Life Sciences Commons^™

Dying Right: Supporting Anti-Cancer Therapy Through Immunogenic Cell Death, Elizabeth Schmitz

Theses & Dissertations

The primary goal of most anti-cancer therapy is to eradicate neoplastic cells. Simultaneously, neoplastic cell death is the first step of the cancer-immunity cycle, which starts with the release of antigens from cancer cells and ends with T-cell directed killing of cancer cells, in addition to long-standing memory to tumor antigens encountered. Immunogenic damage-associated-molecular patterns (DAMPs) are endogenous cell molecules repurposed in times of insurmountable cell stress (e.g., CALR, ATP, HMGB1) to facilitate communication between dying cells and adaptive immune cells, acting as adjuvants for the cancer-immunity cycle, in a cellular fate termed immunogenic cell death (ICD). It …

Targeting Ksr1 To Inhibit Stemness And Therapy Resistance, Heidi M. Vieira

Theses & Dissertations

Tumor heterogeneity is an important contributor to therapy resistance and relapse. Within the tumor, there are subpopulations of tumorigenic, self-renewing cells with enhanced clonogenicity and chemoresistance, termed tumor-initiating cells (TICs). Despite their importance in treatment response, there are no effective therapies to target TICs in solid tumors.

This study identifies a novel role for Kinase Suppressor of Ras 1 (KSR1) in regulating TICs and therapy resistance in Ras-driven cancers. KSR1 is a molecular scaffold in the Raf/MEK/ERK kinase cascade downstream of Ras. KSR1 is necessary for Ras-mediated transformation, but dispensable for normal cell growth; further, ksr1^-/- mice are phenotypically …

Chemotherapy-Induced Modulation Of Tumor Antigen Presentation, Alaina C. Larson

Theses & Dissertations

Pancreatic cancer is a lethal malignancy, with a five-year overall survival rate of just 13%. Current treatment approaches thus require modification and attention has shifted towards improving immunotherapy efficacy. Select chemotherapy drugs possess inherent immunomodulatory activity and could be used to initiate immunotherapeutic success, thereby restoring anti-tumor immunity in pancreatic cancer. In this work, I evaluated the impact of the chemotherapy drug gemcitabine on tumor antigen presentation by human leukocyte antigen class I (HLA-I). Gemcitabine regulated HLA-I expression on multiple levels, increasing pancreatic cancer cells’ HLA-I mRNA transcripts, total protein and surface expression, as well as surface stability. Temperature-dependent assay …

Long-Term Neurodevelopmental Outcomes Post-Chronic Midazolam Exposure During Early Life, Nghi M. Nguyen

Theses & Dissertations

In recent decades, the rising number of neonates born in the Neonatal Intensive Care Unit (NICU) due to prematurity has raised concerns about their overall well-being and development. Premature neonates are at higher risk of health complications and often require invasive procedures. These invasive procedures often induce stress and agitation, prompting physicians and healthcare providers to provide sedation or general anesthesia to manage discomfort. Epidemiological studies of human patients have revealed a correlation between childhood exposure to general anesthetic and sedative agents and subsequent cognitive deficits. This association is also supported in animal models, which shows that exposure to anesthetics …

Pharmacokinetics And Tissue Distribution Of A Lipid-Based Extended-Release Nano-Formulation Of Mo-Oh-Nap Tropolone To Enhance Pulmonary Delivery For The Treatment Of Pulmonary Metastatic Osteosarcoma, Wafaa N. Aldhafiri

Theses & Dissertations

Osteosarcoma is the most common primary bone tumor in children and adolescents. Metastasis is prevalent in 25% of patients, at diagnosis, with the lungs being the most common metastatic site. Pulmonary metastatic osteosarcoma is a significant therapeutic challenge with a 5-year survival rate of ≤30%. Patients with pulmonary metastatic disease at diagnosis receive the same standard of care as patients with local disease, which hasn’t changed over the past 30 years. The treatment and prevention of pulmonary metastatic osteosarcoma represents a significant critical and unmet need.

MO-OH-Nap tropolone is a novel small molecule with cytotoxic activity across multiple human osteosarcoma …

Molecular Characterization Of Viral Escape From Art And Crispr Hiv-1 Excision In Infected Humanized Mice, Chen Zhang

Theses & Dissertations

Not available.

Understanding The Role Of Mastl In Colon Homeostasis And Colitis-Associated Cancer Development, Kristina Pravoverov

Theses & Dissertations

Colitis-associated cancer (CAC) is the most devastating complication of longstanding inflammatory bowel disease (IBD). Understanding the mechanisms underlying the switch from damage-repair to dysplasia in IBD is critical for identifying novel therapies to facilitate mucosal healing while mitigating CAC risk. Microtubule-associated serine-threonine kinase-like (MASTL), though crucial in cell growth and repair, is upregulated in sporadic colorectal cancer and CAC. This study sought to delineate the role of MASTL in colitis and CAC development.

First, we examined whether MASTL is associated with colitis and recovery. Review of publicly available data found significant elevation of MASTL and interleukin (IL)-22 in biopsies from …

Role Of Pycr2 In Colorectal Cancer, Raju Lama Tamang

Theses & Dissertations

Despite significant progress in clinical management, colorectal cancer (CRC) remains the 3rd most common cause of cancer-related deaths. A positive association of PYCR2 (Pyrroline-5-carboxylate reductase-2), a terminal enzyme of proline metabolism, with CRC aggressiveness was recently reported including by us. However, how PYCR2 promotes colon carcinogenesis remains ill understood. In our studies, comprehensive in-silico and biochemical evaluations were performed along with genetic manipulations and in-vivo tumor growth assays to gain mechanistic understanding. Results showed that PYCR2 expression was significantly upregulated in CRC and associated with poor patient survival specifically among PYCR isoforms (PYCR-1, -2 and -3). Genetic inhibition of PYCR2 …

Determining If Cx45 Acts As An Arrythmogenic Substrate In The Diseased Myocardium, Stephen R. Sobota

Theses & Dissertations

Proper contraction of the heart relies on gap junction channels (GJCs) composed of Cx40 and Cx43 in the atrial and ventricular tissues which mediate electrical conductance in the working myocardium. Also expressed is Cx45, which is limited to the pacemaker system. Studies in diseased human hypertrophic cardiac tissue have shown expression of Cx45 and decrease of Cx43 in the myocardium. Cx43 and Cx45 in vitro form heterometric GJCs, where the channel characteristics (metabolite transfer, electrical conductance, etc.) resemble those of Cx45. There is little-to-no data showing whether GJCs composed of Cx43 and Cx45 in cardiac hypertrophy result in altered conductance. …

A Comparative Analysis Of Extant Oceanic Shark Species Using Trait-Based Ecology, Elizabeth A. Johnson

All HCAS Student Capstones, Theses, and Dissertations

Over the past few decades, scientists have been working together to mitigate human impacts on global shark populations, but deciding which species need the most immediate attention can be difficult. This study uses a newly emerging approach to ecology, trait-based ecology, to identify trends in trait expression with depth and determine which species have the most unique sets of traits. While trait-based ecology has already been applied to numerous fields, a trait-based approach to shark research is still in its infancy. A total of 15 traits across 337 oceanic shark species were examined to identify trends in trait expression and …

Qtl Mapping For Fatty Acid Composition In Olive Oil Using A High-Density Genetic Map Based On Snp Markers, Ali̇ Can Kaya, Meryem İpek, Ahmet İpek, Mehmet Ali̇ Gündoğdu, Nesri̇n Aktepe Tangu, Sevi̇n Teoman Duran, Murat Şeker, Mustafa Akbulut

Turkish Journal of Agriculture and Forestry

Olive (Olea europaea L.) is an evergreen tree species that grows naturally in regions with Mediterranean climates. Its oil and fruits are commercially valuable. Olive oil contains high levels of omega-9 (oleic acid). Because the high percentage of oleic acid makes olive oil deterioration-resistant, the development of olive varieties containing high oleic acid is one of the major goals of olive breeding programs. Therefore, this study aimed to determine quantitative trait loci (QTL) affecting fatty acid composition of olive oil. Thus, early selection of olive genotypes with a high oleic acid content can be possible. For the determination of QTLs …

Legal Regime Of The Application Process For Gmo Products In Türkiye, Ünal Yildiz, Özgür Temi̇z, Kami̇l Hali̇loğlu, Nesri̇n Yildiz

Turkish Journal of Agriculture and Forestry

In Turkiye, in accordance with EU harmonization laws, Biosafety Act No. 5977 entered into force on 18.09.2010. The basic legislation regarding the application process is composed of the Biosafety Act, Regulations on Genetically Modified Organisms and Their Products, and Regulations on Working Procedures and Principles of Biosafety Board and Committees. Biosafety legislation foresees a special application procedure for GMO food, food products, feed, and other products. The application regulated in the Biosafety Law is a special administrative procedure in nature. The primary objective of this study is to explain the legal regime of this application procedure. While explaining this issue, …

Determination Of Dry Matter Yield, Some Morphological Characteristics And Rootworm Infestation In Local Sainfoin Populations, Zeynep Gül, Mustafa Tan

Turkish Journal of Agriculture and Forestry

Sainfoin (Onobrychis sativa L.) is a valuable forage plant which is drought resistant and has good nutritional value. However, for a long time, some rootworms that damage sainfoin have caused a decrease in its cultivation areas. As a result of many studies, a variety resistant to rootworms has not been developed yet. Local populations are of great importance in the studies to develop resistant varieties. This research was planned to determine the hay yield, forage quality, morphological characteristics and rootworm infestation of local sainfoin genotypes from 6 different villages in Erzurum province of Türkiye. The research was established in 2017 …

Quantitative Variation Of Phenolic Compounds In Different Tissues Of Pistachio(Pistacia Vera L. Cv. Uzun) Associated With Alternate Bearing, Müjgan Güney, Muhammet Ali̇ Gündeşli̇, Murat Güney, Nesi̇be Ebru Kafkas, Sali̇h Kafkas, Zeynep Ergün

Turkish Journal of Agriculture and Forestry

Alternate bearing is a common challenge in horticultural plants, leading to irregular yield in successive years. The potentialrole of phenolic compounds in regulating this phenomenon, however, is not well understood. This study aimed to investigate thepotential role of phenolic compounds in alternate bearing in pistachio trees by analysing samples from different parts of the “Uzun”cultivar over two consecutive years. Seven phenolic compounds (gallic acid, p-coumaric acid, caffeic acid, ferulic acid, chlorogenic acid,catechin, and quercetin) were analysed using high-performance liquid chromatography at 10-day intervals. Significant variations wereobserved in the levels of certain phenolic compounds between “ON” and “OFF” years, suggesting a …

Developing Micropropagation Protocol For Black Mulberry (Morus Nigra L.), Merve Özkul, Nevzat Sevgi̇n, Mehmet Özkul, Neelam Prabha Negi, Sadi̇ye Peral Eyduran, Bi̇rsen Yilmaz, Melekşen Akin

Turkish Journal of Agriculture and Forestry

This study aims to develop a suitable micropropagation protocol for black mulberry, which cannot be easily clonally propagated like other mulberry species. Clonal propagation of this species is gaining importance due to its health benefits and utilization in pharmacology. The effects of culture media and cytokinin types on micropropagation of Morus nigra L. were investigated. Single-axillary bud explants grown on MS, DKW, and NRM containing 0.25 mg/l benzyl adenine (BA) plus 0.01 mg/l indole-3-butyric acid (IBA) were compared to cultures grown on NRM with thidiazuron, metaTopolin (mT) or BA at 1.25, 2.5, 5.0 or 7.5 mg/l plus 0.01 mg/l IBA. …

Biostimulation Effect On Crithmum Maritimum L. Root Development In Controlled Environment, Stefano Zenobi, Marco Fiorentini, Biagio Di Tella, Vesna Milanovic, Andera Marcelli, Luigi Ledda, Paola Antonia Deligios, Lucia Aquilanti, Roberto Orsini

Turkish Journal of Agriculture and Forestry

Biostimulants can find application in sustainable agriculture contexts as they are regarded as inputs with minimal environmental impact. Microbial inoculants, when applied to the root systems of certain plant species, confer physiological and morphological benefits to the entire plant. In the present study, we focused on some morphometric parameters of the root system of two Crithmum maritimum L. spontaneous populations (Mediterranean and Atlantic). We compared the effects of two different (for number of strains) biostimulants on the weight, length, diameter and number of tips on the root system. The experiment was conducted within two types of controlled environments: i) an …

Evaluation Of Turkish Shallot Genetic Resources For Morphological, Biochemical And Sensory Properties, Gülay Beşi̇rli̇

Turkish Journal of Agriculture and Forestry

Shallots, a subspecies of onion, are considered the gourmet onion and are preferred especially in French and Asian cooking. Its unique taste and aroma especially being caramelized through heat treatment increases its importance for boutique restaurants and niche tables. This study examined the morphological, biochemical, and sensory properties of seven generatively (GMSY-2, GMSY-3, GMSY-4, GMSY-5, GMSY-6, GMSY-7, GMSY-8) and one vegetatively propagated (GMSY-1) shallot genotypes in 2021 and 2022. Sixteen morphological and fifteen biometric features of UPOV were used in characterization. Total phenolic content, total antioxidant capacity, and total monomeric anthocyanin and pyruvic acid contents were determined as biochemical markers. …

Novel Mechanisms For The Neural Control Of Breathing In Acute Lung Injury, Kajal Kamra

Theses & Dissertations

Acute lung injury (ALI) triggers inflammation that disrupts the normal alveolar-capillary endothelial barrier, impairing gas exchange and causing hypoxemia, which reflexively increases respiration. An elevated respiratory rate (fR) usually develops within hours to days following ALI. This acute respiratory failure disorder affects approximately 200,000 new cases annually in the US and accounts for 10% of ICU admissions, with high morbidity and mortality. The neural mechanisms underlying respiratory dysfunction post-ALI are not fully understood. My doctoral dissertation aimed to investigate the mediators of abnormal ventilation during ALI. Systemic hypoxia stimulates the carotid body (CB) chemoreflex, a crucial protective reflex that maintains …

Sport And Environmental Issues: Ncaa Division I Student-Athletes’ Personal Experiences, Ivanna M. Anderson-Villela

Master's Theses

While sport ecology is a growing category in sport management literature, there is a lack of research exploring athletes’ experiences regarding environmental issues, and the impacts environmental issues have on student-athletes. The present study qualitatively explored the personal lived experiences of eight NCAA Division I student-athletes regarding environmental issues with the aim of identifying potential influences on values and beliefs through social norms and understanding the student-athlete perspective. Thematic analysis identified 152 raw data themes and 19 higher order themes, which were organized into four central themes: awareness, care and concern from athletic departments, implications, and advocacy. Generally, student-athletes perceived …

Observations Of Currents, Waves, And Turbulence Within A Giant Kelp Forest In Stillwater Cove, Carmel, California, Logan A. Grady

Master's Theses

Nutrient distribution and propagule dispersal within Giant kelp (Macrocystis pyrifera) forests are significantly influenced by turbulence. In-situ measurements of turbulence within giant kelp forests are limited and driving mechanisms are primarily informed by controlled-flume experiments. This study investigates relationships between currents, surface gravity waves, and turbulence within a kelp forest through deployment of moored instrumentation and kelp surveys in Stillwater Cove, California during summer of 2022. Oceanographic conditions were primarily driven by coastal upwelling and a semi-diurnal internal tide, which was associated with cooling events and enhanced onshore velocity within the kelp forest during rising tides. Estimates of gradient Richardson …

Overnight Rice Fermentation: An Analysis Of The Physicochemical Changes In White, Brown, And Enriched Rice Varieties, Kavin Sivakumar

Master's Theses

Fermentation refers to the activity of microorganisms breaking down substrates, resulting in changes to a food product. One fermented food practice from the Indian subcontinent is overnight fermented rice. The traditional preparation consists of covering cooled cooked rice in water and leaving it at room temperature to ferment overnight. The objective of this project was to investigate overnight rice fermentation through quantifying its physicochemical changes. The study utilized three types of rice: white, enriched white, and brown. Mixtures of cooked rice and water at a 1 gram: 2 milliliter ratio were fermented at 29 degrees Celsius and 60% humidity for …

Seasonal Dynamics Of The Introduced Sponge Hymeniacidon Perlevis In The Elkhorn Slough, California, Usa, Jackson Hoeke

Master's Theses

Hymeniacidon perlevis is a cosmopolitan sponge with a seasonal life cycle We investigated seasonal and interannual dynamics of H. perlevis in Elkhorn Slough estuary, where it is an introduced species, and explored correlations between sponge cover and environmental conditions. We used sponge cover to estimate the potential effects H. perlevis on its environment and how those could vary across its seasonal life cycle. We found that successful recruitment is currently restricted to the upper estuary and while it varies annually, the frequency and density of sponge recruits have generally increased from 2007 to 2023. A seasonal life cycle was confirmed …

Agnotology Of The E-Cigarette Industry: How The E-Cigarette Industry Continues The Tobacco Industry's Legacy Of Creating Controversy And Confusion Within The Scientific Community And The General Population, Calvin Lewis

University Honors Theses

The purpose of this paper is to determine the extent to which the e-cigarette industry follows in the footsteps of the tobacco industry's attempts to disrupt science and cause controversy. Four tactics are described that the tobacco industry uses to disrupt science: funding research that is designed to show results that support their position, criticizing and suppressing research that goes against their position, changing risk assessment and scientific research standards to fit their aims, and spreading data created by their interest groups to politicians and the nonacademic press. Evidence is found to show that both the tobacco industry and e-cigarette …

Fungi Benefit Limber Pine And Bristlecone Pine, James A. Lutz, Joseph D. Birch

Wildland Resources Faculty Publications

Results of research in forest health and forest futures in Utah

Inactivated Rabies-Based Lassa Fever Virus Vaccine Candidate Lassarab Protects Nonhuman Primates From Lethal Disease, Gabrielle Scher, Catherine Yankowski, Drishya Kurup, Nicole Josleyn, Eric Wilkinson, Jay Wells, Jesse Steffens, Ginger Lynn, Sean Vantongeren, Xiankun Zeng, Nancy Twenhafel, Kathleen Cashman, Matthias Schnell

Department of Microbiology and Immunology Faculty Papers

Lassa fever virus (LASV), a member of the Arenavirus family, is the etiological agent of Lassa fever, a severe hemorrhagic disease that causes considerable morbidity and mortality in the endemic areas of West Africa. LASV is a rodent-borne CDC Tier One biological threat agent and is on the World Health Organization's (WHO) Priority Pathogen list. Currently, no FDA-licensed vaccines or specific therapeutics are available. Here, we describe the efficacy of a deactivated rabies virus (RABV)-based vaccine encoding the glycoprotein precursor (GPC) of LASV (LASSARAB). Nonhuman primates (NHPs) were administered a two-dose regimen of LASSARAB or an irrelevant RABV-based vaccine to …

Body Length Determines Flow Refuging For Rainbow Trout (Oncorhynchus Mykiss) Behind Wing Dams, Terry R. Dial, Laura A. Collins, James C. Liao, Bret W. Tobalske

Environment and Society Faculty Publications

Complex hydrodynamics abound in natural streams, yet the selective pressures these impose upon different size classes of fish are not well understood. Attached vortices are produced by relatively large objects that block freestream flow, which fish routinely utilize for flow refuging. To test how flow refuging and the potential harvesting of energy (as seen in Kármán gaiting) varies across size classes in rainbow trout (Oncorhynchus mykiss; fingerling, 8 cm; parr, 14 cm; adult, 21 cm; n = 4 per size class), we used a water flume (4,100 L; freestream flow at 65 cm s^-1) and created …

3d Chromatin Architecture, Brd4, And Mediator Have Distinct Roles In Regulating Genome-Wide Transcriptional Bursting And Gene Network, Pawel Trzaskoma, Seolkyoung Jung, Aleksandra Pękowska, Christopher H Bohrer, Xiang Wang, Faiza Naz, Stefania Dell'orso, Wendy D Dubois, Ana Olivera, Supriya V Vartak, Yongbing Zhao, Subhashree Nayak, Andrew Overmiller, Maria I Morasso, Vittorio Sartorelli, Daniel R Larson, Carson C Chow, Rafael Casellas, John J O'Shea

Faculty, Staff and Student Publications

Discontinuous transcription is evolutionarily conserved and a fundamental feature of gene regulation; yet, the exact mechanisms underlying transcriptional bursting are unresolved. Analyses of bursting transcriptome-wide have focused on the role of cis-regulatory elements, but other factors that regulate this process remain elusive. We applied mathematical modeling to single-cell RNA sequencing data to infer bursting dynamics transcriptome-wide under multiple conditions to identify possible molecular mechanisms. We found that Mediator complex subunit 26 (MED26) primarily regulates frequency, MYC regulates burst size, while cohesin and Bromodomain-containing protein 4 (BRD4) can modulate both. Despite comparable effects on RNA levels among these perturbations, acute depletion …

Balancing Results From Ai-Based Geostatistics Versus Fuzzy Inference By Game Theory Bargaining To Improve A Groundwater Monitoring Network, Masoumeh Hashemi, Richard C. Peralta, Matt Yost

Plants, Soils and Climate Student Research

An artificial intelligence-based geostatistical optimization algorithm was developed to upgrade a test Iranian aquifer's existing groundwater monitoring network. For that aquifer, a preliminary study revealed that a Multi-Layer Perceptron Artificial Neural Network (MLP-ANN) more accurately determined temporally average water table elevations than geostatistical kriging, spline, and inverse distance weighting. Because kriging is usually used in that area for water table estimation, the developed algorithm used MLP-ANN to guide kriging, and Genetic Algorithm (GA) to determine locations for new monitoring well location(s). For possible annual fiscal budgets allowing 1-12 new wells, 12 sets of optimal new well locations are reported. Each …

Identification And Extraction Method Of Fragrant Pear Based On Image Detection Under Internet Of Things Applications, Peng Zhou, Huan Wnag, Pengwei Zhang, Shengzhi Liu, Wei Cehn, Weihang Zhao, Bingyu Cao

Turkish Journal of Agriculture and Forestry

With the continuous development of society, agricultural production technology is also improving. Due to the continuous improvement of economic level, the quality of life has also put forward higher requirements, the quality of agricultural products has gradually received more people’s attention. In the picking and sorting process of traditional fragrant pear, the quality control process is not perfect, and the identification and extraction method is not mature enough. In the complex environment of insufficient light or shade of branches and leaves, the pear picking work cannot quickly and accurately locate the target fruit. Therefore, the traditional identification and extraction methods …

Elucidating The First Protective Mutation From Inherited Alzheimer’S Disease - Apolipoprotein E3 Christchurch (Apoe3ch) And Insights Into Apoe Ligand-Receptor Interactions, Yun Chen

Arts & Sciences Graduate Student Theses and Dissertations

Alzheimer’s disease (AD) is the major cause of dementia. An inherited form of AD (dominant inherited AD) starts much earlier in life, often in the fourth and fifth decade. A recent case report described an individual who was resistant to dominantly inherited AD caused by a PSEN1-E280A mutation and was a homozygous carrier of the APOE3 Christchurch (APOE3ch) variant. A clear separation between amyloid and tau pathology occurred in this unique AD case. However, whether APOE3ch contributed to the protective effect remains unclear. In this thesis, we generated a humanized APOE3ch knock-in mouse and crossed it to an amyloid-β (Aβ) …