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Serafin, S.

Publications and source records attributed to Serafin, S..

2 recordsLinked to original sources

Biomechanical Investigation of Ancient Maya Warfare at Mayapan, Yucatan, Mexico

Despite significant advancements in the reconstruction of activity patterns from skeletal remains and growing scholarly interest in ancient warfare, few biomechanical studies have investigated weaponry use. We adopt a biomechanical approach to investigate who participated in ancient Maya warfare and the types of weaponry used at the Late Postclassic (ca. 1200-1450 A.D.) regional political capital of Mayapan located in northwestern Yucatan, Mexico. This has implications for the nature and scale of Maya warfare and the size of territories that could be controlled by Maya polities. Comparative Finite Element Analysis is a powerful, non-destructive method that can be applied to skeletal remains to model strain, stress and deformation of structures in response to a defined loading regime. Here, biomechanical data extracted using cross-sectional geometry were combined with Finite Element Analysis models of three ancient Maya humeri from Mayapan: one elite male, one elite female, and one commoner female. Models were created with loading conditions of archery and spear use to assess evidence for skeletal adaptation to habitual weapon use. Following suggestions by some Mayanists that elite status males were the principal participants in warfare, we hypothesized that the elite male humerus would exhibit lower strains than the two female humeri in all the loading conditions. This was supported by the Finite Element model results, with the exception of spear throwing. The elite female humerus showed similar trends to the elite male humerus, suggesting the possibility of elite female participation in warfare.

paleontology↗

AAK1 inhibits WNT signaling by promoting clathrin-mediated endocytosis of LRP6

{beta}-catenin-dependent WNT signal transduction governs normal development and adult tissue homeostasis. Inappropriate pathway activity mediates a vast array of human diseases, including bone density disorders, neurodegeneration and cancer. Although several WNT-directed therapeutics are in clinical trials, new targets, compounds and strategies are needed. We performed a gain-of-function screen of the human kinome to identify new druggable regulators of {beta}-catenin-dependent transcription. We found that over-expression of the AP2 Associated Kinase 1 (AAK1) strongly inhibited WNT signaling. Reciprocally, silencing of AAK1 expression or pharmacological inhibition of AAK1 kinase activity using a new, selective and potent small molecule inhibitor activated WNT signaling. This small molecule is a cell active dual AAK1/BMP2K inhibitor that represents the best available tool to study AAK1-dependent signaling pathways. We report that AAK1 and the WNT co-receptor LRP6 physically co-complex and that AAK1 promotes clathrin-mediated endocytosis of LRP6. Collectively, our data support a WNT-induced negative feedback loop mediated by AAK1-driven, clathrin-mediated endocytosis of LRP6.\n\nSummary StatementA gain-of-function screen of the human kinome revealed AAK1 as a negative regulator of WNT signaling. We show that AAK1 promotes clathrin-mediated endocytosis of LRP6, resulting in downregulation of WNT signaling. We use a new selective and potent AAK1/BMP2K small molecule probe to validate our findings.

cell biology↗