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Am 16. April 2019 starb unser hervorragender Kollege und Freund, Literaturwissenschaftler, Hochschulpädagoge und Literaturübersetzer, Dr. habil. Milan Žitný, PhD. Der Absolvent des Studiums der Germanistik und Nordistik an der Philosophischen Fakultät der Comenius-Universität Bratislava begann seine wissenschaftliche Laufbahn als Mitarbeiter des Instituts für Weltsprachen und Literatur an der Slowakischen Akademie der Wissenschaften. Hier promovierte er mit einer Dissertation über junge nonkonformistische DDR-Lyrik.
Ataxin-2 (human gene symbol ATXN2) acts during stress responses, modulating mRNA translation and nutrient metabolism. Ataxin-2 knockout mice exhibit progressive obesity, dyslipidemia, and insulin resistance. Conversely, the progressive ATXN2 gain of function due to the fact of polyglutamine (polyQ) expansions leads to a dominantly inherited neurodegenerative process named spinocerebellar ataxia type 2 (SCA2) with early adipose tissue loss and late muscle atrophy. We tried to understand lipid dysregulation in a SCA2 patient brain and in an authentic mouse model. Thin layer chromatography of a patient cerebellum was compared to the lipid metabolome of Atxn2-CAG100-Knockin (KIN) mouse spinocerebellar tissue. The human pathology caused deficits of sulfatide, galactosylceramide, cholesterol, C22/24-sphingomyelin, and gangliosides GM1a/GD1b despite quite normal levels of C18-sphingomyelin. Cerebellum and spinal cord from the KIN mouse showed a consistent decrease of various ceramides with a significant elevation of sphingosine in the more severely affected spinal cord. Deficiency of C24/26-sphingomyelins contrasted with excess C18/20-sphingomyelin. Spinocerebellar expression profiling revealed consistent reductions of CERS protein isoforms, Sptlc2 and Smpd3, but upregulation of Cers2 mRNA, as prominent anomalies in the ceramide–sphingosine metabolism. Reduction of Asah2 mRNA correlated to deficient S1P levels. In addition, downregulations for the elongase Elovl1, Elovl4, Elovl5 mRNAs and ELOVL4 protein explain the deficit of very long-chain sphingomyelin. Reduced ASMase protein levels correlated to the accumulation of long-chain sphingomyelin. Overall, a deficit of myelin lipids was prominent in SCA2 nervous tissue at prefinal stage and not compensated by transcriptional adaptation of several metabolic enzymes. Myelination is controlled by mTORC1 signals; thus, our human and murine observations are in agreement with the known role of ATXN2 yeast, nematode, and mouse orthologs as mTORC1 inhibitors and autophagy promoters.
The interdependence of selective cues during development of regulatory T cells (Treg cells) in the thymus and their suppressive function remains incompletely understood. Here, we analyzed this interdependence by taking advantage of highly dynamic changes in expression of microRNA 181 family members miR-181a-1 and miR-181b-1 (miR-181a/b-1) during late T-cell development with very high levels of expression during thymocyte selection, followed by massive down-regulation in the periphery. Loss of miR-181a/b-1 resulted in inefficient de novo generation of Treg cells in the thymus but simultaneously permitted homeostatic expansion in the periphery in the absence of competition. Modulation of T-cell receptor (TCR) signal strength in vivo indicated that miR-181a/b-1 controlled Treg-cell formation via establishing adequate signaling thresholds. Unexpectedly, miR-181a/b-1–deficient Treg cells displayed elevated suppressive capacity in vivo, in line with elevated levels of cytotoxic T-lymphocyte–associated 4 (CTLA-4) protein, but not mRNA, in thymic and peripheral Treg cells. Therefore, we propose that intrathymic miR-181a/b-1 controls development of Treg cells and imposes a developmental legacy on their peripheral function.
B-cell development and function depend on stage-specific signaling through the B-cell antigen receptor (BCR). Signaling and intracellular trafficking of the BCR are connected, but the molecular mechanisms of this link are incompletely understood. Here, we investigated the role of the endosomal adaptor protein and member of the LAMTOR/Ragulator complex LAMTOR2 (p14) in B-cell development. Efficient conditional deletion of LAMTOR2 at the pre-B1 stage using mb1-Cre mice resulted in complete developmental arrest. Deletion of LAMTOR2 using Cd19-Cre mice permitted analysis of residual B cells at later developmental stages, revealing that LAMTOR2 was critical for the generation and activation of mature B lymphocytes. Loss of LAMTOR2 resulted in aberrant BCR signaling due to delayed receptor internalization and endosomal trafficking. In conclusion, we identify LAMTOR2 as critical regulator of BCR trafficking and signaling that is essential for early B-cell development in mice.
This article aims to reveal the hitherto unknown circumstances of the creation of the opera "King Roger" ["Król Roger", premiere 1926] by the Polish composer Karol Szymanowski (1882-1932). As will be shown, this opera, with its oriental color, owes its genesis to the concluding of what we call "an emotional pact", referring to the 1918 meetings in Elizavetgrad, and then in Odessa on the Black Sea, between the composer and his cousin, the prose writer and poet Jarosław Iwaszkiewicz (1894-1980). Their Odessa stay, in particular, fostered the crystallization of their conception of beauty, and allowed namely the Dionysian element to emerge. At the same time, Odessa was where the creators were able to share the secret of their homosexuality, a place which functioned as a substitute for the Orient and an escape from the nightmare of World War I - all elements that found a wonderful expression in the libretto and the music of "King Roger".
Im Buch "Arthur Schopenhauer als Interpret des Götheʼschen Faust" (Leipzig 1859) erhebt David Asher den ersten Teil des Dramas zum Prüfstein der Schopenhauer’schen Philosophie. Zugleich aber sieht er den "überwiegenden philosophischen Charakter" der Dichtung nicht der idealen Dialektik Hegels, sondern dem voluntativen Irrationalismus dessen Antipoden Schopenhauer entwachsen. Diese Einsicht kam einem Paradigmenwechsel gleich, bedenkt man, dass der Gedankenaustausch zwischen Schopenhauer und Goethe mit einem pseudoödipalen Fiasko endete.
The dissertation studied reused Roman coins (AD 100 – 400) that were found in medieval cemeteries (AD 400 – 1400) in the territory of Serbia. The evaluation process was traced through three different periods and cultural contexts: (1) in the period of Roman domination in the central Balkans (AD 1 – 400), i.e. the “primary context” of their use and circulation; (2) in the time of transition from the late antiquity to early medieval period (AD 400 – 700); and (3) in the high and late Middle Ages (AD 900 – 1400), where the last two were considered to be a “secondary context” in which the Roman coins were no longer a valid currency.
It was observed that the reused Roman coins, as a distinctive category of archaeological finds, impose a necessity for reconsideration of the relationship between the disciplines of archaeology and numismatics; encouraging a greater cooperation and discussion between the two. Considering the use and evaluation of Roman coins in their “primary context”, it is possible to presume that the strength of the political Roman system was the crucial factor in the formation and maintaining the stability of the value of Roman coins. The act of reuse should not be automatically equalized with recycling; implying only to use value, but at the same time it was not possible to assume that the value was formed only on a purely symbolical level. The (re)use of Roman coins in the funeral practices from c. AD 400 to 700 was considered to be a part of wider and occasional practice of incorporating older Roman issues in the coin pool by the “barbarian” or Byzantine authorities. It could be then concluded that the value of Roman coins was understood more as a potential attribute than as a fixed category; enabling one to simultaneously “overvalue “ and “undervalue” these objects. In the period from c. AD 900 to 1400, the reuse of Roman coins was detected only within the cemeteries of the peasantry and in a context of gradual increase of general coin use in the central Balkan communities of the Middle Ages. This was understood as an indicator that the Roman coins were not perceived as particularly valuable per se, but since the were recognized as category of objects that became more important in defining social relationships they were then incorporated in the funeral rituals and reinterpreted by the medieval population.
The reformation in Germany and Martin Luther did not come out of nothing. A whole century before, the era was characterized by a series of attempts at religious reform. Two of Luther's predecessors lived in Bohemia: Jan Hus (about 1369-1415) and Jerome of Prague (about 1378/79-1416). The latter studied in Oxford where he was inspired by the teachings of John Wyclif and brought these ideas to Prague. There they inspired the Dean of the Arts Faculty, Jan Hus, to deliver great sermons. Jan Hus also received enthusiastic support from the Bohemian aristocracy, the Prague middle class and the common people. His reformation was therefore more than just a theological affair; it became a political power factor and a revolutionary project. In 1415 Hus was summoned to the Council of Constance, where he was condemned and burnt to death, despite being promised safe passage. His death as a martyr triggered revolts in Bohemia, leading to the Hussite civil wars. The Hussites' most important demands (free sermons based on the Bible, Communion provided in bread and wine, separation of church and state rule, the overcoming of social injustices) and church services in the national language were to become central demands of Luther, but they had already been implemented in Bohemia a hundred years earlier.
One of the main controversial topics of German language is the definition of word types and the classification of the principles. There are different views on the definition of 'particle' and 'intensive particle'. An interesting object of study of linguistics in this context are primarily grammaticalized words that lose their actual lexical meaning, assume grammatical functions and act as lexical intensifiers. In the first part of this article, general information is given about the definition and classification of the concepts of 'particle' and 'intensive particle'. The second part of the study handles the 'intensive particle', so called by the German language linguist Hentschel (1998), which have partly metaphorical features. The use of these words as 'intensive particle' in certain areas has been examined with German and Turkish examples and the differences and similarities have been revealed in two languages.