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Skin wounds can be caused by traumatic lacerations or incisions which disrupt the structural and functional integrity of the skin. Wound closure and primary intention treatment of the wound as soon as possible is crucial to avoid or minimize the risk of infection that can result in a compromised healing rate or advanced functional intricacy. The gold standard treatment for skin wound healing is suturing. Light-activated tissue sealing is an appealing alternative to sutures as it seals the wound edges minimizing the risk of infection and scarring, especially when utilized along with biodegradable polymeric biomaterials in the wound bed. Silk fibroins can be used as a biodegradable biomaterial that possesses properties supporting cell migration and proliferation in the tissue it interacts with. In addition, histamine treatment is shown to have extensive effects on cellular functions promoting wound healing. Here, the evaluation of Laser-activated Sealants (LASE) consisting of silk fibroin films induced with Indocyanine Green dye in a wound sealed with laser in the presence of Histamine receptor agonists H1R, H2R and H4R take place. The results were evaluated using Trans-epidermal Water Loss (TEWL), histological and analytical techniques where immune cell biomarkers Arginase-1, Ly6G, iNOS, Alpha-SMA, Proliferating Cell Nuclear Antigen (PCNA), and E-Cadherin were used to study the activity of specific cells such as macrophages, neutrophils, and myofibroblasts that aid in wound healing. PBS was used as a control for histamine receptor agonists. It was found that TEWL increased when treated with H1 receptor agonists while decreasing significantly in H2R and H4R-treated wounds. Arginase-1 activity improved, while it displayed an inverse relationship compared to iNOS. H4R agonist escalated Alpha-SMA cells, while others did not have any significant difference. Ly6G activity depleted in all histamine agonists significantly, while PCNA and E-Cadherin failed to show a positive or negative effect.
ContributorsPatel, Dirghau Manishbhai (Author) / Rege, Kaushal (Thesis advisor) / Massia, Stephen (Committee member) / Brafman, David (Committee member) / Arizona State University (Publisher)
Created2022
Description
This dissertation focuses on the endogenous conceptualization of development and sustainability emerging from settled non-native indigenous communities in the transborder region of Baja California, México. The study is comprised of interview data collected from a sample of 19 (n=19) self-identifying non-native indigenous community members and three key informants residing in various municipalities of the state. The purpose of this research is twofold, on the one hand, it aims to highlight the ways global north conceptualizations and praxis of development and sustainability in México have failed to include indigenous communities and fall short of creating feasible or appropriate practices of development and sustainability for marginalized communities. On the other, it focuses on the future perspectives of non-native indigenous communities to understand what development and sustainability look like for marginalized indigenous communities in México. The research finds that non-native indigenous communities’ settled in Baja California align more closely with the notion of Buen Vivir than development, in efforts to implement holistic approaches to progress and the conservation of their ethnic identity, culture and funds of knowledge. Additionally, the data reveals the bordering processes within ethnic and cultural scapes in Baja California’s society incentivizes merging funds of knowledge to achieve community recognition and progress. In essence, the experience and mobilization of settled non-native indigenous communities in Baja California break the perceived dichotomy between rural and urban, traditional and modern. The research also has some auxiliary findings: (1) indicating that in the state of Baja California the proliferation of development and sustainability discourses are polarized and relatively neglected in public discourses, despite its close transborder relationship with the US and growing concerns of development and sustainability in the northern nation. Second, indigenous women have been and continue to be important catalysts in community formation and representation.
ContributorsMora-Castillo, Brenda (Author) / Cruz-Torres, Maria l (Thesis advisor) / Wutich, Amber (Committee member) / Manuel-Navarrete, David (Committee member) / Arizona State University (Publisher)
Created2022
Description
The advent of CRISPR/Cas9 revolutionized the field of genetic engineering and gave rise to the development of new gene editing tools including prime editing. Prime editing is a versatile gene editing method that mediates precise insertions and deletions and can perform all 12 types of point mutations. In turn, prime editing represents great promise in the design of new gene therapies and disease models where editing was previously not possible using current gene editing techniques. Despite advancements in genome modification technologies, parallel enrichment strategies of edited cells remain lagging behind in development. To this end, this project aimed to enhance prime editing using transient reporter for editing enrichment (TREE) technology to develop a method for the rapid generation of clonal isogenic cell lines for disease modeling. TREE uses an engineered BFP variant that upon a C-to-T conversion will convert to GFP after target modification. Using flow cytometry, this BFP-to-GFP conversion assay enables the isolation of edited cell populations via a fluorescent reporter of editing. Prime induced nucleotide engineering using a transient reporter for editing enrichment (PINE-TREE), pairs prime editing with TREE technology to efficiently enrich for prime edited cells. This investigation revealed PINE-TREE as an efficient editing and enrichment method compared to a conventional reporter of transfection (RoT) enrichment strategy. Here, PINE-TREE exhibited a significant increase in editing efficiencies of single nucleotide conversions, small insertions, and small deletions in multiple human cell types. Additionally, PINE-TREE demonstrated improved clonal cell editing efficiency in human induced pluripotent stem cells (hiPSCs). Most notably, PINE-TREE efficiently generated clonal isogenic hiPSCs harboring a mutation in the APOE gene for in vitro modeling of Alzheimer’s Disease. Collectively, results gathered from this study exhibited PINE-TREE as a valuable new tool in genetic engineering to accelerate the generation of clonal isogenic cell lines for applications in developmental biology, disease modeling, and drug screening.
ContributorsKostes, William Warner (Author) / Brafman, David (Thesis advisor) / Jacobs, Bertram (Committee member) / Lapinaite, Audrone (Committee member) / Tian, Xiaojun (Committee member) / Wang, Xiao (Committee member) / Arizona State University (Publisher)
Created2022
Description
The impact of undergraduate research experiences (UREs) is supported by evidence from physical and life science fields, especially when student-apprentices work in traditional laboratories. Within social sciences specifically, some excellent student outcomes associated with UREs adhere to non–lab-based modalities like course-based research experiences (CUREs). Here, the authors evaluate the laboratory-based undergraduate research experiences (LUREs) as a potentially valuable approach for incorporating social science undergraduates in research. Using comparative analysis of survey data from students completing three types of social science-based UREs (n = 235), individual research experiences (IREs), CUREs, or LUREs, students perceived gains overall regardless of the type of experience, with some indication that LUREs are the most effective.
ContributorsRuth, Alissa (Author) / Brewis, Alexandra (Author) / Beresford, Melissa (Author) / Smith, Michael E. (Author) / Stojanowski, Christopher (Author) / Wutich, Amber (Author)
Created2023-11-13
Description
The purpose of this investigation was to evaluate the influence of tap water safety perceptions on plain water intake (PWI) and hydration status in US Latinx adults. Participants (n=492; age, 28±7 y; 37.4% female) completed an Adapted Survey of Water Issues in Arizona and household watersecurity experience-based scales. A sub-sample (n=55; age, 33±14 y; body mass index, 27.77±6.60 kg·m2) completed dietary recalls on two weekdays and one weekend day via Automated Self-Administered 24-hour Dietary Assessment Tool to determine average PWI and total water intake (TWI). A 24-h urine sample was collected on one recall day and analyzed for urine osmolality (UOsm). Binary logistic regression determined odds ratios (OR) for the odds of perceiving tap water to be unsafe. Hierarchical linear regression was employed with 24-h UOsm and PWI as primary outcomes for the sub-sample. Overall, 51.2% of all participants and 52.7% of the sub-sample mistrust their tap water safety. The odds of mistrusting tap water were significantly greater (P<0.05) for each additional favorable perception of bottled over tap water (OR=1.94, 95% CI=1.50, 2.50), each additional negative home tap water experience (OR=1.32, 95% CI=1.12, 1.56), each additional use of alternatives and/or modifications to home tap water (OR=1.25, 95% CI=1.04, 1.51), and decreased water quality and acceptability (OR=1.21, 95% CI=1.01, 1.45). The odds of mistrusting tap water were significantly lower (P<0.05) for those whose primary source of drinking water is the public supply (municipal) (OR=0.07, 95% CI=0.01, 0.63) and for those with decreased water access (OR=0.56, 95% CI=0.48, 0.66). There were no differences (n=55, P>0.05) in TWI (2,678±1,139 mL), PWI (1,357±971), or 24-h UOsm (460±234 mosm·kg-1). Tap water safety perceptions did not significantly explain variance in PWI or 24-h UOsm (P > 0.05). In conclusion, Latinx mistrust in tap water safety is prevalent. Mistrust appears to be influenced by organoleptic perceptions and to lead to reliance on alternatives to the home drinking water system. Perceptions of tap water safety do not appear to be related to PWI, TWI, or hydration status in Latinx adults.
ContributorsColburn, Abigail (Author) / Kavouras, Stavros (Thesis advisor) / Buman, Matthew (Committee member) / Ohri-Vachaspati, Punam (Committee member) / Vega-Lopez, Sonia (Committee member) / Wutich, Amber (Committee member) / Arizona State University (Publisher)
Created2022
Description
Ecology has been an actively studied topic recently, along with the rapid development of human microbiota-based technology. Scientists have made remarkable progress using bioinformatics tools to identify species and analyze composition. However, a thorough understanding of interspecies interactions of microbial ecosystems is still lacking, which has been a significant obstacle in the further development of related technologies. In this work, a genetic circuit design principle with synthetic biology approaches is developed to form two-strain microbial consortia with different inter-strain interactions. The microbial systems are well-defined and inducible. Co-culture experiment results show that our microbial consortia behave consistently with previous ecological knowledge and thus serves as excellent model systems to simulate ecosystems with similar interactions. Colony patterns also emerge when co-culturing multiple species on solid media. With the engineered microbial consortia, image-processing based methods were developed to quantify the shape of co-culture colonies and distinguish microbial consortia with different interactions. Factors that affect the population ratios were identified through induction and variations in the inoculation process. Further time-lapse experiments revealed the basic rules of colony growth, composition variation, patterning, and how spatial factors impact the co-culture colony.
ContributorsChen, Xingwen (Author) / Wang, Xiao (Thesis advisor) / Kuang, Yang (Committee member) / Tian, Xiaojun (Committee member) / Brafman, David (Committee member) / Plaisier, Christopher (Committee member) / Arizona State University (Publisher)
Created2022
Description
Climate change is a threat to food security and food system stability, especially towards small islands. Climate change is increasing the frequency of extreme weather events, further putting island rural farming communities at greater risk for reduced crop yields and food insecurity. Puerto Rico’s dependence on food imports exacerbates vulnerabilities during natural disasters including reduced food quality, rural impoverishment, and periodic food insecurity. Despite these vulnerabilities, Puerto Rican farmers serve as cultural emblems within their community, providing fresh foods in times of disaster when federal aid was not available. There is very limited research focusing on how the informal social structures of these rural communities contribute to community-level disaster preparedness and mitigation strategies. Since the devastating Hurricane Maria in 2017, there has been little literature focusing on increasing rural farming community resilience against natural disasters like hurricanes in Puerto Rico. Using literature mapping software, this scoping review identifies a very limited existing set of research concerning adaptive capacity strategies in rural farming communities in Puerto Rico since 2017, discusses the strengths and weaknesses of aid organizations like the Southern Sustainable Agricultural Research and Education grant in Utuado, Puerto Rico, and suggests value in additional focused research specific to identifying how communities implement disaster preparedness and mitigation strategies.
ContributorsCastro, Andrea (Author) / Brundiers, Katja (Thesis director) / Wutich, Amber (Committee member) / Barrett, The Honors College (Contributor) / School of Sustainability (Contributor) / School of Human Evolution & Social Change (Contributor)
Created2023-05
Description
Annually, approximately 1.7 million people suffer a traumatic brain injury (TBI) in the United States. After initial insult, a TBI persists as a series of molecular and cellular events that lead to cognitive and motor deficits which have no treatment. In addition, the injured brain activates the regenerative niches of the adult brain presumably to reduce damage. The subventricular zone (SVZ) niche contains neural progenitor cells (NPCs) that generate astrocytes, oligodendrocyte, and neuroblasts. Following TBI, the injury microenvironment secretes signaling molecules like stromal cell derived factor-1a (SDF-1a). SDF-1a gradients from the injury contribute to the redirection of neuroblasts from the SVZ towards the lesion which may differentiate into neurons and integrate into existing circuitry. This repair mechanism is transient and does not lead to complete recovery of damaged tissue. Further, the mechanism by which SDF-1a gradients reach SVZ cells is not fully understood. To prolong NPC recruitment to the injured brain, exogenous SDF-1a delivery strategies have been employed. Increases in cell recruitment following stroke, spinal cord injury, and TBI have been demonstrated following SDF-1a delivery. Exogenous delivery of SDF-1a is limited by its 28-minute half-life and clearance from the injury microenvironment. Biomaterials-based delivery improves stability of molecules like SDF-1a and offer control of its release.
This dissertation investigates SDF-1a delivery strategies for neural regeneration in three ways: 1) elucidating the mechanisms of spatiotemporal SDF-1a signaling across the brain, 2) developing a tunable biomaterials system for SDF-1a delivery to the brain, 3) investigating SDF-1a delivery on SVZ-derived cell migration following TBI. Using in vitro, in vivo, and in silico analyses, autocrine/paracrine signaling was necessary to produce SDF-1a gradients in the brain. Native cell types engaged in autocrine/paracrine signaling. A microfluidics device generated injectable hyaluronic-based microgels that released SDF-1a peptide via enzymatic cleavage. Microgels (±SDF-1a peptide) were injected 7 days post-TBI in a mouse model and evaluated for NPC migration 7 days later using immunohistochemistry. Initial staining suggested complex presence of astrocytes, NPCs, and neuroblasts throughout the frontoparietal cortex.
Advancement of chemokine delivery was demonstrated by uncovering endogenous chemokine propagation in the brain, generating new approaches to maximize chemokine-based neural regeneration.
ContributorsHickey, Kassondra (Author) / Stabenfeldt, Sarah E (Thesis advisor) / Holloway, Julianne (Committee member) / Caplan, Michael (Committee member) / Brafman, David (Committee member) / Newbern, Jason (Committee member) / Arizona State University (Publisher)
Created2021
Description
Introduction: Often it is presumed that in high-income countries, like the United States, water insecurity is not an issue. Yet, more than 2 million individuals in the United States are affected by water insecurity. Experiencing the effects of water insecurity are informal settlements and impoverished communities termed as “colonias”, characterized by the lack of possessing basic infrastructures and services, including water systems and wastewater disposal amongst many. Purpose: To critically analyze how water insecurity manifests in the colonias and the impacts it has on the health and well-being of the community members.
Methods: An extensive systematic literature review was conducted in the effort to bring a meaningful framework of existing challenges and potential resolutions and theorize water insecurity in colonias.
Results: The effects of water insecurity due to water scarcity and water contamination in the colonias led to health complications, unsanitary living conditions and mental distress for residents. The causes of water insecurity in the colonias were because of political exclusion, municipal underbounding and the failure to monitor water quality.
Conclusion: The dire consequences of household water insecurity to an individual, no less an entire population, are detrimental to health and well-being. Despite this acknowledgement of a critical and basic human necessity, literature reveals a robust water governance infrastructure is much needed for the people in colonias. For meaningful progress and developments to be made in addressing water insecurity for the people of colonias, this review was approached through a transdisciplinary lens - one that achieves convergence.
ContributorsPatwoary, Nargish (Author) / Wutich, Amber (Thesis advisor) / Sabo, John (Thesis advisor) / Roque, Anais (Committee member) / Arizona State University (Publisher)
Created2021
Description
The RNA editing enzyme adenosine deaminase acting on double stranded RNA 2 (ADAR2) converts adenosine into inosine in regions of double stranded RNA. Here, it was discovered that this critical function of ADAR2 was dysfunctional in amyotrophic lateral sclerosis (ALS) mediated by the C9orf72 hexanucleotide repeat expansion, the most common genetic abnormality associated with ALS. Typically a nuclear protein, ADAR2 was localized in cytoplasmic accumulations in postmortem tissue from C9orf72 ALS patients. The mislocalization of ADAR2 was confirmed using immunostaining in a C9orf72 mouse model and motor neurons differentiated from C9orf72 patient induced pluripotent stem cells. Notably, the cytoplasmic accumulation of ADAR2 coexisted in neurons with cytoplasmic accumulations of TAR DNA binding protein 43 (TDP-43). Interestingly, ADAR2 overexpression in mammalian cell lines induced nuclear depletion and cytoplasmic accumulation of TDP-43, reflective of the pathology observed in ALS patients. The mislocalization of TDP-43 was dependent on the catalytic activity of ADAR2 and the ability of TDP-43 to bind directly to inosine containing RNA. In addition, TDP-43 nuclear export was significantly elevated in cells with increased RNA editing. Together these results describe a novel cellular mechanism by which alterations in RNA editing drive the nuclear export of TDP-43 leading to its cytoplasmic mislocalization. Considering the contribution of cytoplasmic TDP-43 to the pathogenesis of ALS, these findings represent a novel understanding of how the formation of pathogenic cytoplasmic TDP-43 accumulations may be initiated. Further research exploring this mechanism will provide insights into opportunities for novel therapeutic interventions.
ContributorsMoore, Stephen Philip (Author) / Sattler, Rita (Thesis advisor) / Zarnescu, Daniela (Committee member) / Brafman, David (Committee member) / Van Keuren-Jensen, Kendall (Committee member) / Mangone, Marco (Committee member) / Arizona State University (Publisher)
Created2021