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     

Lipid complexes with cationic peptides and OAKs; their role in antimicrobial action and in the delivery of antimicrobial agents

Antimicrobial agents are toxic to bacteria by a variety of mechanisms. One mechanism that is very dependent on the lipid composition of the bacterial membrane is the clustering of anionic lipid by cationic antimicrobial agents. Certain species of oligo-acyl-lysine (OAK) antimicrobial agents are particularly effective in clustering anionic lipids in mixtures mimicking the composition of bacterial membranes. The clustering of anionic lipids by certain cationic antimicrobial agents contributes to the anti-bacterial action of these agents. Bacterial membrane lipids are a determining factor, resulting in some species of bacteria being more susceptible than others. In addition, lipids can be used to increase the effectiveness of antimicrobial agents when administered in vivo. Therefore, we review some of the structures in which lipid mixtures can assemble, to more effectively be utilized as antimicrobial delivery systems. We describe in more detail the complexes formed between mixtures of lipids mimicking bacterial membranes and an OAK and their usefulness in synergizing with antibiotics to overcome bacterial multidrug resistance.     

Bafilomycin A1 activates respiration of neuronal cells via uncoupling associated with flickering depolarization of mitochondria

Bafilomycin A1 (Baf) induces an elevation of cytosolic Ca²⁺ and acidification in neuronal cells via inhibition of the V-ATPase. Also, Baf uncouples mitochondria in differentiated PC12 (_dPC12), _dSH-SY5Y cells and cerebellar granule neurons, and markedly elevates their respiration. This respiratory response in _dPC12 is accompanied by morphological changes in the mitochondria and decreases the mitochondrial pH, Ca²⁺ and ΔΨm. The response to Baf is regulated by cytosolic Ca²⁺ fluxes from the endoplasmic reticulum. Inhibition of permeability transition pore opening increases the depolarizing effect of Baf on the ΔΨm. Baf induces stochastic flickering of the ΔΨm with a period of 20 ± 10 s. Under conditions of suppressed ATP production by glycolysis, oxidative phosphorylation impaired by Baf does not provide cells with sufficient ATP levels. Cells treated with Baf become more susceptible to excitation with KCl. Such mitochondrial uncoupling may play a role in a number of (patho)physiological conditions induced by Baf.     

Immune biology of Ag-specific γδ T cells in infections

Accumulating evidence suggests that human γδ T cells act as non-classical T cells and contribute to both innate and adaptive immune responses in infections. Vγ2 Vδ2 T (also termed Vγ9 Vδ2 T) cells exist only in primates, and in humans represent a dominant circulating γδ T-cell subset. Primate Vγ2 Vδ2 T cells are the only γδ T cell subset capable of recognizing microbial phosphoantigen. Since nonhuman primate Vγ2 Vδ2 T cells resemble their human counterparts, in-depth studies have been undertaken in macaques to understand the biology and function of human Vγ2 Vδ2 T cells. This article reviews the recent progress for immune biology of Vγ2 Vδ2 T cells in infections.     

SecA,a remarkable nanomachine

Biological cells harbor a variety of molecular machines that carry out mechanical work at the nanoscale. One of these nanomachines is the bacterial motor protein SecA which translocates secretory proteins through the protein-conducting membrane channel SecYEG. SecA converts chemically stored energy in the form of ATP into a mechanical force to drive polypeptide transport through SecYEG and across the cytoplasmic membrane. In order to accommodate a translocating polypeptide chain and to release transmembrane segments of membrane proteins into the lipid bilayer, SecYEG needs to open its central channel and the lateral gate. Recent crystal structures provide a detailed insight into the rearrangements required for channel opening. Here, we review our current understanding of the mode of operation of the SecA motor protein in concert with the dynamic SecYEG channel. We conclude with a new model for SecA-mediated protein translocation that unifies previous conflicting data.     

Competing Definitions of Information Versus Entropy in Physics

As was mentioned by Nicolas Lori in his (Found Sci, 2010) commentary, the definition of Information in Physics is something about which not all authors agreed. According to physicists like me Information decreases when Entropy increases (so entropy would be a negative measure of information), while many physicists, seemingly the majority of them, are convinced of the contrary (even in the camp of Quantum Information Theoreticians). In this reply I reproduce, and make more precise, some of my arguments, that appeared here and there in my (2010) paper, in order to clarify the presentation of my personal point of view on the subject.     

Multiscale Integration in Scale Relativity Theory

We give a “direction for use” of the scale relativity theory and apply it to an example of spontaneous multiscale integration including four embedded levels of organization (intracellular, cell, tissue and organism-like levels). We conclude by an update of our analysis of the arctic sea ice melting.     

MFI-type zeolite membrane on hollow fiber substrate for hydrogen separation

High performance MFI-type zeolite membranes on the outer surface of α-Al 2 O 3 hollow fibers were synthesized by secondary growth method using pure silica sol without an organic template. X-ray diffraction was used to characterize the phase structure of both the seed layer and zeolite membrane. The morphologies of the seed layer and zeolite membrane were examined by scanning electron microscopy. The zeolite membrane achieved an extraordinary H 2 /CO 2 separation factor of 10 with a high H 2 permeance of 5.56 10 -7 mol m -2 s -1 Pa -1 at 723 K.     

Transient pressure analysis for the reactor core and containment of a HTGR after a primary loop pressure boundary break accident

The pressure variances in the reactor core and containment of a High Temperature Gas-cooled Reactor (HTGR) after a primary loop pressure boundary break accident determine the structural integrity and safety of the reactor. Based on mass conservation, energy conservation and state equations, explicit formulae for the transient pressure and temperature variances in the pressure vessels were deduced, and a set of differential equations for the transient pressure and temperature variances in the containment were developed. Numerical simulation was also conducted to investigate the transient pressure and temperature variances in the pressure vessels and containment. The results show that energy transformation due to expansion work cannot be neglected. The maximum pressure in the containment could increase by 40 percent due to blockage caused by air in the containment. Detailed numerical simulations of the transient pressure and temperature variance in the reactor core flow passages were also conducted. The results show that the pressures acting on the reactor core and containment are below acceptable values.