Mechanistic Insights into the Adenosine A1 Receptor's Positive Allosteric Modulation for Non-Opioid Analgesics.

The adenosine A1 receptor (AR) is a promising target for pain treatment. However, the development of therapeutic agonists is hampered by adverse effects, mainly including sedation, bradycardia, hypotension, or respiratory depression. Recently discovered molecules able to overcome this impediment are the positive allosteric modulator MIPS521 and the A1R-selective agonist BnOCPA, which are both potent and powerful analgesics with fewer side effects.

Polarized Semi-Inclusive Deep-Inelastic Scattering at Next-to-Next-to-Leading Order in QCD.

Semi-inclusive hadron production in longitudinally polarized deep-inelastic lepton-nucleon scattering is a powerful tool for resolving the quark flavor decomposition of the proton's spin structure. We present the full next-to-next-to-leading order QCD corrections to the coefficient functions of polarized semi-inclusive deep-inelastic scattering (SIDIS) in analytical form, enabling the use of SIDIS measurements in precision studies of the proton spin structure. The numerical impact of these corrections is illustrated by a comparison with data of polarized single-inclusive hadron spectra from the DESY HERMES and CERN COMPASS experiments.

Ablation of CCL17-positive hippocampal neurons induces inflammation-dependent epilepsy.

Objective: Neuronal cell death and neuroinflammation are characteristic features of epilepsy, but it remains unclear whether neuronal cell death as such is causative for the development of epileptic seizures. To test this hypothesis, we established a novel mouse line permitting inducible ablation of pyramidal neurons by inserting simian diphtheria toxin (DT) receptor (DTR) cDNA into the Ccl17 locus. The chemokine CCL17 is expressed in pyramidal CA1 neurons in adult mice controlling microglial quiescence.

Hypersensitive quantification of major astringency markers in food and wine by substoichiometric quenching of silicon-rhodamine conjugates.

Tannins are chemically diverse polyphenols in plant-derived products that not only show diverse biological activities but also play a crucial role in determining the sensory attributes of food and beverages. Therefore, their accurate and cost-effective quantification is essential. Here, we identified a novel fluorescence quenching mechanism of different synthetic rhodamine fluorophores, with a high selectivity towards tannic acid (TA) and catechin-3-gallate (C3G) compared to a structurally diverse panel of tannins and polyphenols.

Silicon-Rhodamine Functionalized Evocalcet Probes Potently and Selectively Label Calcium Sensing Receptors , , and .

The calcium sensing receptor (CaSR) is a ubiquitously expressed G-protein coupled receptor (GPCR) that regulates extracellular calcium signals the parathyroid glands. CaSR has recently also been implicated in noncalcitropic pathophysiologies like asthma, gut inflammation, and cancer. To date, molecular tools that enable the bioimaging of CaSR in tissues are lacking.