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Type I interferons (IFNs) signal for their diverse biological effects by binding a common receptor on target cells, composed of the two transmembrane IFNAR1 and IFNAR2 proteins. We have previously differentially enhanced the antiproliferative activity of IFN by increasing the weak binding affinity of IFN to IFNAR1. In this study, we further explored the affinity interdependencies between the two receptor subunits and the role of IFNAR1 in differential IFN activity. For this purpose, we generated a panel of mutations targeting the IFNAR2 binding site on the background of the IFNalpha2 YNS mutant, which increases the affinity to IFNAR1 by 60-fold, resulting in IFNAR2-to-IFNAR1 binding affinity ratios ranging from 1000:1 to 1:1000. Both the antiproliferative and antiviral potencies of the interferon mutants clearly correlated to the in situ binding IC(50) values, independently of the relative contributions of the individual receptors, thus relating to the integral lifetime of the complex. However, the antiproliferative potency correlated throughout the entire range of affinities, as well as with prolonged IFNAR1 receptor down-regulation, whereas the antiviral potency reached a maximum at binding affinities equivalent to that of wild-type IFNalpha2. Our data suggest that (i) the specific activity of interferon is related to the ternary complex binding affinity and not to affinity toward individual receptor components and (ii) although the antiviral pathway is strongly dependent on pSTAT1 activity, the cytostatic effect requires additional mechanisms that may involve IFNAR1 down-regulation. This differential interferon response is ultimately mediated through distinct gene expression profiling.
Symbiosis represents a widely distributed principle of mutual relationships among organisms, belonging to different systematic groups. The cell endosymbiosis is considered to be the most important event, which starts the evolution of all eukaryotic organisms. We recognize about five successful endosymbioses. Some of them resulted in obtaining mitochondria the peroxisomes, perhaps derived from different groups of bacterial ancestors. The special interest represents the origin of the chloroplasts. As it was suggested using the molecular methods, the single-celled cyanobacteria were the ancestors of chloroplasts in glaucophytes, red and green algae. All these groups are classified into kingdom Plantae. Green algae and vascular plants form a monophyletic group. Their chloroplasts are surrounded only by double membrane envelopes, no connection with endoplasmic reticulum or with the nuclear envelope were observed. Endosymbiosis with cyanobacterial chloroplast ancestor is considered to be the primary endosymbiosis. It was of an ancient origin with the age of about 2 billion years. Chloroplasts of other algal divisions were obtained via secondary, sometimes even as tertiary endosymbioses. In dinophytes and euglenophytes, the plastids are the remainder of single celled eukaryotic algae, covered with the triple envelope membranes. Two inner membranes are similar to the chloroplast envelopes in plant chloroplasts, the third outer membrane is of unknown origin. Some experts consider the third plastid membrane as a phagosome (food vacuole) membrane. No connections with the nuclear envelope were observed. In cryptophytes and chromophyte algae (Chromophyta, syn. Heterocontophyta, syn. Ochrista) and Haptophyta (syn. Prymnesiophyta) plastids are covered with four membranes, two additional membranes are derived from the rough endoplasmic reticulum, which is often connected with the outer membrane of nuclear envelope. This kind of endosymbiosis is called the secondary symbiosis, and is much younger than the primary symbioses. Taking in account the six- kingdoms system of life proposed by CAVALIER-SMITH (1998), the secondary endosymbioses are classified into two different kingdoms: Protozoa (Dinophyta, Euglenophyta) and Chromista. The primary endosymbioses form the kingdom Plantae. The classification of Chlorarachniophyta is not clear and recently they are not mentioned as a separate division. Besides Chlorarachnion reptans, some other filarplasmodium forming protozoans containing plastids (Chrysarachnion, Chrysophyceae, Myxochloris, Xanthophyceae) or without plastids (Corallomyxa, Reticulosphaera, GRELL 1991) were recognized.
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.
Resilience has been defined as the maintenance or quick recovery of mental health during and after times of adversity. How to operationalize resilience and to determine the factors and processes that lead to good long-term mental health outcomes in stressor-exposed individuals is a matter of ongoing debate and of critical importance for the advancement of the field. One of the biggest challenges for implementing an outcome-based definition of resilience in longitudinal observational study designs lies in the fact that real-life adversity is usually unpredictable and that its substantial qualitative as well as temporal variability between subjects often precludes defining circumscribed time windows of inter-individually comparable stressor exposure relative to which the maintenance or recovery of mental health can be determined. To address this pertinent issue, we propose to frequently and regularly monitor stressor exposure (E) and mental health problems (P) throughout a study's observation period [Frequent Stressor and Mental Health Monitoring (FRESHMO)-paradigm]. On this basis, a subject's deviation at any single monitoring time point from the study sample's normative E–P relationship (the regression residual) can be used to calculate that subject's current mental health reactivity to stressor exposure (“stressor reactivity,” SR). The SR score takes into account the individual extent of experienced adversity and is comparable between and within subjects. Individual SR time courses across monitoring time points reflect intra-individual temporal variability in SR, where periods of under-reactivity (negative SR score) are associated with accumulation of fewer mental health problems than is normal for the sample. If FRESHMO is accompanied by regular measurement of potential resilience factors, temporal changes in resilience factors can be used to predict SR time courses. An increase in a resilience factor measurement explaining a lagged decrease in SR can then be considered to index a process of adaptation to stressor exposure that promotes a resilient outcome (an allostatic resilience process). This design principle allows resilience research to move beyond merely determining baseline predictors of resilience outcomes, which cannot inform about how individuals successfully adjust and adapt when confronted with adversity. Hence, FRESHMO plus regular resilience factor monitoring incorporates a dynamic-systems perspective into resilience research.
Eine Studie zur fehleranalytischen Kompetenz der Studierenden in der Deutschlehrendenausbildung
(2018)
Die Fehleranalyse gilt seit langem als eine wertvolle Hilfe beim Fremdsprachenunterricht, weil sowohl Lernende als auch Lehrende dadurch wichtige Informationen über den Spracherwerbsprozess bekommen können. Auch die vorliegende Arbeit beabsichtigt mit Hilfe der Fehleranalyse zu Erkenntnissen über die fehleranalytische Kompetenz der künftigen Deutschlehrer zu gelangen. Ausgangspunkt dieser Studie war die Frage, ob es eine direkte Verbindung zwischen dem Sprachniveau und der fehleranalytischen Kompetenz der Studierenden gebe. An der Untersuchung haben 37 Studierenden der Gazi Universität teilgenommen, von denen sieben Rückkehrende aus Deutschland waren und über gute Sprachkenntnisse verfügten. Alle Probanden befanden sich im sechsten Semester und hatten sich im Rahmen der angewandten Linguistik ein semesterlang mit der Fehleranalyse befasst. Den Probanden wurden zwei Texte vorgelegt, deren Fehler sie identifizieren und anhand eines Rasters klassifizieren mussten. Es hat sich herausgestellt, dass bei der Fehleridentifizierung die Fremdsprachenkenntnisse ein entscheidender Faktor waren. Bei der Fehlerklassifizierung dagegen, schienen die Fremdsprachenkenntnisse eher eine untergeordnete Rolle zu spielen.
An der erfolgreichen Inszenierung "Verrücktes Blut" des Kreuzberger Theaters 'Ballhaus Naunynstraße' interessiert in diesem Beitrag vor allem die Bühnensprache und die Diskrepanz zwischen der Intention der Künstler und der Rezeption der Inszenierung durch das Berliner Publikum. Die Frage nach der Rolle der Ironie in der Bühnensprache des Ballhauses führt zur Antwort auf die Frage nach den Gründen für den Erfolg dieser Inszenierung.
Im Bereich des Naturschutzgebietes "Untere Seegeniederung" (Landkreis Lüchow-Dannenberg/Niedersachsen), nahe der Elbe wurde nach Überschwemmungsjahren auf Ackerflächen die Quirltänel-Sand-binsengesellschaft (Elatino alsinastri-Juncetum tenageiae Libbert 1933) mit der Niederliegenden Teichbinse (Schoenoplectus supinus) gefunden. Dieses Vorkommen wird beschrieben, Verbreitung, Gefährdung und Schutzmaßnahmen werden besprochen. Das Elatino alsinastri-Juncetum tenageiae ist eine spezialisierte Gesellschaft sehr unregelmäßig überfluteter, offener nährstoff- und kalkarmer Sandböden im stärker kontinental getönten Klimabereich. Die allesamt höchst seltenen Charakterarten und die ebenso gefährdete Artenkombination, bedürfen intensiven Schutzes. Voraussetzung für das Vorkommen ist einerseits der ungestörte Überschwemmungsrhytmus der Elbe, andererseits die Beibehaltung der Nutzung.
Reelle Bestandsgrößen und Verteilung gebäudebrütender Vogelarten sind vielfach nicht bekannt. Dauerhaft genutzte Lebensstätten dieser Arten sind jedoch nach dem Bundesnaturschutzgesetz ganzjährig geschützt. Um Anträge auf Befreiung vom Zerstörungsverbot von Niststätten für geplante Abriss- und Sanierungsarbeiten von Gebäuden zügig bearbeiten zu können, wird der Gebäudebrüterbestand in der Stadt Dessau im Auftrag der Stadt seit 2002 erfasst. Die Bearbeitung wurde zunächst innerhalb des unmittelbaren Stadtgebietes begonnen und seither im Rahmen der finanziellen Möglichkeiten auch auf die äußeren Stadtteile ausgedehnt. Als Ergebnis liegen der Stadt gebäudespezifische Angaben über Brutvögel vor.