Flowing sand - a possible physical realization of Directed Percolation

A simple model for flowing sand on an inclined plane is introduced. The model is related to recent experiments by Douady and Daerr [Nature 399, 241 (1999)] and reproduces some of the experimentally observed features. Avalanches of intermediate size appear to be compact, placing the critical behavior of the model into the universality class of compact directed percolation. On very large scales, however, the avalanches break up into several branches leading to a crossover from compact to ordinary directed percolation. Thus, systems of flowing granular matter on an inclined plane could serve as a first physical realization of directed percolation.Comment: 9 pages, 12 eps figure

The first World Cell Race

Motility is a common property of animal cells. Cell motility is required for embryogenesis [1], tissue morphogenesis [2] and the immune response [3] but is also involved in disease processes, such as metastasis of cancer cells [4]. Analysis of cell migration in native tissue in vivo has yet to be fully explored, but motility can be relatively easily studied in vitro in isolated cells. Recent evidence suggests that cells plated in vitro on thin lines of adhesive proteins printed onto culture dishes can recapitulate many features of in vivo migration on collagen fibers 5, 6. However, even with controlled in vitro measurements, the characteristics of motility are diverse and are dependent on the cell type, origin and external cues. One objective of the first World Cell Race was to perform a large-scale comparison of motility across many different adherent cell types under standardized conditions. To achieve a diverse selection, we enlisted the help of many international laboratories, who submitted cells for analysis. The large-scale analysis, made feasible by this competition-oriented collaboration, demonstrated that higher cell speed correlates with the persistence of movement in the same direction irrespective of cell origin

The non-equilibrium phase transition of the pair-contact process with diffusion

The pair-contact process 2A->3A, 2A->0 with diffusion of individual particles is a simple branching-annihilation processes which exhibits a phase transition from an active into an absorbing phase with an unusual type of critical behaviour which had not been seen before. Although the model has attracted considerable interest during the past few years it is not yet clear how its critical behaviour can be characterized and to what extent the diffusive pair-contact process represents an independent universality class. Recent research is reviewed and some standing open questions are outlined.Comment: Latexe2e, 53 pp, with IOP macros, some details adde

Soluble CD36 Ectodomain Binds Negatively Charged Diacylglycerol Ligands and Acts as a Co-Receptor for TLR2

BACKGROUND:Cluster of differentiation 36 (CD36) is a transmembrane glycoprotein involved in many biological processes, such as platelet biology, angiogenesis and in the aetiopathology of atherosclerosis and cardiovascular diseases. Toll-like receptors (TLRs) are one of the most important receptors of the innate immune system. Their main function is the recognition of conserved structure of microorganisms. This recognition triggers signaling pathways that activate transcription of cytokines and co-stimulatory molecules which participate in the generation of an immune response against microbes. In particular, TLR2 has been shown to recognize a broad range of ligands. Recently, we showed that CD36 serves as a co-receptor for TLR2 and enhances recognition of specific diacylglycerides derived from bacteria. METHODOLOGY/ PRINCIPAL FINDINGS:Here, we investigate the mechanism by which CD36 contributes to ligand recognition and activation of TLR2 signaling pathway. We show that the ectodomain of murine CD36 (mCD36ED) directly interacts with negatively charged diacylglycerol ligands, which explains the specificity and selectivity of CD36 as a TLR2 co-receptor. We also show that mCD36ED amplifies the pro-inflammatory response to lipoteichoic acid in macrophages of wild-type mice and restores the pro-inflammatory response of macrophages from mice deficient in CD36 (oblivious), but not from mice deficient in cluster of differentiation 14 (CD14) (heedless). CONCLUSION/ SIGNIFICANCE: These data indicate that the CD36 ectodomain is the only relevant domain for activation of TLR2 signaling pathway and that CD36 and CD14 have a non-redundant role for loading ligands onto TLR2 in the plasma-membrane. The pro-inflammatory role of soluble CD36 can be relevant in the activation of the immune response against pathogens, as well as in the progression of chronic diseases. Therefore, an increased level of soluble forms of CD36, which has been reported to be increased in type II diabetic patients, could accelerate atherosclerosis by increasing the pro-inflammatory response to diacylglycerol ligands

Microbial recognition by TLR2 and CD36

The discovery of the first Toll-like receptor in 1998 was a crucial step towards understanding how the innate immune response is established. Although there have been significant advances in understanding the molecular pathways activated by Toll-like receptors, still little is known about the molecular mechanism leading to the recognition of specific ligands by Toll-like receptors. In particular, Toll-like receptor 2 (TLR2) has the broadest range ofligand recognition among Toll-like receptors. In order to study the interaction ofTLR2 with its ligands, the ectodomain ofTLR2 was expressed in insect cells. An analysis of its N-linked glycosylation showed the presence ofhigh-mannose-type glycans. Circular dichroism showed that TLR2 has a predominantly p-sheet secondary structure and that its Tm point lies between 45°C and 55 °C. A direct interaction between the TLR2 ectodomain and its ligands was demonstrated using native PAGE. I concluded that the diacylglycerol is a relevant ligand moiety for interacting with TLR2. I also demonstrated that the TLR2 ectodomain is able to bind its ligands at physiological conditions and independently of its association with co-receptors TLR6 and TLRI. Recently CD36, a member of the scavenger receptor family, was reported as a coreceptor ofTLR2. In order to investigate the mechanism by which CD36 enhances TLR2 activation, the CD36 ectodomain was expressed in insect eells. Binding assays demonstrated a selective binding towards negatively charged ligands at physiological conditions. The selective binding explains the fact that CD36 is a selective co-receptor ofTLR2. Furthermore, the activation ofTLR2 in macrophages from CD36 deficient (CD36 Obl·/Obl-) mice was restored by addition ofthe CD36 ectodomain. This result clearly demonstrated that the ectodomain, but not the transmembrane or intracellular domain ofCD36, is the essential domain for the activity of CD36 as TLR2 co-receptor. Moreover, the inability of soluble CD36 to restore TNF-a secretion from CD14 deficient macrophages, shows that CD14 is a necessary molecule for the function of CD36 as a TLR2 co-receptor. Finally, we expressed the LRR domain of 18-Wheeler and Windpipe, two transmembrane LRR proteins ofDrosophila melanogaster. 18-Wheeler belongs to the Toll receptor family, while Windpipe is a novel transmembrane protein with a predicted LRR domain in its extracellular domain. Both receptors are involved in the morphogenesis ofDrosophila melanogaster. Although crystallisation conditions for both the LRR domain ofWindpipe and the ectodomain of 18-Wheeler were found, optimisation ofthese crystallisation conditions are required to determine the crystal structure ofthese LRR proteins.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Microbial recognition by TLR2 and CD36

The discovery of the first Toll-like receptor in 1998 was a crucial step towards understanding how the innate immune response is established. Although there have been significant advances in understanding the molecular pathways activated by Toll-like receptors, still little is known about the molecular mechanism leading to the recognition of specific ligands by Toll-like receptors. In particular, Toll-like receptor 2 (TLR2) has the broadest range ofligand recognition among Toll-like receptors. In order to study the interaction ofTLR2 with its ligands, the ectodomain ofTLR2 was expressed in insect cells. An analysis of its N-linked glycosylation showed the presence ofhigh-mannose-type glycans. Circular dichroism showed that TLR2 has a predominantly p-sheet secondary structure and that its Tm point lies between 45°C and 55 °C. A direct interaction between the TLR2 ectodomain and its ligands was demonstrated using native PAGE. I concluded that the diacylglycerol is a relevant ligand moiety for interacting with TLR2. I also demonstrated that the TLR2 ectodomain is able to bind its ligands at physiological conditions and independently of its association with co-receptors TLR6 and TLRI. Recently CD36, a member of the scavenger receptor family, was reported as a coreceptor ofTLR2. In order to investigate the mechanism by which CD36 enhances TLR2 activation, the CD36 ectodomain was expressed in insect eells. Binding assays demonstrated a selective binding towards negatively charged ligands at physiological conditions. The selective binding explains the fact that CD36 is a selective co-receptor ofTLR2. Furthermore, the activation ofTLR2 in macrophages from CD36 deficient (CD36 Obl·/Obl-) mice was restored by addition ofthe CD36 ectodomain. This result clearly demonstrated that the ectodomain, but not the transmembrane or intracellular domain ofCD36, is the essential domain for the activity of CD36 as TLR2 co-receptor. Moreover, the inability of soluble CD36 to restore TNF-a secretion from CD14 deficient macrophages, shows that CD14 is a necessary molecule for the function of CD36 as a TLR2 co-receptor. Finally, we expressed the LRR domain of 18-Wheeler and Windpipe, two transmembrane LRR proteins ofDrosophila melanogaster. 18-Wheeler belongs to the Toll receptor family, while Windpipe is a novel transmembrane protein with a predicted LRR domain in its extracellular domain. Both receptors are involved in the morphogenesis ofDrosophila melanogaster. Although crystallisation conditions for both the LRR domain ofWindpipe and the ectodomain of 18-Wheeler were found, optimisation ofthese crystallisation conditions are required to determine the crystal structure ofthese LRR proteins.EThOS - Electronic Theses Online ServiceGBUnited Kingdo