Dramatic cytoskeletal activities and protein movements are seen when T cells engage cognate targets or antigen presenting cells. These include formation of a specialized contact site known as the immunological synapse (IS), clustering of vesicles around the microtubule organizing center (MTOC) and translocation of the MTOC up to the IS. Ultimately, this leads to focused secretion towards the cognate target. In an effort to understand how MTOC translocation takes place, we have investigated the roles of dynein, p150Glued, Lis1,NDE1 and NDEL1 using Jurkat cells as a model system. Using expressed molecular traps aimed at dynein intermediate chain (DIC) or LC8 (a dynein light chain), and Jurkat cells expressing fluorescent CTLA-4 constructs targeting secretory vesicles, we have shown that dynein is required for both vesicle clustering and MTOC translocation. When p150Glued expression was reduced, vesicles became dispersed but MTOC translocation was unaffected suggesting that dynactin was needed for vesicle movements but not MTOC translocation. MTOC translocation was potently blocked when Lis1 expression was reduced. We also find that NDE1 accumulates at the IS and pulls down with DIC and Lis1. Overexpression of GFP-NDE1 blocks MTOC polarization. The combination of localization and functional data suggests that there are two separate dynein complexes, a dynein-Lis1-NDE1/NDEL complex that mediates MTOC translocation and a dynein-dynactin complex that mediates vesicle clustering.
Background: The types of central nervous system (CNS) tumors in a patient population with a history of military service were compared to the types of CNS tumors in a similar patient population without a military service history to determine if a relationship exists between military service and CNS tumor type.
Methods: This study analyzed data for adult patients diagnosed with an intra- or extra-axial CNS tumor from January 2016 to July 2019. One cohort was constructed of patients who had a history of military service (MIL), and the other cohort was made of patients who did not have a history of military service (NMIL). Appropriate parametric and non-parametric analyses were used to compare frequencies of tumor types between cohorts adjusting for potential confounders.
Results: We identified 2001 patients (MIL,
n
= 190; NMIL,
n
= 1811). In the MIL cohort, most patients were males, younger, and more racially diverse. In the primary analysis, the MIL cohort showed higher diagnoses of metastatic tumors compared with the NMIL cohort (X
2
(1)= 3.71,
p
=.05). The MIL cohort also showed lower diagnoses of meningioma compared to the NMIL cohort. There was no statically significant difference between cohorts or tumors after adjusting for primary source by gender.
Conclusions: MIL experience was associated with lower diagnoses of meningioma but higher diagnoses of metastatic cancer, providing support that there may be potential differences in tumor types between patients with a history of military service and those without military history regarding primary CNS tumor frequency.
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