Evaluating the applicability of mouse SINEs as an alternative normalization approach for RT-qPCR in brain tissue of the APP23 model for Alzheimer's disease.

Background: The choice of appropriate reference genes (RGs) for use in reverse transcription quantitative polymerase chain reaction (RT-qPCR) has been thoroughly investigated, since the inclusion of unstable RGs might cause inaccurate gene expression results.

New Method: Short interspersed nuclear elements (SINEs) such as B elements, might represent an alternative solution given the high occurrence of these repetitive elements in the rodent genome and transcriptome. We performed RT-qPCR to investigate the stability of nine commonly used RGs and two B elements, B1 and B2, across different age- and genotype-related experimental conditions in the hippocampus and cortex of the APP23 amyloidosis mouse model for Alzheimer's disease.

The validation of Short Interspersed Nuclear Elements (SINEs) as a RT-qPCR normalization strategy in a rodent model for temporal lobe epilepsy.

Background: In gene expression studies via RT-qPCR many conclusions are inferred by using reference genes. However, it is generally known that also reference genes could be differentially expressed between various tissue types, experimental conditions and animal models. An increasing amount of studies have been performed to validate the stability of reference genes.

Synthesis toward Bivalent Ligands for the Dopamine D and Metabotropic Glutamate 5 Receptors.

In this study, we designed and synthesized heterobivalent ligands targeting heteromers consisting of the metabotropic glutamate 5 receptor (mGluR5) and the dopamine D receptor (DR). Bivalent ligand 22a with a linker consisting of 20 atoms showed 4-fold increase in affinity for cells coexpressing DR and mGluR5 compared to cells solely expressing DR. Likewise, the affinity of 22a for mGluR5 increased 2-fold in the coexpressing cells.

Design, Synthesis, and Biological Evaluation of Bivalent Ligands Targeting Dopamine D -Like Receptors and the μ-Opioid Receptor.

Currently, there is mounting evidence that intermolecular receptor-receptor interactions may result in altered receptor recognition, pharmacology and signaling. Heterobivalent ligands have been proven useful as molecular probes for confirming and targeting heteromeric receptors. This report describes the design and synthesis of novel heterobivalent ligands for dopamine D -like receptors (D -likeR) and the μ-opioid receptor (μOR) and their evaluation using ligand binding and functional assays.

Molecular dissection of the human A adenosine receptor coupling with β-arrestin2.

Besides classical G protein coupling, G protein-coupled receptors (GPCRs) are nowadays well known to show significant signalling via other adaptor proteins, such as β-arrestin2 (βarr2). The elucidation of the molecular mechanism of the GPCR-βarr2 interaction is a prerequisite for the structure-activity based design of biased ligands, which introduces a new chapter in drug discovery. The general mechanism of the interaction is believed to rely on phosphorylation sites, exposed upon agonist binding.