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The taxonomic classification of a falcon population found in the Mongolian Altai region in Asia has been heavily debated for two centuries and previous studies have been inconclusive, hindering a more informed conservation approach. Here, we generated a chromosome-level gyrfalcon reference genome using the Vertebrate Genomes Project (VGP) assembly pipeline. Using whole genome sequences of 49 falcons from different species and populations, including "Altai" falcons, we analyzed their population structure, admixture patterns, and demographic history. We find that the Altai falcons are genomic mosaics of saker and gyrfalcon ancestries, and carry distinct W and mitochondrial haplotypes that cluster with the lanner falcon. The Altai maternally-inherited haplotypes diverged 422,000 years before present (290,000-550,000 YBP) from the ancestor of sakers and gyrfalcons, both of which, in turn, split 109,000 YBP (70,000-150,000 YBP). The Altai W chromosome has 31 coding variants in 29 genes that may possibly influence important structural, behavioral, and reproductive traits. These findings provide insights into the question of Altai falcons as a candidate distinct species.

Editor's note: This is the 25th article in a series on clinical research by nurses coordinated by the Heilbrunn Family Center for Research Nursing at Rockefeller University. The series is designed to be used as a resource for nurses to understand the concepts and principles essential to research. Each column will present the concepts that underpin evidence-based practice-from research design to data interpretation. To see all the articles in the series, go to https://links.lww.com/AJN/A204.

G protein-coupled receptors (GPCRs) comprise a family of heptahelical membrane proteins that mediate intracellular and intercellular transmembrane signaling. Defects in GPCR signaling pathways are implicated in the pathophysiology of many diseases, including cardiovascular disease, endocrinopathies, immune disorders, and cancer. Although GPCRs are attractive drug targets, only a small number of Food and Drug Administration-approved anticancer therapeutics target GPCRs. Targeted protein degradation (TPD) technology allows for the direct modulation of the cellular expression level of a protein of interest. TPD methods such as proteolysis-targeting chimeras (PROTACs) use the ubiquitin-proteasome system to degrade a protein of interest selectively. Although the PROTAC system has not been widely applied to GPCRs and other membrane proteins, there is evidence that PROTACs or other TPD methods could be applied to the GPCRome. Current GPCR PROTACs show the feasibility of using PROTACs to degrade GPCRs; however, the degradation mechanism for some of these GPCR PROTACs is uncertain. Additional studies aimed at elucidating the degradation mechanism of GPCRs with PROTACs are necessary. Discovery of new allosteric intracellular small molecule binders of GPCRs will be required for the development of intracellularly oriented PROTACs. Promising early results in targeted degradation of GPCRs suggest that TPD drug discovery platforms will be useful in developing PROTACs targeting pathological GPCRs. Significance Statement: Aberrant signaling of G protein-coupled receptors (GPCRs) can contribute to the pathophysiology of cancer. Although GPCRs are generally highly attractive drug targets, many individual GPCRs are currently undrugged using traditional drug discovery approaches. Targeted protein degradation technologies, such as proteolysis-targeting chimeras, provide a new approach to drug discovery for targeting previously undruggable GPCRs relevant to the molecular pathophysiology of cancer. (c) 2024 The Author(s). Published by Elsevier Inc. on behalf of American Society for Pharmacology and Experimental Therapeutics. This is an open access article under the CC BY-NC-ND license (http:// creativecommons.org/licenses/by-nc-nd/4.0/).