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Open Access Publications from the University of California

Scholarly Works (8 results)

  • Thesis
  • Peer Reviewed
UC San Francisco Electronic Theses and Dissertations (2011)

The ability to reside and proliferate in macrophages is characteristic of several infectious agents that are of major importance to public health. In order for these pathogens to survive in the hostile macrophage environment, they must develop mechanisms to evade the microbicidal activities of the macrophage and to subvert the host immune response. Using broad transcriptional profiling as well as more targeted approaches, we have further elucidated the ways intracellular protozoan pathogens interact with the host macrophage, providing a better understanding of parasite immune evasion.

In order to determine how the macrophage response to intracellular parasites fits into the diverse range of possible macrophage activation programs, we utilized genome-wide microarray analysis to compare the responses of mouse macrophages following infection by the intracellular parasites Trypanosoma cruzi and Leishmania mexicana, the bacterial product lipopolysaccharide (LPS), and various cytokines. We found that infection by L. mexicana produced so few transcriptional changes that the infected macrophages were almost indistinguishable from uninfected cells. Furthermore, the transcriptional response of macrophages infected by the protozoan pathogens more closely resembled the transcriptional response of macrophages stimulated by the cytokines IL-4, IL-10, and IL-17 than macrophages stimulated by Th1 cytokines IFNG, TNF, and IFNB. These observation suggested that infection by L. mexicana may have a suppressive effect on host macrophage activation.

In order to determine if L. mexicana actively suppresses macrophage activation, we compared the response to live vs. heat-killed L. mexicana. Macrophages treated with heat-killed parasites were activated, producing a transcriptional signature that included upregulation of many interferon-stimulated genes, indicating that live L. mexicana actively suppresses this activation. In order to determine the mechanism of suppression, we analyzed the macrophage response to cysteine protease B (CPB)- and cysteine protease A (CPA)-deficient L. mexicana. CPB and CPA are related cathepsin L-like proteases that have been shown to play an important role in the inhibition of Th1 immunity in several mouse models of leishmaniasis. We found that infection with CPB-/- and CPB/CPA-/- L. mexicana also resulted in upregulation of interferon-stimulated genes, suggesting that suppression of host transcriptional responses by L. mexicana is at least partially dependent on CPB and CPA.

    Cover page: Characterization of the host macrophage response to intracellular protozoan pathogens
    • Article
    • Peer Reviewed
    UC Irvine Previously Published Works (2015)
    The exceptional activity for methane combustion of modular palladium-ceria core-shell subunits on silicon-functionalized alumina that was recently reported has created renewed interest in the potential of core-shell structures as catalysts. Here we report on our use of advanced ex situ and in situ electron microscopy with atomic resolution to show that the modular palladium-ceria core-shell subunits undergo structural evolution over a wide temperature range. In situ observations performed in an atmospheric gas cell within this temperature range provide real-time evidence that the palladium and ceria nanoparticle constituents of the palladium-ceria core-shell participate in a dynamical process that leads to the formation of an unanticipated structure comprised of an intimate mixture of palladium, cerium, silicon and oxygen, with very high dispersion. This finding may open new perspectives about the origin of the activity of this catalyst.
      Cover page: Dynamic structural evolution of supported palladium-ceria core-shell catalysts revealed by in situ electron microscopy.
      • Article
      • Peer Reviewed
      UC Irvine Previously Published Works (2015)
      The exceptional activity for methane combustion of modular palladium-ceria core-shell subunits on silicon-functionalized alumina that was recently reported has created renewed interest in the potential of core-shell structures as catalysts. Here we report on our use of advanced ex situ and in situ electron microscopy with atomic resolution to show that the modular palladium-ceria core-shell subunits undergo structural evolution over a wide temperature range. In situ observations performed in an atmospheric gas cell within this temperature range provide real-time evidence that the palladium and ceria nanoparticle constituents of the palladium-ceria core-shell participate in a dynamical process that leads to the formation of an unanticipated structure comprised of an intimate mixture of palladium, cerium, silicon and oxygen, with very high dispersion. This finding may open new perspectives about the origin of the activity of this catalyst.
        Cover page: Dynamic structural evolution of supported palladium–ceria core–shell catalysts revealed by in situ electron microscopyCreative Commons 'BY' version 4.0 license
        • Article
        • Peer Reviewed
        UC Irvine Previously Published Works (2017)
        The catalytic performance of core-shell platinum alloy nanoparticles is typically superior to that of pure platinum nanoparticles for the oxygen reduction reaction in fuel cell cathodes. Thorough understanding of core-shell formation is critical for atomic-scale design and control of the platinum shell, which is known to be the structural feature responsible for the enhancement. Here we reveal details of a counter-intuitive core-shell formation process in platinum-cobalt nanoparticles at elevated temperature under oxygen at atmospheric pressure, by using advanced in situ electron microscopy. Initial segregation of a thin platinum, rather than cobalt oxide, surface layer occurs concurrently with ordering of the intermetallic core, followed by the layer-by-layer growth of a platinum shell via Ostwald ripening during the oxygen annealing treatment. Calculations based on density functional theory demonstrate that this process follows an energetically favourable path. These findings are expected to be useful for the future design of structured platinum alloy nanocatalysts.Core-shell platinum alloy nanoparticles are promising catalysts for oxygen reduction, however a deeper understanding of core-shell formation is still required. Here the authors report oxygen-driven formation of core-shell Pt3Co nanoparticles, seen at the atomic scale with in situ electron microscopy at ambient pressure.
          Cover page: In situ atomic-scale observation of oxygen-driven core-shell formation in Pt3Co nanoparticlesCreative Commons 'BY' version 4.0 license
          • Article
          • Peer Reviewed
          UC Irvine Previously Published Works (2017)
          The catalytic performance of core-shell platinum alloy nanoparticles is typically superior to that of pure platinum nanoparticles for the oxygen reduction reaction in fuel cell cathodes. Thorough understanding of core-shell formation is critical for atomic-scale design and control of the platinum shell, which is known to be the structural feature responsible for the enhancement. Here we reveal details of a counter-intuitive core-shell formation process in platinum-cobalt nanoparticles at elevated temperature under oxygen at atmospheric pressure, by using advanced in situ electron microscopy. Initial segregation of a thin platinum, rather than cobalt oxide, surface layer occurs concurrently with ordering of the intermetallic core, followed by the layer-by-layer growth of a platinum shell via Ostwald ripening during the oxygen annealing treatment. Calculations based on density functional theory demonstrate that this process follows an energetically favourable path. These findings are expected to be useful for the future design of structured platinum alloy nanocatalysts.Core-shell platinum alloy nanoparticles are promising catalysts for oxygen reduction, however a deeper understanding of core-shell formation is still required. Here the authors report oxygen-driven formation of core-shell Pt3Co nanoparticles, seen at the atomic scale with in situ electron microscopy at ambient pressure.
            Cover page: In situ atomic-scale observation of oxygen-driven core-shell formation in Pt3Co nanoparticles.
            • Article
            • Peer Reviewed
            UC Irvine Previously Published Works (2018)
            Understanding the growth pathway of faceted alloy nanoparticles at the atomic level is crucial to morphology control and property tuning. Yet, it remains a challenge due to complexity of the growth process and technical limits of modern characterization tools. We report a combinational use of multiple cutting-edge in situ techniques to study the growth process of octahedral Pt3Ni nanoparticles, which reveal the particle growth and facet formation mechanisms. Our studies confirm the formation of octahedral Pt3Ni initiates from Pt nuclei generation, which is followed by continuous Pt reduction that simultaneously catalyzes Ni reduction, resulting in mixed alloy formation with moderate elemental segregation. Carbon monoxide molecules serve as a facet formation modulator and induce Ni segregation to the surface, which inhibits the (111) facet growth and causes the particle shape to evolve from a spherical cluster to an octahedron as the (001) facet continues to grow.
              Cover page: Deconvolution of octahedral Pt3Ni nanoparticle growth pathway from in situ characterizationsCreative Commons 'BY' version 4.0 license
              • Article
              • Peer Reviewed
              UC Davis Previously Published Works (2015)
                Cover page: Joint China-US Call for Employing a Transdisciplinary Approach to Emerging Infectious Diseases
                • Article
                • Peer Reviewed
                UC San Francisco Previously Published Works (2020)
                Inflammatory response heterogeneity has impeded high-resolution dissection of diverse immune cell populations during activation. We characterize mouse cutaneous immune cells by single-cell RNA sequencing, after inducing inflammation using imiquimod and oxazolone dermatitis models. We identify 13 CD45+ subpopulations, which broadly represent most functionally characterized immune cell types. Oxazolone pervasively upregulates Jak2/Stat3 expression across T cells and antigen-presenting cells (APCs). Oxazolone also induces Il4/Il13 expression in newly infiltrating basophils, and Il4ra and Ccl24, most prominently in APCs. In contrast, imiquimod broadly upregulates Il17/Il22 and Ccl4/Ccl5. A comparative analysis of single-cell inflammatory transcriptional responses reveals that APC response to oxazolone is tightly restricted by cell identity, whereas imiquimod enforces shared programs on multiple APC populations in parallel. These global molecular patterns not only contrast immune responses on a systems level but also suggest that the mechanisms of new sources of inflammation can eventually be deduced by comparison to known signatures.
                  Cover page: Single-Cell Profiling Reveals Divergent, Globally Patterned Immune Responses in Murine Skin Inflammation
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