Life Sciences Commons^™

Ultrafine Black Carbon: A Cumulative Assessment On The Physiology Of Lung - Derived Cells, M Esther Salinas

Open Access Theses & Dissertations

Combustion-derived nanomaterials are noxious ultrafine (<100 nm) aerosolized by-products generated by human activity. They pose threats to pulmonary health due to their small size, allowing them to penetrate deep into the alveolar regions causing detrimental responses downstream. Indeed, an examination between nanocarbon particle exposure and poor pulmonary health via cellular behavior was needed. I hypothesized that low-dose and long-term administrations of carbonaceous nanoparticles contribute to respiratory conditions by irritating lung-derived cells. Responses to ultrafine black carbon (UBC), a key component of airborne pollutants, by human lung A549 and murine lung LA4 epithelial cells, human peripheral-blood monocytes THP1, and murine macrophages RAW264.7 were investigated. These lines were chosen because epithelial cells and mononuclear cells (monocytes and macrophages) are the first to come in contact with inhaled particulate matter (PM) and contribute to stress and inflammation of pulmonary tissues. The cells were first plated on day zero and fed fresh UBC suspended in culture media on days one, four, and seven. The exposure regimen included three different low-level concentrations of UBC. On day ten, all cells were prepared for subsequent assays. Effects on cellular viability revealed that UBC was modestly cytotoxic while ATPase and esterase activity (termed enzyme vitality for the purpose of this study) were significantly diminished in a dose-dependent manner. Additionally, beta-galactosidase proportionally increased with UBC concentration compared to untreated cells, indicating that cellular senescence was promoted across all cell types. Multiple markers of oxidative stress were subsequently measured, showing non-uniform trends and displaying moderate accumulation of oxidative damage, contingent upon cell line and UBC treatment. However, a significant induction of inner mitochondrial membrane depolarization of human UBC-treated cells was observed; an aberrant cell-cycle progression was found across all cells. The implemented regimen of UBC exposure elicited an imbalance of free (reduced) glutathione, altered mitochondrial potential, and abnormal cell-cycle activity. This method demonstrated that modifications across both species induced changes to cellular fitness overall. The data supported that compounding nanosized black carbon exposure could negatively affect overall pulmonary cell health by distinctively modifying intracellular activity. Additionally, we further surmised that sustained exposure to nanocarbon could impair innate immunity. Therefore, reactive oxygen species (ROS), reactive nitrogen species (RNS), and cytokine levels upon continuous administrations to 3.0 μg/mL UBC after brief challenges to microbial proxies were assessed; on day 9, the cells were succumbed to three different microbial insults (LPS, Poly I:C, and Zymosan). On day 10, measurements demonstrated a moderate accumulation of oxidative stress, conditional to each cell type. Thus, UBC plus microbe approach triggered pro-oxidant levels and cytokine production across different cell types and diminished phagocytic response by murine macrophages. Based on the results, ultrafine-PM exposure may impair inflammatory function in response to pathogenic infections. In summation, our findings indicated that additive nanosized UBC in combination with microbe-like challenges may compromise cellular behavior, suggesting potential ways by which inhalation of ultrafine-PM may contribute to or exacerbate poor pulmonary health.

Dust Storms And The Dispersal Of Aquatic Invertebrates In The Chihuahuan Desert Ecoregion, Jose Rivas Jr.

Open Access Theses & Dissertations

The Chihuahuan Desert surrounding El Paso, Texas is one of the most intense sources of dust in the Western Hemisphere. Within this vast desert are ephemeral wetlands with micrometazoan propagules contained within their sediment egg banks. Dispersal of aquatic microinvertebrates between habitats is vital for the success of their populations. Passive dispersal of the propagules provides an escape mechanism from unfavorable conditions. Upon desiccation of these habitats, windstorms can potentially transport propagules mixed within entrained sediments across regional scales. To study this process, I collected falling sediment from 91 windstorms, with 59 samples collected at the University of Texas at …

Assessing Rotifer Diversity In Desert Wetlands Through Sediment Rehydration And Amplicon Sequencing, Sergio David Samaniego

Open Access Theses & Dissertations

Species living in temporary wetlands can be threatened due to the instability and fluctuation of rising temperatures and evaporation caused by global climate change. In addition, regions characterized by dry climates, where most temporary wetlands exist, are expected to have a stronger response to climate change than other ecosystems. While most organisms are not able to respond to rapid changes in their environments, others like freshwater invertebrates have shown great resiliency to short- and long-term ecological disturbances. Rotifers for example, inhabit temporary waters that remain desiccated for indefinite periods of time making assessment of rotifer biodiversity challenging. Fortunately, many microinvertebrates …

Movement Ecology Of A Cryptic Ambush Predator: Integrating Radio Telemetry And Tri-Axial Accelerometry To Evaluate Spatial Strategies And Activity Patterns By Western Diamond-Backed Rattlesnakes (Crotalus Atrox), Dominic L. Desantis

Open Access Theses & Dissertations

An animal's decision to move from one location to another within its environment is determined by a complex blend of internal and external factors. Teasing apart the relative roles of specific variables in this web of interacting mechanisms has been a long-standing challenge in animal movement ecology. Historically, this problem was viewed as a sort of black box for which a myriad of methodological limitations precluded rigorous study. Recently, a diversity of animal-borne transmitters and dataloggers (i.e., bio-loggers) have circumvented many of these traditional limitations and transformed field studies of animal movement, behavior, and physiology - in some cases, allowing …

Evaluation Of Ctla-4 Blockage Therapy With Metronomic Chemotherapy For The Treatment Of Preclinical Breast Cancer, Karla Parra

Open Access Theses & Dissertations

Background Although there are reports that metronomic cyclophosphamide can be immune stimulating, the impact of its combination with anti-CTLA-4 immunotherapy for the treatment of cancer remains to be evaluated.

Methods Murine EMT-6/P breast cancer, or its cisplatin or cyclophosphamide (CTX) resistant variants, or CT-26 colon, were implanted into Balb/c mice. Established tumors were monitored for relative growth following treatment with anti-CTLA-4 antibody alone or in combination with; a) metronomic CTX (ldCTX; 20mg/kg/day), b) Bolus (150mg/kg) plus ldCTX, or c) sequential treatment with gemcitabine (160mg/kg every 3 days).

Results EMT-6/P tumors responded to anti-CTLA-4 therapy, but this response was less effective …

Molecular Mechanism Of Neurodegeneration Induced By 4-Nonylphenol, Michelle Alejandra Aranda

Open Access Theses & Dissertations

Neurodegeneration, a progressive loss of nerve cells, occurs in many neurological disorders, including Alzheimer's disease (AD) and Parkinson's diseases (PD), as well as in dementia. The pathogenesis of these diseases is unknown, and recent evidence suggests that environmental factors, which act as endocrine-disrupting compounds (EDCs) could play a significant role in developing the disease process. 4-Nonylphenol (4-NP), an EDC, and a ubiquitous environmental toxin has been shown to affect brain development and may cause neurodegeneration. 4-NP is produced in large quantities in the U.S. and used as raw materials for making detergents, pesticides, plastics, paints, cosmetics, rubber, and other industrial/household …

Shining Light On An Amygdala -- Brainstem Connection Important For Attention Processing, Jose Carlos Cano

Open Access Theses & Dissertations

We are continuously being exposed to an exorbitant amount of sensory information, which should result overwhelming. However, the nervous system operates several intrinsic sensory filtering mechanisms that allow us to cope with such sensory cluttering and shape appropriate behavior. Sensorimotor gating is a pre-attentive neuronal filtering mechanism that gates superfluous sensory information, and orients attentional resources towards salient information processing. Its relevance becomes in individuals suffering from schizophrenia and several otherwise unrelated neuropsychiatric disorders where sensorimotor gating is impaired. To understand the neural impaired mechanisms, extensive research studies have focused on first identifying the neural substrates underlying sensorimotor gating. This …

The Role Of P62/Imp2 In Hepatocellular Carcinoma Progression, Mengtao Xing

Open Access Theses & Dissertations

The family of insulin- like growth factor 2 mRNA binding proteins (IMPs) contains three members: IMP1, p62/IMP2 and IMP3. All these proteins are oncofetal proteins, expressed during embryogenesis and lost in most tissues in adults. However, p62/IMP2 were found overexpressed in various cancers but its function in carcinogenesis remains to be investigated. Our previous studies found that p62/IMP2 was not only overexpressed in hepatocellular carcinoma (HCC) tissues, but also overexpressed in HCC cell lines. To explore the biological roles of p62/IMP2 in HCC progression, p62/IMP2 was knockout in two p62/IMP2 positive HCC cell lines (SNU449, HepG2). Due to the low …

Serosurvey For Evidence Of Dengue And West Nile Virus Human Infections In El Paso, Texas, Veronica Suarez

Open Access Theses & Dissertations

Dengue viruses (DENV), including the 4 serotypes are the cause of dengue fever and dengue hemorrhagic fever. The viruses are transmitted by Aedes aegypti mosquitoes in urban communities in tropical, sub-tropical, and temperate regions and are the cause of the highest rate of infection and death of all known Flaviviruses. DENV are endemic in United States (US) -Mexico (MX) border communities in the Rio Grande Valley and suspected of being endemic in Ciudad Juarez, a sister city to El Paso, TX. To determine if DENV were endemic in the El Paso community, cord-blood samples from mothers were tested for antibody …

Recent Changes In The Zooplankton Communities Of Arctic Tundra Ponds In Response To Warmer Temperatures And Nutrient Enrichment, Mariana Vargas Medrano

Open Access Theses & Dissertations

Warming is altering Arctic freshwater ecosystems, enriching the water column, increasing primary productivity and shifting the composition, dominance and the timing of emergence and reproduction of zooplankton communities. Historic data from arctic tundra ponds near UtqiaÄ¡vik, AK have given us valuable insight into changes that have occurred in recent times. A change of dominance from cyclopoid copepods to Daphnia middendorffiana has occurred over a 40 year period. Daphnia are more common, abundant and larger, which may be explained by increased primary productivity stimulated by nutrient release from permafrost thaw. Copepods and fairy shrimp emerged earlier from the overwintering states, which …

Hspg2 Mediates Mandibular Jaw Joint Development, Barbara Samantha Castellanos

Open Access Theses & Dissertations

We present a patient diagnosed with a multiple congenital anomaly syndrome characterized by scoliosis, intellectual disabilities, and craniofacial defects. Trio-based whole exome sequencing identified compound heterozygous variants in the HSPG2 gene: a maternally inherited c.5998-7A>G variant in the promoter region and a paternally inherited c.4916C>T variant in the coding sequence. HSPG2 encodes for perlecan, a large proteoglycan that plays an important role in cartilage formation, cell adhesion, and basement membrane stability. Mutations in HSPG2 have been associated with Schwartz-Jampel syndrome and Dyssegmental Dysplasia Silverman-Handmaker Type, two disorders characterized by skeletal abnormalities (1). These data indicate a function for …

Trypanosoma Cruzi Trypomastigote Glycosylphosphatidylinositol-Anchored Mucins And A Synthetic Alpha-Gal-Containing Neoglycoprotein As Potential Biomarkers And Vaccines For Chagas Disease, Igor Leandro Estevao

Open Access Theses & Dissertations

Chagas disease (CD), caused by the protozoan Trypanosoma cruzi, is a neglected tropical disease that kills or permanently disable thousands of people annually. About 6-8 million people are estimated to be infected worldwide. Although many efforts have been made for the development of an effective immunotherapy, currently there is no vaccine to prevent or treat CD in humans. Despite their toxicity, the two current drugs for CD, benznidazole (BZN) and nifurtimox (NFX), have medium-to-high efficacy in the chronic stage of the disease and could save or improve the lives of thousands of patients. However, negative seroconversion in treated patients, as …

Preclinical Models Of Metastatic Disease, Paloma Alejandra Valenzuela

Open Access Theses & Dissertations

Breast cancer is a disease that continues to take the life of approximately 40,000 men and women in the United States each year [1]. Tumor drug resistance represents a major problem for the treatment of many breast cancer patients. The mechanisms underlying such resistance remain to be elucidated, and one approach to study this issue involves the development of tumor drug-resistant breast cancer models in mice. HER-2 positive breast cancer is considered to be one of the most aggressive subtypes of breast cancer and has become a major target for treatment. HER-2 status is a routinely checked marker for breast …

Platelet Biology And Thrombosis: Juul E-Cigarette Exposure And 5ht2a Receptor Drug Discovery, Jean Emmanuel Montes Ramirez

Open Access Theses & Dissertations

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