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Targeting Ion Channel TRPM4
Get PDFThe transient receptor potential melastatin 4 (TRPM4) ion channel is ubiquitously expressed. Dysregulation and/or functional mutations of TRPM4 lead to several diseases. Within our studies, we screened for TRPM4 inhibitors and identified small molecules that block TRPM4 in the low µM range. Furthermore, we investigated the pathophysiology of TRPM4 in cardiac conditions, immune diseases and cancer using these novel inhibitors, molecular biology techniques and functional assays
The NCCR TransCure: An Incubator for Interdisciplinary Research
Get PDFThe National Center of Competence in Research (NCCR) TransCure, funded by the Swiss National Science Foundation and the University of Bern, was active from 2010 to 2022. It provided unique research and educational framework in the membrane transporter and ion channel field. Thanks to an interdisciplinary approach comprising physiology, structural biology, and chemistry, in parallel to a rich offer in complementary areas such as education and technology transfer, the network achieved outstanding scientific results and contributed to the education of young scientists. In this review, we present the main features and milestones of the NCCR TransCure
Challenges in the Analysis of Gangliosides by LC-MS
Get PDFGangliosides are a family of conjugates consisting of a polar sialoglycan head group and a hydrophobic ceramide tail. Gangliosides are of high abundance in neuronal tissues and are involved in numerous biological processes, such as cell-cell recognition, adhesion, and signal transduction. Alteration of the ganglioside profile is associated with various neurodegenerative diseases and there is indication that gangliosides are involved in the pathogenesis of Parkinson’s and Huntington’s disease. The development of refined methods for the analysis of gangliosides by high-performance liquid chromatography coupled to mass spectrometry (HPLC-MS) has supported research with qualitative and quantitative data. However, the amphiphilic character of gangliosides renders their separation and mass spectrometric analysis challenging. In this article, the strengths of hydrophilic interaction liquid chromatography (HILIC) for baseline separation of gangliosides, including two structural isomers, and their structural characterization by tandem mass spectrometry are demonstrated. The importance of ion source parameter optimization is highlighted to prevent misleading ganglioside transformation due to in-source dissociation
Mass Spectrometry: An Essential Tool for the Flavor and Fragrance Industry
Get PDFOver the past decades, mass spectrometers have become standard instruments in the analytical laboratories of the flavor and fragrance (F&F) industry. As the expansion of the fields of use of flavors and fragrances and the launch of numerous new technologies designed to enhance their performance have led to a diversification and increased complexity of the questions asked to the analytical chemists, mass spectrometry remains an essential tool to address them. The capabilities of the latest generation of instruments combined with advanced molecular separation and data processing tools allow to tackle many of these challenges. Through different examples, and focusing on the period that followed our 2014 review [1], this article illustrates different ways MS is contributing to the discovery development and commercialization of F&F ingredients and technologies, for both volatile and non-volatile molecules
On-surface Synthesis: What Happens Behind the Scenes?
Get PDFOn-surface synthesis has become a powerful approach to produce low-dimensional carbon-based nanostructures with atomistic precision. A large variety of analytical tools and methods are available to provide efficient monitoring of on-surface reactions, among which, scanning probe microscopy (SPM) has proven to be particularly efficient to characterize reaction intermediates and products down to the atomic scale. Nevertheless, due to limited temporal resolution, difficulties to explore the full temperature range, and lack of identifying the chemical environment of all elements involved in on-surface processes, SPM is ideally complemented with temperature programmed X-ray photoelectron spectroscopy (TP-XPS). In this short review, we aim to unveil some of the capabilities of synchrotron based TP-XPS reporting on our own research on Ullmann-type on-surface coupling reactions
High-Precision Micro/Macro-Analysis with Laser-induced XUV Spectroscopy (LIXS): Highlights of Analytical Sciences in Switzerland
No full textSpin-Mapping Methods for Simulating Ultrafast Nonadiabatic Dynamics
Get PDFMany chemical reactions exhibit nonadiabatic effects as a consequence of coupling between electronic states and/or interaction with light. While a fully quantum description of nonadiabatic reactions is unfeasible for most realistic molecules, a more computationally tractable approach is to combine a classical description of the nuclei with a quantum description of the electronic states. Combining the formalisms of quantum and classical dynamics is however a difficult problem for which standard methods (such as Ehrenfest dynamics and surface hopping) may be insufficient. In this article, we review a new trajectory-based approach developed in our group that is able to describe nonadiabatic dynamics with a higher accuracy than previous approaches but for a similar level of computational effort. This method treats the electronic states with a phase-space representation for discrete-level systems, which in the two-level case is analogous to a spin-½. We point out the key features of the method and demonstrate its use in a variety of applications, including ultrafast transfer through conical intersections, damped coherent excitation under coupling to a strong light field, and nonlinear spectroscopy of light-harvesting complexes