Zur Entstehung des Lungenödems

Ohne Zusammenfassung     

Probing met repressor-operator recognition in solution.

The three-dimensional crystal structure of the Escherichia coli methionine repressor, MetJ, complexed with a DNA operator fragment is described in an accompanying article. The complex exhibits several novel features of DNA-protein interaction. DNA sequence recognition is achieved largely by hydrogen-bond contacts between the bases and amino-acid side chains located on a beta-ribbon, a mode of recognition previously hypothesized on the basis of modelling of idealized beta-strands and DNA, and mutagenesis of the Salmonella phage P22 repressors Arc and Mnt. The complex comprises a pair of MetJ repressor dimers which bind to adjacent met-box sites on the DNA, and contact each other by means of a pair of antiparallel alpha-helices. Here we assess the importance of these contacts, and also of contacts that would be made between the C-helices of the protein and DNA in a previous model of the complex, by studying mutations aimed at disrupting them. The role of the carboxy-terminal helix face in operator binding was unclear, but we demonstrate that recognition of operator sequences occurs through side chains in the beta-strand motif and that dimer-dimer interactions are required for effective repression.     

Overcompensation and population cycles in an ungulate.

Although theoretical studies show that overcompensatory density-dependent mechanisms can potentially generate regular or chaotic fluctuations in animal numbers, the majority of realistic single-species models of invertebrate populations are not overcompensatory enough to cause sustained population cycles. The possibility that overcompensation may generate cycles or chaos in vertebrate populations has seldom been considered. Here we show that highly overcompensatng density-dependent mortality can generate recurrent population crashes consistent with those observed in a naturally limited population of Soay sheep. The observed interval of three or more years between crashes points to sharp 'focusing' of mortality over a narrow range of population density.     

On the limitations of comparing mean square forecast errors

Linear models are invariant under non-singular, scale-preserving linear transformations, whereas mean square forecast errors (MSFEs) are not. Different rankings may result across models or methods from choosing alternative yet isomorphic representations of a process. One approach can dominate others for comparisons in levels, yet lose to another for differences, to a second for cointegrating vectors and to a third for combinations of variables. The potential for switches in ranking is related to criticisms of the inadequacy of MSFE against encompassing criteria, which are invariant under linear transforms and entail MSFE dominance. An invariant evaluation criterion which avoids misleading outcomes is examined in a Monte Carlo study of forecasting methods.     

Ca2+ release induced by inositol 1,4,5-trisphosphate is a steady-state phenomenon controlled by luminal Ca2+ in permeabilized cells.

Low concentrations of inositol 1,4,5-trisphosphate (InsP3) evoke a very rapid mobilization of intracellular Ca2+ stores in many cell types, which can be followed by a further, much slower efflux. Two explanations have been suggested for this biphasic release. The first proposes that the Ca2+ stores vary in their sensitivity to InsP3, and each store releases either its entire contents or nothing (all-or-none release); the second proposes instead that the stores are uniformly sensitive to the effects of InsP3, but that they can release only a fraction of their Ca2+ before their sensitivity is somehow attenuated (steady-state release). Experiments using purified InsP3 receptor molecules reconstituted into lipid vesicles have shown heterogeneity of the receptors in their response to InsP3 under conditions in which the total Ca2+ level at both sides of the receptor is held constant. We now report that in permeabilized A7r5 smooth-muscle cells incubated in Ca(2+)-free medium, the amount of 45Ca2+ remaining in the stores after the rapid transient phase of release is independent of their initial Ca2+ levels, indicating that partially depleted stores are less sensitive to InsP3. Moreover, if the stores are reloaded with 40Ca2+ after the first stimulus, reapplication of the same low concentration of InsP3 will release further 45Ca2+. This recovery of InsP3 sensitivity is almost complete. Under these conditions, Ca2+ release must thus occur by a steady-state mechanism, in which the decreasing Ca2+ content of the stores slows down further release.     

Trying times for human insulin.

The introduction of human insulin to treat diabetics seemed straightforward. What can account for the problems that have followed?