Steady-state visual evoked potentials and phase synchronization in migraine

We investigate phase synchronization in EEG recordings from migraine patients. We use the analytic signal technique, based on the Hilbert transform, and find that migraine brains are characterized by enhanced alpha band phase synchronization in presence of visual stimuli. Our findings show that migraine patients have an overactive regulatory mechanism that renders them more sensitive to external stimuli.Comment: 4 page

Phase ordering in chaotic map lattices with conserved dynamics

Dynamical scaling in a two-dimensional lattice model of chaotic maps, in contact with a thermal bath, is numerically studied. The model here proposed is equivalent to a conserved Ising model with coupligs which fluctuate over the same time scale as spin moves. When couplings fluctuations and thermal fluctuations are both important, this model does not belong to the class of universality of a Langevin equation known as model B; the scaling exponents are continuously varying with the temperature and depend on the map used. The universal behavior of model B is recovered when thermal fluctuations are dominant.Comment: 6 pages, 4 figures. Revised version accepted for publication on Physical Review E as a Rapid Communicatio

Phase shifts of synchronized oscillators and the systolic/diastolic blood pressure relation

We study the phase-synchronization properties of systolic and diastolic arterial pressure in healthy subjects. We find that delays in the oscillatory components of the time series depend on the frequency bands that are considered, in particular we find a change of sign in the phase shift going from the Very Low Frequency band to the High Frequency band. This behavior should reflect a collective behavior of a system of nonlinear interacting elementary oscillators. We prove that some models describing such systems, e.g. the Winfree and the Kuramoto models offer a clue to this phenomenon. For these theoretical models there is a linear relationship between phase shifts and the difference of natural frequencies of oscillators and a change of sign in the phase shift naturally emerges.Comment: 8 figures, 9 page

Clustering data by inhomogeneous chaotic map lattices

A new approach to clustering, based on the physical properties of inhomogeneous coupled chaotic maps, is presented. A chaotic map is assigned to each data-point and short range couplings are introduced. The stationary regime of the system corresponds to a macroscopic attractor independent of the initial conditions. The mutual information between couples of maps serves to partition the data set in clusters, without prior assumptions about the structure of the underlying distribution of the data. Experiments on simulated and real data sets show the effectiveness of the proposed algorithm.Comment: 8 pages, 6 figures. Revised version accepted for publication on Physical Review Letter

Phase diagram of a generalized Winfree model

We study the phase diagram of a generalized Winfree model. The modification is such that the coupling depends on the fraction of synchronized oscillators, a situation which has been noted in some experiments on coupled Josephson junctions and mechanical systems. We let the global coupling k be a function of the Kuramoto order parameter r through an exponent z such that z=1 corresponds to the standard Winfree model, z<1 strengthens the coupling at low r (low amount of synchronization) and, at z>1, the coupling is weakened for low r. Using both analytical and numerical approaches, we find that z controls the size of the incoherent phase region, and one may make the incoherent behavior less typical by choosing z<1. We also find that the original Winfree model is a rather special case, indeed the partial locked behavior disappears for z>1. At fixed k and varying gamma, the stability boundary of the locked phase corresponds to a transition that is continuous for z1. This change in the nature of the transition is in accordance with a previous study on a similarly modified Kuramoto model.Comment: 9 pages, 3 figure

Selective αv integrin depletion identifies a core, targetable molecular pathway that regulates fibrosis across solid organs

Myofibroblasts are the major source of extracellular matrix components that accumulate during tissue fibrosis, and hepatic stellate cells (HSCs) are the major source of myofibroblasts in the liver. To date, robust systems to genetically manipulate these cells have not existed. We report that Pdgfrb-Cre inactivates genes in murine HSCs with high efficiency. We used this system to delete the αv integrin subunit because of the suggested role of multiple αv integrins as central mediators of fibrosis in multiple organs. Depletion of the αv integrin subunit in HSCs protected mice from CCl4-induced hepatic fibrosis, whereas global loss of αvβ3, αvβ5 or αvβ6 or conditional loss of αvβ8 on HSCs did not. Pdgfrb-Cre effectively targeted myofibroblasts in multiple organs, and depletion of αv integrins using this system was also protective in models of pulmonary and renal fibrosis. Critically, pharmacological blockade of αv integrins by a novel small molecule (CWHM 12) attenuated both liver and lung fibrosis, even when administered after fibrosis was established. These data identify a core pathway that regulates fibrosis, and suggest that pharmacological targeting of all αv integrins may have clinical utility in the treatment of patients with a broad range of fibrotic diseases

Effect of dietary supplementation with ultramicronized palmitoylethanolamide in maintaining remission in cats with nonflea hypersensitivity dermatitis: a double-blind, multicentre, randomized, placebo-controlled study

Background Feline nonflea hypersensitivity dermatitis (NFHD) is a frequent cause of over-grooming, scratching and skin lesions. Multimodal therapy often is necessary. Hypothesis/Objectives To investigate the efficacy of ultramicronized palmitoylethanolamide (PEA-um) in maintaining methylprednisolone-induced remission in NFHD cats. Animals Fifty-seven NFHD cats with nonseasonal pruritus were enrolled originally, of which 25 completed all study requirements to be eligible for analysis. Methods and materials Cats were randomly assigned to PEA-um (15 mg/kg per os, once daily; n = 29) or placebo (n = 28) while receiving a 28 day tapering methylprednisolone course. Cats responding favourably to methylprednisolone were then administered only PEA-um (n = 21) or placebo (n = 23) for another eight weeks, followed by a four week long treatment-free period. Cats were maintained in the study until relapse or study end, whichever came first. Primary outcome was time to relapse. Secondary outcomes were pruritus Visual Analog Scale (pVAS), SCORing Feline Allergic Dermatitis scale (SCORFAD) and owner Global Assessment Score (GAS). Results Mean relapse time was 40.5 days (+/- 7.8 SE) in PEA-um treated cats (n = 13) and 22.2 days (+/- 3.7 SE) for placebo (n = 12; P = 0.04). On Day 28, the severity of pruritus was lower in the PEA-um treated cats compared to placebo (P = 0.03). Mean worsening of pruritus at the final study day was lower in the PEA-um group compared to placebo (P = 0.04), whereas SCORFAD was not different between groups. Mean owner GAS at the final study day was better in the PEA-um than the placebo-treated group (P = 0.05). Conclusion and clinical importance Ultramicronized palmitoylethanolamide could represent an effective and safe option to delay relapse in NFHD cats

IFN-λ3, not IFN-λ4, likely mediates IFNL3-IFNL4 haplotype-dependent hepatic inflammation and fibrosis

Genetic variation in the IFNL3-IFNL4 (interferon-λ3-interferon-λ4) region is associated with hepatic inflammation and fibrosis. Whether IFN-λ3 or IFN-λ4 protein drives this association is not known. We demonstrate that hepatic inflammation, fibrosis stage, fibrosis progression rate, hepatic infiltration of immune cells, IFN-λ3 expression, and serum sCD163 levels (a marker of activated macrophages) are greater in individuals with the IFNL3-IFNL4 risk haplotype that does not produce IFN-λ4, but produces IFN-λ3. No difference in these features was observed according to genotype at rs117648444, which encodes a substitution at position 70 of the IFN-λ4 protein and reduces IFN-λ4 activity, or between patients encoding functionally defective IFN-λ4 (IFN-λ4-Ser70) and those encoding fully active IFN-λ4-Pro70. The two proposed functional variants (rs368234815 and rs4803217) were not superior to the discovery SNP rs12979860 with respect to liver inflammation or fibrosis phenotype. IFN-λ3 rather than IFN-λ4 likely mediates IFNL3-IFNL4 haplotype-dependent hepatic inflammation and fibrosis

Macrophage-derived Wnt opposes Notch signaling to specify hepatic progenitor cell fate in chronic liver disease

During chronic injury a population of bipotent hepatic progenitor cells (HPCs) become activated to regenerate both cholangiocytes and hepatocytes. Here we show in human diseased liver and mouse models of the ductular reaction that Notch and Wnt signaling direct specification of HPCs via their interactions with activated myofibroblasts or macrophages. In particular, we found that during biliary regeneration, expression of Jagged 1 (a Notch ligand) by myofibroblasts promoted Notch signaling in HPCs and thus their biliary specification to cholangiocytes. Alternatively, during hepatocyte regeneration, macrophage engulfment of hepatocyte debris induced Wnt3a expression. This resulted in canonical Wnt signaling in nearby HPCs, thus maintaining expression of Numb (a cell fate determinant) within these cells and the promotion of their specification to hepatocytes. By these two pathways adult parenchymal regeneration during chronic liver injury is promoted