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Open Access Publications from the University of California

Scholarly Works (31 results)

  • Article
  • Peer Reviewed
Dermatology Online Journal, Volume 17, Issue 3 (2011)
    • Thesis
    • Peer Reviewed
    UC San Francisco Electronic Theses and Dissertations (2010)

    Clonal diversity within the adaptive immune system, while endowing organisms with the ability to respond to a broad range of potential pathogens, presents a substantial risk for autoimmunity. Numerous complementary mechanisms have evolved to prevent such deleterious outcomes, and to establish and maintain appropriate tolerance to self. Medullary epithelial cells of the thymus play an essential role in this process by displaying a diverse set of tissue-specific antigens via a mechanism dependent on the Autoimmune regulator (Aire) gene. Here we describe a discrete population of extrathymic Aire-expressing cells (eTACs) in the secondary lymphoid organs. We show that Aire regulates a diverse range of tissue-specific antigen genes in eTACs distinct from those presented in the thymus. To define a potential role for this population in immune tolerance, we demonstrate that self-antigen expression in eTACs is sufficient to prevent T cell-mediated autoimmune diabetes mediated by CD4+ or CD8+ T cells. We demonstrate that such tolerance is established via anergic or deletional mechanisms for CD4+ or CD8+ cells, respectively, and does not require the presence or induction of regulatory populations. Further, we show that tolerance induction by eTACs is highly resistant to conversion to immunogenicity. Finally, we describe the development of a novel transgenic mouse model for depletion of mTECs and eTACs, and suggest that the absence of these populations predisposes to autoimmunity. Together this work identifies self-antigen expressing eTACs as a population with potential significance in both physiologic and therapeutic maintenance of self-tolerance.

      Cover page: Extrathymic Aire-Expressing Cells
      • Article
      • Peer Reviewed
      UC Berkeley Previously Published Works (2015)
      To assess the eruption and emplacement of volumetrically diverse rhyolite lavas, we measured microlite number densities and orientations from samples collected from nine lavas in Yellowstone Caldera and two from Mono Craters, USA. Microlite populations are composed of Fe-Ti oxides ± alkali feldspar ± clinopyroxene. Number densities range from 108.11 ± 0.03 to 109.45 ± 0.15 cm−3 and do not correlate with distance from the vent across individual flows and are remarkably similar between large- and small-volume lavas. Together, those observations suggest that number densities are unmodified during emplacement and that ascent rates in the conduit are similar between small domes and large lava flows. Microtextures produced by continuous decompression experiments best replicate natural textures at decompression rates of 1–2 MPa hr−1. Acicular microlites have a preferred orientation in all natural samples. Because the standard deviation of microlite orientation does not become better aligned with distance travelled, we conclude that microlites exit the conduit aligned and that strain during subaerial flow was insufficient to further align microlites. The orientations of microlite trend and plunge in near-vent samples indicate that pure shear was the dominant style of deformation in the conduit. We speculate that collapsing permeable foam(s) provides a mechanism to concurrently allow microlite formation and alignment in response to the combination of degassing and flattening by pure shear.
        Cover page: Ascent and emplacement dynamics of obsidian lavas inferred from microlite textures
        • Article
        • Peer Reviewed
        UC San Francisco Previously Published Works (2024)
        Spleen marginal zone (MZ) B cells are important for antibody responses against blood-borne antigens. The signals they use to detect exposure to blood are not well defined. Here, using intravital two-photon microscopy in mice, we observe transient contacts between MZ B cells and red blood cells that are in flow. We show that MZ B cells use adhesion G-protein-coupled receptor ADGRE5 (CD97) for retention in the spleen. CD97 function in MZ B cells depends on its ability to undergo autoproteolytic cleavage and signaling via Gα13 and ARHGEF1. Red blood cell expression of the CD97 ligand CD55 is required for MZ B cell homeostasis. Applying a pulling force on CD97-transfected cells using an optical C-trap and CD55+ beads leads to accumulation of active RhoA and membrane retraction. Finally, we show that CD97 deficiency leads to a reduced T cell-independent IgM response. Thus, our studies provide evidence that MZ B cells use mechanosensing to position in a manner that enhances antibody responses against blood-borne antigens.
          Cover page: Dynamic encounters with red blood cells trigger splenic marginal zone B cell retention and function.
          • Article
          • Peer Reviewed
          UC Riverside Previously Published Works (2018)
            Cover page: In Situ Rheological Method to Evaluate Feedstock Physical Properties Throughout Enzymatic Deconstruction
            • Article
            Recent Work (2001)

            In this paper we describe a coding, modulation, and spatial processing technique for fixed broadband wireless Internet access applications and provide examples of its performance. This technique is built on Orthogonal Frequency Division Multiplexing (OFDM) and is known as Vector OFDM (VOFDM). We compare VOFDM with conventional Single Carrier Modulation (SCM), and show that it provides substantial performance improvements over SCM. 1. It divides the channel into narrowband, flat fading, subchannels and thus it is more resistant to frequency selective fading as compared to single carrier systems. 2. By using FFT techniques, it is computationally efficient. 3. It can be combined with coding and interleaving to recover symbols lost due to the frequency selectivity of

              Cover page: VOFDM Broadband Wireless Transmission and Its Advantages
              • Article
              • Peer Reviewed
              2018 Publications (2018)
                Cover page: In Situ Rheological Method to Evaluate Feedstock Physical Properties Throughout Enzymatic Deconstruction
                • Article
                • Peer Reviewed
                UC San Francisco Previously Published Works (2013)
                The autoimmune regulator (Aire) is essential for prevention of autoimmunity; its role is best understood in the thymus, where it promotes self-tolerance through tissue-specific antigen (TSA) expression. Recently, extrathymic Aire-expressing cells (eTACs) have been described in murine secondary lymphoid organs, but the identity of such cells and their role in immune tolerance remains unclear. Here we have shown that eTACs are a discrete major histocompatibility complex class II (MHC II)(hi), CD80(lo), CD86(lo), epithelial cell adhesion molecule (EpCAM)(hi), CD45(lo) bone marrow-derived peripheral antigen-presenting cell (APC) population. We also have demonstrated that eTACs can functionally inactivate CD4⁺ T cells through a mechanism that does not require regulatory T cells (Treg) and is resistant to innate inflammatory stimuli. Together, these findings further define eTACs as a distinct tolerogenic cell population in secondary lymphoid organs.
                  Cover page: Extrathymic Aire-expressing cells are a distinct bone marrow-derived population that induce functional inactivation of CD4⁺ T cells.
                  • Article
                  • Peer Reviewed
                  UC San Francisco Previously Published Works (2013)
                  Thymic epithelial cells in the medulla (mTECs) play a critical role in enforcing central tolerance through expression and presentation of tissue-specific antigens (TSAs) and deletion of autoreactive thymocytes. TSA expression requires autoimmune regulator (Aire), a transcriptional activator present in a subset of mTECs characterized by high CD80 and major histocompatibility complex II expression and a lack of potential for differentiation or proliferation. Here, using an Aire-DTR transgenic line, we show that short-term ablation specifically targets Aire(+) mTECs, which quickly undergo RANK-dependent recovery. Repeated ablation also affects Aire(-) mTECs, and using an inducible Aire-Cre fate-mapping system, we find that this results from the loss of a subset of mTECs that showed prior expression of Aire, maintains intermediate TSA expression, and preferentially migrates toward the center of the medulla. These results clearly identify a distinct stage of mTEC development and underscore the diversity of mTECs that play a key role in maintaining tolerance.
                    Cover page: Lineage Tracing and Cell Ablation Identify a Post-Aire-Expressing Thymic Epithelial Cell Population
                    • Article
                    • Peer Reviewed
                    UC San Francisco Previously Published Works (2022)
                    Parathyroid allotransplantation is a burgeoning treatment for severe hypoparathyroidism. Deceased donor parathyroid gland (PTG) procurement can be technically challenging due to lack of normal intraoperative landmarks and exposure constraints in the neck of organ donors. In this study, we assessed standard 4-gland exposure in situ and en bloc surgical techniques for PTG procurement and ex vivo near-infrared autofluorescence (NIRAF) imaging for identification of PTGs during organ recovery.

                    Methods

                    Research tissue consent was obtained from organ donors or donor families for PTG procurement. All donors were normocalcemic, brain-dead, solid organ donors between 18 and 65 y of age. PTGs were procured initially using a standard 4-gland exposure technique in situ and subsequently using a novel en bloc resection technique after systemic organ preservation flushing. Parathyroid tissue was stored at 4 °C in the University of Wisconsin solution up to 48 h post-procurement. Fluoptics Fluobeam NIRAF camera and Image J software were utilized for quantification of NIRAF signal.

                    Results

                    Thirty-one brain-dead deceased donor PTG procurements were performed by abdominal transplant surgeons. In the initial 8 deceased donors, a mean of 1.75 glands (±1.48 glands SD) per donor were recovered using the 4-gland in situ technique. Implementation of combined en bloc resection with ex vivo NIRAF imaging in 23 consecutive donors yielded a mean of 3.60 glands (±0.4 SD) recovered per donor (P < 0.0001). Quantification of NIRAF integrated density signal demonstrated >1-fold log difference in PTG (2.13 × 105 pixels) versus surrounding anterior neck structures (1.9 × 104 pixels; P < 0.0001). PTGs maintain distinct NIRAF signal from the time of recovery (1.88 × 105 pixels) up to 48 h post-procurement (1.55 × 105 pixels) in organ preservation cold storage (P = 0.34).

                    Conclusions

                    The use of an en bloc surgical technique with ex vivo NIRAF imaging significantly enhances the identification and recovery of PTG from deceased donors.
                      Cover page: Procurement of Deceased Donor Parathyroid Glands With the Aid of Near-infrared Autofluorescence Imaging
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