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The promotion and extension of continuous cover mixed stands with a simultaneous reduction of conifer-monocultures play a major role in current silvicultural practices in Central Europe. It is assumed that the admixture of the natural dominant beech (Fagus sylvatica) in pure non site-specific conifer stands automatically indicates better conditions in terms of nature conservation and forest management. To test this hypothesis three different conifer-beech-comparisons of pure and mixed stands in Lower Saxony are studied, analyzing plant species diversity and naturalness of understory vegetation as one important indicator for the ecological status of forests. Each comparison includes pure coniferous stands (Picea abies, Pinus sylvestris, Pseudotsuga menziesii), mixed coniferous-beech-stands, and pure beech stands on similar acidic mineral soils where the potential natural vegetation will be an oligotrophic beech forest (L u z u l o - Fa g e t um). The age of stands varies between 50 and 150 years. To specify tree species influence on site conditions and vegetation, the study also includes light climate and soil data of the stands. It is observed that, with regard to all comparisons, the admixture of beech reduces plant species diversity but increases naturalness of the stands. The intensity of beech admixture effects differs. While in Scots pine stands the impact of admixed beech is very noticeable, with the mixed stands being nearly identical with pure beech stands, the species change in Douglas-fir and Norway spruce stands proceeds more slowly. Assuming that the status in nature conservation and forest management is improving with increasing plant species diversity and increasing naturalness, the results of this study show a contrary development on a stand scale, as the potential natural vegetation of the L u z u l o - F a g e t u m is in its self very species poor on vascular plants.
Auf einer 1 ha umfassenden Fläche in einem Mischwald aus Fichte (Picea abies) und Karpatenbirke (Betula pubescens subsp. carpatica) wurden die Flora und Vegetation der Stammepiphyten untersucht. Die Untersuchungsfläche liegt im Hochharz an der Ostflanke des Bruchbergs auf einer Meereshöhe von rund 900 m. Insgesamt wurden 35 epiphytische Arten nachgewiesen, wobei die Flechten die dominierende Gruppe stellen. Als Besonderheiten treten dabei Mycoblastus sanguinarius, Hypogymnia farinacea und Parmeliopsis hyperopta auf. Die Epiphytengemeinschaft auf Fichtenstämmen wird als Lecanoretum pytireae beschrieben, während die Artengemeinschaft auf den untersuchten Birkenstämmen zum Parmelietum furfuraceae gestellt werden kann.
Anhand von Vergleichen vegetationskundlicher Aufnahmen aus den Jahren 1966-1968 und 1999-2000 werden die zeitlichen Veränderungen der Vegetation in bodensauren Buchenwäldern und Fichtenbeständen des Solling (Niedersachsen) untersucht. Besonders für die Fichtenbestände lässt sich dabei ein Rückgang im Deckungsgrad der Bodenvegetation bei gleichzeitiger Zunahme der Artenzahlen pro Fläche belegen. Arten der Waldschläge und -verlichtungen sind neu zu der ursprünglichen Artenkombination der Bestände hinzugekommen. Steigende Tendenzen bei den mittleren Stickstoffzahlen belegen eine Zunahme von Stickstoffzeigern in der Bodenvegetation von Buchen- und Fichtenbeständen, während mit den Säurezeigern die Trennarten des Luzulo-Fagetum abgenommen haben. In Zusammenhang mit diesen anthropogenen Veränderungen der Bodenvegetation durch Eutrophierung und Kalkung wird die zukünftige Entwicklung mitteleuropäischer bodensaurer Buchenwaldgesellschaften diskutiert.
The multistep PROTAC (PROteolysis TArgeting Chimeras) degradation process poses challenges for their rational development, as rate limiting steps determining PROTAC efficiency remain largely unknown. Moreover, the slow throughput of currently used endpoint assays does not allow the comprehensive analysis of larger series of PROTACs. Here we developed cell-based assays using NanoLuciferase and HaloTags, that allow measuring PROTAC induced degradation and ternary complex formation kinetics and stability in cells. Using PROTACs developed for degradation of WDR5, the characterization of the mode of action of these PROTACs in the early degradation cascade revealed a key role of ternary complex formation and stability. Comparing a series of ternary complex crystal structures highlighted the importance of an efficient E3-target interface for ternary complex stability. The developed assays outline a strategy for the rational optimization of PROTACs using a series of live cell assays monitoring key steps of the early PROTAC induced degradation pathway.
Significance The multistep PROTAC induced degradation process of a POI poses a significant challenge for the rational design of these bifunctional small molecules as critical steps that limit PROTAC efficacy cannot be easily assayed at required throughput. In addition, the cellular location of the POI may pose additional challenges as some cellular compartments, such as the nucleus, may not be easily reached by PROTAC molecules and the targeted E3 ligases may not be present in this cellular compartment. We propose therefore a comprehensive assay panel for PROTACs evaluation in cellular environments using a sensor system that allows continuous monitoring of the protein levels of the endogenous POI. We developed a cell line expressing WDR5 from its endogenous locus in fusion with a small sequence tag (HiBIT) that can be reconstituted to functional NanoLuciferase (NLuc). This system allowed continuous monitoring of endogenous WDR5 levels in cells and together with HaloTag system also the continuous monitoring of ternary complex (E3, WDR5 and PROTAC) formation. As this assay can be run at high throughput, we used this versatile system monitoring three diverse chemical series of WDR5 PROTACs that markedly differ in their degradation properties. Monitoring cell penetration, binary complex formation (PROTAC-WDR5 and PROTAC-VHL) as well as ternary complex formation we found that PROTAC efficiency highly correlated with synergy of ternary complex formation in cells. This study represents a first data set on diverse PROTACs studying this property in cellulo and it outlines a strategy for the rational optimization of PROTACs. It also provided kinetic data on ternary complex assembly and dissociation that may serve as a benchmark for future studies utilizing also kinetic properties for PROTAC development. Comparative structural studies revealed larger PROTAC mediated interaction surfaces for PROTACs that efficiently formed ternary complexes highlighting the utility of structure based optimization of PROTAC induced ternary complexes in the development process.