Filtern
Volltext vorhanden
- ja (23) (entfernen)
Erscheinungsjahr
- 2012 (23) (entfernen)
Gehört zur Bibliographie
- ja (23) (entfernen)
Schlagworte
- X-rays: binaries (2)
- arabidopsis-thaliana (2)
- metabolic network (2)
- stars: mass loss (2)
- Ar-Ar white-mica dating (1)
- Asian monsoon (1)
- BHLH transcription factor (1)
- Be (1)
- EGFR (1)
- HT/LP metamorphism (1)
Institut
- Mathematisch-Naturwissenschaftliche Fakultät (23) (entfernen)
Cell-level kinetic models for therapeutically relevant processes increasingly benefit the early stages of drug development. Later stages of the drug development processes, however, rely on pharmacokinetic compartment models while cell-level dynamics are typically neglected. We here present a systematic approach to integrate cell-level kinetic models and pharmacokinetic compartment models. Incorporating target dynamics into pharmacokinetic models is especially useful for the development of therapeutic antibodies because their effect and pharmacokinetics are inherently interdependent. The approach is illustrated by analysing the F(ab)-mediated inhibitory effect of therapeutic antibodies targeting the epidermal growth factor receptor. We build a multi-level model for anti-EGFR antibodies by combining a systems biology model with in vitro determined parameters and a pharmacokinetic model based on in vivo pharmacokinetic data. Using this model, we investigated in silico the impact of biochemical properties of anti-EGFR antibodies on their F(ab)-mediated inhibitory effect. The multi-level model suggests that the F(ab)-mediated inhibitory effect saturates with increasing drug-receptor affinity, thereby limiting the impact of increasing antibody affinity on improving the effect. This indicates that observed differences in the therapeutic effects of high affinity antibodies in the market and in clinical development may result mainly from Fc-mediated indirect mechanisms such as antibody-dependent cell cytotoxicity.
The size of plant organs, such as leaves and flowers, is determined by an interaction of genotype and environmental influences. Organ growth occurs through the two successive processes of cell proliferation followed by cell expansion. A number of genes influencing either or both of these processes and thus contributing to the control of final organ size have been identified in the last decade. Although the overall picture of the genetic regulation of organ size remains fragmentary, two transcription factor/microRNA-based genetic pathways are emerging in the control of cell proliferation. However, despite this progress, fundamental questions remain unanswered, such as the problem of how the size of a growing organ could be monitored to determine the appropriate time for terminating growth. While genetic analysis will undoubtedly continue to advance our knowledge about size control in plants, a deeper understanding of this and other basic questions will require including advanced live-imaging and mathematical modeling, as impressively demonstrated by some recent examples. This should ultimately allow the comparison of the mechanisms underlying size control in plants and in animals to extract common principles and lineage-specific solutions.
All's well that ends well
(2012)
The transition from cell proliferation to cell expansion is critical for determining leaf size. Andriankaja et al. (2012) demonstrate that in leaves of dicotyledonous plants, a basal proliferation zone is maintained for several days before abruptly disappearing, and that chloroplast differentiation is required to trigger the onset of cell expansion.