Fluorescence spectroscopy and molecular dynamics simulations in studies on the mechanism of membrane destabilization by antimicrobial peptides

Since their initial discovery, 30 years ago, antimicrobial peptides (AMPs) have been intensely investigated as a possible solution to the increasing problem of drug-resistant bacteria. The interaction of antimicrobial peptides with the cellular membrane of bacteria is the key step of their mechanism of action. Fluorescence spectroscopy can provide several structural details on peptide–membrane systems, such as partition free energy, aggregation state, peptide position and orientation in the bilayer, and the effects of the peptides on the membrane order. However, these “low-resolution” structural data are hardly sufficient to define the structural requirements for the pore formation process. Molecular dynamics simulations, on the other hand, provide atomic-level information on the structure and dynamics of the peptide–membrane system, but they need to be validated experimentally. In this review we summarize the information that can be obtained by both approaches, highlighting their versatility and complementarity, suggesting that their synergistic application could lead to a new level of insight into the mechanism of membrane destabilization by AMPs.     

An Holistic Approach to the Management of Information Systems Development—A View Using a Soft Systems Approach and Multiple Viewpoints

This paper argues that only a systems-based approach to information systems development is likely to cover all the recognized problem issues reported in the literature. It is then shown that software development can be characterized by the structure of the Soft Systems Methodology, so that this methodology acts as a metaphor for the process of information systems development. The structure of this methodology can be seen at lower levels of the development process, and so the model generated here is seen as recursive. Further, information systems development is seen as an unstructured business problem that can be characterized by the Multiple Viewpoint approach. The connections between this approach and the methodology are identified. Finally, the unifying link between these approaches and all forms of action research is identified.     

R-spondin1 is essential in sex determination, skin differentiation and malignancy

R-spondins are a recently characterized small family of growth factors. Here we show that human R-spondin1 (RSPO1) is the gene disrupted in a recessive syndrome characterized by XX sex reversal, palmoplantar hyperkeratosis and predisposition to squamous cell carcinoma of the skin. Our data show, for the first time, that disruption of a single gene can lead to complete female-to-male sex reversal in the absence of the testis-determining gene, SRY.     

Monocyte chemoattractant protein-1 and the blood–brain barrier

The blood–brain barrier (BBB) is a dynamic structure that maintains the homeostasis of the brain and thus proper neurological functions. BBB compromise has been found in many pathological conditions, including neuroinflammation. Monocyte chemoattractant protein-1 (MCP1), a chemokine that is transiently and significantly up-regulated during inflammation, is able to disrupt the integrity of BBB and modulate the progression of various diseases, including excitotoxic injury and hemorrhage. In this review, we first introduce the biochemistry and biology of MCP1, and then summarize the effects of MCP1 on BBB integrity as well as individual BBB components.     

Interaction between peripheral blood leucocytes and X-irradiated cells from lymphoid cell lines

Résumé Une interaction stimulante très marquée s'observe dans les cultures de lymphocytes frais du sang humain merlées à des cellules lymphoïdes de plusieurs lignées continues exposées aux rayons X.

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We thank Dr. R. M.Flinn (Department of Anatomy) for the use of his computer programme for the calculation of radioactivity and Mrs. J.Wallin for her excellent technical help. D.A.H. gratefully acknowledges a studentship from the Wellcome Trust. This work was financed, in part, by grants from the Wellcome Trust and the Medical Research Council.