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Ultrasound Biomicroscopic Imaging For Interleukin-1 Receptor Antagonist-Inhibiting Atherosclerosis And Markers Of Inflammation In Atherosclerotic Development In Apolipoprotein-E Knockout Mice, Rong-Juan Li, Yan Sun, Qin Wang, Jiao Yang, Ya Yang, Li Song, Zheng Wang, Xiang-Hong Luo, Rui-Juan Su

The Texas Heart Institute Journal

We sought to validate the hypothesis that the development of atherosclerosis can be suppressed by the interleukin-1 receptor antagonist (IL-1Ra) in murine models of atherosclerosis in vivo, noninvasively seen by means of high-resolution ultrasound biomicroscopy, and we studied changes in inflammatory markers such as IL-1 and C-reactive protein (CRP) plasma levels in these models of atherosclerosis.

We divided IL-1Ra+/−/apolipoprotein-E (apoE)−/− and IL-1Ra+/+/apoE−/− mice into 2 age groups, used as atherosclerotic models. The control groups were age-matched IL-1Ra+/+/apoE+/+ mice. Plaque thickness was measured in the ascending aorta in short-axis images by means of ultrasound and histology. Plasma levels of IL-1 and …

Jove: Journal Of Visualized Experiments, Joanne Romano

TMC Library Newsletter (2015-)

JoVE is a peer-reviewed scientific video journal. It is published in sections, of which the library subscribes to four: Biology, Clinical and Translational Medicine, Immunology and Infection, and Neuroscience. Videos are accompanied by text.

Families, Family Strengths And The Changing World, Robert Sanborn, Angelo P. Giardino, William V. Flores, E. Christopher Lloyd

Journal of Family Strengths

Angelo P. Giardino, Robert Sanborn, William V. Flores and E. Christopher Lloyd discuss the latest issue of the Journal of Family Strengths.

Deconstructing The Lgbt-Victimization Association: The Case Of Sexual Assault And Alcohol-Related Problems, Shanna Felix, Justin Hoyle, Chad Posick, Bryan Lee Miller, John Stogner

Journal of Family Strengths

Research on lesbian, gay, bisexual and/or transgender (LGBT) students has been gaining traction in the fields of criminology, victimology, and education, but available data lag behind the demand for studies on this underserved population. While LGBT students are often perceived to face greater risk of victimization and subsequent health problems than their counterparts, little research has investigated the mechanisms behind problematic outcomes for LGBT students. This research uses data from a Southeastern University to examine sexual assault among LGBT students and their experiences with alcohol-related problems. The results show that LGBT youth are at an increased risk for sexual victimization …

Is Autologous Or Heterologous Pericardium Better For Valvuloplasty? A Comparative Study Of Calcification Propensity, Wen-Jian Jiang, Yong-Chao Cui, Jin-Hua Li, Xiu-Hui Zhang, Huan-Huan Ding, Yong-Qiang Lai, Hong-Jia Zhang

The Texas Heart Institute Journal

Pericardial calcification is detrimental to the long-term durability of valvuloplasty. However, whether calcification susceptibility differs between heterologous and autologous pericardium is unclear. In this study, we compared the progression of calcification in vivo between autologous and heterologous pericardium.

We randomly divided 28 rabbits into 4 equal groups. Resected rabbit pericardium served as autologous pericardium, and commercial bovine pericardium served as heterologous pericardium. We subcutaneously embedded one of each pericardial patch in the abdominal walls of 21 of the rabbits. The 7 control rabbits (group A) received no implants. The embedded samples were removed at 2 months in group B, at …

Is Autologous Or Heterologous Pericardium Better For Valvuloplasty? A Comparative Study Of Calcification Propensity, Arthur W Bracey

The Texas Heart Institute Journal

No abstract provided.

Work-Related Musculoskeletal Disorders: Psychological Factors In Licensed Nurses, Cynthia Pipkins

Dissertations and Theses (Open Access)

Background: Physical risk factors for work-related musculoskeletal disorders (WMSD) among licensed nurses have been well established. Rehabilitation following WMSD traditionally focuses on physical dimensions, but both physical and psychological factors may be useful during rehabilitation, as suggested by the Fear Avoidance Model of Chronic Pain (FAMCP) and the Pain Experience Psychological View model (PE).

Purpose: The purpose was to describe demographic characteristics of nurses with and without WMSD and relationships among related psychological factors of pain (intensity, severity, and interference), personality traits (extraversion and neuroticism), and coping strategies (catastrophizing, diversion, reinterpreting, cognitive coping, fear avoidance, and depression) as postulated in …

Activity-Rest And Skin Temperature Circadian Rhythms And Sleep Patterns In Community-Dwelling Women, Kristina L. Leyden

Dissertations and Theses (Open Access)

Purpose: The purpose of the study was to explore activity-rest and temperature circadian rhythms and sleep patterns in ambulatory women of reproductive, perimenopausal, and postmenopausal stages. Study aims were to (1) correlate the patterns of activity-rest with skin temperature and determine (2) lead-lag relation between activity-rest and circadian temperature rhythm, (3) stability of activity-rest patterns during work and non-work days, (4) duration of actigraphy sampling sufficient to reliably capture activity-rest patterns, and (5) sleep parameters in participating women across reproductive stages.

Design: Analysis of extant data sets.

Sample and Setting: Seven community-dwelling women, 27-to-54-years old

Methods: Participants wore an actigraph …

Induction Of Caspase-Dependent Death By Proteasome Targeted Therapy In Glioblastoma, Christa A. Manton

Dissertations and Theses (Open Access)

New therapeutic options are needed for glioblastoma, a deadly disease with a median survival of only 14 months with current treatment. The proteasome inhibitor bortezomib (BTZ) shows efficacy in cancers like myeloma, but its clinical utility in other cancer types has been more limited. Newer proteasome inhibitors such as marizomib (MRZ) have unique inhibitory and death inducing properties that have not been well examined in GBM. Additionally, targeting other components of the ubiquitin-proteasome system is possible, but has not been explored in GBM. Questions also still remain about the ability of BTZ and MRZ to be delivered to brain tumors …

Multilevel Deregulation Of Survival Mechanisms In Npm-Alk+ T-Cell Lymphoma, Deeksha Vishwamitra

Dissertations and Theses (Open Access)

The anaplastic lymphoma kinase (ALK) is a single chain transmembrane receptor tyrosine kinase that belongs to the insulin receptor superfamily. Other members of this superfamily include the insulin receptor (IR), type I insulin-like growth factor receptor (IGF-IR), and the leukocyte tyrosine kinase. The common structural finding among these tyrosine kinases is the YXXXYY motif present within their respective tyrosine kinase domains. Binding of its ligands causes ALK receptor homodimerization and protein kinase activation. ALK has been previously shown to play a significant role during early developmental stages. In human embryos, the expression of ALK is mainly seen in …

Serum Omentin As A Potential Biomarker For Complex Atypical Hyperplasia And Endometrioid Endometrial Adenocarcinoma, Laura L. Holman Md

Dissertations and Theses (Open Access)

Obesity is a significant risk factor for endometrial cancer, the most common gynecologic malignancy in the United States, but much remains unclear about the relationship between obesity-related factors and the development of endometrial cancer. Omentin, a recently discovered adipokine, has been shown to be present in lower levels in patients who are obese and/or insulin resistant. A case-control study was conducted using the serum of 140 women with endometrial cancer and 75 women with endometrial hyperplasia who were matched 1:1 based on body mass index (BMI) and menopausal status to women with no history of endometrial cancer (controls). The concentration …

Cancer Incidence In First And Second Degree Relatives Of Brca1 And Brca2 Mutation Carriers, Haley Streff

Dissertations and Theses (Open Access)

Mutations in the BRCA1 or BRCA2 genes are associated with increased risks for breast, ovarian, and several other cancers. The purpose of this study was to evaluate the incidence of cancers in first and second degree relatives of BRCA mutation carriers compared to the general population. A total of 1086 pedigrees of BRCA mutation carriers were obtained from a prospectively maintained, internal review board approved study of persons referred for clinical genetic counseling at The University of Texas MD Anderson Cancer Center. We identified 9032 first and second degree relatives from 784 pedigrees which demonstrated a clear indication of parental …

Obstetrician And Gynecologist Utilization Of The Nipt Expanded Testing Option, Sarah Mayes Ba

Dissertations and Theses (Open Access)

Noninvasive prenatal testing (NIPT) enables the detection of common fetal aneuploidies such as trisomy 21, trisomy 18, trisomy 13, and sex chromosome abnormalities via analysis of cell-free fetal DNA circulating in maternal serum. Although the accuracy of NIPT for fetal aneuploidy is expected to be higher than that of currently available alternative maternal serum screening options, the implications of results are not straight forward. In October 2013, the option to screen for additional trisomies and select microdeletion syndromes, such as 22q11.2 deletion syndrome and 5 p- syndrome, became clinically available. Due to this rapidly evolving prenatal screening technology, clinicians must …

Two-Color Fluorescent Analysis Of Connexin 36 Turnover And Trafficking – Relationship To Functional Plasticity, Yanran Wang

Dissertations and Theses (Open Access)

Gap junctions (GJ) formed of Cx36 show tremendous functional plasticity on several time scales. Changes in connexin phosphorylation modify coupling in minutes through an order of magnitude, but recent studies also imply involvement of connexin turnover in regulating cell-cell communication. We utilized Cx36 with an internal HaloTag to study Cx36 turnover and trafficking in cultured cells to discriminate newly formed and pre-existing Cx36. New Cx36 in cargo vesicles was added directly to existing gap junctions and newly made Cx36 was not confined to points of addition, but diffused throughout existing gap junctions. Existing connexins also diffused into photobleached areas with …

Investigation Of Genetic Alterations In Emt Suppressor, Dear1, Through Pan-Cancer Analysis And Ultra-Deep Targeted Sequencing In Ductal Carcinoma In Situ, Jacquelyn Reuther

Dissertations and Theses (Open Access)

Ductal carcinoma in situ (DCIS) is thought to be one of the earliest pre-invasive form of and non-obligate precursor to invasive ductal carcinoma (IDC). There is an urgent need to identify predictive and prognostic biomarkers for breast cancers with a heightened risk of progression from DCIS to IDC. Our laboratory has previously discovered a novel TRIM family member, DEAR1 (Ductal Epithelium Associated Ring Chromosome 1, annotated as TRIM62) within chromosome 1p35.1, that is mutated and homozygously deleted in breast cancer and whose expression is downregulated/lost in DCIS. Previous work has shown that DEAR1 is a novel tumor suppressor …

Igfbp2 Potentiates Egfr-Stat3 Signaling In Glioma, Yingxuan Chua

Dissertations and Theses (Open Access)

Gliomas are clinically challenging brain tumors with dismal survival rates due to its infiltrative nature and ineffective standard therapy. Insulin-like growth factor binding protein 2 (IGFBP2) is a pleiotropic oncogenic protein that has both extracellular and intracellular functions. Despite a clear causal role in cancer development, the contributions of intracellular IGFBP2 to tumor development and progression are poorly understood. Here we present evidence that both exogenous IGFBP2 treatment and cellular IGFBP2 overexpression lead to aberrant activation of EGFR, which subsequently activates STAT3 signaling. Furthermore, we demonstrate that IGFBP2 augments the nuclear accumulation of EGFR to potentiate STAT3 transactivation activities, via …

Genetics Of Obesity In Starr County, Texas Mexican Americans, Heather M. Highland

Dissertations and Theses (Open Access)

Currently, over two-thirds of Americans are classified as over-weight or obese. Obesity increases risk for many other diseases including type 2 diabetes, heart disease, stroke, and cancer, making obesity the largest public health problem in America and most other Westernized nations. Hispanics have a higher rate of both obesity and type 2 diabetes, making them a particularly interesting population in which to study obesity. For the last 33 years, the Starr County Health Studies has collected an array of phenotypes and biological samples from residents of Starr County, along Texas-Mexico border. This study includes 825 subjects who were not known …

The Effect Of Activation Induced Cytidine Deaminase Phosphorylation And Herpes Virus Uracil Dna Glycosylase On Antibody Diversification, Marc Macaluso

Dissertations and Theses (Open Access)

Activation-induced cytidine deaminase (AID) is a mutagenic enzyme that is expressed in mammalian B-cells and initiates the antibody diversification processes of somatic hypermuntation (SHM) and isotype class switch recombination (CSR). AID is targeted to the immunoglobulin gene locus where it deaminates cytosines to generate uracil residues in DNA. This generates guanine-uracil (U:G) mismatch lesion which are recognized by uracil DNA glycosylase (UNG), a DNA repair enzyme that removes uracil from DNA and triggers downstream repair of the lesion. While UNG is a ubiquitously expressed DNA repair enzyme, its recognition and removal of AID introduced uracils is essential in both SHM …

Investigation Of The Role Of The Scaffold Protein Shc In Erk Signaling, Kin Man Suen

Dissertations and Theses (Open Access)

Cells respond to environmental changes by converting extracellular signals into intracellular events. Scaffolding proteins play important roles in generating specificity in intracellular signaling through the combinatorial use of protein domains and posttranslational modifications. Using the scaffold Shc (Src-homology collagen-like) as a model system, we explored novel mechanisms whereby this class of protein shapes signaling output. In the present work, we focused on the role of Shc in the MAP kinase Erk signaling both prior to and post-growth factor stimulation. Prior to growth factor stimulation, we found Erk to be a direct interacting partner of Shc. The two proteins associate through …

Src Homology 2 Domain-Containing 5’-Inositol Phosphatase-2 (Ship2) Is An Effector Of Lymphatic Dysfunction, Germaine D. Agollah

Dissertations and Theses (Open Access)

The lymphatic system is essential for the transport of excess fluid, protein, and foreign materials from interstitial tissues to lymph nodes; for immune surveillance, and to maintain fluid homeostasis. Dysregulated lymphatics can be attributed to pathological conditions including tumor metastasis, inflammation, chronic wounds, obesity, blood vascular disorders, and lymphedema. Of these, lymphedema is the most extreme of lymphatic disorders and is represented by a spectrum of symptoms ranging from mild, subtle presentation to severe, disfiguring, overt presentation. Lymphedema is more manageable in the early stages of disease but severely reduces quality of life with progression. Due to lack of molecular …

Characterization Of The Roles Of Carma3 And Bcl10 In Virus-Triggered Rig-I/Mavs Signaling Pathway, Zhicheng Zhou Mr

Dissertations and Theses (Open Access)

After RNA virus infection, the innate immunity utilizes RIG-I family of receptors in the cytoplasm to initiate the production of type-I IFNs and proinflammatory cytokines by mitochondrial protein MAVS, which forms a prion-like structure to recruit TBK1and IKK complex to activate IRF3 and NF-κB, respectively. Herein, we revealed the important roles of CARMA3 and BCL10 in RIG-I/MAVS signaling pathway for the first time. CARMA3 or BCL10 deficient cells exhibited partially defective NF-κB activation but hyperactivation of TBK1-IRF3 signaling pathway upon ssRNA virus infection. It led to less production of IL6 but more production of type I IFNs and resulted in …

Targeting An Ancient Retrovirus During Melanoma Using Adoptive T Cells Therapy, Janani Krishnamurthy

Dissertations and Theses (Open Access)

Patients with metastatic melanoma have a poor prognosis due to resistance to conventional therapies. Thus, new targeted treatment strategies are required to improve therapeutic outcome. One prospective approach is to infuse T cells that are rendered specific for tumor-associated antigens (TAAs) preferentially expressed on melanoma cells. Recognition of cell-surface TAAs independent of major histocompatibility complex can be achieved by introducing a TAA-specific chimeric antigen receptor (CAR) on T cells using gene therapy. This approach is being used in clinical trials to adoptively transfer CD19-specific CAR⁺ T cells in patients with B-lineage malignancies. To generate T-cell therapy for melanoma we …

Nfat1 Contributes To Melanoma Tumor Growth And Metastasis By Regulating Il-8 And Mmp-3, Einav Shoshan

Dissertations and Theses (Open Access)

Studies from our laboratory have recently demonstrated that Gal-3 regulates autotaxin through NFAT1 and support melanoma progression. These findings prompted us to further study the role of NFAT1 in melanoma progression and metastasis. NFAT1 is a transcription factor that was first identified in immune cells, acting as a positive regulator of interleukin-2 by binding to its promoter during T cell activation. NFAT1 has an important role in the innate and adaptive immune response. In this dissertation I studied the mechanisms by which NFAT1 contributes to the acquisition of the melanoma metastatic phenotype.

To identify the role of NFAT1 in melanoma …

Elucidating The Role Of Rumi And O-Glucosylation In The Drosophila Eye, Amanda Haltom

Dissertations and Theses (Open Access)

Rumi is a protein O-glucosyltransferase that adds the sugar O-glucose onto the serine in the target sequence C-S-X-S-(P/A)-C found within properly folded EGF repeats. It was first discovered to modify the Drosophila Notch extracellular domain and to be required for Notch signaling in a temperature dependent manner, but other targets of Rumi remained unknown. Several other proteins in the Drosophila proteome harbor multiple consensus sequence highly predictive of O-glucose, including the transmembrane protein Crumbs and the secreted protein Eyes shut (Eys). Both of these proteins are required for proper eye development and mutations in their human homologs …

Dna Polymerase Θ (Polq) And The Cellular Defense Against Dna Damage, Matthew J. Yousefzadeh

Dissertations and Theses (Open Access)

In mammalian cells, DNA polymerase θ (POLQ) is an unusual specialized DNA polymerase whose in vivo function is under active investigation. The protein is comprised of an N-terminal helicase-like domain, a C-terminal DNA polymerase domain, and a large central domain that spans between the two. This arrangement is also found in the Drosophila Mus308 protein, which helps confer resistance to DNA interstrand crosslinking agents. Homologs of POLQ and Mus308 are found in eukaryotes, including plants, but a comparison of phenotypes suggests that not all of these genes are functional orthologs. Flies with defective Mus308 are sensitive to DNA interstrand crosslinking …

Cancer Associated Fibroblast Derived Angiogenic Factor Mfap5 In Ovarian Cancer Progression, Sze Lee Cecilia Leung

Dissertations and Theses (Open Access)

Advanced stage ovarian cancer is the most lethal gynecologic malignancy. No major improvement on patient survival has been achieved in the past decade. Therefore, identification of predictive or prognostic markers and further understanding of the molecular mechanisms in ovarian cancer progression are of paramount importance.

While cancer cells have always been the targets for the identification of prognostic and predictive markers, the potential for developing new diagnosis and treatments based on the tumor supporting stromal microenvironment is relatively unexplored. Using transcriptome profiling analysis on microdissected stromal and epithelial components of normal and malignant ovarian tissues, we identified a gene signature …

Synthetic Lethality Of Cdk Inhibition And Doxorubicin In Triple-Negative Breast Cancer Requires P53 Inactivation, Natalie A. Jabbour-Leung

Dissertations and Theses (Open Access)

Triple-negative breast cancer (TNBC) is an aggressive malignancy in which the tumors lack expression of estrogen receptor, progesterone receptor and HER2. As such, TNBC patients cannot benefit from clinically available targeted therapies and must rely on chemotherapy and surgery for treatment. While initially responding well to chemotherapy, TNBC patients are at increased risk of developing distant metastasis and have decreased overall survival compared to non-TNBC patients. A majority of TNBC tumors carry p53 mutations, enabling them to bypass the G1 checkpoint and complete the cell cycle even in the presence of DNA damage. Therefore, we hypothesized that TNBC cells are …

Sunitinib-Induced Cardiotoxicity Exposes Microvascular And Metabolic Derangements In The Failing Heart, Meredith R. Rodriguez

Dissertations and Theses (Open Access)

Cardiac dysfunction is one of the largest obstacles to effective cancer treatment. Not only do a growing number of cancer patients have significant cardiovascular risk factors at the time of diagnosis, but a number of targeted therapies can themselves cause cardiac dysfunction. These newer treatment options are also increasingly effective, placing a growing emphasis on post-cancer quality of life. In some instances, a patient may outlive his or her cancer only to succumb to heart failure in as little as five years. One such targeted therapy is the small molecular receptor tyrosine kinase sunitinib. Sunitinib was developed in the early …

Influx And Efflux Of Adenine Nucleotides From Erythrocytes Regulate Oxygen Transport And Systemic Metabolism, William G. O'Brien Iii

Dissertations and Theses (Open Access)

Erythrocytes are responsible for ensuring a sufficient supply of oxygen to meet activity demands. The mammalian erythrocytes primarily modulate their oxygen-carrying capacity by varying the levels of organic phosphates, such as 2,3-BPG. In other organisms, such as fish, ATP instead of 2,3-BPG is used to modulate their erythrocyte’s oxygen binding ability. Here, using a series of genetically modified mice, we investigated a previously unrecognized pathway of adenine nucleotide influx and efflux that modulates erythrocyte’s oxygen binding ability and controls systemic metabolism. Our studies show that the loss of AMPD3 and CD73, two important enzymes in regulating AMP levels intra- and …

Oxidative Protein Folding Pathways In Gram-Positive Actinobacteria, Melissa E. Robinson

Dissertations and Theses (Open Access)

Disulfide bonds are important for the stability of many secreted proteins. These covalent linkages, which result from the oxidation of neighboring cysteine (Cys) residues, are often rate-limiting steps for protein folding and maturation. Disulfide bond formation is restricted to extracellular oxidizing compartments like the eukaryotic endoplasmic reticulum and Gram-negative bacterial periplasm. Protein oxidation has been well-studied in these organisms, but largely ignored in Gram-positive bacteria. Due to the absence of an outer membrane, these organisms are thought to lack compartments in which to catalyze oxidative protein folding.

This thesis reveals that Gram-positive Actinobacteria use disulfide bond formation to help fold …