Digital Commons Network^™

Manf Is Neuroprotective Against Ethanol-Induced Neurodegeneration Through Ameliorating Er Stress, Yongchao Wang, Wen Wen, Hui Li, Marco Clementino, Hong Xu, Mei Xu, Murong Ma, Jacqueline A. Frank, Jia Luo

Pharmacology and Nutritional Sciences Faculty Publications

Fetal alcohol spectrum disorders (FASD) are a spectrum of developmental disorders caused by prenatal alcohol exposure. Neuronal loss or neurodegeneration in the central nervous system (CNS) is one of the most devastating features in FASD. It is imperative to delineate the underlying mechanisms to facilitate the treatment of FASD. Endoplasmic reticulum (ER) stress is a hallmark and an underlying mechanism of many neurodegenerative diseases, including ethanol-induced neurodegeneration. Mesencephalic astrocyte-derived neurotrophic factor (MANF) responds to ER stress and has been identified as a protein upregulated in response to ethanol exposure during the brain development. To investigate the role of MANF in …

Genetic And Epigenetic Determinants Of Diffuse Large B-Cell Lymphoma, Tanner Bakhshi, Philippe T. Georgel

Biomedical Sciences

Diffuse large B-cell lymphoma (DLBCL) is the most common type of lymphoma and is notorious for its heterogeneity, aggressive nature, and the frequent development of resistance and/or relapse after treatment with standard chemotherapy. To address these problems, a strong emphasis has been placed on researching the molecular origins and mechanisms of DLBCL to develop effective treatments. One of the major insights produced by such research is that DLBCL almost always stems from genetic damage that occurs during the germinal center (GC) reaction, which is required for the production of high-affinity antibodies. Indeed, there is significant overlap between the mechanisms that …

Causes Of Color Blindness: Function And Failure Of The Genes That Detect Color, Dylan Taylor

Senior Honors Theses

Color blindness affects nearly 10% of the entire population, with multiple types of color blindness from various genetic mutations. In the following sections, the nature of light and how the human eye perceives light will be discussed. Afterward, the major forms of color blindness and their genetic causes will be considered. Once these genetic causes have been established, the current method for diagnosing color blindness will be investigated, followed by a discussion of the current treatments available to those with color blindness. Finally, a brief discussion will address possible future work for color blindness with the hope of finding better …

Immune Phenotype Of Patients With Stage Iv Metastatic Inflammatory Breast Cancer., Sandra V Fernandez, Alexander W Macfarlane, Mowafaq Jillab, Maria F Arisi, Jennifer Yearley, Lakshmanan Annamalai, Yulan Gong, Kathy Q Cai, R Katherine Alpaugh, Massimo Cristofanilli, Kerry S Campbell

Student Papers, Posters & Projects

BACKGROUND: Inflammatory breast cancer (IBC) is a rare but aggressive carcinoma characterized by severe erythema and edema of the breast, with many patients presenting in advanced metastatic disease. The "inflammatory" nature is not due to classic immune-mediated inflammation, but instead results from tumor-mediated blockage of dermal lymphatic ducts. Previous work has shown that expression of PD-L1 on tumor cells can suppress T cell activation in triple-negative (TN) non-IBC breast cancer. In the present work, we investigated immune parameters in peripheral blood of metastatic IBC patients to determine whether cellular components of the immune system are altered, thereby contributing to pathogenesis …

Fluorescence Spectroscopic And Molecular Modelling Studies On The Molecular Interaction Mechanism Of Bromodeoxyuridine With Human Serum Albumin, Amira Adlin Roslan

Student Works (2020-2029)

The interaction of a nucleoside analogue, bromodeoxyuridine (BrdU) with human serum albumin (HSA) was studied to investigate the binding phenomenon and analyze the protein conformation upon BrdU binding. Multiple spectroscopic techniques, viz. intrinsic and three-dimensional (3-D) fluorescence, ultraviolet-visible (UV-Vis) absorption and circular dichroism (CD) spectroscopy along with molecular docking were used. A decrease in the Stern-Volmer constant (Ksv) with the increase in temperature suggested BrdU-induced quenching of protein fluorescence as static quenching and thus implied BrdU−HSA complex formation. This was also supported by UV-Vis absorption spectral results, showing hyperchromism in the absorption spectrum of HSA upon BrdU addition. Intermediate binding …

A Telescope Gwas Analysis Strategy, Based On Snps-Genes-Pathways Ensamble And On Multivariate Algorithms, To Characterize Late Onset Alzheimer’S Disease, Margherita Squillario, Giulia Abate, Federico Tomasi, Veronica Tozzo, Annalisa Barla, Daniela Uberti, Michael W. Weiner, Paul Aisen, Ronald Petersen, Jack R. Clifford, William Jagust, John Q. Trojanowki, Arthur W. Toga, Laurel Beckett, Robert C. Green, Andrew J. Saykin, John Morris, Leslie M. Shaw, Zaven Khachaturian, Greg Sorensen, Maria Carrillo, Lew Kuller, Marc Raichle, Steven Paul, Peter Davies, Howard Fillit, Franz Hefti, Davie Holtzman, M. Marcel Mesulam, William Potter, Peter Snyder, Tom Montine

Medical Biophysics Publications

Genome–wide association studies (GWAS) have revealed a plethora of putative susceptibility genes for Alzheimer’s disease (AD), with the sole exception of APOE gene unequivocally validated in independent study. Considering that the etiology of complex diseases like AD could depend on functional multiple genes interaction network, here we proposed an alternative GWAS analysis strategy based on (i) multivariate methods and on a (ii) telescope approach, in order to guarantee the identification of correlated variables, and reveal their connections at three biological connected levels. Specifically as multivariate methods, we employed two machine learning algorithms and a genetic association test and we considered …

Spatial Profiling Of Gangliosides In Mouse Brain By Mass Spectrometry Imaging, Douglas A. Andres, Lyndsay E. A. Young, Matthew S. Gentry, Ramon C. Sun

Molecular and Cellular Biochemistry Faculty Publications

No abstract provided.

Characterization Of Adiposity And Inflammation Genetic Pleiotropy Underlying Cardiovascular Risk Factors In Hispanics., Mohammad Yaser (Anwar)

Electronic Theses and Dissertations

The observed overlap between genetic variants associated with both adiposity and inflammatory markers suggests that changes in both adiposity and inflammation could be partially mediated by common pathways. The pervasive but sparsely characterized “pleiotropic” genetic variants associated with both adiposity and inflammation have been hypothesized to provide insight into the shared biology. This study explored and characterized the genetic pleiotropy underpinning adiposity and inflammation using genetic and phenotypic observations from the Cameron County Hispanic Cohort (CCHC). A total of 3,313 samples and >9 million single nucleotide polymorphisms (SNPs) were examined in this study. Mixed model genome-wide association studies (GWAS) were …

Plasma Resuscitation Attenuates Intestinal Barrier Disturbance Following Hemorrhagic Shock., Jessica E. Schucht

Electronic Theses and Dissertations

Background: Intestinal ischemia-reperfusion injury (IIRI) following resuscitated hemorrhagic shock (HS/RES) leads to endothelial damage, microcirculatory dysfunction and intestinal barrier breakdown, increasing intestinal permeability. This pathologic process contributes pathophysiology of multiple organ dysfunction syndrome (MODS) in some trauma patients. Although vascular smooth muscle machinery remains intact, microvascular vasoconstriction occurs secondary to endothelial cell damage, resulting in further ischemia and organ injury. Used separately, resuscitation with Fresh Frozen Plasma (FFP) or Direct Peritoneal Resuscitation (DPR) improves the intestinal microcirculation and alleviates organ injury. Further examination of these effects individually or combined could aid in the resuscitation of hemorrhagic shock. Methods: Sprague Dawley …

Sleep Induction By Mechanosensory Stimulation In Drosophila., Arzu Öztürk-Çolak, Sho Inami, Joseph R. Buchler, Patrick D. Mcclanahan, Andri Cruz, Christopher Fang-Yen, Kyunghee Koh

Department of Neuroscience Faculty Papers

People tend to fall asleep when gently rocked or vibrated. Experimental studies have shown that rocking promotes sleep in humans and mice. However, the mechanisms underlying the phenomenon are not well understood. A habituation model proposes that habituation, a form of non-associative learning, mediates sleep induction by monotonous stimulation. Here, we show that gentle vibration promotes sleep in Drosophila in part through habituation. Vibration-induced sleep (VIS) leads to increased homeostatic sleep credit and reduced arousability, and can be suppressed by heightened arousal or reduced GABA signaling. Multiple mechanosensory organs mediate VIS, and the magnitude of VIS depends on vibration frequency …

Proteomic Analysis Of Platelet-Rich And Platelet-Poor Plasma, Olga Miroshnychenko, Robert J. Chalkley, Ryan D. Leib, Peter A. Everts, Jason L. Dragoo

Publications and Research

Background

Autologous blood products, such as platelet-rich plasma (PRP) are commercial products broadly used to accelerate healing of tissues after injuries. However, their content is not standardized and significantly varies in composition, which may lead to differences in clinical efficacy. Also, the underlying molecular mechanisms for therapeutic effects are not well understood.

Purpose

A proteomic study was performed to compare the composition of low leukocyte PRP, platelet poor plasma (PPP), and blood plasma. Pathway analysis of the proteomic data was performed to evaluate differences between plasma formulations at the molecular level. Low abundance regulatory proteins in plasma were identified and …

The Link Between Heart Disease In Low Socioeconomic Communities In America, Khristopher Chea

Nursing | Senior Theses

As a future medical professional in the healthcare field, we continue to see patients admitted for cardiovascular issues. Cardiovascular diseases (CVDs) remain the leading cause of mortality among adults living in the U.S. despite advances in treatment throughout the past century. A number of risk factors such as hypertension, obesity, smoking, and physical inactivity contribute to the significant rise of cardiovascular disease. Research data suggests that there is correlation between cardiovascular disease, low socioeconomic status, and diet. According to the American Phycological Association socioeconomic status is measured by income, educational status, and occupation, and has been shown to be closely …

The Effects Of Moderate-Severe Plaque Psoriasis On Patient Well-Being And Prevention Of Flares, Glenn Devera

Nursing | Senior Theses

Psoriasis is a chronic skin condition that is indicated by red, patchy and scaly skin that can be painful when irritated. Patients with psoriasis have an increased risk for a number of chronic diseases. Despite the expansion of treatments for moderate-to-severe psoriasis over the last decade, patients may still find that treatment strategies are not as successful, leaving them dissatisfied with their treatments. A relationship built upon trust between the nurse and the patient diagnosed with psoriasis may serve to help ensure optimal care. A comprehensive literature review was performed and found that best practices for patient management need to …

Organic Cation Transporter 3 And The Dopamine Transporter Differentially Regulate Catecholamine Uptake In The Basolateral Amygdala And Nucleus Accumbens, Katherine M. Holleran, Jamie H. Rose, Steven C. Fordahl, Kelsey C. Benton, Kayla E. Rohr, Paul J. Gasser, Sara R. Jones

Biomedical Sciences Faculty Research and Publications

Regional alterations in kinetics of catecholamine uptake are due in part to variations in clearance mechanisms. The rate of clearance is a critical determinant of the strength of catecholamine signaling. Catecholamine transmission in the nucleus accumbens core (NAcc) and basolateral amygdala (BLA) is of particular interest due to involvement of these regions in cognition and motivation. Previous work has shown that catecholamine clearance in the NAcc is largely mediated by the dopamine transporter (DAT), but clearance in the BLA is less DAT‐dependent. A growing body of literature suggests that organic cation transporter 3 (OCT3) also contributes to catecholamine clearance in …

Functional And Physiological Role Of Extra-Hypothalamic Corticotropin Releasing Hormone Neurons In The Nucleus Of The Hippocampal Commissure In Regulation Of Stress Response, Hakeem Kadhim

Graduate Theses and Dissertations

Corticotropin releasing hormone (CRH) neurons located within the paraventricular nucleus (PVN) are known to be involved in regulation of stress responses. Recently, CRH neurons were identified above the PVN within the nucleus of the hippocampal commissure (NHpC) that located in the septum. We hypothesized that CRH neurons in the NHpC play a critical role in the stress response due to their rapid activation and could be a part of the traditional hypothalamo-pituitary-adrenal (HPA) axis. The dissertation addresses the role of 1) CRH expressing neurons in the NHpC compared with those within the PVN utilizing two different stressors, food deprivation (FD) …

Dean's Update December 2020, Jerry L. Nadler

SOM Dean's Research Newsletter

No abstract provided.

The Role Of Liver Sinusoidal Endothelial Cells In Liver Malady Homeostasis, Fatima Cabral

Department of Biochemistry: Dissertations, Theses, and Student Research

Current literature described techniques for the purification of liver cell types through text alone. The techniques described for the isolation of liver sinusoidal endothelial cells as well as hepatocytes described here are modified from a published article in the Journal of Visualized experiments. The video protocol allows for the user to successfully isolate cells as the most difficult parts of the procedure are demonstrated visually. The detection of liver maladies such as the non-alcoholic fatty liver disease, the stage if this disease and differentiation between non-alcoholic and alcoholic fatty liver disease is demonstrated in the development of a unique panel …

Hyperpolarized Carbon-13 Magnetic Resonance Measurements Of Tissue Perfusion And Metabolism, Keith Michel

Dissertations and Theses (Open Access)

Hyperpolarized Magnetic Resonance Imaging (HP MRI) is an emerging modality that enables non-invasive interrogation of cells and tissues with unprecedented biochemical detail. This technology provides rapid imaging measurements of the activity of a small quantity of molecules with a strongly polarized nuclear magnetic moment. This polarization is created in a polarizer separate from the imaging magnet, and decays continuously towards a non-detectable thermal equilibrium once the imaging agent is removed from the polarizer and administered by intravenous injection. Specialized imaging strategies are therefore needed to extract as much information as possible from the HP signal during its limited lifetime.

In …

Investigation Of The Functional Impact Of Anti-Pd-1 On Tumor-Infiltrating Lymphocytes (Til) And Mapping Of Tumor Genomic Features Relevant For Response To Til Therapy, Caitlin Creasy

Dissertations and Theses (Open Access)

With the growing use of both cellular and antibody-based immunotherapies, it has become more important to uncover biomarkers to predict patient response to therapy and ideally aid in patient selection for specific therapeutics, thereby enhancing treatment outcome. At MD Anderson, we have a 43% response rate to therapy when treating metastatic melanoma patients with adoptive cell therapy (ACT) of tumor-infiltrating lymphocytes (TIL), but it is unknown what makes the other 57% of patients not respond to therapy. It is further unknown how particularly early doses of checkpoint inhibitors, like anti-PD-1, attribute to TIL functionality, adding another confounding factor in determining …

Nuclear-Targeted Gold Nanoparticles Enhance The Effects Of Radiation Therapy With And Without Liposomal Delivery, Maureen Aliru

Dissertations and Theses (Open Access)

Less that 10% of pancreatic cancer patients are eligible for curative resection, and clinical trials evaluating chemoradiation in locally advanced patients with unresectable disease have been largely disappointing. New and creative therapeutic approaches are needed to address the unment need for treatment options. The objective of this thesis is to advance radiosensitization of treatment-resistant densely desmoplastic pancreatic cancer using nanoparticles to surmount biological barriers to effective particle distribution for DNA-targeting.

Clinical translation of radiosensitizing nanoparticles has stalled owing to technical challenges. Current strategies to use AuNPs for radiosensitization require large quantities of gold, kilovoltage x-rays, immediate irradiation after intravenous administration, …

Great Expectations: Phosph(On)Ate Prodrugs In Drug Design—Opportunities And Limitations, Victoria Yan

Dissertations and Theses (Open Access)

Phosphate and phosphonates are chemical moieties with historical precedence in anticancer and antiviral nucleotide analogues. Synchronous to modern efforts identifying novel therapeutic targets in cancer, such chemical moieties are being investigated in the design of novel inhibitors with antineoplastic potential. A central challenge to the delivery of phosph(on)ate-containing drugs is their anionic character at physiological pH, which portends poor membrane permeability. This limitation has been successfully overcome through the use of prodrugs. When attached to the phosph(on)ate moiety, prodrugs mask the negative charge and easily enable cell permeability. Upon cellular entry, the promoieties are enzymatically or environmentally cleaved to unveil …

Howard's "Showing: What Pregnancy Tells Us About Being Human" (Book Review), Kyle D. Diroberts

The Christian Librarian

No abstract provided.

Systems Genetics And Systems Biology Analysis Of Paraquat Effects In Bxd Recombinant Inbred Mice, Carolina Del Valle Torres Rojas

Theses and Dissertations (ETD)

Paraquat (PQ) is a chemical herbicide that is used in many countries including the United States. It is also highly acutely toxic to humans and has been used as a means of suicide. As PQ is applied mainly in agricultural settings, it moves to soil and well water. Chronic low dose exposure via drinking water may have adverse effects on humans, including increased risk for sporadic Parkinson’s disease (sPD). The etiology of sPD is unclear and the most accepted hypothesis states it is the result of the interaction between environmental factors and genetic susceptibility. Increasing evidence led us to infer …

Depletion Of Essential Isoprenoids And Er Stress Induction Following Acute Liver-Specific Deletion Of Hmg-Coa Reductase, Marco De Giorgi, Kelsey E Jarrett, Jason C Burton, Alexandria M Doerfler, Ayrea Hurley, Ang Li, Rachel H Hsu, Mia Furgurson, Kalyani R Patel, Jun Han, Christoph H Borchers, William R Lagor

Faculty, Staff and Students Publications

HMG-CoA reductase (Hmgcr) is the rate-limiting enzyme in the mevalonate pathway and is inhibited by statins. In addition to cholesterol, Hmgcr activity is also required for synthesizing nonsterol isoprenoids, such as dolichol, ubiquinone, and farnesylated and geranylgeranylated proteins. Here, we investigated the effects of Hmgcr inhibition on nonsterol isoprenoids in the liver. We have generated new genetic models to acutely delete genes in the mevalonate pathway in the liver using AAV-mediated delivery of Cre-recombinase (AAV-Cre) or CRISPR/Cas9 (AAV-CRISPR). The genetic deletion of Hmgcr by AAV-Cre resulted in extensive hepatocyte apoptosis and compensatory liver regeneration. At the biochemical …

Model For End-Stage Liver Disease-Sodium Underestimates 90-Day Mortality Risk In Patients With Acute-On-Chronic Liver Failure, Ruben Hernaez, Yan Liu, Jennifer R Kramer, Abbas Rana, Hashem B El-Serag, Fasiha Kanwal

Faculty, Staff and Students Publications

BACKGROUND & AIMS: It is unclear whether the model for end-stage liver disease-sodium (MELD-Na) score captures the clinical severity of acute-on-chronic liver failure (ACLF). We compared observed 90-day mortality in patients with ACLF with expected mortality based on the calculated MELD-Na and examined the consequences of underestimating clinical severity.

METHODS: We identified patients with ACLF during hospitalization for cirrhosis in 127 VA hospitals between 01/01/2004 and 12/31/2014. We examined MELD-Na scores by ACLF presence and grade. We used actual and observed 90-day mortality to estimate a standardized mortality ratio (SMR) by ACLF presence and grade. We used transplant center-specific median …

Electrical Identification Of Innate Immune Cells, Rasha Ayman Nasser

Theses

This thesis is concerned with the electrical characterization of the key players of the innate immune cells. Innate immunity is basically the nonspecific immune response that is triggered by any foreign body that attacks the human system. The key players of the innate immune system are mainly dendritic cells and macrophages. Accurately classifying these cell types helps us understand the mechanism of the immune system thereby enabling the development of models to improve new prospects for therapeutics and diagnostics. The characterization described in this thesis is based on extracting the capacitance for each biological cell using I-V curves. The main …

Mouse Models To Study The Pathophysiology Of Combined Methylmalonic Acidemia And Homocystinuria, Cblc Type, Tiffany Chern, Annita Achilleos, Xuefei Tong, Chih-Wei Hsu, Leeyean Wong, Ross A Poché

Faculty, Staff and Students Publications

Combined methylmalonic acidemia and homocystinuria, cblC type, is the most common inherited disorder of cobalamin metabolism and is characterized by severe fetal developmental defects primarily impacting the central nervous system, hematopoietic system, and heart. CblC was previously shown to be due to mutations in the MMACHC gene, which encodes a protein thought to function in intracellular cobalamin trafficking and biosynthesis of adenosylcobalamin (AdoCbl) and methylcobalamin (MeCbl). These coenzymes are required for the production of succinyl-CoA and methionine, respectively. However, it is currently unclear whether additional roles for MMACHC exist outside of cobalamin metabolism. Furthermore, due to a lack of sufficient …

The Cancer Patient And Cardiology, José Luis Zamorano, Christer Gottfridsson, Riccardo Asteggiano, Dan Atar, Lina Badimon, Jeroen J Bax, Daniela Cardinale, Antonella Cardone, Elizabeth A M Feijen, Péter Ferdinandy, Teresa López-Fernández, Chris P Gale, John H Maduro, Javid Moslehi, Torbjørn Omland, Juan Carlos Plana Gomez, Jessica Scott, Thomas M Suter, Giorgio Minotti

Faculty, Staff and Students Publications

Advances in cancer treatments have improved clinical outcomes, leading to an increasing population of cancer survivors. However, this success is associated with high rates of short- and long-term cardiovascular (CV) toxicities. The number and variety of cancer drugs and CV toxicity types make long-term care a complex undertaking. This requires a multidisciplinary approach that includes expertise in oncology, cardiology and other related specialties, and has led to the development of the cardio-oncology subspecialty. This paper aims to provide an overview of the main adverse events, risk assessment and risk mitigation strategies, early diagnosis, medical and complementary strategies for prevention and …

Design Of Hfgf1 Variant(S) With Increased Stability And Enhanced Bioactivity, Shilpi P. Agrawal

Graduate Theses and Dissertations

Fibroblast growth factors (FGFs) are involved in various cellular processes such as cell growth,proliferation, differentiation, migration, angiogenesis, wound healing and embryonic development. Human acidic fibroblast growth factor (hFGF1) binds non-selectively to all the four FGF-receptors and is therefore considered as a powerful mitogen with broadest specificity. However, pharmacological applications of hFGF1 are restricted due to the low thermal stability of the growth factor. hFGF1 has low thermodynamic stability under physiological temperatures which leads to impairment of cellular signaling process thereby preventing its potential mitogenic properties. hFGF1 has a heparin binding pocket at the C-terminus which comprises of positively charges residues. …

Stat1 Dissociates Adipose Tissue Inflammation From Insulin Sensitivity In Obesity, Aaron R Cox, Natasha Chernis, David A Bader, Pradip K Saha, Peter M Masschelin, Jessica B Felix, Robert Sharp, Zeqin Lian, Vasanta Putluri, Kimal Rajapakshe, Kang Ho Kim, Dennis T Villareal, Reina Armamento-Villareal, Huaizhu Wu, Cristian Coarfa, Nagireddy Putluri, Sean M Hartig

Faculty, Staff and Students Publications

Obesity fosters low-grade inflammation in white adipose tissue (WAT) that may contribute to the insulin resistance that characterizes type 2 diabetes. However, the causal relationship of these events remains unclear. The established dominance of STAT1 function in the immune response suggests an obligate link between inflammation and the comorbidities of obesity. To this end, we sought to determine how STAT1 activity in white adipocytes affects insulin sensitivity. STAT1 expression in WAT inversely correlated with fasting plasma glucose in both obese mice and humans. Metabolomic and gene expression profiling established STAT1 deletion in adipocytes (STAT1a-KO) enhanced mitochondrial function …