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901.

Nitrogen (N) inputs from atmospheric deposition can increase soil organic carbon (SOC) storage in temperate and boreal forests, thereby mitigating the adverse effects of anthropogenic CO2 emissions on global climate. However, direct evidence of N-induced SOC sequestration from low-dose, long-term N addition experiments (that is, addition of < 50 kg N ha−1 y−1 for > 10 years) is scarce worldwide and virtually absent for European temperate forests. Here, we examine how tree growth, fine roots, physicochemical soil properties as well as pools of SOC and soil total N responded to 20 years of regular, low-dose N addition in two European coniferous forests in Switzerland and Denmark. At the Swiss site, the addition of 22 kg N ha−1 y−1 (or 1.3 times throughfall deposition) stimulated tree growth, but decreased soil pH and exchangeable calcium. At the Danish site, the addition of 35 kg N ha−1 y−1 (1.5 times throughfall deposition) impaired tree growth, increased fine root biomass and led to an accumulation of N in several belowground pools. At both sites, elevated N inputs increased SOC pools in the moderately decomposed organic horizons, but decreased them in the mineral topsoil. Hence, long-term N addition led to a vertical redistribution of SOC pools, whereas overall SOC storage within 30 cm depth was unaffected. Our results imply that an N-induced shift of SOC from older, mineral-associated pools to younger, unprotected pools might foster the vulnerability of SOC in temperate coniferous forest soils.

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902.
903.
Conservation genetics is a well‐established scientific field. However, limited information transfer between science and practice continues to hamper successful implementation of scientific knowledge in conservation practice and management. To mitigate this challenge, we have established a conservation genetics community, which entails an international exchange‐and‐skills platform related to genetic methods and approaches in conservation management. First, it allows for scientific exchange between researchers during annual conferences. Second, personal contact between conservation professionals and scientists is fostered by organising workshops and by popularising knowledge on conservation genetics methods and approaches in professional journals in national languages. Third, basic information on conservation genetics has been made accessible by publishing an easy‐to‐read handbook on conservation genetics for practitioners. Fourth, joint projects enabled practitioners and scientists to work closely together from the start of a project in order to establish a tight link between applied questions and scientific background. Fifth, standardised workflows simplifying the implementation of genetic tools in conservation management have been developed. By establishing common language and trust between scientists and practitioners, all these measures help conservation genetics to play a more prominent role in future conservation planning and management.  相似文献   
904.
Inspired by marine compounds the derivatization of the natural pyrrolo[2,3-d]pyrimidine lead scaffold led to a series of novel compounds targeting the histamine H3 receptor. The focus was set on improved binding towards the receptor and to establish an initial structure-activity relationship for this compound class based on the lead structure (compound V, Ki value of 126 nM). As highest binding affinities were found with 1,4-bipiperidines as basic part of the ligands, further optimization was focused on 4-([1,4′-bipiperidin]-1′-yl)-pyrrolo[2,3-d]pyrimidines. Related pyrrolo[2,3-d]pyrimidines that were isolated from marine sponges like 4-amino-5-bromopyrrolo[2,3-d]pyrimidine (compound III), showed variations in halogenation pattern, though in a next step the impact of halogenation at 2-position was evaluated. The chloro variations did not improve the affinity compared to the dehalogenated compounds. However, the simultaneous introduction of lipophilic cores with electron-withdrawing substitution patterns in 7-position and dehalogenation at 2-position (11b, 12b) resulted in compounds with significantly higher binding affinities (Ki values of 7 nM and 6 nM, respectively) than the initial lead structure compound V. The presented structures allow for a reasonable structure-activity relationship of pyrrolo[2,3-d]pyrimidines as histamine H3 receptor ligands and yielded novel lead structures within the natural compound library against this target.  相似文献   
905.
Cell division needs to be tightly regulated and closely coordinated with other cellular processes to ensure the generation of fully viable offspring. Here, we investigate division site placement by the cell division regulator MipZ in the alphaproteobacterium Magnetospirillum gryphiswaldense, a species that forms linear chains of magnetosomes to navigate within the geomagnetic field. We show that M. gryphiswaldense contains two MipZ homologs, termed MipZ1 and MipZ2. MipZ2 localizes to the division site, but its absence does not cause any obvious phenotype. MipZ1, by contrast, forms a dynamic bipolar gradient, and its deletion or overproduction cause cell filamentation, suggesting an important role in cell division. The monomeric form of MipZ1 interacts with the chromosome partitioning protein ParB, whereas its ATP‐dependent dimeric form shows non‐specific DNA‐binding activity. Notably, both the dimeric and, to a lesser extent, the monomeric form inhibit FtsZ polymerization in vitro. MipZ1 thus represents a canonical gradient‐forming MipZ homolog that critically contributes to the spatiotemporal control of FtsZ ring formation. Collectively, our findings add to the view that the regulatory role of MipZ proteins in cell division is conserved among many alphaproteobacteria. However, their number and biochemical properties may have adapted to the specific needs of the host organism.  相似文献   
906.
The flea’s lumen gut is a poorly documented environment where the agent of flea‐borne plague, Yersinia pestis, must replicate to produce a transmissible infection. Here, we report that both the acidic pH and osmolarity of the lumen’s contents display simple harmonic oscillations with different periods. Since an acidic pH and osmolarity are two of three known stimuli of the OmpR‐EnvZ two‐component system in bacteria, we investigated the role and function of this Y. pestis system in fleas. By monitoring the in vivo expression pattern of three OmpR‐EnvZ‐regulated genes, we concluded that the flea gut environment triggers OmpR‐EnvZ. This activation was not, however, correlated with changes in pH and osmolarity but matched the pattern of nutrient depletion (the third known stimulus for OmpR‐EnvZ). Lastly, we found that the OmpR‐EnvZ and the OmpF porin are needed to produce the biofilm that ultimately obstructs the flea’s gut and thus hastens the flea‐borne transmission of plague. Taken as a whole, our data suggest that the flea gut is a complex, fluctuating environment in which Y. pestis senses nutrient depletion via OmpR‐EnvZ. Once activated, the latter triggers a molecular program (including at least OmpF) that produces the biofilm required for efficient plague transmission.  相似文献   
907.
Cell‐, tissue‐ or organ‐specific inducible expression systems are powerful tools for functional analysis of changes to the pattern, level or timing of gene expression. However, plant researchers lack standardised reagents that promote reproducibility across the community. Here, we report the development and functional testing of a Gateway‐based system for quantitatively, spatially and temporally controlling inducible gene expression in Arabidopsis that overcomes several drawbacks of the legacy systems. We used this modular driver/effector system with intrinsic reporting of spatio‐temporal promoter activity to generate 18 well‐characterised homozygous transformed lines showing the expected expression patterns specific for the major cell types of the Arabidopsis root; seed and plasmid vectors are available through the Arabidopsis stock centre. The system's tight regulation was validated by assessing the effects of diphtheria toxin A chain expression. We assessed the utility of Production of Anthocyanin Pigment 1 (PAP1) as an encoded effector mediating cell‐autonomous marks. With this shared resource of characterised reference driver lines, which can be expanded with additional promoters and the use of other fluorescent proteins, we aim to contribute towards enhancing reproducibility of qualitative and quantitative analyses.  相似文献   
908.
909.

In this work, an overview of the biosimilars market, pipeline and industry targets is discussed. Biosimilars typically have a shorter timeline for approval (8 years) compared to 12 years for innovator drugs and the development cost can be 10–20% of the innovator drug. The biosimilar pipeline is reviewed as well as the quality management system (QMS) that is needed to generate traceable, trackable data sets. One difference between developing a biosimilar compared to an originator is that a broader analytical foundation is required for biosimilars and advances made in developing analytical similarity to characterize these products are discussed. An example is presented on the decisions and considerations explored in the development of a biosimilar and includes identification of the best process parameters and methods based on cost, time, and titer. Finally factors to consider in the manufacture of a biosimilar and approaches used to achieve the target-directed development of a biosimilar are discussed.

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910.
Warming and nutrient enrichment are major environmental factors shaping ecological dynamics. However, cross‐scale investigation of their combined effects by linking theory and experiments is lacking. We collected data from aquatic microbial ecosystems investigating the interactive effects of warming (constant and rising temperatures) and enrichment across levels of organisation and contrasted them with community models based on metabolic theory. We found high agreement between our observations and theoretical predictions: we observed in many cases the predicted antagonistic effects of high temperature and high enrichment across levels of organisation. Temporal stability of total biomass decreased with warming but did not differ across enrichment levels. Constant and rising temperature treatments with identical mean temperature did not show qualitative differences. Overall, we conclude that model and empirical results are in broad agreement due to robustness of the effects of temperature and enrichment, that the mitigating effects of temperature on effects of enrichment may be common, and that models based on metabolic theory provide qualitatively robust predictions of the combined ecological effects of enrichment and temperature.  相似文献   
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