Publications by authors named "Brian M Steele"

Wnt signaling is involved in numerous aspects of vertebrate development and homeostasis, including the formation and function of blood cells. Here, we show that canonical and noncanonical Wnt signaling pathways are present and functional in megakaryocytes (MKs), with several Wnt effectors displaying MK-restricted expression. Using the CHRF288-11 cell line as a model for human MKs, the canonical Wnt3a signal was found to induce a time and dose-dependent increase in β-catenin expression.

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Article Synopsis
  • WNT-3a regulates platelet function by influencing the activity of four GTPase proteins: Rap1, Cdc42, Rac1, and RhoA.
  • It inhibits integrin-α(IIb)β(3) adhesion through the inactive form of Rap1b, while enhancing Cdc42 and Rac1-GTP levels, which disrupts normal platelet spreading.
  • Additionally, WNT-3a affects the interaction between Daam-1 and Dishevelled upon platelet activation, leading to changes in RhoA-GTP levels, suggesting WNT-3a's role as an upstream regulator of GTPase activity in platelets.
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Wnts regulate important intracellular signaling events, and dysregulation of the Wnt pathway has been linked to human disease. Here, we uncover numerous Wnt canonical effectors in human platelets where Wnts, their receptors, and downstream signaling components have not been previously described. We demonstrate that the Wnt3a ligand inhibits platelet adhesion, activation, dense granule secretion, and aggregation.

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Natural populations worldwide are increasingly fragmented by habitat loss. Isolation at small population size is thought to reduce individual and population fitness via inbreeding depression. However, little is known about the time-scale over which adverse genetic effects may develop in natural populations or the number and types of traits likely to be affected.

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The urgent need for an effective monitoring scheme for grizzly bear (Ursus arctos) populations led us to investigate the effort required to detect changes in populations of low-density dispersed animals, using sign (mainly scats and tracks) they leave on trails. We surveyed trails in Glacier National Park for bear tracks and scats during five consecutive years. Using these data, we modeled the occurrence of bear sign on trails, then estimated the power of various sampling schemes.

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