The role of site accessibility in microRNA target recognition

MicroRNAs are key regulators of gene expression, but the precise mechanisms underlying their interaction with their mRNA targets are still poorly understood. Here, we systematically investigate the role of target-site accessibility, as determined by base-pairing interactions within the mRNA, in microRNA target recognition. We experimentally show that mutations diminishing target accessibility substantially reduce microRNA-mediated translational repression, with effects comparable to those of mutations that disrupt sequence complementarity. We devise a parameter-free model for microRNA-target interaction that computes the difference between the free energy gained from the formation of the microRNA-target duplex and the energetic cost of unpairing the target to make it accessible to the microRNA. This model explains the variability in our experiments, predicts validated targets more accurately than existing algorithms, and shows that genomes accommodate site accessibility by preferentially positioning targets in highly accessible regions. Our study thus demonstrates that target accessibility is a critical factor in microRNA function.     

Churchman's “process of unfolding”—Its significance for policy analysis and evaluation

Churchman's process of unfolding is one of his lesser known concepts, yet it is essential for understanding his dialectical systems approach. This paper gives a brief introduction to the concept and presents a simple framework for applying it to policy analysis and program evaluation.     

Testament to conversations on critical systems thinking between two systems practitioners

This is a testament to conversations held in Berne and Fribourg, Switzerland, in late 1988. The main theme that we present concerns seeking to find an adequate epistemology for systems practice, to find a truly critical approach, by shifting our interests from systems science to systems rationality (i.e., by reaching out toward a systems epistemological ideal) and by dealing with sociological phenomena such as the effects of material conditions and false consciousness and inequalities associated with these. Social rationalities relating to positivism, interpretivism, and critique are considered. Limitations and legitimacies of these rationalities in social contexts are made explicit in these discussions.Conversations were held in Berne and Fribourg, Switzerland, between 30 November and 5 December 1988.     

Von Boltzmann zu Planck

Ohne Zusammenfassung Vorgelegt von S. Flügge     

A deep dynamo generating Mercury's magnetic field

Mercury has a global magnetic field of internal origin and it is thought that a dynamo operating in the fluid part of Mercury's large iron core is the most probable cause. However, the low intensity of Mercury's magnetic field--about 1% the strength of the Earth's field--cannot be reconciled with an Earth-like dynamo. With the common assumption that Coriolis and Lorentz forces balance in planetary dynamos, a field thirty times stronger is expected. Here I present a numerical model of a dynamo driven by thermo-compositional convection associated with inner core solidification. The thermal gradient at the core-mantle boundary is subadiabatic, and hence the outer region of the liquid core is stably stratified with the dynamo operating only at depth, where a strong field is generated. Because of the planet's slow rotation the resulting magnetic field is dominated by small-scale components that fluctuate rapidly with time. The dynamo field diffuses through the stable conducting region, where rapidly varying parts are strongly attenuated by the skin effect, while the slowly varying dipole and quadrupole components pass to some degree. The model explains the observed structure and strength of Mercury's surface magnetic field and makes predictions that are testable with space missions both presently flying and planned.     

Unified spatial scaling of species and their trophic interactions

Two largely independent bodies of scaling theory address the quantitative relationships between habitat area, species diversity and trophic interactions. Spatial theory within macroecology addresses how species richness scales with area in landscapes, while typically ignoring interspecific interactions. Complexity theory within community ecology addresses how trophic links scale with species richness in food webs, while typically ignoring spatial considerations. Recent studies suggest unifying these theories by demonstrating how spatial patterns influence food-web structure and vice versa. Here, we follow this suggestion by developing and empirically testing a more unified scaling theory. On the basis of power-law species-area relationships, we develop link-area and non-power-law link-species models that accurately predict how trophic links scale with area and species richness of microcosms, lakes and streams from community to metacommunity levels. In contrast to previous models that assume that species richness alone determines the number of trophic links, these models include the species' spatial distribution, and hence extend the domain of complexity theory to metacommunity scales. This generality and predictive success shows how complexity theory and spatial theory can be unified into a much more general theory addressing new domains of ecology.     

Functional and spatial segregation of secretory vesicle pools according to vesicle age

Synaptic terminals and neuroendocrine cells are packed with secretory vesicles, only a few of which are docked at the plasma membrane and readily releasable. The remainder are thought to constitute a large cytoplasmic reserve pool awaiting recruitment into the readily releasable pool (RRP) for exocytosis. How vesicles are prioritized in recruitment is still unknown: the choice could be random, or else the oldest or the newest ones might be favoured. Here we show, using a fluorescent cargo protein that changes colour with time, that vesicles in bovine adrenal chromaffin cells segregate into distinct populations, based on age. Newly assembled vesicles are immobile (morphologically docked) at the plasma membrane shortly after biogenesis, whereas older vesicles are mobile and located deeper in the cell. Different secretagogues selectively release vesicles from the RRP or, surprisingly, selectively from the deeper cytoplasmic pool. Thus, far from being equal, vesicles are segregated functionally and spatially according to age.     

Pathogenic bacteria attach to human fibronectin through a tandem beta-zipper

Staphylococcus aureus and Streptococcus pyogenes, two important human pathogens, target host fibronectin (Fn) in their adhesion to and invasion of host cells. Fibronectin-binding proteins (FnBPs), anchored in the bacterial cell wall, have multiple Fn-binding repeats in an unfolded region of the protein. The bacterium-binding site in the amino-terminal domain (1-5F1) of Fn contains five sequential Fn type 1 (F1) modules. Here we show the structure of a streptococcal (S. dysgalactiae) FnBP peptide (B3) in complex with the module pair 1F12F1. This identifies 1F1- and 2F1-binding motifs in B3 that form additional antiparallel beta-strands on sequential F1 modules-the first example of a tandem beta-zipper. Sequence analyses of larger regions of FnBPs from S. pyogenes and S. aureus reveal a repeating pattern of F1-binding motifs that match the pattern of F1 modules in 1-5F1 of Fn. In the process of Fn-mediated invasion of host cells, therefore, the bacterial proteins seem to exploit the modular structure of Fn by forming extended tandem beta-zippers. This work is a vital step forward in explaining the full mechanism of the integrin-dependent FnBP-mediated invasion of host cells.