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.     

Analog Module Placement Design Using Genetic Algorithm

This paper presents a novel genetic algorithm for analog module placement based on a generalization of the two-dimensional bin packing problem. The genetic encoding and operators assure that all problem constraints are always satisfied. Thus the potential problems of adding penalty terms to the cost function are eliminated so that the search configuration space is drastically decreased. The dedicated cost function is based on the special requirements of analog integrated circuits. A fractional factorial experiment was conducted using an orthogonal array to study the algorithm parameters. A meta-GA was applied to determine the optimal parameter values. The algorithm was tested with several local benchmark circuits. The experimental results show that the algorithm has better performance than the simulated annealing approach with satisfactory results comparable to manual placement. This study demonstrates the effectiveness of the genetic algorithm in the analog module placement problem. The algorithm has b     

Forecast Combinations in a DSGE‐VAR Lab

We explore the benefits of forecast combinations based on forecast‐encompassing tests compared to simple averages and to Bates–Granger combinations. We also consider a new combination algorithm that fuses test‐based and Bates–Granger weighting. For a realistic simulation design, we generate multivariate time series samples from a macroeconomic DSGE‐VAR (dynamic stochastic general equilibrium–vector autoregressive) model. Results generally support Bates–Granger over uniform weighting, whereas benefits of test‐based weights depend on the sample size and on the prediction horizon. In a corresponding application to real‐world data, simple averaging performs best. Uniform averages may be the weighting scheme that is most robust to empirically observed irregularities. Copyright © 2016 John Wiley & Sons, Ltd.     

Molecular diversity and ecology of microbial plankton

The history of microbial evolution in the oceans is probably as old as the history of life itself. In contrast to terrestrial ecosystems, microorganisms are the main form of biomass in the oceans, and form some of the largest populations on the planet. Theory predicts that selection should act more efficiently in large populations. But whether microbial plankton populations harbour organisms that are models of adaptive sophistication remains to be seen. Genome sequence data are piling up, but most of the key microbial plankton clades have no cultivated representatives, and information about their ecological activities is sparse.     

A refined test for X-ray induced dominant lethals inDrosophila

Zusammenfassung Die nach Röntgenbestrahlung frisch abgelegter besamterDrosophila-Eier registrierbare Letalität kann nach verschiedenen Letalsyndromen aufgegliedert werden. Zur Auswertung stehen Computerprogramme zur Verfügung. Spezielle Tests zeigten, dass mit der beschriebenen Zuchtanordnung bestrahlte und unbestrahlte Populationen, von denen 25–30 Puppen (bzw. Fliegen) pro Zuchtglas überleben, ohne Beeinflussung durch ungünstige Zuchtbedingungen auf dominante Letalfaktoren geprüft werden können.

---

---

Work supported by Schweizerischer Nationalfonds zur Förderung der wissenschaftlichen Forschung and Jubiläumsfonds 1930 der ETH.