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Open Access Publications from the University of California

Scholarly Works (41 results)

  • Thesis
  • Peer Reviewed
UC San Francisco Electronic Theses and Dissertations (2005)

    Cover page: Injectable tricalcium phosphate cement (Norian®) for periodontal osseous defects
    • Article
    • Peer Reviewed
    UCLA Previously Published Works (2010)
    Orthopaedists make great use of eponymous equipment, however the origins of these tools are unknown to many users. This history enriches, enlightens, and enhances surgical education, and may inspire modern innovation. We explored the origins of common and eponymous orthopaedic equipment. We selected pieces of equipment named for their inventors and in the broadest use by modern orthopaedists. We do not describe specialized orthopaedic implants and instruments owing to the overwhelming number of these devices. The history of this equipment reflects the coevolution of orthopaedics and battlefield medicine. Additionally, these stories evidence the primacy of elegant design and suggest that innovation is often a process of revision and refinement rather than sudden inspiration. Their history exposes surgical innovators as brilliant, lucky, hardworking, and sometimes odd. These stories amuse, enlighten, and may inspire modern orthopaedists to develop creative solutions of their own. The rich history of the field’s eponymous instruments informs an ongoing tradition of innovation in orthopaedics.
      Cover page: Origins of Eponymous Orthopaedic Equipment
      • Thesis
      • Peer Reviewed
      UC Berkeley Electronic Theses and Dissertations (2023)

      The delivery of biomacromolecules such as DNA, RNA, and proteins to plants enables the bioengineering of plant physiology to meet evolving demands in food and other plant-derived products. Currently, technologies for the delivery biomacromolecules a delivery are highly species specific and low efficiency. A growing asymmetry between an explosion of synthetic biology tools and the means to implement these tools in plants motivates the development of more efficacious biomacromolecule delivery technology. However, the delivery of these materials is greatly hampered by the presence of the cell wall, the principal defense plants possess against pathogen invasion. While great strides have been made in delivering these biomolecules in the form of new nanoparticle carriers, the design of the carriers is bottlenecked by methods to screen them. For example, the localization of cargoes within plant tissues is obfuscated by the optical diffraction limit of visible light being on the same order as the plant cell wall. To address this challenge, we designed a fluorescence complementation based biological sensor that reports the successful cytosolic delivery of proteins and peptides in intact plant tissues. Delivered complementation in planta (DCIP) allows unambiguous and quantitative imaging of cytosolic protein delivery in plant tissues. We used DCIP to explore current cell-penetrating peptide-based protein and peptide delivery in plants, elucidate the endocytosis independence of poly-arginine mediated delivery in plant cells, engineer ectopic protein-protein interactions, and discover a new plant-derived cell penetrating peptide. Finally, we used DCIP to guide the delivery of a plant morphogenic transcription factor, WUSCHEL, to leaves and seedlings. The facile delivery of morphogenic regulators to plants may address a major bottleneck in plant bioengineering: the regeneration of modified plants from parent tissue.Our work exemplifies the necessity for engineers to not only consider the design of nanomaterials and carriers for delivery to plants, but also the methodology used in assessing prototype designs. An integration of synthetic biology reporters with high fidelity and low ambiguity is critical for the development of broadly applicable tools that advance plant biology. In this dissertation, I first motivate the need for developing novel delivery tools and summarize the state-of-the-art while describing potentially underexploited areas of biomacromolecule delivery. Next, I describe DCIP and how we used this tool to guide our efforts to deliver bioactive proteins to plant tissues. Finally, in the concluding chapter, I describe potential nanomaterials-based strategies to improve the efficiency of protein delivery in plants. This dissertation provides a framework in which the development of nanomaterial-based delivery of biomolecules to plants can be accelerated by the integration of synthetic biology reporters.

        • Article
        • Peer Reviewed
        LBL Publications (2019)
        Studying the single cell protein secretome offers the opportunity to understand how a phenotypically heterogeneous population of individual cells contribute to ensemble physiology and signaling. Polarized secretion events such as neurotransmitter release and cytokine signaling necessitates spatiotemporal information to elucidate structure-function relationships. Polymer functionalized single-walled carbon nanotube protein sensor arrays allow microscopic imaging of secreted protein footprints and enable the study of the spatiotemporal heterogeneity of protein secretion at the single-cell level. The protocols for carbon nanotube sensor creation, sensor array preparation, and imaging secreted proteins in both prokaryotic and mammalian cells are presented in this chapter. Secreted RAP1 and HIV-1 integrase proteins were used as proof-of-concept examples. Additionally, we discuss potential variety of protein and non-protein analyte effluxes that can be imaged using this platform, as well as current and future perspectives related to sensor development and deployment.
          Cover page: Synthetic probe development for measuring single or few-cell activity and efflux.
          • Article
          • Peer Reviewed
          UC San Diego Previously Published Works (2019)
          An increasing number of surgical strabismus patients are taking oral anticoagulant and antiplatelet agents, with more diverse mechanisms of action than those used in the past. The decision as to whether to continue these drugs throughout the perioperative period is difficult and must be based on the balance between hemorrhagic and thrombotic risk. To help guide strabismus surgeons with clinical management in these cases, we review potential hemorrhagic complications of strabismus surgery and examine the use of anticoagulant and antiplatelet drugs during the perioperative period. Surgical strategies that might help minimize intraoperative hemorrhage in patients on anticoagulant therapy are also discussed.
            Cover page: Anticoagulation: a practical guide for strabismus surgeons
            • Article
            • Peer Reviewed
            UC Berkeley Previously Published Works (2020)
            Intracellular pathogens are responsible for an enormous amount of worldwide morbidity and mortality, and each has evolved specialized strategies to establish and maintain their replicative niche. Listeria monocytogenes is a facultative intracellular pathogen that secretes a pore-forming cytolysin called listeriolysin O (LLO), which disrupts the phagosomal membrane and, thereby, allows the bacteria access to their replicative niche in the cytosol. Nonsynonymous and synonymous mutations in a PEST-like domain near the LLO N terminus cause enhanced LLO translation during intracellular growth, leading to host cell death and loss of virulence. Here, we explore the mechanism of translational control and show that there is extensive codon restriction within the PEST-encoding region of the LLO messenger RNA (mRNA) (hly). This region has considerable complementarity with the 5' UTR and is predicted to form an extensive secondary structure that overlaps the ribosome binding site. Analysis of both 5' UTR and synonymous mutations in the PEST-like domain that are predicted to disrupt the secondary structure resulted in up to a 10,000-fold drop in virulence during mouse infection, while compensatory double mutants restored virulence to WT levels. We showed by dynamic protein radiolabeling that LLO synthesis was growth phase-dependent. These data provide a mechanism to explain how the bacteria regulate translation of LLO to promote translation during starvation in a phagosome while repressing it during growth in the cytosol. These studies also provide a molecular explanation for codon bias at the 5' end of this essential determinant of pathogenesis.
              Cover page: Secondary structure of the mRNA encoding listeriolysin O is essential to establish the replicative niche of L. monocytogenes
              • Article
              • Peer Reviewed
              LBL Publications (2021)
              Delivery of proteins into walled plant cells remains a challenge with few tractable solutions. Recent advances in biomacromolecule delivery using nanotechnology may evince methods to be exploited for protein delivery. While protein delivery remains no small feat, even in mammalian systems, the ability for nanoparticles to penetrate the cell wall and be decorated with a plethora of functional moieties makes them ideal protein vehicles in plants. As advances in protein biotechnology accelerate, so does the need for commensurate delivery systems. However, the road to nanoparticle-mediated protein delivery is fraught with challenges in regard to cell wall penetration, intracellular delivery, endosomal escape, and nanoparticle chemistry and design. The dearth of literature surrounding protein delivery in walled plant cells hints at the challenge of this problem but also indicates vast opportunity for innovations in plant-tailored nanotechnology.
                Cover page: Nanoparticles for protein delivery in planta.
                • Article
                • Peer Reviewed
                UCLA Previously Published Works (2009)
                A congenitally narrow cervical spinal canal has been established as an important risk factor for the development of cervical spondylotic myelopathy. However, few reports have described the mechanism underlying this risk. In this study, we investigate the relationship between cervical spinal canal narrowing and pathological changes in the cervical spine using positional magnetic resonance imaging (MRI). Two hundred and ninety-five symptomatic patients underwent cervical MRI in the weight-bearing position with dynamic motion (flexion, neutral, and extension) of the cervical spine. The sagittal cervical spinal canal diameter and cervical segmental angular motion were measured and calculated. Each segment was assessed for the extent of intervertebral disc degeneration and cervical cord compression. Based on the sagittal canal diameter, the subjects were classified into three groups: A, subjects with a congenitally narrow canal, diameter of less than 13 mm; B, subjects with a normal canal, diameter of 13–15 mm; C, subjects with a wide canal, diameter of more than 15 mm. When compared with Groups A and B, the disc degeneration grades at the C3-4, C5-6, and C6-7 segments and the cervical cord compression scores at the C3-4 and C5-6 segments showed significant differences. Additionally, when compare with Groups A and C, the disc degeneration grades at all segments, except C2-3, and the cervical cord compression scores at all segments, except C2-3, showed significant differences. With respect to the cervical kinematics, few differences in the kinematics were observed between Groups B and C, however, the kinematics in Group A was different with other two groups. In Group A, the segmental mobility at the C4-5 and C6-7 segments were significantly higher than those observed in Group B, and the segmental mobility at the C3-4 segment was significantly lower than that observed in Groups B or C. We demonstrated the unique pathological and kinematic traits of cervical spine that exist in a congenitally narrow canal. We hypothesize that kinematic trait associated with a congenitally narrow canal may greatly contribute to pathological changes in the cervical spine. Our results suggest that cervical spinal canal diameter of less than 13 mm may be associated with an increased risk for development of pathological changes in cervical intervertebral discs. Subsequently, the presence of a congenitally narrow canal can expose individuals to a greater risk of developing cervical spinal stenosis.
                  Cover page: The relationship between the cervical spinal canal diameter and the pathological changes in the cervical spine
                  • Article
                  • Peer Reviewed
                  UC Davis Previously Published Works (2020)
                  Tools for standardizing patient care can take many forms, including but not limited to, bundles, quality improvement and performance measures, guidelines, and protocols. Each is intended to improve compliance with interventions believed to be supported by the best available evidence, ensuring consistency of management across all patients with the ultimate goal of improving outcomes. However, in the ICU, patients typically present with complex acute illnesses and accompanying comorbidities, requiring careful tailoring of interventions and treatments for each individual patient. The rapidly changing nature of the underlying conditions also demands continuous reassessment and modification of each patient’s management on a frequent and sometimes moment-by-moment basis. Disrupting this individualized treatment approach by imposing prescriptive, overly restrictive, “one-size-fits-all” standardized treatments in the critical care setting may prevent the clinician from meeting individual patients’ needs and decrease care quality (1). This problem is compounded if the standardization tools adopted are not only inflexible but also have a poorly supported or entirely absent scientific basis. Importantly, identifiable patient subcategories often exist that fit poorly into the populations for which many interventions were developed and tested. Of equal concern, critical care trainees may become dependent on a standardized/cookbook approach to care and fail to recognize and learn how treatments must be tailored for the unique needs of each critically ill patient. Rather than rigidly standardizing critical care, approaches that recognize this complexity and are both scientifically sound and responsive to patient differences should be readily available to critical care clinicians without replacing sensible clinical judgment. Such strategies that acknowledge the limitations of available evidence hold more hope of improving, rather than inadvertently worsening, the outcome.
                    Cover page: Individualized Care Is Superior to Standardized Care for the Majority of Critically Ill Patients.
                    • Article
                    • Peer Reviewed
                    UC Riverside Previously Published Works (2013)
                    RNAi-mediated antiviral immunity in Caenorhabditis elegans requires Dicer-related helicase 1 (DRH-1), which encodes the helicase and C-terminal domains homologous to the mammalian retinoic acid inducible gene I (RIG-I)-like helicase (RLH) family of cytosolic immune receptors. Here we show that the antiviral function of DRH-1 requires the RIG-I homologous domains as well as its worm-specific N-terminal domain. We also demonstrate that the helicase and C-terminal domains encoded by either worm DRH-2 or human RIG-I can functionally replace the corresponding domains of DRH-1 to mediate antiviral RNAi in C. elegans. Notably, substitutions in a three-residue motif of the C-terminal regulatory domain of RIG-I that physically interacts with viral double-stranded RNA abolish the antiviral activity of C-terminal regulatory domains of both RIG-I and DRH-1 in C. elegans. Genetic analysis revealed an essential role for both DRH-1 and DRH-3 in C. elegans antiviral RNAi targeting a natural viral pathogen. However, Northern blot and small RNA deep sequencing analyses indicate that DRH-1 acts to enhance production of viral primary siRNAs, whereas DRH-3 regulates antiviral RNAi by participating in the biogenesis of secondary siRNAs after Dicer-dependent production of primary siRNAs. We propose that DRH-1 facilitates the acquisition of viral double-stranded RNA by the worm dicing complex for the subsequent processing into primary siRNAs. The strong parallel for the antiviral function of RLHs in worms and mammals suggests that detection of viral double-stranded RNA may activate completely unrelated effector mechanisms or, alternatively, that the mammalian RLHs have a conserved activity to stimulate production of viral siRNAs for antiviral immunity by an RNAi effector mechanism.
                      Cover page: Homologous RIG-I-like helicase proteins direct RNAi-mediated antiviral immunity in C. elegans by distinct mechanisms.
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