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receptor (RAR) and vitamin D receptor (VDR). The RXR/RAR dimer is activated by ligand all
trans retinoic acid (ATRA), which culminates in gut-specific effector T cell migration. Similarly,
the VDR/RXR dimer binds 1,25(OH)2D3 to cause skin-specific effector T cell migration.
Targeted migration is a potent addition to current vaccines, as it would induce activated T cell
trafficking to appropriate areas of the immune system and ensure optimal stimulation (40).
ATRA, while in use clinically, is limited by toxicity and chemical instability. Rexinoids
are stable, synthetically developed ligands specific for the RXR. We have previously shown that
select rexinoids can enhance upregulation of gut tropic CCR9 receptors on effector T cells.
However, it is important to establish whether these cells can actually migrate, to show the
potential of rexinoids as vaccine adjuvants that can cause gut specific T cell migration.
Additionally, since the RXR is a major contributor to VDR-mediated transcription and
epidermotropism (15), it is worth investigating whether these compounds can also function as
adjuvants that promote migration by increasing expression of skin tropic CCR10 receptors on T
cells.
Prior experiments have demonstrated that select rexinoids can induce gut tropic migration
of CD8+ T cells in an in vitro assay and are comparable in effectiveness to ATRA (7). The effect
of rexinoids on CD4+ T cells is unknown however, so the aim of this project was to determine if
rexinoids can cause gut tropic migration in CD4+ T cells to a similar extent. A secondary aim
was to investigate whether varying concentrations in 1,25-Dihydroxyvitamin D3 can be linked to
increasing CCR10 upregulation on Jurkat CD4+ T cells, with the future aim to combine 1,25
Dihydroxyvitamin D3 with rexinoids.
These hypotheses were tested using murine splenocytes for the migration experiment, and
human Jurkat CD4+ T cells for the vitamin D experiment. Migration was assessed using a
Transwell chemotaxis assay. Our findings support the potential of rexinoids as compounds
capable of causing gut-tropic migration in murine CD4+ T cells in vitro, like ATRA. We did not
observe conclusive evidence that vitamin D3 causes upregulated CCR10 expression, but this
experiment must be repeated with a human primary T cell line.
The Pacific–North American plate boundary in California is composed of a 400-km-wide network of faults and zones of distributed deformation. Earthquakes, even large ones, can occur along individual or combinations of faults within the larger plate boundary system. While research often focuses on the primary and secondary faults, holistic study of the plate boundary is required to answer several fundamental questions. How do plate boundary motions partition across California faults? How do faults within the plate boundary interact during earthquakes? What fraction of strain accumulation is relieved aseismically and does this provide limits on fault rupture propagation? Geodetic imaging, broadly defined as measurement of crustal deformation and topography of the Earth’s surface, enables assessment of topographic characteristics and the spatio-temporal behavior of the Earth’s crust.
We focus here on crustal deformation observed with continuous Global Positioning System (GPS) data and Interferometric Synthetic Aperture Radar (InSAR) from NASA’s airborne UAVSAR platform, and on high-resolution topography acquired from lidar and Structure from Motion (SfM) methods. Combined, these measurements are used to identify active structures, past ruptures, transient motions, and distribution of deformation. The observations inform estimates of the mechanical and geometric properties of faults. We discuss five areas in California as examples of different fault behavior, fault maturity and times within the earthquake cycle: the M6.0 2014 South Napa earthquake rupture, the San Jacinto fault, the creeping and locked Carrizo sections of the San Andreas fault, the Landers rupture in the Eastern California Shear Zone, and the convergence of the Eastern California Shear Zone and San Andreas fault in southern California. These examples indicate that distribution of crustal deformation can be measured using interferometric synthetic aperture radar (InSAR), Global Navigation Satellite System (GNSS), and high-resolution topography and can improve our understanding of tectonic deformation and rupture characteristics within the broad plate boundary zone.