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Open Access Publications from the University of California

Scholarly Works (13 results)

  • Thesis
  • Peer Reviewed
UCLA Electronic Theses and Dissertations (2022)

The objective of this dissertation was to design and study a transformative model of climate change education that foregrounded sociopolitical processes and was socially relevant to Black and Latinx urban high school students. The intervention was implemented at the Mann-UCLA Community School in South Los Angeles while distance learning was mandated by the COVID-19 pandemic and was part of a research-practice partnership with a chemistry teacher. Using the Participatory Design Research methodology, I designed the learning context and documented how this instructional model structured classroom engagement and supported the outcomes of learning climate science and developing critical climate awareness. A mixed methods approach was used for analysis of data including pre/post assessments of climate science knowledge and climate concern, formative assessments of critical awareness of climate change, classroom artifacts, classroom observations, and interviews with focal students. Findings on classroom engagement, organized with the Connective and Productive Disciplinary Engagement framework, show that organizing instruction around the sociopolitical dimensions of climate change was productive. Participation was structured around students’ critical awareness of social issues in their community and their imagined futures when they could participate in the transition to low-emission energy sources. Student engagement embodied the four principles of Connective and Productive Disciplinary Engagement more strongly over time as they grappled with authentic problems of climate change in their community. The sociopolitical framing of climate change was also productive for learning climate science concepts and developing students’ critical climate awareness. Findings show a statistically significant improvement in students’ understanding of canonical scientific concepts and a shift towards awareness of and concern about climate change. Performance on formative assessments shows students made progress in explaining critical aspects of climate change, specifically in ascribing agency for causes and solutions. The significance of these findings is that centering sociopolitical, local dimensions of climate change does not diminish canonical, standard-aligned learning opportunities. Foregrounding social justice and inviting students’ critical awareness into the science classroom as a sense-making resource supported many students in developing sophisticated explanations of climate change in their community. This research contributes an approach to climate change instruction that advances culturally-relevant, justice-centered science pedagogy.

    Cover page: Critical Climate Awareness: Re-imagining Climate Change Teaching and Learning
    • Article
    • Peer Reviewed
    UC Irvine Previously Published Works (2024)
    Abstract: Instructional practices in science education often create dichotomies of “expert” and “outsider” that produce distinct power differences in classrooms. Building upon the idea of “making present practice” to disrupt these binaries, this paper presents select findings from a year-long study investigating two urban teachers' use of community-based science (CBS) instructional practices to create relational shifts that reframe expert and expertise in science instruction. By examining how CBS instructional practices reframe power through co-learning experiences, our findings demonstrated that teachers positioned youth as knowledge constructors through three instructional practices: (a) creating space for students to share their knowledge and experiences, (b) positioning students’ lives and experiences as assets to/within science, and (c) being responsive to assets in future lessons. We use these findings to demonstrate how CBS instructional practices support shifts in relational dynamics by creating spaces of rightful presence, where students are viewed as legitimate classroom members who contribute scientific knowledge in practice and have power in the classroom space. By relinquishing traditional boundaries in science teaching to deconstruct ideas of who holds power, we position CBS instructional practices as a means to expand educational equity by legitimizing students’ diverse sensemaking and re-mediating hierarchical structures in classroom spaces.
      Cover page: (Re)defining expert in science instruction: a community-based science approach to teaching
      • Article
      • Peer Reviewed
      UC San Francisco Previously Published Works (2017)
      Optical nanoparticle (NP)-based sensors have been widely implemented as tools for detection of targeted ions and biomolecules. The NP sensing platform offer a modular design that can incorporate different sensing components for greater target specificity and the ability to tune the dynamic range, as well as encapsulation of multiple dyes to generate a ratiometric signal with varying spectra. Despite these advantages, demonstrating quantitative ion imaging for intracellular measurement still possess a major challenge. Here, we describe fundamentals that enable intracellular validation of this approach using ion-selective nanosensors for investigating calcium (Ca2+) as a model ion. While conventional indicators can improve individual aspects of indicator performance such as Kd, wavelength, and ratiometric measurements, the use of NP sensors can achieve combined benefits of addressing these issues simultaneously. The nanosensor incorporates highly calcium-selective ionophores and two fluorescence indicators that act as signal transducers to facilitate quantitative ratiometric imaging. For intracellular Ca2+ application, the sensors are fine-tuned to physiological sensing range, and live-cell imaging and quantification are demonstrated in HeLa cells loaded with nanosensors and their responsiveness to carbachol-evoked store release (~400 nM). The current nanosensor design thus provides a promising sensing platform for real-time detection and optical determination of intracellular ions.
        Cover page: A method for estimating intracellular ion concentration using optical nanosensors and ratiometric imaging
        • Article
        • Peer Reviewed
        UC Irvine Previously Published Works (2023)
        Fusarium, Aspergillus and Candida are important fungal pathogens that cause visual impairment and blindness in the USA and worldwide. This review will summarize the epidemiology and clinical features of corneal infections and discuss the immune and inflammatory responses that play an important role in clinical disease. In addition, we describe fungal virulence factors that are required for survival in infected corneas, and the activities of neutrophils in fungal killing, tissue damage and cytokine production.
          Cover page: Immunity to pathogenic fungi in the eye.
          • Article
          • Peer Reviewed
          UC Irvine Previously Published Works (2018)
          Neutrophil extracellular trap (NET) formation requires chromatin decondensation before nuclear swelling and eventual extracellular release of DNA, which occurs together with nuclear and cytoplasmic antimicrobial proteins. A key mediator of chromatin decondensation is protein deiminase 4 (PAD4), which catalyzes histone citrullination. In the current study, we examined the role of PAD4 and NETosis following activation of neutrophils by A. fumigatus hyphal extract or cell wall β-glucan (curdlan) and found that both induced NET release by human and murine neutrophils. Also, using blocking antibodies to CR3 and Dectin-1 together with CR3-deficient CD18-/- and Dectin-1-/- murine neutrophils, we found that the β-glucan receptor CR3, but not Dectin-1, was required for NET formation. NETosis was also dependent on NADPH oxidase production of reactive oxygen species (ROS). Using an antibody to citrullinated histone 3 (H3Cit) as an indicator of PAD4 activity, we show that β-glucan stimulated NETosis occurs in neutrophils from C57BL/6, but not PAD4-/- mice. Similarly, a small molecule PAD4 inhibitor (GSK484) blocked NET formation by human neutrophils. Despite these observations, the ability of PAD4-/- neutrophils to release calprotectin and kill A. fumigatus hyphae was not significantly different from C57BL/6 neutrophils, whereas CD18-/- neutrophils exhibited an impaired ability to perform both functions. We also detected H3Cit in A. fumigatus infected C57BL/6, but not PAD4-/- corneas; however, we found no difference between C57BL/6 and PAD4-/- mice in either corneal disease or hyphal killing. Taken together, these findings lead us to conclude that although PAD4 together with CR3-mediated ROS production is required for NET formation in response to A. fumigatus, PAD4-dependent NETosis is not required for A. fumigatus killing either in vitro or during infection.
            Cover page: Protein Deiminase 4 and CR3 Regulate Aspergillus fumigatus and β-Glucan-Induced Neutrophil Extracellular Trap Formation, but Hyphal Killing Is Dependent Only on CR3Creative Commons 'BY' version 4.0 license
            • Article
            • Peer Reviewed
            UC Irvine Previously Published Works (2018)

            Purpose

            Aspergillus and Fusarium molds cause blinding corneal infections as a consequence of ocular trauma and in association with contact lens wear. As these fungi require zinc for fungal growth, we examined the effect of atovaquone, a ubiquinone analog that disrupts zinc homeostasis, on fungal growth in vitro and in vivo.

            Methods

            In vitro: Aspergillus and Fusarium germinating conidia were incubated overnight with atovaquone, and hyphal growth was measured by fluorimetry. In vivo: C57BL/6 mouse corneas were infected with Aspergillus or Fusarium conidia. Atovaquone was added topically and corneal opacification and fungal growth were quantified.

            Results

            Atovaquone has antifungal activity against Aspergillus and Fusarium clinical isolates, with Fusarium species being more sensitive to atovaquone than Aspergillus species. Atovaquone also reduced labile intracellular zinc levels and increased the sensitivity of Aspergillus to metal shock. Atovaquone reduced vacuolar acidification, which regulates storage of intracellular free zinc, and also acted synergistically with voriconazole and itraconazole to kill hyphae. Furthermore, mitochondrial potential and ATP production were reduced in both Aspergillus and Fusarium following atovaquone treatment. Finally, topical application of atovaquone to the ocular surface significantly inhibited fungal growth and corneal opacification in murine models of fungal keratitis.

            Conclusions

            These studies demonstrate that atovaquone has pronounced in vitro and in vivo antifungal activity against filamentous fungi by disrupting both metal homeostasis and mitochondrial function, and therefore has potential as a novel antifungal agent.
              Cover page: Atovaquone Impairs Growth of Aspergillus and Fusarium Keratitis Isolates by Modulating Mitochondrial Function and Zinc HomeostasisCreative Commons 'BY' version 4.0 license
              • Article
              • Peer Reviewed
              UC San Francisco Previously Published Works (2018)
              Fluorescent nanosensors and molecular probes are next-generation tools for imaging chemical signaling inside and between cells. Electrophysiology has long been considered the gold standard in elucidating neural dynamics with high temporal resolution and precision, particularly on the single-cell level. However, electrode-based techniques face challenges in illuminating the specific chemicals involved in neural cell activation with adequate spatial information. Measuring chemical dynamics is of fundamental importance to better understand synergistic interactions between neurons as well as interactions between neurons and non-neuronal cells. Over the past decade, significant technological advances in optical probes and imaging methods have enabled entirely new possibilities for studying neural cells and circuits at the chemical level. These optical imaging modalities have shown promise for combining chemical, temporal, and spatial information. This potential makes them ideal candidates to unravel the complex neural interactions at multiple scales in the brain, which could be complemented by traditional electrophysiological methods to obtain a full spatiotemporal picture of neurochemical dynamics. Despite the potential, only a handful of probe candidates have been utilized to provide detailed chemical information in the brain. To date, most live imaging and chemical mapping studies rely on fluorescent molecular indicators to report intracellular calcium (Ca2+) dynamics, which correlates with neuronal activity. Methodological advances for monitoring a full array of chemicals in the brain with improved spatial, temporal, and chemical resolution will thus enable mapping of neurochemical circuits with finer precision. On the basis of numerous studies in this exciting field, we review the current efforts to develop and apply a palette of optical probes and nanosensors for chemical sensing in the brain. There is a strong impetus to further develop technologies capable of probing entire neurobiological units with high spatiotemporal resolution. Thus, we introduce selected applications for ion and neurotransmitter detection to investigate both neurons and non-neuronal brain cells. We focus on families of optical probes because of their ability to sense a wide array of molecules and convey spatial information with minimal damage to tissue. We start with a discussion of currently available molecular probes, highlight recent advances in genetically modified fluorescent probes for ions and small molecules, and end with the latest research in nanosensors for biological imaging. Customizable, nanoscale optical sensors that accurately and dynamically monitor the local environment with high spatiotemporal resolution could lead to not only new insights into the function of all cell types but also a broader understanding of how diverse neural signaling systems act in conjunction with neighboring cells in a spatially relevant manner.
                Cover page: Optical Probes for Neurobiological Sensing and Imaging
                • Article
                • Peer Reviewed
                UC Irvine Previously Published Works (2018)

                Neutrophil extracellular trap (NET) formation requires chromatin decondensation before nuclear swelling and eventual extracellular release of DNA, which occurs together with nuclear and cytoplasmic antimicrobial proteins. A key mediator of chromatin decondensation is protein deiminase 4 (PAD4), which catalyzes histone citrullination. In the current study, we examined the role of PAD4 and NETosis following activation of neutrophils by A. fumigatus hyphal extract or cell wall β-glucan (curdlan) and found that both induced NET release by human and murine neutrophils. Also, using blocking antibodies to CR3 and Dectin-1 together with CR3-deficient CD18-/- and Dectin-1-/- murine neutrophils, we found that the β-glucan receptor CR3, but not Dectin-1, was required for NET formation. NETosis was also dependent on NADPH oxidase production of reactive oxygen species (ROS). Using an antibody to citrullinated histone 3 (H3Cit) as an indicator of PAD4 activity, we show that β-glucan stimulated NETosis occurs in neutrophils from C57BL/6, but not PAD4-/- mice. Similarly, a small molecule PAD4 inhibitor (GSK484) blocked NET formation by human neutrophils. Despite these observations, the ability of PAD4-/- neutrophils to release calprotectin and kill A. fumigatus hyphae was not significantly different from C57BL/6 neutrophils, whereas CD18-/- neutrophils exhibited an impaired ability to perform both functions. We also detected H3Cit in A. fumigatus infected C57BL/6, but not PAD4-/- corneas; however, we found no difference between C57BL/6 and PAD4-/- mice in either corneal disease or hyphal killing. Taken together, these findings lead us to conclude that although PAD4 together with CR3-mediated ROS production is required for NET formation in response to A. fumigatus, PAD4-dependent NETosis is not required for A. fumigatus killing either in vitro or during infection.

                  Cover page: Protein Deiminase 4 and CR3 Regulate Aspergillus fumigatus and β-Glucan-Induced Neutrophil Extracellular Trap Formation, but Hyphal Killing Is Dependent Only on CR3.
                  • Article
                  • Peer Reviewed
                  UC San Francisco Previously Published Works (2021)
                  The ability to monitor the release of neurotransmitters during synaptic transmission would significantly impact the diagnosis and treatment of neurological diseases. Here, we present a DNA-based enzymatic nanosensor for quantitative detection of acetylcholine (ACh) in the peripheral nervous system of living mice. ACh nanosensors consist of DNA as a scaffold, acetylcholinesterase as a recognition component, pH-sensitive fluorophores as signal generators, and α-bungarotoxin as a targeting moiety. We demonstrate the utility of the nanosensors in the submandibular ganglia of living mice to sensitively detect ACh ranging from 0.228 to 358 μM. In addition, the sensor response upon electrical stimulation of the efferent nerve is dose dependent, reversible, and we observe a reduction of ∼76% in sensor signal upon pharmacological inhibition of ACh release. Equipped with an advanced imaging processing tool, we further spatially resolve ACh signal propagation on the tissue level. Our platform enables sensitive measurement and mapping of ACh transmission in the peripheral nervous system.
                    Cover page: Imaging in vivo acetylcholine release in the peripheral nervous system with a fluorescent nanosensor
                    • Article
                    • Peer Reviewed
                    UC Irvine Previously Published Works (2024)
                    This article examines two teachers' efforts to re-organize their science teaching around issues of environmental and food justice in the urban community where they teach through the pedagogical approach of community-oriented framing. We introduce this approach to teachers' framing of phenomena in community as supporting students' framing of phenomena as personally and locally relevant. Drawing on classroom observations of remote learning during the COVID-19 pandemic, we took an analytic approach that characterized features of classroom discourse to rate community-oriented framing at the lesson level. Results show that teachers framed phenomena as both social and scientific, and as rooted in students' lived experiences, with classroom activities designed to gather localized and personalized evidence needed to explain or model phenomena. We also share examples of how Black and Latinx students took up this framing of phenomena in their classroom work. By providing a detailed description of the launch and implementation of activities, findings illustrate how community-oriented framing supported teachers in posing local questions of equity and justice as simultaneously social and scientific, and helping students perceive science learning as meaningful to their everyday lives. Community-oriented framing offers a practical means of designing locally and socially relevant instruction. We contribute to justice-centered science pedagogies by conceptualizing transformative science learning environments as those in which students understand their goal in science class as understanding, and later addressing, inequities in how socioscientific issues manifest in their community.
                      Cover page: Exploring science teachers' efforts to frame phenomena in the community
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