In Vivo Systems Analysis Identifies Spatial and Temporal Aspects of the Modulation of TNF-α-Induced Apoptosis and Proliferation by MAPKs

Cellular responses to external stimuli depend on dynamic features of multipathway network signaling; thus, cell behavior is influenced in a complex manner by the environment and by intrinsic properties. Methods of multivariate systems analysis have provided an understanding of these convoluted effects, but only for relatively simplified examples in vitro. To determine whether such approaches could be successfully used in vivo, we analyzed the signaling network that determines the response of intestinal epithelial cells to tumor necrosis factor–α (TNF-α). We built data-driven, partial least-squares discriminant analysis (PLSDA) models based on signaling, apoptotic, and proliferative responses in the mouse small intestinal epithelium after systemic exposure to TNF-α. The extracellular signal–regulated kinase (ERK) signaling axis was a critical modulator of the temporal variation in apoptosis at different doses of TNF-α and of the spatial variation in proliferation in distinct intestinal regions. Inhibition of MEK, a mitogen-activated protein kinase kinase upstream of ERK, altered the signaling network and changed the temporal and spatial phenotypes consistent with model predictions. Our results demonstrate the dynamic, adaptive nature of in vivo signaling networks and identify natural, tissue-level variation in responses that can be deconvoluted only with quantitative, multivariate computational modeling. This study lays a foundation for the use of systems-based approaches to understand how dysregulation of the cellular network state underlies complex diseases.National Institute of General Medical Sciences (U.S.) (Grant R01-GM088827)National Cancer Institute (U.S.) (Grant U54-CA112967

How management intensity and neighborhood composition affect the structure of beech (Fagus sylvatica L.) trees

The intensity of silvicultural interventions and the neighborhood composition determine branching patterns, crown shape, and trunk attributes of beech ( Fagus sylvatica L.) trees. The intensity of silvicultural interventions and the composition of tree species are important forest management decisions. Both determine tree shape and thus influence the value of a tree, be it in terms of economy (trunk form, branchiness), or in terms of ecology (microhabitats). However, our knowledge on the distinct changes in tree architecture due to silvicultural management intensity or different neighborhood diversities is still limited, especially if the focus is on single tree attributes, e.g., branching patterns or crown shapes. We used terrestrial laser scanner data to calculate 25 structural measures for 55 European beech (Fagus sylvatica L.) trees that grew either in pure stands along a gradient of management intensity or in intra or interspecific neighborhoods in unmanaged stands. We found a lower height of maximal horizontal crown extension, a higher crown surface area, and straighter trunks with increasing management intensity. Moreover, our study revealed that beech trees surrounded by valuable hardwoods showed a lower height of maximal horizontal crown extension, a lower height-diameter ratio, and longer branches with flatter branch angles than beech trees surrounded by conspecific neighbors. Our findings provide evidence of phenotypic plasticity of European beech to diverse environmental conditions. The differences in tree structure indicate an increasing crown competition with decreasing management intensity and stronger competitive pressure for beech surrounded by conspecific neighbors in comparison to alien neighbors

ITES. Teilprojekt: Konfektionierung eines mikromechanischen Drucksensors fuer industriellen Einsatz Schlussbericht

Available from TIB Hannover: DtF QN1(77,10) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEBundesministerium fuer Bildung und Forschung (BMBF), Bonn (Germany)DEGerman