How Florence Bell's work laid the foundation for a vital field of research - DNA

Biased signaling by G protein–coupled receptors (GPCRs) occurs when ligands selectively activate G proteins or β-arrestins, offering therapeutic potential with fewer side effects. In class A GPCRs, which include the targets of approximately one-third of all marketed drugs, the structural basis of this selectivity remains unclear. Recent cryo–electron microscopy studies, supported by real-time functional assays such as bioluminescence resonance energy transfer and NanoLuc Binary Technology, reveal how distinct ligand binding modes reshape receptor conformations to favor specific transducer engagement. Integrating structural and functional insights enables mapping of isoform- and tissue-specific signaling. Here, we review key mechanisms of bias, including microswitch transitions, intracellular interface remodeling, and allosteric modulation, and provide a mechanistic basis for pathway-selective GPCR-targeting therapeutics with improved efficacy and reduced off-target effects.

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Blue Jays famed ‘postseason sofa’ goes on display at Toronto Marriott hotel, marking the historic story behind Addison Barger’s World Series grand slam.

Unfortunately, the last comeback of the season went to the Dodgers, a cruel blow that puts an end to what had been one of the most remarkable Blue Jays seasons in memory.