Publications by authors named "Lucas M Newton"

Osteosarcoma is the most common form of primary bone cancer, which primarily afflicts children and adolescents. Chemotherapy, consisting of doxorubicin, cisplatin and methotrexate (MAP) increased the 5-year osteosarcoma survival rate from 20% to approximately 60% by the 1980s. However, osteosarcoma survival rates have remained stagnant for several decades.

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Erythroid enucleation, the penultimate step in mammalian erythroid terminal differentiation, is a unique cellular process by which red blood cells (erythrocytes) remove their nucleus and accompanying nuclear material. This complex, multi-stage event begins with chromatin compaction and cell cycle arrest and ends with generation of two daughter cells: a pyrenocyte, which contains the expelled nucleus, and an anucleate reticulocyte, which matures into an erythrocyte. Although enucleation has been compared to asymmetric cell division (ACD), many mechanistic hallmarks of ACD appear to be absent.

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A critical stage of T cell development is β-selection; at this stage, the T cell receptor β (TCRβ) chain is generated, and the developing T cell starts to acquire antigenic specificity. Progression through β-selection is assisted by low-affinity interactions between the nascent TCRβ chain and peptide presented on stromal major histocompatibility complex and cues provided by the niche. In this study, we identify a cue within the developing T cell niche that is critical for T cell development.

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Article Synopsis
  • T cell development starts with genetic recombination of the TCRβ chain, which is evaluated at the β-selection checkpoint where most cells fail and die.
  • Researchers used the histone deacetylase 6 inhibitor ACY1215, revealing that it disrupts this checkpoint and highlights a crucial stage called "DN3b."
  • This stage involves up-regulation of certain proteins (TCR, CD28, CD5, Lef1) that influence TCR signaling strength, ultimately leading to successful progression beyond the β-selection checkpoint.
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