Proline-rich antimicrobial peptides: converging to a non-lytic mechanism of action

Proline-rich antimicrobial peptides are a group of cationic host defense peptides of vertebrates and invertebrates characterized by a high content of proline residues, often associated with arginine residues in repeated motifs. Those isolated from some mammalian and insect species, although not evolutionarily related, use a similar mechanism to selectively kill Gram-negative bacteria, with a low toxicity to animals. Unlike other types of antimicrobial peptides, their mode of action does not involve the lysis of bacterial membranes but entails penetration into susceptible cells, where they then act intracellularly. Some aspects of the transport system and cytoplasmic targets have been elucidated. These features make them attractive both as anti-infective lead compounds and as a new class of potential cell-penetrating peptides capable of internalising membrane-impermeant drugs into both bacterial and eukaryotic cells     

Structural relaxation in supercooled water by time-resolved spectroscopy

Water has many kinetic and thermodynamic properties that exhibit an anomalous dependence on temperature, in particular in the supercooled phase. These anomalies have long been interpreted in terms of underlying structural causes, and their experimental characterization points to the existence of a singularity at a temperature of about 225 K. Further insights into the nature and origin of this singularity might be gained by completely characterizing the structural relaxation in supercooled water. But until now, such a characterization has only been realized in simulations that agree with the predictions of simple mode-coupling theory; unambiguous experimental support for this surprising conclusion is, however, not yet available. Here we report time-resolved optical Kerr effect measurements that unambiguously demonstrate that the structural relaxation of liquid and weakly supercooled water follows the behaviour predicted by simple mode-coupling theory. Our findings thus support the interpretation of the singularity as a purely dynamical transition. That is, the anomalous behaviour of weakly supercooled water can be explained using a fully dynamic model and without needing to invoke a thermodynamic origin. In this regard, water behaves like many other, normal molecular liquids that are fragile glass-formers.     

Suppression of Polycomb group proteins by JNK signalling induces transdetermination in Drosophila imaginal discs

During the regeneration of Drosophila imaginal discs, cellular identities can switch fate in a process known as transdetermination. For leg-to-wing transdetermination, the underlying mechanism involves morphogens such as Wingless that, when activated outside their normal context, induce ectopic expression of the wing-specific selector gene vestigial. Polycomb group (PcG) proteins maintain cellular fates by controlling the expression patterns of homeotic genes and other developmental regulators. Here we report that transdetermination events are coupled to PcG regulation. We show that the frequency of transdetermination is enhanced in PcG mutant flies. Downregulation of PcG function, as monitored by the reactivation of a silent PcG-regulated reporter gene, is observed in transdetermined cells. This downregulation is directly controlled by the Jun amino-terminal kinase (JNK) signalling pathway, which is activated in cells undergoing regeneration. Accordingly, transdetermination frequency is reduced in a JNK mutant background. This regulatory interaction also occurs in mammalian cells, indicating that the role of this signalling cascade in remodelling cellular fates may be conserved.     

A Fuzzy Clustering Model for Multivariate Spatial Time Series

Clustering of multivariate spatial-time series should consider: 1) the spatial nature of the objects to be clustered; 2) the characteristics of the feature space, namely the space of multivariate time trajectories; 3) the uncertainty associated to the assignment of a spatial unit to a given cluster on the basis of the above complex features. The last aspect is dealt with by using the Fuzzy C-Means objective function, based on appropriate measures of dissimilarity between time trajectories, by distinguishing the cross-sectional and longitudinal aspects of the trajectories. In order to take into account the spatial nature of the statistical units, a spatial penalization term is added to the above function, depending on a suitable spatial proximity/ contiguity matrix. A tuning coefficient takes care of the balance between, on one side, discriminating according to the pattern of the time trajectories and, on the other side, ensuring an approximate spatial homogeneity of the clusters. A technique for determining an optimal value of this coefficient is proposed, based on an appropriate spatial autocorrelation measure. Finally, the proposed models are applied to the classification of the Italian provinces, on the basis of the observed dynamics of some socio-economical indicators.     

Role of vasostatin-1 C-terminal region in fibroblast cell adhesion

Fibroblast adhesion can be modulated by proteins released by neuroendocrine cells and neurons, such as chromogranin A (CgA) and its N-terminal fragment vasostatin-1 (VS-1, CgA_1–78). We have investigated the mechanisms of the interaction of VS-1 with fibroblasts and of its pro-adhesive activity and have found that the proadhesive activity of VS-1 relies on its interaction with the fibroblast membrane via a phospholipid-binding amphipathic α-helix located within residues 47–66, as well as on the interaction of the adjacent C-terminal region 67–78, which is structurally similar to ezrin–radixin–moesin-binding phosphoprotein 50 (a membrane-cytoskeleton adapter protein), with other cellular components critical for the regulation of cell cytoskeleton.