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Open Access Publications from the University of California

Scholarly Works (5 results)

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TRANSMODERNITY: Journal of Peripheral Cultural Production of the Luso-Hispanic World, Volume 6, Issue 2 (2016)

Post-Apocalyptic Visions: Biopolitics, Late Capitalism, and Trauma in Children of Men and Naked City Spleen

    Cover page: Post-Apocalyptic Visions: Biopolitics, Late Capitalism, and Trauma in Children of Men and Naked City SpleenCreative Commons 'BY' version 4.0 license
    • Thesis
    • Peer Reviewed
    UC San Diego Electronic Theses and Dissertations (2022)

    Chronic heart failure (CHF) and traumatic brain injury (TBI) are among the most commonpathologies that afflict Americans today. While CHF and TBI affect different organs, they share the fact that both patient populations face a great unmet need for a therapeutic that aims to regenerate or preserve organ function. Thus, we investigated the use of two different types of ECM derived biomaterials for the treatment of chronic myocardial infarction (MI) and acute TBI. First, we investigated the efficacy and mechanism of action of an injectable myocardial matrix hydrogel in a chronic model of MI. In these studies, we showed the ability of the matrix to preserve cardiac function as well as its ability to modulate gene expression through methods of medium and high throughput gene expression analyses. Next, we moved onto a new ECM derived biomaterial that isolates the low molecular weight components of a traditional myocardial matrix hydrogel to create an infusible ECM biomaterial (iECM). Applying this iECM in an acute model of TBI, we found that the material can modulate vascular permeability and BBB integrity through methods of in vivo and in vitro assessments. While the iECM was not shown to improve sensorimotor function on rotarod, we did see modulation of the neuroinflammatory response as well as a neuroprotective response via gene expression analyses. These studies together have advanced the understanding of ECM therapeutics in chronic MI as well as shown the importance of BBB and vascular integrity in modulating neuroinflammation in acute TBI using a new type of ECM biomaterial.

      Cover page: Decellularized Extracellular Matrix Therapeutics for the Treatment of Acute and Chronic Injuries
      • Article
      • Peer Reviewed
      UC San Diego Previously Published Works (2023)
      Traumatic brain injury (TBI) affects millions of people each year and, in many cases, results in long-term disabilities. Once a TBI has occurred, there is a significant breakdown of the blood-brain barrier resulting in increased vascular permeability and progression of the injury. In this study, the use of an infusible extracellular matrix-derived biomaterial (iECM) for its ability to reduce vascular permeability and modulate gene expression in the injured brain is investigated. First, the pharmacokinetics of iECM administration in a mouse model of TBI is characterized, and the robust accumulation of iECM at the site of injury is demonstrated. Next, it is shown that iECM administration after injury can reduce the extravasation of molecules into the brain, and in vitro, iECM increases trans-endothelial electrical resistance across a monolayer of TNFα-stimulated endothelial cells. In gene expression analysis of brain tissue, iECM induces changes that are indicative of downregulation of the proinflammatory response 1-day post-injury/treatment and neuroprotection at 5 days post-injury/treatment. Therefore, iECM shows potential as a treatment for TBI.
        Cover page: Infusible Extracellular Matrix Biomaterial Promotes Vascular Integrity and Modulates the Inflammatory Response in Acute Traumatic Brain Injury.
        • Article
        • Peer Reviewed
        UC San Diego Previously Published Works (2023)
        Decellularized extracellular matrix in the form of patches and locally injected hydrogels has long been used as therapies in animal models of disease. Here we report the safety and feasibility of an intravascularly infused extracellular matrix as a biomaterial for the repair of tissue in animal models of acute myocardial infarction, traumatic brain injury and pulmonary arterial hypertension. The biomaterial consists of decellularized, enzymatically digested and fractionated ventricular myocardium, localizes to injured tissues by binding to leaky microvasculature, and is largely degraded in about 3 d. In rats and pigs with induced acute myocardial infarction followed by intracoronary infusion of the biomaterial, we observed substantially reduced left ventricular volumes and improved wall-motion scores, as well as differential expression of genes associated with tissue repair and inflammation. Delivering pro-healing extracellular matrix by intravascular infusion post injury may provide translational advantages for the healing of inflamed tissues 'from the inside out'.
          Cover page: Intravascularly infused extracellular matrix as a biomaterial for targeting and treating inflamed tissues
          • Article
          • Peer Reviewed
          UC Davis Previously Published Works (2016)
          Toxoplasma gondii is among the most prevalent parasites worldwide, infecting many wild and domestic animals and causing zoonotic infections in humans. T. gondii differs substantially in its broad distribution from closely related parasites that typically have narrow, specialized host ranges. To elucidate the genetic basis for these differences, we compared the genomes of 62 globally distributed T. gondii isolates to several closely related coccidian parasites. Our findings reveal that tandem amplification and diversification of secretory pathogenesis determinants is the primary feature that distinguishes the closely related genomes of these biologically diverse parasites. We further show that the unusual population structure of T. gondii is characterized by clade-specific inheritance of large conserved haploblocks that are significantly enriched in tandemly clustered secretory pathogenesis determinants. The shared inheritance of these conserved haploblocks, which show a different ancestry than the genome as a whole, may thus influence transmission, host range and pathogenicity.
            Cover page: Local admixture of amplified and diversified secreted pathogenesis determinants shapes mosaic Toxoplasma gondii genomes
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