Digital Commons Network^™

The Emerging Role Of Suppressors Of Cytokine Signaling (Socs) In The Development And Progression Of Leukemia, Esra'a Keewan, Ksenia Matlawska-Wasowska

Pediatrics Research and Scholarship

Cytokines are pleiotropic signaling molecules that execute an essential role in cell-to-cell communication through binding to cell surface receptors. Receptor binding activates intracellular signaling cascades in the target cell that bring about a wide range of cellular responses, including induction of cell proliferation, migration, differentiation, and apoptosis. The Janus kinase and transducers and activators of transcription (JAK/STAT) signaling pathways are activated upon cytokines and growth factors binding with their corresponding receptors. The SOCS family of proteins has emerged as a key regulator of cytokine signaling, and SOCS insufficiency leads to constitutive activation of JAK/STAT signaling and oncogenic transformation. Dysregulation of …

Mitophagy Protein Pink1 Suppresses Colon Tumor Growth By Metabolic Reprogramming Via P53 Activation And Reducing Acetyl-Coa Production, Kunlun Yin, Jordan Lee, Zhaoli Liu, Hyeoncheol Kim, David R Martin, Dandan Wu, Meilian Liu, Xiang Xue

Pathology Research and Scholarship

Colorectal cancer (CRC) is the third leading cause of cancer-related deaths in the US. Understanding the mechanisms of CRC progression is essential to improve treatment. Mitochondria is the powerhouse for healthy cells. However, in tumor cells, less energy is produced by the mitochondria and metabolic reprogramming is an early hallmark of cancer. The metabolic differences between normal and cancer cells are being interrogated to uncover new therapeutic approaches. Mitochondria targeting PTEN-induced kinase 1 (PINK1) is a key regulator of mitophagy, the selective elimination of damaged mitochondria by autophagy. Defective mitophagy is increasingly associated with various diseases including CRC. However, a …

Cd44 Engagement Enhances Acute Myeloid Leukemia Cell Adhesion To The Bone Marrow Microenvironment By Increasing Vla-4 Avidity, Julia C. Gutjahr, Elisabeth Bayer, Xiaobing Yu, Julia M. Laufer, Jan P. Höpner, Suzana Tesanovic, Andrea Härzschel, Georg Auer, Tanja Rieß, Astrid Salmhofer, Eva Szenes, Theresa Haslauer, Valerie Durand-Onayli, Andrea Ramspacher, Sandra P. Pennisi, Marc Artinger, Nadja Zaborsky, Alexandre Chigaev, Fritz Aberger, Daniel Neureiter, Lisa Pleyer, Daniel F. Legler, Veronique Orian-Rousseau, Richard Greil, Tanja N. Hartmann

Pathology Research and Scholarship

Adhesive properties of leukemia cells shape the degree of organ infiltration and the extent of leukocytosis. CD44 and the integrin VLA-4, a CD49d/CD29 heterodimer, are important factors of progenitor cell adhesion in bone marrow (BM). Here, we report their cooperation in acute myeloid leukemia (AML) by a novel non-classical CD44-mediated way of inside-out VLA-4 activation. In primary AML BM samples from patients and the OCI-AML3 cell line, CD44 engagement by hyaluronan induced inside-out activation of VLA-4 resulting in enhanced leukemia cell adhesion on VCAM-1. This was independent from VLA-4 affinity regulation but based on ligand-induced integrin clustering on the cell …

Acute Myeloid Leukemia: Therapy Resistance And A Potential Role For Tetraspanin Membrane Scaffolds, Muskan Floren, Jennifer M. Gillette

Pathology Research and Scholarship

Acute myeloid leukemia (AML) is characterized by the disruption of myeloid differentiation and accumulation of blast cells in the bone marrow. While AML patients respond favorably to induction chemotherapy, long-term outcomes remain poor due to a high rate of chemoresistance. Advances with targeted therapies, which can be used in combination with conventional chemotherapy, have expanded therapeutic options for patients. However, remission is often short-lived and followed by disease relapse and drug resistance. Therefore, there is a substantial need to improve treatment options by identifying novel molecular and cellular targets that regulate AML chemosensitivity. Membrane scaffolds such as the tetraspanin family …

Using Virus-Like Particles To Combat Cardiovascular Disease And Identify An Immunogenic Target Of Natural Zika Virus Infection In Humans, Alexandra Marie Fowler

Biomedical Sciences ETDs

Virus-like particles (VLPs) derived from bacteriophages have been utilized as highly immunogenic vaccine platforms for displaying antigen targets of interest. Bacteriophage VLPs have a highly repetitive structure made of protein subunits that self-assemble into an icosahedral particle. These structures can strongly activate the immune system, especially B cells. Arraying antigens on the surface of VLPs in a multivalent manner can, in turn, confer the ability to induce strong antibody responses to virtually any target. This technique can even be used to elicit antibody responses against self-antigens. Here we have exploited these features for developing VLP-based vaccines that target self-molecules involved …

Weedy Relations: Narratives Of Invasion And Intimacy With Tamarisk In The Chihuahuan Desert, Shannon S. Pepper

Geography ETDs

Tamarix spp., also known as salt cedar or tamarisk, is a shrub that has garnered a notorious reputation in North America as an invasive plant, with widespread policy and research advocating for its eradication in the Southwest U.S. and Northern Mexico. This study examines both governmental conservation documents and news articles to investigate narrative trends on tamarisk in the Southwestern U.S. and Northern Mexico as a contiguous region (the Chihuahuan Desert), expanding on current research to include transborder effects on the perception and management of introduced species. This paper asks: In the last 25 years, how has the movement, …

Regulation Of H2s Production And Signaling Within Vascular Endothelium, Perenkita J. Mendiola

Biomedical Sciences ETDs

Hydrogen sulfide (H2S) is a vasodilator primarily produced by cysthathionine

gamma-lyase (CSE) within the vasculature. Previous studies suggest there are

differences in CSE expression and the contribution of H2S to vasodilation in

different sized arteries. This led us to postulate that there are also regional

differences of regulators of H2S-mediated vasodilatory pathways.

This study examined the role of endothelial cell plasma membrane (EC

PM) cholesterol in regulating H2S-induced vasodilation and the role of

intracellular calcium [Ca2+]i in regulating CSE activity in vascular EC. We

hypothesized that CSE activation in EC by receptor-dependent second

messenger signaling enhances H2S production and subsequent …

Rac1 In Ovarian Cancer Metastasis And Tumor Microenvironment Remodeling: An Experimental And Computational Analysis, Melanie Rivera

Biomedical Sciences ETDs

Ovarian cancer is the leading cause of gynecologic malignancies, and the patient survival rate has not changed significantly in 20 years. Patients are often diagnosed at an advanced stage of disease with widespread tumor cell dissemination and metastasis. Therefore, drivers of ovarian cancer metastasis need to be identified. In Chapter 2, we reveal the role of Rac1 in ovarian cancer metastasis using a combination of experimental and computational approaches. In Chapter 3, we demonstrate that changes in gene expression and cytokine levels within the immunosuppressive ovarian cancer tumor microenvironment are dependent on Rac1 expression and activity. Collectively, the …

Developing An Epitope-Based Malaria Vaccine Targeting The Circumsporozoite Protein, Lucie Jelinkova

Biomedical Sciences ETDs

Malaria is a life-threatening parasitic disease that is spread to humans by mosquitos. Developing a successful vaccine for malaria has been a remarkable challenge. Plasmodium falciparum, the causative agent of malaria, is a complex organism that transforms into unique forms and infects multiple organs within the human host throughout its life cycle. In these studies we describe a virus-like particle (VLP)-based approach to developing a vaccine for malaria that targets discrete and specific sites on invading sporozoites during the pre-erythrocytic stage of infection. VLPs are noninfectious, self-assembling particles derived from viral structural proteins, and are safe and highly immunogenic. …

Lysmd3: A Mammalian Pattern Recognition Receptor For Chitin, Xin He, Brad A. Howard, Yang Liu, Aaron K. Neumann, Liwu Li, Nidhi Menon, Tiffany Roach, Shiv D. Kale, David C. Samuels, Hongyan Li, Trenton Kite, Hirohito Kita, Tony Y. Hu, Mengyao Luo, Caroline N. Jones, Uju Joy Okaa, Diane L. Squillace, Bruce S. Klein, Christopher B. Lawrence

Pathology Research and Scholarship

Chitin, a major component of fungal cell walls, has been associated with allergic disorders such as asthma. However, it is unclear how mammals recognize chitin and the principal receptor(s) on epithelial cells that sense chitin remain to be determined. In this study, we show that LYSMD3 is expressed on the surface of human airway epithelial cells and demonstrate that LYSMD3 is able to bind chitin, as well as β-glucan, on the cell walls of fungi. Knockdown or knockout of LYSMD3 also sharply blunts the production of inflammatory cytokines by epithelial cells in response to chitin and fungal spores. Competitive inhibition …

Directional Integrity And Landmark Anchoring Of The Head Direction Cell System In The Tgf344-Ad Rat Model Of Alzheimer’S Disease, Laura E. Berkowitz

Psychology ETDs

Spatial navigation and memory are impaired in the early stages of Alzheimer's disease (AD) and are prominent behavioral markers of preclinical AD. The TgF344-AD rat model of AD exhibits similar behavioral and pathological features to humans and thus serves as an excellent model to investigate the mechanisms underlying spatial impairment in AD. Brain regions in the parahippocampal cortex contain spatially responsive pyramidal cells that support spatial navigation and memory including place cells, grid cells, and head direction cells. Furthermore, GABAergic interneurons in these regions support precise temporal organization of spike dynamics and may play a critical role in maintaining reliable …

Eeg Features Of Explore-Exploit Decision-Making In Alcohol Use Disorder, Ethan Campbell

Psychology ETDs

Little research has assessed explore-exploit behavior in addiction using drug cues and even fewer studies have measured the neural activity underlying these behaviors. The present study aims to explore brain mechanisms of disordered decision-making in alcohol use disorder (AUD) through electroencephalography (EEG) during performance of a novelty bandit task with alcohol imagery and using a validated computational model of explore-exploit dynamics. Individuals with AUD (n = 28) and age and sex-matched controls (n = 27) showed differences in choice behavior and showed differences in EEG activity as a function of exploratory behavior, chosen stimulus type, and explore-exploit computational …

Immodest Immortality: Emperor Maximilian I'S Artistic Program And The Ambraser Heldenbuch, 1504-1519, Jessica Cochran

History ETDs

Maximilian I (r. 1493-1519) utilized various forms of artistic and literary media throughout his reign to control his public image after his death. This thesis focuses on a manuscript project that has historically received little scholarly attention. The Ambraser Heldenbuch, produced between 1504 and 1517, preserves German heroic epics, many of which would otherwise be lost today. The manuscript has been highly valued for its literary and linguistic significance, but this thesis argues that the entire project sheds light on Maximilian’s plan to immortalize not only his own reputation, but also that of his family. This thesis focuses on …

The Role Of Brain-Derived Neurotrophic Factor In The Link Between Physical Activity And Psychosocial Recovery From Alcohol Use Disorder, Adam D. Wilson

Psychology ETDs

Objective: Alcohol Use Disorder (AUD) is a common, chronically relapsing condition with substantial health and economic costs. United States federal agencies have put out calls in the last decade to expand the scientific evidence base for broad biopsychosocial recovery from AUD and other substance use disorders (SUD). The present study examined the role of physical activity and exercise in early recovery from AUD, with specific attention to changes in brain-derived neurotrophic factor (BDNF) as a marker of neuroplasticity and a potential mechanism for instantiation of recovery-aligned behaviors. Method: Individuals in the first year of recovery from AUD were …

From Stasis To Ecstasy: Tracing Bernard Of Clairvaux's "Queer" Influence On French Gothic Art, Jackson O. Larson

Art & Art History ETDs

I trace the progression of figural sculpture in the Latin West from the static statues of the late-tenth century to the ecstatic statues of the mid-thirteenth century. I explore the various reasons for the return of freestanding figural sculpture and suggest that the return is indicative of an eroticization of the Christian holy figures. I suggest that Bernard of Clairvaux’s erotic theology in the twelfth century resulted in a synthesis of eros and Christian devotion that allowed latent classicism to find purchase in Christian art. I submit that Bernard’s influence on European art is a form of “queering”—a process by …

The Role Of Toxoplasma Gondii Dense Granule Protein Gra24 In Signaling And Immunity During Infection, Heather L. Mercer

Biology ETDs

Toxoplasma gondii is a pathogen whose control partly depends upon Toll-like receptors (TLR) 11 and 12, that signal through MyD88. Yet, human TLR11 and TLR12 are nonfunctional, motivating us to investigate MyD88-independent immune pathways. Parasite dense granule protein GRA24 activates p38 MAPK independently of MyD88 in macrophages. Using wild-type and GRA24-deleted T. gondii strains, I demonstrate GRA24 activates p38 MAPK, resulting in IL-12 production, and protective immunity. Furthermore, GRA24 triggers p38 MAPK-dependent CX3CL1 production. GRA24 also induces CCL17 and Ppbp independently of p38 MAPK. Additionally, I demonstrate GRA24 downregulates CCL12. Furthermore, IL-15 is negatively regulated by GRA24 through activation …

The Transformation Of Identity In Early Medieval England: Continuity, Disruption, And Creolization, Michael Sean Limmer

History ETDs

The period following Rome’s administrative withdrawal from Britain (c. 410 CE) has sparked intense debate for centuries, spawning a variety of theories concerning ethnic identity and the nature of cultural exchange on the island. Presently, the very nature of the term “Anglo-Saxon” itself is at the center of these discussions. This thesis examines historical, archaeological, and genetic evidence to cast a light on who constituted the people of Britain during this migration period through to the time of Alfred, and to what extent creolization might have played out. Ultimately, the evidence from this period suggests that ethnic identities cannot reasonably …

The Effect Of Interval And Continuous Work On Markers Of Acute Kidney Injury In A Hot Environment, Jonathan M. Houck, Fabiano Amorim, Christine Mermier, Michael Deyhle, Orlando Laitano, Zachary Mckenna, Zac Fennel, Jeremy Ducharme, Andrew Wells

Health, Exercise, and Sports Sciences ETDs

Purpose: To examine the effect of high intensity interval work (HIIW) and moderate intensity continuous work (MICW) patterns on markers of acute kidney injury (AKI) and kidney damage in a hot environment. Methods: Nine males completed two hours of physical work in a hot environment, performing either HIIW [2 minutes at 80% maximum oxygen consumption (VO₂max) and 3 minutes at 30% VO₂max] or MICW. Blood and urine samples were collected immediately before (Pre) and after (Post), one hour (1hr Post), and 24 hours after (24hr Post) the trials. Urine flow rate (UFR), osmolality (Uosm), and …

Factors Influencing Rural Women’S Physical Activity Behaviors: A Social Ecological Perspective, Karen Lynn Webb

Nursing ETDs

ABSTRACT

Chronic disease and poor mental health are disproportionally impacting adults living in rural America. Regular physical activity has been shown to promote overall well-being and prevent many chronic diseases. Yet, research shows that many rural adults do not engage in enough physical activity to meet the recommended levels put forth by the federal government. The purpose of this descriptive qualitative study was to explore and describe the experiences of physical activity as perceived by rural women in their own words. Data were collected through semi-structured individual interviews of 20 women aged 25 to 34 living in McDowell County, West …

The Development Of An Instrument To Measure Transdermal Hydrogen Sulfide As A Way To Evaluate Microvascular Health In Humans, Benjamin Thomas Matheson

Biomedical Engineering ETDs

Hydrogen sulfide (H₂S) is a gasotransmitter critical in maintaining microcirculation homeostasis. Impaired microcirculation occurs in multiple disease states such as peripheral vascular disease, diabetes mellitus (DM), and hypertension. Early detection and identification of patients with DM who are at risk for heart attack, stroke and amputation due to microvascular disease is crucial. Human skin is an accessible vascular bed that provides an opportunity to non-invasively measure H₂S, which could be used as a biomarker to evaluate microvascular health.

In this work, a novel H₂S gas sensor, called the transdermal arterial gasotransmitter sensor (TAGS^{TM …}

Disrupting The (Post) Neoliberal Order In Latin America Through The Representation Of Fictional Corporate Office Narratives In Argentina And Mexico (2007-2010), Juliana Todescan

Spanish and Portuguese ETDs

Due to the expansion of the neoliberal and global order in Latin America in the 1990s, national states and citizens are subjected to the free market interests regulated and managed by for profit corporations and the financial industry. Considering this a critical change in the social organization of Latin America, I compare narratives from Argentina and Mexico that imagine cosmopolitan cities being colonized by the corporate logic of profit. My analysis focuses on the representation of low level office workers in Antonio Ortuño’s novel Recursos humanos (2007), Guillermo Saccomanno’s novel El oficinista (2010), and Aníbal Jarkowski’s El trabajo (2007), and …

Closing The Loop And Opening The Possibilities: Augmenting Sleep-Dependent Consolidation To Improve Long Term Memory, Aaron Paul Jones

Psychology ETDs

Memory consolidation occurs during slow-wave sleep. This is a complex process that can be studied using electroencephalography (EEG) and modulated with brain stimulation. Previous studies have shown that transcranial alternating current stimulation (tACS) can be used to entrain or disrupt endogenous oscillations in cortical networks and can be used for the manipulation of consolidation processes during sleep. In this series of experiments, sleep-dependent memory consolidation was modulated using closed-loop tACS (CL-tACS to improve memory performance for three tasks: a verbal paired associates task (PAT), an interference paired associates task (iPAT), and a visual category learning task. EEG was collected during …

Q’Iij Metaphysics: Vico’S Theologia Indorum And The Gods, Ancestors, And Idols Of The 16th Century K’Ichee’ Mayas, Phillip Salazar

Latin American Studies ETDs

Domingo de Vico completed the Theologia Indorum, a K’iche’ Christian manuscript, in Guatemala in 1554. In the manuscript, Vico distinguishes between the idols, ancestors, and gods of the K’iche’s. This paper shows that Vico believed the idols to be inanimate objects, ancestors to be the older generations that have passed away, and gods to be demons. This paper then develops a theory of animist ontology for the K’iche’s. Using that ontological theory, this paper argues that, for the K’iche’s, their idols and gods were indistinguishable and that their ancestors were still alive, present, and active among them.

Brief For American Indian Law Scholars As Amicus Curiae, Stephen C., Et Al V. Bureau Of Indian Education, Et Al.,, Barbara L. Creel, Tierra N. Marks, Randolph H. Barnhouse

Faculty Scholarship

Indian Civil Rights/Education Lawsuit

View this and other court documents at Turtle Talk.

Congress’s declared federal policy is “to fulfill the Federal Government’s unique and continuing trust relationship with and responsibility to the Indian people for the education of Indian children.” 25 U.S.C. § 2000. This federal policy is the touchstone of the federal government’s trust obligation to Indian families and their children. When the BIA (through the BIE) fails to protect the rights of Indian children to “educational opportunities that equal or exceed those for all other students in the United States,” courts have a vital role to …

In Pursuit Of Comparability: Evaluating Influence And Interaction Among Components Of The Home Range Estimation Process In Chimpanzee Datasets, Jillian J. Rutherford

Geography ETDs

The home range (HR) is a fundamental manifestation of an animal’s spatial behavior, but its study has been limited by unclear, unreliable, and unstandardized methodological approaches for measurement. The lack of a comprehensive evaluation of the influence of components of the HR estimation process has hampered consensus over best practices for collecting and analysing movement data. This leads to wide variation in practice, thwarting direct comparability between HR estimates and curtailing the cohesive power of cross-study findings necessary for testing hypotheses and developing appropriate conservation and management strategies. In this thesis I explore the influence of and interaction between common …

Unm Pathology Pathfinder Summer 2021, Unm Department Of Pathology

Newsletters

No abstract provided.

Hand Of The Potter, Hand Of The State: Pottery Production And Control In Tawantinsuyu, James A. Davenport

Anthropology ETDs

In empires, material culture plays an important role in creating and maintaining state power and legitimizing imperial rule. Through their form and decoration in imperial styles, these objects convey messages about state power, yet their production is often decentralized and carried out by subjects. This dissertation asks the question, how do imperial authorities organize the production of material culture? This question is addressed through a study of one category of material culture—Inka imperial pottery—from the site of Pachacamac, in Peru.

The Inka empire, called Tawantinsuyu, was a territorial empire spanning over 2 million km² in Andean South America …

Individual Exposure Potential Assessment For Livestock Based On Spatial-Temporal Analysis Of Gps Data And Behavior Patterns Classification In Cove Wash Watershed, Arizona, Zhuoming Liu

Geography ETDs

This thesis examined the geospatial and temporal grazing patterns of domesticated livestock to model individual-level exposure potential to abandoned uranium mine (AUM) waste in a tribal community in the Southwest United States. Lotek Litetrack Global Positioning System (GPS) collars collected data at 20-minute-intervals for 2 flocks of sheep and goats during the Spring and Summer of 2019. Depending on the flock and individual animals, tracking time ranges from 10 days to four months. This research developed a GIS-based exposure potential framework that built on existing methodologies in time geography, GIS, and exposure mapping. This thesis aims to: 1) classify GPS …

Front Matter, Unm Department Of Orthopaedic Surgery

Western Journal of Orthopaedics

No abstract provided.

The University Of New Mexico Orthopaedics Research Journal 2021, Unm Department Of Orthopaedic Surgery

Western Journal of Orthopaedics

No abstract provided.