Topology and Phase Transitions: towards a proper mathematical definition of finite N transitions

A new point of view about the deep origin of thermodynamic phase transitions is sketched. The main idea is to link the appearance of phase transitions to some major topology change of suitable submanifolds of phase space instead of linking them to non-analyticity, as is usual in the Yang-Lee and in the Dobrushin-Ruelle-Sinai theories. In the new framework a new possibility appears to properly define a mathematical counterpart of phase transitions also at finite number of degrees of freedom. This is of prospective interest to the study of those systems that challenge the conventional approaches, as is the case of phase transitions in nuclear clusters.Comment: 6 pages, 1 figur

Clust&See: A Cytoscape plugin for the identification, visualization and manipulation of network clusters

International audienceBackground and scope Large networks, such as protein interaction networks, are extremely difficult to analyze as a whole. We developed Clust&See, a Cytoscape plugin dedicated to the identification, visualization and analysis of clusters extracted from such networks. Implementation and performance Clust&See provides the ability to apply three different, recently developed graph clustering algorithms to networks and to visualize: (i) the obtained partition as a quotient graph in which nodes correspond to clusters and (ii) the obtained clusters as their corresponding subnetworks. Importantly, tools for investigating the relationships between clusters and vertices as well as their organization within the whole graph are supplied

Topology and phase transitions: a paradigmatic evidence

We report upon the numerical computation of the Euler characteristic \chi (a topologic invariant) of the equipotential hypersurfaces \Sigma_v of the configuration space of the two-dimensional lattice $\phi^4$ model. The pattern \chi(\Sigma_v) vs. v (potential energy) reveals that a major topology change in the family {\Sigma_v}_{v\in R} is at the origin of the phase transition in the model considered. The direct evidence given here - of the relevance of topology for phase transitions - is obtained through a general method that can be applied to any other model.Comment: 4 pages, 4 figure

Logical modelling of cellular decision processes with GINsim

International audienc

Topological aspects of geometrical signatures of phase transitions

Certain geometric properties of submanifolds of configuration space are numerically investigated for classical lattice phi^4 models in one and two dimensions. Peculiar behaviors of the computed geometric quantities are found only in the two-dimensional case, when a phase transition is present. The observed phenomenology strongly supports, though in an indirect way, a recently proposed topological conjecture about a topology change of the configuration space submanifolds as counterpart of a phase transition.Comment: REVTEX file, 4 pages, 5 figure

Guanabenz inhibits TLR9 signaling through a pathway that is independent of eIF2α dephosphorylation by the GADD34/PP1c complex

Endoplasmic reticulum (ER) stress triggers or amplifies inflammatory signals and cytokine production in immune cells. Upon the resolution of ER stress, the inducible phosphatase 1 cofactor GADD34 promotes the dephosphorylation of the initiation factor eIF2α, thereby enabling protein translation to resume. Several aminoguanidine compounds, such as guanabenz, perturb the eIF2α phosphorylation-dephosphorylation cycle and protect different cell or tissue types from protein misfolding and degeneration. We investigated how pharmacological interference with the eIF2α pathway could be beneficial to treat autoinflammatory diseases dependent on proinflammatory cytokines and type I interferons (IFNs), the production of which is regulated by GADD34 in dendritic cells (DCs). In mouse and human DCs and B cells, guanabenz prevented the activation of Toll-like receptor 9 (TLR9) by CpG oligodeoxynucleotides or DNA-immunoglobulin complexes in endosomes. In vivo, guanabenz protected mice from CpG oligonucleotide-dependent cytokine shock and decreased autoimmune symptom severity in a chemically induced model of systemic lupus erythematosus. However, we found that guanabenz exerted its inhibitory effect independently of GADD34 activity on eIF2α and instead decreased the abundance of CH25H, a cholesterol hydroxylase linked to antiviral immunity. Our results therefore suggest that guanabenz and similar compounds could be used to treat type I IFN-dependent pathologies and that CH25H could be a therapeutic target to control these diseases.publishe

Guanabenz Prevents d-Galactosamine/Lipopolysaccharide-Induced Liver Damage and Mortality

Multi-organ failure in response to uncontrolled microbial infection is characterized by low blood pressure accompanied by a systemic over-inflammation state, caused by massive pro-inflammatory cytokines release and liver damage. Recently, the integrated stress response (ISR), characterized by eukaryotic translation initiation factor 2α (eIF2α) phosphorylation, was involved with controlling apoptosis in stressed hepatocytes and associated with poor survival to endotoxin challenge. Lipopolysaccharide (LPS) alone is able to induce the ISR in hepatocytes and can trigger massive liver damage along with tumor necrosis factor-alpha (TNF-α) expression. Consequently, drugs interfering with eIF2α phosphorylation may represent potential candidates for the treatment of such pathologies. We, therefore, used Guanabenz (GBZ), a small compound with enhancing eIF2α phosphorylation activity to evaluate its effect on bacterial LPS sensing and endotoxemia. GBZ is confirmed here to have an anti-inflammatory activity by increasing in vitro interleukin-10 (IL-10) production by LPS-stimulated dendritic cells. We further show that in the d-galactosamine (d-galN)/LPS-dependent lethality model, intraperitoneal injection of GBZ promoted mice survival, prevented liver damage, increased IL-10 levels, and inhibited TNF-α production. GBZ and its derivatives could therefore represent an interesting pharmacological solution to control systemic inflammation and associated acute liver failure