all Tajikistan); ♂ A. koponeni Marusik, Zamani & Mirshamsi, 2014 (Iran); ♂♀ A. oxiana sp. nov.; ♂♀ A. pallida sp. nov.; ♂ A. parvula sp. nov. (all Tajikistan); ♂♀ A. pococki sp. nov. (Turkmenistan); ♂♀ A. sogdiana sp. nov. (Uzbekistan, Tajikistan) and ♂♀ A. tubifex (Pocock, 1889), the type species (Afghanistan, Turkmenistan). Nine species are newly described; others are redescribed from types and/or conspecific material. Males of A. tubifex and females of A. birulai, hitherto unknown, are described for the first time. Data on the variability, relationships, distribution, and ecology of all considered species are provided.
Secondary multidrug (Mdr) transporters utilize ion concentration gradients to actively remove antibiotics and other toxic compounds from cells. The model Mdr transporter MdfA from Escherichia coli exchanges dissimilar drugs for protons. The transporter should open at the cytoplasmic side to enable access of drugs into the Mdr recognition pocket. Here we show that the cytoplasmic rim around the Mdr recognition pocket represents a previously overlooked important regulatory determinant in MdfA. We demonstrate that increasing the positive charge of the electrically asymmetric rim dramatically inhibits MdfA activity and sometimes even leads to influx of planar, positively charged compounds, resulting in drug sensitivity. Our results suggest that unlike the mutants with the electrically modified rim, the membrane-embedded wild-type MdfA exhibits a significant probability of an inward-closed conformation, which is further increased by drug binding. Since MdfA binds drugs from its inward-facing environment, these results are intriguing and raise the possibility that the transporter has a sensitive, drug-induced conformational switch, which favors an inward-closed state.
This paper addresses the question of how to account for the semantic variability of weak free adjuncts. Weak free adjuncts are non-clausal adjuncts that associate with an argument of the main predicate, contribute propositional content, and can interact with temporal or modal operators, which leads to different, adverbial-clause-like interpretations. I focus on a specific type of weak adjuncts, non-clausal as-phrases, and propose a unified semantic analysis for the full range of interpretational possibilities that takes into account the interpretational contingency on different syntactic positions. I show that this analysis improves on Stump’s (1985) original analysis of weak adjuncts. I then go on to discuss the limitations of both Stump’s account and the unified account. Both accounts fail to capture that the interaction of weak adjuncts with modal operators underlies certain restrictions on the properties of the modal operators—an observation that has not been discussed in the literature so far.
The article provides an insight into the Czech translations of the lecture 'Weihnachtsgeheimnis' by Edith Stein (1891-1942), which were published in 1991 and 2003. The analysis of the translations is based on Skopos theory, the ideas of Christiane Nord and hermeneutic approaches; the author points out the specific features and demands of translating religious texts.
Die Monographie 'Die Kaschauer Zeitung in Kontexten I' geht auf die Darlegung der Prägung, historischer Metamorphosen und des sprachlichen, kulturellen und literarischen Bildes dieses Periodikums ein. Die Abhandlungen berücksichtigen dabei kulturhistorische Kontexte und interdisziplinäre Zusammenhänge.
In the latest contribution to the Democracy Papers, Thomas Zittel explores when and how polarization becomes a cause for democratic anxiety. He argues that polarization over traditional policy issues is not in itself harmful, and can even be beneficial for democracies. However, he warns that polarization in which parties become divided over the acceptable rules of the game is a problem for democracies. Unfortunately, this latter type of division is increasingly common on both sides of the Atlantic today.
Evoked potentials (EPs) are well established in clinical practice for diagnosis and prognosis in multiple sclerosis (MS). However, their value is limited to the assessment of their respective functional systems. Here, we used transcranial magnetic stimulation (TMS) coupled with electroencephalography (TMS-EEG) to investigate cortical excitability and spatiotemporal dynamics of TMS-evoked neural activity in MS patients. Thirteen patients with early relapsing–remitting MS (RRMS) with a median Expanded Disability Status Scale (EDSS) of 1.0 (range 0–2.5) and 16 age- and gender-matched healthy controls received single-pulse TMS of left and right primary motor cortex (L-M1 and R-M1), respectively. Resting motor threshold for L-M1 and R-M1 was increased in MS patients. Latencies and amplitudes of N45, P70, N100, P180, and N280 TMS-evoked EEG potentials (TEPs) were not different between groups, except a significantly increased amplitude of the N280 TEP in the MS group, both for L-M1 and R-M1 stimulation. Interhemispheric signal propagation (ISP), estimated from the area under the curve of TEPs in the non-stimulated vs. stimulated M1, also did not differ between groups. In summary, findings show that ISP and TEPs were preserved in early-stage RRMS, except for an exaggerated N280 amplitude. Our findings indicate that TMS-EEG is feasible in testing excitability and connectivity in cortical neural networks in MS patients, complementary to conventional EPs. However, relevance and pathophysiological correlates of the enhanced N280 will need further study.
AMP-activated protein kinase (AMPK) is frequently reported to phosphorylate Ser1177 of the endothelial nitric-oxide synthase (eNOS), and therefore, is linked with a relaxing effect. However, previous studies failed to consistently demonstrate a major role for AMPK on eNOS-dependent relaxation. As AMPK also phosphorylates eNOS on the inhibitory Thr495 site, this study aimed to determine the role of AMPKα1 and α2 subunits in the regulation of NO-mediated vascular relaxation. Vascular reactivity to phenylephrine and acetylcholine was assessed in aortic and carotid artery segments from mice with global (AMPKα−/−) or endothelial-specific deletion (AMPKαΔEC) of the AMPKα subunits. In control and AMPKα1-depleted human umbilical vein endothelial cells, eNOS phosphorylation on Ser1177 and Thr495 was assessed after AMPK activation with thiopental or ionomycin. Global deletion of the AMPKα1 or α2 subunit in mice did not affect vascular reactivity. The endothelial-specific deletion of the AMPKα1 subunit attenuated phenylephrine-mediated contraction in an eNOS- and endothelium-dependent manner. In in vitro studies, activation of AMPK did not alter the phosphorylation of eNOS on Ser1177, but increased its phosphorylation on Thr495. Depletion of AMPKα1 in cultured human endothelial cells decreased Thr495 phosphorylation without affecting Ser1177 phosphorylation. The results of this study indicate that AMPKα1 targets the inhibitory phosphorylation Thr495 site in the calmodulin-binding domain of eNOS to attenuate basal NO production and phenylephrine-induced vasoconstriction.
Mechanistic and structural studies of membrane proteins require their stabilization in specific conformations. Single domain antibodies are potent reagents for this purpose, but their generation relies on immunizations, which impedes selections in the presence of ligands typically needed to populate defined conformational states. To overcome this key limitation, we developed an in vitro selection platform based on synthetic single domain antibodies named sybodies. To target the limited hydrophilic surfaces of membrane proteins, we designed three sybody libraries that exhibit different shapes and moderate hydrophobicity of the randomized surface. A robust binder selection cascade combining ribosome and phage display enabled the generation of conformation-selective, high affinity sybodies against an ABC transporter and two previously intractable human SLC transporters, GlyT1 and ENT1. The platform does not require access to animal facilities and builds exclusively on commercially available reagents, thus enabling every lab to rapidly generate binders against challenging membrane proteins.
The democratic boundary problem raises the question of who has democratic participation rights in a given polity and why. One possible solution to this problem is the all-affected principle (AAP), according to which a polity ought to enfranchise all persons whose interests are affected by the polity’s decisions in a morally significant way. While AAP offers a plausible principle of democratic enfranchisement, its supporters have so far not paid sufficient attention to economic participation rights. I argue that if one commits oneself to AAP, one must also commit oneself to the view that political participation rights are not necessarily the only, and not necessarily the best, way to protect morally weighty interests. I also argue that economic participation rights raise important worries about democratic accountability, which is why their exercise must be constrained by a number of moral duties.
Divergent selection between ecologically dissimilar habitats promotes local adaptation, which can lead to reproductive isolation (RI). Populations in the Poecilia mexicana species complex have independently adapted to toxic hydrogen sulfide and show varying degrees of RI. Here, we examined the variation in the mate choice component of prezygotic RI. Mate choice tests across drainages (with stimulus males from another drainage) suggest that specific features of the males coupled with a general female preference for yellow color patterns explain the observed variation. Analyses of male body coloration identified the intensity of yellow fin coloration as a strong candidate to explain this pattern, and common-garden rearing suggested heritable population differences. Male sexual ornamentation apparently evolved differently across sulfide-adapted populations, for example because of differences in natural counterselection via predation. The ubiquitous preference for yellow color ornaments in poeciliid females likely undermines the emergence of strong RI, as female discrimination in favor of own males becomes weaker when yellow fin coloration in the respective sulfide ecotype increases. Our study illustrates the complexity of the (partly non-parallel) pathways to divergence among replicated ecological gradients. We suggest that future work should identify the genomic loci involved in the pattern reported here, making use of the increasing genomic and transcriptomic datasets available for our study system.
Theodor W. Adornos berühmt-berüchtigte Verteidigung des Fremdworts als "Exogamie der Sprache" wirft neben anderen Fragen auch die auf, ob denn hier Fremdsprache gleich Fremdsprache sei. [...] Immerhin lenkt Adornos Vergleich die Aufmerksamkeit auf einen in der Begriffsgeschichte unterschätzten Aspekt: Bedeutungsveränderungen, die eine Terminologie durchläuft, sind nicht selten mit sich wandelnden emotionalen Konnotationen verbunden. Begriffsgeschichte ist auch eine Geschichte der 'languages of emotion'. Besonders deutlich wird das an Begriffen wie 'Roboter'.
Loperamide, pimozide, and STF-62247 trigger autophagy-dependent cell death in glioblastoma cells
(2018)
Autophagy is a well-described degradation mechanism that promotes cell survival upon nutrient starvation and other forms of cellular stresses. In addition, there is growing evidence showing that autophagy can exert a lethal function via autophagic cell death (ACD). As ACD has been implicated in apoptosis-resistant glioblastoma (GBM), there is a high medical need for identifying novel ACD-inducing drugs. Therefore, we screened a library containing 70 autophagy-inducing compounds to induce ATG5-dependent cell death in human MZ-54 GBM cells. Here, we identified three compounds, i.e. loperamide, pimozide, and STF-62247 that significantly induce cell death in several GBM cell lines compared to CRISPR/Cas9-generated ATG5- or ATG7-deficient cells, pointing to a death-promoting role of autophagy. Further cell death analyses conducted using pharmacological inhibitors revealed that apoptosis, ferroptosis, and necroptosis only play minor roles in loperamide-, pimozide- or STF-62247-induced cell death. Intriguingly, these three compounds induce massive lipidation of the autophagy marker protein LC3B as well as the formation of LC3B puncta, which are characteristic of autophagy. Furthermore, loperamide, pimozide, and STF-62247 enhance the autophagic flux in parental MZ-54 cells, but not in ATG5 or ATG7 knockout (KO) MZ-54 cells. In addition, loperamide- and pimozide-treated cells display a massive formation of autophagosomes and autolysosomes at the ultrastructural level. Finally, stimulation of autophagy by all three compounds is accompanied by dephosphorylation of mammalian target of rapamycin complex 1 (mTORC1), a well-known negative regulator of autophagy. In summary, our results indicate that loperamide, pimozide, and STF-62247 induce ATG5- and ATG7-dependent cell death in GBM cells, which is preceded by a massive induction of autophagy. These findings emphasize the lethal function and potential clinical relevance of hyperactivated autophagy in GBM.
The Scarabaeus subgenus Scarabaeolus Balthasar, 1965 (Scarabaeidae: Scarabaeinae: Scarabaeini) is defined and nine new species are described, six from the Republic of South Africa [S. (S.) fragilis sp. n., S. (S.) krugeri sp. n., S. (S.) lizleri sp. n., S. (S.) orientalis sp. n., S. (S.) rugosipennis sp. n., S. (S.) similis sp. n.] and one each from Angola [S. (S.) cunene sp. n.], Namibia [S. (S.) namibensis sp. n.] and Kenya [S. (S.) werneri sp. n.], bringing the number of recorded species up to 41. Species accounts listing original descriptions, subsequent accounts, type localities, type repositories, and geographic distributions are provided for all the species. The status of S. (S.) reichei Waterhouse, 1890 and of S. (S.) bohemani Harold, 1868, both formerly synonymized and reinstated, are discussed. It is concluded that S. (S.) reichei is synonymous with S. (S.) canaliculatus Fairmaire, 1888, whereas S. (S.) bohemani differs from S. (S.) palemo Olivier, 1789 in the color of antennal club and shape of paramere tips, and is upheld pending availability of molecular data.
Sunrise Poison
(2018)
A new species complex, the eparmata complex, is established within the subgenus Phortica s. str., based on eight known and five new species, all of which are endemic to the Oriental Region: P. bipartita (Toda & Peng, 1992), P. eparmata (Okada, 1977), P. lanuginosa Chen & Toda, 2007, P. latipenis Chen & Gao, 2005, P. pangi Chen & Wen, 2005, P. setitabula Chen & Gao, 2005, P. unipetala Chen & Wen, 2005 and P. zeta Chen & Toda, 2007; P. jadete sp. nov., P. kava sp. nov., P. mengda sp. nov., P. wongding sp. nov. and P. yena sp. nov. A key to all species of this complex is provided. Barcoding sequences (mitochondrial COI gene) were obtained for 22 specimens of five known and the five abovementioned new species. The intra- and inter-specific pairwise K-2P (Kimura’s two-parameter) distances of COI were determined. Phylogenetic analysis was performed using Bayesian inference based on COI sequences, confirming the monophyletic status of the eparmata complex, which is distinct from the species complexes of magna, omega, variegata and another two ungrouped species.
In this proceeding we review our recent work using supervised learning with a deep convolutional neural network (CNN) to identify the QCD equation of state (EoS) employed in hydrodynamic modeling of heavy-ion collisions given only final-state particle spectra ρ(pT, Ф). We showed that there is a traceable encoder of the dynamical information from phase structure (EoS) that survives the evolution and exists in the final snapshot, which enables the trained CNN to act as an effective “EoS-meter” in detecting the nature of the QCD transition.