Activation of G protein gated inwardly rectifying potassium (GIRK) channels in keratinocytes mediates peripheral kappa opioid receptor-mediated antinociception.

Kappa opioid receptors (KOR) expressed by peripheral pain-sensing neurons (nociceptors) are a promising target for development of effective and safer analgesics for inflammatory pain that are devoid of central nervous system adverse effects. Here we sought to delineate the signaling pathways that underlie peripheral KOR-mediated antinociception in adult male and female Sprague-Dawley rats. In an inflammatory model of pain, local intraplantar (i.

Concentric Ring Trajectory Sampling With k-Space Reordering Enables Assessment of Tissue-Specific T and T Relaxation for H-Labeled Substrates in the Human Brain at 7 T.

Deuterium metabolic imaging (DMI) is an emerging Magnetic Resonance technique providing valuable insight into the dynamics of cellular glucose (Glc) metabolism of the human brain in vivo using deuterium-labeled (H) glucose as non-invasive tracer. Reliable concentration estimation of H-Glc and downstream synthesized neurotransmitters glutamate + glutamine (Glx) requires accurate knowledge of relaxation times, but so far tissue-specific T and T relaxation times (e.g.

Insurmountable antagonism of human mu opioid receptors by buprenorphine is due to hemi-equilibrium.

Buprenorphine is an FDA approved drug for the treatment of opioid use disorder and is a long-lasting, low efficacy (partial) agonist of the μ opioid receptor. As a partial agonist, buprenorphine can act as either an agonist or an antagonist depending on the efficiency of the cellular signaling system. Here we investigated the antagonist properties of buprenorphine using a genetically-encoded biosensor to monitor cAMP levels in real time in HEK293 cells expressing a relatively low density of the human μ receptor.

Predicting Long-Term Stability from Short-Term Measurement: Insights from Modeling Degradation in Perovskite Solar Cells during Voltage Scans and Impedance Spectroscopy.

A drift-diffusion model is used to investigate the effect of device degradation on current-voltage and impedance measurements of perovskite solar cells (PSCs). Modifications are made to the open-source drift-diffusion software IonMonger to model degradation via an increasing recombination rate during the course of characterization experiments. Impedance spectroscopy is shown to be a significantly more sensitive measure of degradation than current-voltage curves, reliably detecting a power conversion efficiency drop of as little as 0.

Regulated GATA1 expression as a universal gene therapy for Diamond-Blackfan anemia.

Gene therapy using hematopoietic stem and progenitor cells is altering the therapeutic landscape for patients with hematologic, immunologic, and metabolic disorders but has not yet been successfully developed for individuals with the bone marrow failure syndrome Diamond-Blackfan anemia (DBA). More than 30 mutations cause DBA through impaired ribosome function and lead to inefficient translation of the erythroid master regulator GATA1, providing a potential avenue for therapeutic intervention applicable to all patients with DBA, irrespective of the underlying genotype. Here, we report the development of a clinical-grade lentiviral gene therapy that achieves erythroid lineage-restricted expression of GATA1.