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Free, publicly-accessible full text available March 1, 2026
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The contributions of skeletal cells to the processes of B cell development in the bone marrow (BM) have not been completely described. The von-Hippel Lindau protein (VHL) plays a key role in cellular responses to hypoxia. Previous work showed that Dmp1 -Cre; Vhl conditional knockout mice ( Vhl cKO), which deletes Vhl in subsets of mesenchymal stem cells, late osteoblasts and osteocytes, display dysregulated bone growth and reduction in B cells. Here, we investigated the mechanisms underlying the B cell defects using flow cytometry and high-resolution imaging. In the Vhl cKO BM, B cell progenitors were increased in frequency and number, whereas Hardy Fractions B-F were decreased. Vhl cKO Fractions B-C cells showed increased apoptosis and quiescence. Reciprocal BM chimeras confirmed a B cell-extrinsic source of the Vhl cKO B cell defects. In support of this, Vhl cKO BM supernatant contained reduced CXCL12 and elevated EPO levels. Intravital and ex vivo imaging revealed Vhl cKO BM blood vessels with increased diameter, volume, and a diminished blood-BM barrier. Staining of Vhl cKO B cells with an intracellular hypoxic marker indicated the natural existence of distinct B cell microenvironments that differ in local oxygen tensions and that the B cell developmental defects in Vhl cKO BM are not initiated by hypoxia. Our studies identify novel mechanisms linking altered bone homeostasis with drastic BM microenvironmental changes that dysregulate B cell development.more » « less
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The development and application of luminescence dating and dosimetry techniques have grown exponentially in the last several decades. Luminescence methods provide age control for a broad range of geological and archaeological contexts and can characterize mineral and glass properties linked to geologic origin, Earth-surface processes, and past exposure to light, heat, and ionizing radiation. The applicable age range for luminescence methods spans the last 500,000 years or more, which covers the period of modern human evolution, and provides context for rates and magnitudes of geological processes, hazards, and climate change. Given the growth in applications and publications of luminescence data, there is a need for unified, community-driven guidance regarding the publication and interpretation of luminescence results. This paper presents a guide to the essential information necessary for publishing and archiving luminescence ages as well as supporting data that is transportable and expandable for different research objectives and publication outlets. We outline the information needed for the interpretation of luminescence data sets, including data associated with equivalent dose, dose rate, age models, and stratigraphic context. A brief review of the fundamentals of luminescence techniques and applications, including guidance on sample collection and insight into laboratory processing and analysis steps, is presented to provide context for publishing and data archiving.more » « less
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