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Open Access Publications from the University of California

Scholarly Works (12 results)

  • Thesis
  • Peer Reviewed
UC Davis Electronic Theses and Dissertations (2022)

Gene regulatory systems contribute to an organism’s fitness by providing a way to dynamically tune cellular responses in response to fluctuating environmental conditions. In this work, we compare the regulatory tuning of genes involved in the catabolism of glucose, maltose, and sucrose in the metabolically versatile halophilic archaeon Halogeometricum borinquense through functional transcriptomic profiling, targeted qRT-PCR, and sugar utilization assays. This work provides the first transcriptomic study for this organism, preliminarily characterizes the unique and shared responses of H. borinquense to single- and multiple-sugar growth conditions, identifies key metabolic regulatory points in the organism, and advances the discussion of archaeal carbon catabolite repression (CCR) by identifying putative targets of CCR that can be probed in future work to further explore underlying mechanisms.

Halophilic organisms are also suitable for use in educational settings. Here, I present the development and study examining the impact of a quantitative biology-focused Course Based Undergraduate Research Experience (CURE) on the development of student interest in and self-efficacy for quantitative biology. Students in the course isolate halophilic organisms from environmental samples, quantitatively characterize their growth, and thereafter sequence the genomes of the isolates. We found that although students initially reported high math-biology values, we saw improvements with regard to students seeing higher value in using quantitative calculations in biology and increased interest in pursuing future quantitative experiences (e.g., coursework, occupation).

Lastly, I present collaborative research that explores how students express affect when they engage with one another in the context of an online course textbook-based annotation and discussion forum. This work includes efforts to use machine learning to predict student affect and better understand student confusion, to increase student engagement with the course content by seeding forums, and to create and validate a limited emoji-hashtag pair set that enables more reliable student-driven affect tagging of forum posts.

    • Article
    • Peer Reviewed
    UC San Diego Previously Published Works (2024)
    Mass spectrometry-based methods can provide a global expression profile and structural readout of proteins in complex systems. Preserving the in vivo conformation of proteins in their innate state is challenging during proteomic experiments. Here, we introduce a whole animal in vivo protein footprinting method using perfusion of reagents to add dimethyl labels to exposed lysine residues on intact proteins which provides information about protein conformation. When this approach is used to measure dynamic structural changes during Alzheimers disease (AD) progression in a mouse model, we detect 433 proteins that undergo structural changes attributed to AD, independent of aging, across 7 tissues. We identify structural changes of co-expressed proteins and link the communities of these proteins to their biological functions. Our findings show that structural alterations of proteins precede changes in expression, thereby demonstrating the value of in vivo protein conformation measurement. Our method represents a strategy for untangling mechanisms of proteostasis dysfunction caused by protein misfolding. In vivo whole-animal footprinting should have broad applicability for discovering conformational changes in systemic diseases and for the design of therapeutic interventions.
      Cover page: Using in vivo intact structure for system-wide quantitative analysis of changes in proteins.
      • Article
      • Peer Reviewed
      UC Davis Previously Published Works (2021)
      This article provides computational and rule-based approaches for detecting confusion that is expressed in students' comments in couse forums. To obtain reliable, ground truth data about which posts exhibit student confusion, we designed a decision tree that facilitates the manual labeling of forum posts by experts. However, manual labeling is costly in time and resources, which limits the amount of data that can be generated using this process. Our strategy for overcoming these limitations was to generate rules for detecting confusion based on student input via hashtags, which reflect the student's affective states. We show that the resulting rules closely align with the ground truth judgement of experts. We next applied these rules to datasets of students' forum posts in a large-scale biology course, thereby automatically generating thousands of labeled instances of 'confused posts.' Finally, the resulting dataset was used to train a machine learning model for detecting whether students' posts exhibit confusion in the absence of hashtags. In this task, the pretrained language model based on bidirectional encoder representation from transformers (BERT) was able to outperform traditional machine learning models for classifying confusion in posts. This model was also able to generalize and detect student confusion across different offerings of the same course. Ultimately, the use of pretrained language models of this type will provide teachers with better technologies for detecting and alleviating confusion in online discussion forums by leveraging the combined input of teachers and students.
        Cover page: New Methods for Confusion Detection in Course Forums: Student, Teacher, and Machine
        • Article
        • Peer Reviewed
        UC Davis Previously Published Works (2020)
        Quantitative techniques are a critical part of contemporary biology research, but students interested in biology enter college with widely varying quantitative skills and attitudes toward mathematics. Course-based undergraduate research experiences (CUREs) may be an early way to build student competency and positive attitudes. Here we describe the design, implementation, and assessment of an introductory quantitative CURE focused on halophilic microbes. In this CURE, students culture and isolate halophilic microbes from environmental and food samples, perform growth assays, then use mathematical modeling to quantify the growth rate of strains in different salinities. To assess how the course may impact students' future academic plans and attitudes toward the use of math in biology, we used pre- and post-quarter surveys. Students who completed the course showed more positive attitudes toward science learning and an increased interest in pursuing additional quantitative biology experiences. We argue that the classroom application of microbiology methods, combined with mathematical modeling using student-generated data, provides a degree of student ownership, collaboration, iteration, and discovery that makes quantitative learning both relevant and exciting to students.
          Cover page: Combining Microbial Culturing With Mathematical Modeling in an Introductory Course-Based Undergraduate Research Experience.
          • Article
          • Peer Reviewed
          LBL Publications (2018)
          In all known fermionic superfluids, Cooper pairs are composed of spin-1/2 quasi-particles that pair to form either spin-singlet or spin-triplet bound states. The "spin" of a Bloch electron, however, is fixed by the symmetries of the crystal and the atomic orbitals from which it is derived and, in some cases, can behave as if it were a spin-3/2 particle. The superconducting state of such a system allows pairing beyond spin-triplet, with higher spin quasi-particles combining to form quintet or septet pairs. We report evidence of unconventional superconductivity emerging from a spin-3/2 quasi-particle electronic structure in the half-Heusler semimetal YPtBi, a low-carrier density noncentrosymmetric cubic material with a high symmetry that preserves the p-like j = 3/2 manifold in the Bi-based Γ8 band in the presence of strong spin-orbit coupling. With a striking linear temperature dependence of the London penetration depth, the existence of line nodes in the superconducting order parameter Δ is directly explained by a mixed-parity Cooper pairing model with high total angular momentum, consistent with a high-spin fermionic superfluid state. We propose a k ⋅ p model of the j = 3/2 fermions to explain how a dominant J = 3 septet pairing state is the simplest solution that naturally produces nodes in the mixed even-odd parity gap. Together with the underlying topologically nontrivial band structure, the unconventional pairing in this system represents a truly novel form of superfluidity that has strong potential for leading the development of a new series of topological superconductors.
            Cover page: Beyond triplet: Unconventional superconductivity in a spin-3/2 topological semimetal
            • Article
            • Peer Reviewed
            LBL Publications (2022)
              Cover page: c-axis transport in UTe2: Evidence of three-dimensional conductivity componentCreative Commons 'BY-NC' version 4.0 license
              • Article
              • Peer Reviewed
              UC Davis Previously Published Works (2020)
              Volume 9, no. 8, e01540-19, 2020, https://doi.org/10.1128/MRA.01540-19. Page 2: Lines 3 and 4 of Acknowledgments should read as follows. "This work was supported by a Howard Hughes Medical Institute Professor grant awarded to Mark Goldman (grant number 52008137). We thank Jonathan Eisen, Katherine Dahlhausen, Mark Goldman, Ashley Vater, and David Coil for help with course design and planning".
                Cover page: Correction for Rodriguez-Medina et al., “Draft Genome Sequences of 16 Halophilic Prokaryotes Isolated from Diverse Environments”
                • Article
                • Peer Reviewed
                UC Davis Previously Published Works (2020)
                Halophile-specific enzymes have wide-ranging industrial and commercial applications. Despite their importance, there is a paucity of available halophile whole-genome sequences. Here, we report the draft genome sequences of 16 diverse salt-tolerant strains of bacteria and archaea isolated from a variety of high-salt environments.
                  Cover page: Draft Genome Sequences of 16 Halophilic Prokaryotes Isolated from Diverse Environments
                  • Article
                  • Peer Reviewed
                  UC Davis Previously Published Works (2023)
                  Genetic alterations help predict the clinical behavior of diffuse gliomas, but some variability remains uncorrelated. Here, we demonstrate that haploinsufficient deletions of chromatin-bound tumor suppressor NFKB inhibitor alpha (NFKBIA) display distinct patterns of occurrence in relation to other genetic markers and are disproportionately present at recurrence. NFKBIA haploinsufficiency is associated with unfavorable patient outcomes, independent of genetic and clinicopathologic predictors. NFKBIA deletions reshape the DNA and histone methylome antipodal to the IDH mutation and induce a transcriptome landscape partly reminiscent of H3K27M mutant pediatric gliomas. In IDH mutant gliomas, NFKBIA deletions are common in tumors with a clinical course similar to that of IDH wild-type tumors. An externally validated nomogram model for estimating individual patient survival in IDH mutant gliomas confirms that NFKBIA deletions predict comparatively brief survival. Thus, NFKBIA haploinsufficiency aligns with distinct epigenome changes, portends a poor prognosis, and should be incorporated into models predicting the disease fate of diffuse gliomas.
                    Cover page: Haploinsufficiency of NFKBIA reshapes the epigenome antipodal to the IDH mutation and imparts disease fate in diffuse gliomas
                    • Article
                    • Peer Reviewed
                    UCLA Previously Published Works (2024)
                    BACKGROUND: Recent clinical trials established the benefit of dual antiplatelet therapy with aspirin and clopidogrel (DAPT-AC) in early-presenting patients with minor ischemic stroke. However, the impact of these trials over time on the use and outcomes of DAPT-AC among the patients with nonminor or late-presenting stroke who do not meet the eligibility criteria of these trials has not been delineated. METHODS AND RESULTS: In a multicenter stroke registry, this study examined yearly changes from April 2008 to August 2022 in DAPT-AC use for stroke patients ineligible for CHANCE/POINT (Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events/Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke) clinical trials due to National Institutes of Health Stroke Scale >4 or late arrival beyond 24 hours of onset. A total of 32 118 patients (age, 68.1±13.1 years; male, 58.5%) with National Institutes of Health Stroke Scale of 4 (interquartile range, 1-7) were analyzed. In 2008, DAPT-AC was used in 33.0%, other antiplatelets in 62.7%, and no antiplatelet in 4.3%. The frequency of DAPT-AC was relatively unchanged through 2013, when the CHANCE trial was published, and then increased steadily, reaching 78% in 2022, while other antiplatelets decreased to 17.8% in 2022 (Ptrend<0.001). From 2011 to 2022, clinical outcomes nonsignificantly improved, with an average relative risk reduction of 2%/y for the composite of stroke, myocardial infarction, and all-cause mortality, both among patients treated with DAPT-AC and patients treated with other antiplatelets. CONCLUSIONS: Use of DAPT-AC in stroke patients with stroke ineligible for recent DAPT clinical trials increased markedly and steadily after CHANCE publication in 2013, reaching deployment in nearly 4 of every 5 patients by 2022. The secondary prevention in patients with ischemic stroke seems to be gradually improving, possibly due to the enhancement of risk factor control.
                      Cover page: Trends in Dual Antiplatelet Therapy of Aspirin and Clopidogrel and Outcomes in Ischemic Stroke Patients Noneligible for POINT/CHANCE Trial Treatment.
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