GPCR-induced YAP activation sensitizes fibroblasts to profibrotic activity of TGFβ1.

Tissue fibrosis is a pathological condition characterized by uncontrolled fibroblast activation that ultimately leads to organ failure. The TGFβ1 pathway, one of the major players in establishment of the disease phenotype, is dependent on the transcriptional co-activators YAP/TAZ. We were interested whether fibroblasts can be sensitized to TGFβ1 by activation of the GPCR/YAP/TAZ axis and whether this mechanism explains the profibrotic properties of diverse GPCR ligands.

S1P Modulator-Induced G Signaling and -Arrestin Recruitment Are Both Necessary to Induce Rapid and Efficient Reduction of Blood Lymphocyte Count In Vivo.

S1P (sphingosine-1-phosphate receptor 1) agonists prevent lymphocyte egress from secondary lymphoid organs and cause a reduction in the number of circulating blood lymphocytes. We hypothesized that S1P receptor modulators with pathway-selective signaling properties could help to further elucidate the molecular mechanisms involved in lymphocyte trapping. A proprietary S1P receptor modulator library was screened for compounds with clear potency differences in -arrestin recruitment and G protein alpha i subunit (G ) protein-mediated signaling.

Impact of scale space search on age- and gender-related changes in MRI-based cortical morphometry.

In magnetic resonance imaging based brain morphometry, Gaussian smoothing is often applied to increase the signal-to-noise ratio and to increase the detection power of statistical parametric maps. However, most existing studies used a single smoothing filter without adequately justifying their choices. In this article, we want to determine the extent for which performing a morphometry analysis using multiple smoothing filters, namely conducting a scale space search, improves or decreases the detection power.

Anisotropic diffusion of tensor fields for fold shape analysis on surfaces.

The folding pattern of the human cortical surface is organized in a coherent set of troughs and ridges, which mark important anatomical demarcations that are similar across subjects. Cortical surface shape is often analyzed in the literature using isotropic diffusion, a strategy that is questionable because many anatomical regions are known to follow the direction of folds. This paper introduces anisotropic diffusion kernels to follow neighboring fold directions on surfaces, extending recent literature on enhancing curve-like patterns in images.

Oriented morphometry of folds on surfaces.

The exterior surface of the brain is characterized by a juxtaposition of crests and troughs that together form a folding pattern. The majority of the deformations that occur in the normal course of adult human development result in folds changing their length or width. Current statistical shape analysis methods cannot easily discriminate between these two cases.

Depth potential function for folding pattern representation, registration and analysis.

Some surfaces present folding patterns formed by juxtapositions of ridges and valleys as, for example, the cortical surface of the human brain. The fundamental problem with ridges is to find a correspondence among and analyze the variability among them. Many techniques to achieve these goals exist but use scalar functions.

An unbiased iterative group registration template for cortical surface analysis.

Accurate alignment of explicit surface representations of human cerebral cortices is necessary in order to compare local individual differences in cortical morphometric measurements (thickness, surface area, gyrification, etc.) in both normal and clinical populations. This paper presents a methodology for developing unbiased, high resolution iterative registration templates from a group of 222 subject hemispheres and shows that the resulting template provides better alignment of a separate set of test data than single-subject templates.