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Recently, we discovered a novel lipoglycopeptide antibiotic family gausemycin with exceptional structural novelty. We reported two major constituents of the family gausemycins A and B and characterized their antimicrobial activities. Here-in we studied the molecular mechanism of action of gausemycins and report the isolation and structure elucidation of other members of the family gausemycins C, D, E and F, the minor components of the mixture. Antimicrobial activity of the new congeners was found to be lower than that of the previously reported gausemycins A and B, thus suggesting the importance of the free δ amino group of Orn2 and O-glycosylation of Tyr5 for biological function. To disclose the mecha-nism of action of gausemycin family we investigated the antimicrobial activity of the most active compounds, gausemy-cins A and B, in the presence of Ca2+, other metal ions, and phosphate. Gausemycins require significantly higher Ca2+ con-centration for maximum activity than daptomycin, but lower than that required for malacidine and cadasides. Species-specific antimicrobial activity was found upon testing against a wide panel of Gram-positive bacteria. Membranes were previously proposed as a plausible target of gausemycins, therefore, we explored their interactions with various model membrane systems, including lipid bilayers and micelles. The pore-forming ability was found to be dramatically depend-ent on Ca2+ concentration and the lipid composition of the membrane. The NMR study of gausemycin B in zwitterionic and anionic micelles suggested putative structure of the gausemycin/membrane complex and revealed binding of Ca2+ by the macrocyclic domain of the antibiotic.

Im Kontext des neu aufgekommenen theoretischen Interesses für die Werkkategorie wird überwiegend das ,Einzelwerk‘ fokussiert. Im vorliegenden Aufsatz wird das heuristische Potenzial des Konzepts ,Gesamtwerk‘ als ein anderer Teil der Werkkategorie herausgearbeitet. Neben dem üblichen Aspekt eines ,Lebenswerks‘ schließt das Gesamtwerk vielfältige Werkkomplexe und Werkgruppierungen ein, die auf Produktions- oder Rezeptionsseite entstehen. Analysiert werden feste und variable Anordnungen, Ab- und Entgrenzungen zwischen Einzelwerken eines Autors, die das Gesamtwerk zu einem dynamischen Gefüge machen. Ein Werkkomplex bildet eine Zwischenstufe und ein Bindeglied zwischen ,Einzelwerk‘ und ,Gesamtwerk‘. Daher besitzt er eine besondere Relevanz für die semantische Zusammensetzung der Werkkategorie als Trias, deren Teile sich aufeinander beziehen: Opus – Werkkomplex – Œuvre.The newly arisen theoretical research on the literary work category focuses mainly on the ,single work‘. This paper argues for the heuristic potential of the ,oeuvre‘ as another part of the work category. In addition to the usual aspect of a ,life’s work‘, the oeuvre includes diverse work complexes and work groupings that emerge on the production or reception side. The paper analyzes a dynamic structure of the oeuvre: fixed and variable arrangements, boundaries and dissolution of borders between single works by the same author. A work complex forms an intermediate stage and a link between ,single work‘ and ,oeuvre‘. It therefore has a special relevance for the semantic composition of the work category as a triad, the parts of which refer to each other: single work – work complex – oeuvre.

Was sind ,große Formen‘? Ein Bewusstsein für den Textumfang ist für die Literatur grundlegend, prägt er doch – mindestens implizit – Gattungskategorien und Systematiken mit aus. Dabei lässt sich die ,Größe‘ jedoch nur in wenigen Fällen durch absolute Quantifizierung festlegen (so etwa beim Haiku und Sonett). Sie bestimmt sich vielmehr relativ bzw. relational, wobei sich unterschiedliche Möglichkeiten der Perspektivierung ergeben.

Der Aufsatz analysiert die performative Poetologie der Großform im Roman Dein Name (2011) von Navid Kermani. Zu dessen Leitmotiven gehören die Vermessung einer ausufernden Textmasse und die Suche nach einer literarischen Form, um die Wahrnehmung der Wirklichkeit in ihrer Endlosigkeit zu vermitteln. Davon ausgehend fokussiert der Aufsatz den Zusammenhang zwischen Großform und Komposition, eine ästhetische Werklogik und eine epistemische Ordnung der Großform sowie eine Poetik der Ausdehnung.The paper analyzes a performative poetology of the literary ,large form‘ in Navid Kermani’s novel Dein Name (2011). Its leitmotifs include the measuring of an overflowing written text as well as the search for a literary form in order to convey the perception of reality as infinite. Taking this into account, the paper focuses on the relations between the ,large form‘ and textual composition, on the aesthetic and epistemic orders of the ,large form‘ as well as on the poetics of textual extension.

Polyene antifungal amphotericin B (AmB) has been used for over 60 years, and remains a valuable clinical treatment for systemic mycoses, due to its broad antifungal activity and low rate of emerging resistance. There is no consensus on how exactly it kills fungal cells but it is certain that AmB and the closely-related nystatin (Nys) can form pores in membranes and have a higher affinity towards ergosterol than cholesterol. Notably, the high nephro- and hemolytic toxicity of polyenes and their low solubility in water have led to efforts to improve their properties. We present the synthesis of new amphotericin and nystatin amides and a comparative study of the effects of identical modifications of AmB and Nys on the relationship between their structure and properties. Generally, increases in the activity/toxicity ratio were in good agreement with increasing ratios of selective permeabilization of ergosterol- vs. cholesterol-containing membranes. We also show that the introduced modifications had an effect on the sensitivity of mutant yeast strains with alterations in ergosterol biosynthesis to the studied polyenes, suggesting a varying affinity towards intermediate ergosterol precursors. Three new water-soluble nystatin derivatives showed a prominent improvement in safety and were selected as promising candidates for drug development.

We report a novel family of natural lipoglycopeptides produced by Streptomyces sp. INA-Ac-5812. Two major components of the mixture, named gausemycins A and B, were isolated, and their structures were elucidated. The com-pounds are cyclic peptides with a unique peptide core and several remarkable structural features, including unusual posi-tions of D-amino acids, lack of the Ca2+-binding Asp-X-Asp-Gly (DXDG) motif, tyrosine glycosylation with arabinose, presence of 2-amino-4-hydroxy-4-phenylbutyric acid (Ahpb) and chlorinated kynurenine (ClKyn), N-acylation of the or-nithine side chain. These major components of the peptide antibiotic family have pronounced activity against Gram-positive bacteria. The mechanism of action of gausemycins was explored by a number of methods, showing significant differences compared to glycopeptides and related lipopeptides. Gausemycins exhibit only slight Ca2+-dependence of an-timicrobial activity and induce no pore formation at low concentrations. Moreover, there is no detectable accumulation of cell wall biosynthesis precursors under treatment with gausemycins.

This article offers a new interpretation of Boris Pasternak’s novel Doctor Zhivago in the cultural and historical context of the first half of the 20th century, with an emphasis on the interrelationship between religion and philosophy of history in the text. Doctor Zhivago is analysed as a condensed representation of a religious conception of Russian history between 1901 and 1953 and as a cyclical repetition of the Easter narrative. This bipartite narrative consists of the Passion and Resurrection of Christ as symbols of violence and renewal (liberation). The novel cycles through this narrative several times, symbolically connecting the ‘Easter’ revolution (March 1917) and the Thaw (the spring of 1953). The sources of Pasternak’s Easter narrative include the Gospels, Leo Tolstoy’s philosophy of history and pre-Christian mythology. The model of cyclical time in the novel brings together the sacred, natural and historical cycles. This concept of a cyclical renewal of life differs from the linear temporality of the Apocalypse as an expectation of the end of history.

Das Konzept ‚Weltliteraturʻ halt nicht etwas Gegebenes fest, sondern befindet sich im Prozess als ein historisches und variables Produkt einer Reihe von modernen Praktiken und Strategien unterschiedlicher Akteure. Bedeutungsstiftend wirkt fur Konzepte der ‚Weltliteraturʻ eine Worlding-Praxis unterschiedlicher Autoren und ‚Mitautorenʻ (von einem Herausgeber bis zu einem Forscher). Diese Praxis hat einen epistemisch-kommunikativen Charakter und steht in einem Wechselverhaltnis mit Wissensfigurationen und Weltbildern.

DeutschDieser Beitrag analysiert unterschiedliche Formen der materiellen Interaktion von Text und Bild in Theodor Fontanes Notizbuchern und fuhrt sie auf die epistemischen Prozesse der Wahrnehmungsverarbeitung zuruck. Fontanes schematisierende Notierpraxis (Lageplane, Skizzen der Gebaude- und Gemaldestruktur) wird mit dem Konzept der 'abstrahierenden Wahrnehmung' von Rudolf Arnheim gefasst sowie mit einem Forschungsvorgang verglichen. Zugleich werden Spuren dieser Notierpraxis als wissenschaftlicher Schreibgestus in Fontanes 'Wanderungen durch die Mark Brandenburg' aufgezeigt EnglishThis article analyses different forms of material interaction between text and image in Theodor Fontane’s notebooks and traces them back to the epistemic procedures of perceptual processing. Fontane’s schematised notational practice (location plans, sketches of the structure of buildings and paintings) is described using Rudolf Arnheim’s concept of 'abstractive perception' and compared with a research process. At the same time, traces of this notational practice as a form of scientific writing are noted in Fontane’s 'Wanderungen durch die Mark Brandenburg'

The fast changing world around dictates need for the same speed to change structure of the enterprise to save clients and compliance to world around. The virtual enterprises provide such opportunity. Existence of a large number of various services in the Cloud does potentially possible both fast changing of the enterprise, and assembly of the new enterprises of atomic services. It is known that algorithms of automated planning are important part of such synthesis.