An expanded LUXendin color palette for GLP1R detection and visualization in vitro and in vivo

The glucagon-like peptide-1 receptor (GLP1R) is expressed in peripheral tissues and the brain, where it exerts pleiotropic actions on metabolic and inflammatory processes. Detection and visualization of GLP1R remains challenging, partly due to a lack of validated reagents. Previously, we generated LUXendins, antagonistic red and far-red fluorescent probes for specific labeling of GLP1R in live and fixed cells/tissue. We now extend this concept to the green and near-infrared color ranges by synthesizing and testing LUXendin492, LUXendin551, LUXendin615 and LUXendin762. All four probes brightly and specifically label GLP1R in cells and pancreatic islets. Further, LUXendin551 acts as chemical beta cell reporter in preclinical rodent models, while LUXendin762 allows non-invasive imaging, highlighting differentially-accessible GLP1R populations. We thus expand the color palette of LUXendins to seven different spectra, opening up a range of experiments using widefield microscopy available in most labs through super-resolution imaging and whole animal imaging. With this, we expect that LUXendins will continue to generate novel and specific insight into GLP1R biology

Anxiety and depression in caregivers of patients with malignant brain tumors

The assembly process of optical components consists of two phases-the alignment and the bonding phase. Precision-or better process repeatability-is limited by the latter one. The limitation of the alignment precision is given by the measurement equipment and the manipulation technology applied. Today's micromanipulators in combination with beam imaging setups allow for an alignment in the range of far below 100nm. However, once precisely aligned optics need to be fixed in their position. State of the art in optics bonding for laser systems is adhesive bonding with UV-curing adhesives. Adhesive bonding is a multi-factorial process and thus subject to statistical process deviations. As a matter of fact, UV-curing adhesives inherit shrinkage effects during their curing process, making offsets for shrinkage compensation mandatory. Enhancing the process control of the adhesive bonding process is the major goal of the activities described in this paper

TGF-β1 and Smad4 overexpression induce a less invasive phenotype in highly invasive spindle carcinoma cells

We have examined the effect of transforming growth factor β1 (TGF-β1) and overexpression of the Smad4 gene on the phenotype of Car C, a ras mutated highly malignant spindle carcinoma cell line. TGF-β1-treated Car C cells overexpressing Smad4 spread with a flattened morphology with membrane ruffles abundant in vinculin and show a reduction in their invasive abilities. TGF-β1 treatment and overexpression of Smad4 also enhanced the production of PAI-1 measured by the activation of the p3TP-lux reporter gene containing a PAI-1-related promoter. This activation was abolished with a dominant-negative Smad4 construct. These results lead us to conclude that both TGF-β1 and Smad4 overexpression reduce the invasive potential of Car C cells, probably via the Smad pathway.This work was supported by Fondecyt 3000045 and post-graduate fellowship of Fundación Andes (to J.F.S.),1010703 (to J.M.) and by the Comisión Interministerial de Ciencia y Tecnología and Comunidad Autónoma de Madrid of Spain (Grants SAF98-0085-CO3-02 and 8.1/22/97,to M.Q.).Peer Reviewe