Isotopic portrayal of the Earth's upper mantle flow field

It is now well established that oceanic plates sink into the lower mantle at subduction zones, but the reverse process of replacing lost upper-mantle material is not well constrained. Even whether the return flow is strongly localized as narrow upwellings or more broadly distributed remains uncertain. Here we show that the distribution of long-lived radiogenic isotopes along the world's mid-ocean ridges can be used to map geochemical domains, which reflect contrasting refilling modes of the upper mantle. New hafnium isotopic data along the Southwest Indian Ridge delineate a sharp transition between an Indian province with a strong lower-mantle isotopic flavour and a South Atlantic province contaminated by advection of upper-mantle material beneath the lithospheric roots of the Archaean African craton. The upper mantle of both domains appears to be refilled through the seismically defined anomaly underlying South Africa and the Afar plume. Because of the viscous drag exerted by the continental keels, refilling of the upper mantle in the Atlantic and Indian domains appears to be slow and confined to localized upwellings. By contrast, in the unencumbered Pacific domain, upwellings seem comparatively much wider and more rapid.     

Shiga toxin induces tubular membrane invaginations for its uptake into cells

Clathrin seems to be dispensable for some endocytic processes and, in several instances, no cytosolic coat protein complexes could be detected at sites of membrane invagination. Hence, new principles must in these cases be invoked to account for the mechanical force driving membrane shape changes. Here we show that the Gb3 (glycolipid)-binding B-subunit of bacterial Shiga toxin induces narrow tubular membrane invaginations in human and mouse cells and model membranes. In cells, tubule occurrence increases on energy depletion and inhibition of dynamin or actin functions. Our data thus demonstrate that active cellular processes are needed for tubule scission rather than tubule formation. We conclude that the B-subunit induces lipid reorganization that favours negative membrane curvature, which drives the formation of inward membrane tubules. Our findings support a model in which the lateral growth of B-subunit-Gb3 microdomains is limited by the invagination process, which itself is regulated by membrane tension. The physical principles underlying this basic cargo-induced membrane uptake may also be relevant to other internalization processes, creating a rationale for conceptualizing the perplexing diversity of endocytic routes.     

Sul meccanismo di azione della vaccinoterapia nella infezione tifoidea

Summary Having observed before that the blood serum of typhoid patients acquires under the stimulus of the vaccine an evident bacteriolytic action on the typhoid bacillus, we have studied variations brought about by the vaccine stimulus in the blood of the patients as to the redox-potential and to the glutathione in the blood.It has been seen that under vaccine stimulus there is a rapid increase of redox-potential and of the glutathione in the blood: lasting in the cases which tend to recovery, temporary in the cases in which the illness takes its natural course.The values of the total glutathione increase more than those of reduced glutathione, so that an increase of the values of the oxidized glutathione is found.The variations of the values of the redox-potential and of the oxidized glutathione brought about by the vaccine reaction in the blood of the patients leads us to consider the mechanism of the action of vaccine therapy in typhoid infection, on the same principle described by us regarding the action of penicillin.     

Positive and negative influence of the matrix architecture on antitumor immune surveillance

The migration of T cells and access to tumor antigens is of utmost importance for the induction of protective anti-tumor immunity. Once having entered a malignant site, T cells encounter a complex environment composed of non-tumor cells along with the extracellular matrix (ECM). It is now well accepted that a deregulated ECM favors tumor progression and metastasis. Recent progress in imaging technologies has also highlighted the impact of the matrix architecture found in solid tumor on immune cells and especially T cells. In this review, we argue that the ability of T cells to mount an antitumor response is dependent on the matrix structure, more precisely on the balance between pro-migratory reticular fiber networks and unfavorable migration zones composed of dense and aligned ECM structures. Thus, the matrix architecture, that has long been considered to merely provide the structural framework of connective tissues, can play a key role in facilitating or suppressing the antitumor immune surveillance. A new challenge in cancer therapy will be to develop approaches aimed at altering the architecture of the tumor stroma, rendering it more permissive to antitumor T cells.     

The structure and function of Escherichia coli penicillin-binding protein 3

Escherichia coli penicillin-binding protein PBP3 is a key element in cell septation. It is presumed to catalyse a transpeptidation reaction during biosynthesis of the septum peptidoglycan but, in vitro, its enzymatic activity has only been demonstrated with thiolester analogues of the natural peptide substrate. It has no detectable transglycosylase activity with lipid II as substrate. This tripartite protein is constructed of an N-terminal membrane anchor-containing module that is essential for cell septation, a non-penicillin-binding (n-PB) module of unknown function and a C-terminal penicillin-binding (PB) module exhibiting all the characteristic motifs of penicilloyl serine transferases. The n-PB module, which is required for the folding and stability of the PB module, may provide recognition sites for other cell division proteins. Initiation of septum formation is not PBP3-dependent but rests on the appearance of the FtsZ ring, and is thus penicillin-insensitive. The control of PBP3 activity during the cell cycle is briefly discussed.