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Sex-Specific Effects And Gene-Sex Interactions In Serum Metabolome Levels: The Atherosclerosis Risk In Communities Study, Zhe Wang

Dissertations and Theses (Open Access)

Metabolomic signatures associated with complex disease have been identified. Metabolomic profiling and the integration of genomic data have proven to be powerful tools to investigate genetic effects underlying intermediate phenotype levels and may facilitate improved understanding of pathophysiologic processes of disease. However, most published studies did not consider sex as an effect modifier, analyze sex-specific effects, nor gene by sex interactions. One reason can be incomplete knowledge of the power of statistical methods used in a given dataset.

I first investigated sex-specific genetic effects by performing sex-stratified exome-wide association studies for 271 chromatography-mass spectrometry measured metabolites in the Atherosclerosis Risk …

Observed Cooking Behaviors Of Families With And Without Childhood Cancer Survivors And The Development Of A Healthy Cooking Assessment Tool, Margaret Pleta Raber

Dissertations and Theses (Open Access)

Diet is a modifiable risk factor for several cancers and other chronic diseases. Cooking skills are a target for dietary intervention, with much of the general population reporting infrequent and inadequate home preparation of meals. Childhood cancer survivors (CCS) are a population at high risk of several chronic conditions including secondary cancers that may be influenced by home cooking behaviors. We conducted observations of food preparation practices in 29 parents of healthy school-aged children and 11 parents of CCS. Observations included an audio and video recording of one evening meal per family. Parents were asked to wear a small body …

Impacts Of Cold Weather On Health In Texas, Tsun-Hsuan Chen

Dissertations and Theses (Open Access)

Recent events with recorded low temperature and unusual snow accumulation in the United States and Europe have raised the public awareness of the potential health impacts of extreme winter weather. Excessive cold was the leading cause of weather-related death during 2006-2010 in the U.S., accounting for 63% of weather related deaths. Several studies worldwide have demonstrated that, in general, mortality rates are higher in winter compared to summer. Studies have also shown that the association between cold temperature and death vary across cities, regions and countries and is especially relevant with decreasing latitude or in regions with mild winter climate. …

Investigation Of Hantavirus And Leptospira As Possible Contributing Factors Of The Unexplained Kidney Disease Epidemic In Nicaragua, Nicole J. Delgado

Dissertations and Theses (Open Access)

Throughout Latin America, an epidemic of a kidney disease of an unknown etiology has been occurring since the late 1990s, and this disease is being called “Mesoamerican nephropathy.” Mesoamerican nephropathy predominantly affects male sugarcane workers. In Chichigalpa, Chinandega, Nicaragua, there is sugarcane plantation that is being heavily impacted by the Mesoamerican nephropathy epidemic, and they invited researchers from Baylor College of Medicine to investigate the epidemic. The prospective epidemic investigation began in 2015, and it is an ongoing investigation. Based on the compilation of data collected during the preliminary investigation, our hypothesis is that a possible zoonotic disease, such as …

Exposure To Ambient Air Pollution And Fetal Death In Harris County, Texas, Amal Rammah

Dissertations and Theses (Open Access)

The evidence from studies of maternal ambient air pollutant exposure (including O3, fine particulate matter (PM2.5) and PM2.5 metal constituents) and stillbirth is limited and equivocal. There is also limited evidence of the acute effect of temperature increases in the week preceding delivery and stillbirth. In the first investigation of ambient air pollution, temperature and stillbirth among a large cohort of women in Harris County, Texas, we obtained birth and fetal death records from 2008-2013 and estimated weekly residential levels of apparent temperature and ozone (O3), fine particulate matter (PM2.5), nitrogen dioxide (NO2) and PM2.5 metals from the local monitoring …

Examining The Effect Of Service Delivery Factors On Timely Initiation Of Tuberculosis Treatment Within Primary Care Settings In Uganda, Michael Juma

Dissertations and Theses (Open Access)

Background: Timeliness of Tuberculosis (TB) treatment is critical to stopping its transmission and preventing disease complications and death. Efficiency in identifying and treating presumptive TB cases is critical to reducing delays.

Aims: We determined the association between health service-related factors and delays in initiating TB treatment within primary care settings in Uganda. Perspectives of healthcare workers on practices underlying healthcare facility level delays were also described.

Methods: A mixed methods study was conducted based on facility-register records of 1199 treated TB cases and key informant interviews with 27 outpatient staffs. Health service-related factors (size, ownership, number of …

Does Space Matter? An Investigation Of The Spatial Variation In Gestational Weight Gain Associations With Country Of Birth Among Hispanic Women And Access To Care In Texas, Christopher R. Webb

Dissertations and Theses (Open Access)

Inadequate and excess gestational weight gain (GWG) are serious, but potentially preventable adverse pregnancy outcomes which affect as many as two-thirds of pregnant women in the United States. While location and space are associated with a variety of pregnancy outcomes, limited research has investigated potential spatial variation in GWG. The goal of this research is to improve the knowledge of how spatial geography is associated with GWG through secondary analyses of 70,000 to 160,000 birth certificate registry records for Texas mothers with a live birth delivery in 2014. Specifically, this research attempts to assess whether access to obstetrics and gynecologist …

Adverse Childhood Experiences, Depression, And Resilience In African-American Adolescents, Jamie C. Freeny

Dissertations and Theses (Open Access)

Research shows that exposure to adverse childhood experiences (ACEs) is common among adolescents; however, no studies have examined the prevalence of ACEs in a racially homogenous sample of African-American adolescents. Thus, the present study examined the cumulative and individual prevalence of ACEs in African-American adolescents. Data were collected from African-American adolescents (n = 241) who attended youth events hosted by churches in Houston, TX. An expanded ACEs tool was used to collect data. ACE scores were summed and dichotomized to 0-3 ACEs versus 4-19 ACEs because a score of four or more indicates a higher risk for adverse mental and …

A Secondary Data Analysis For The Refinement Of Empirical Modelling For The Estimation Of Environmental Health & Safety Program Resourcing For Colleges And Universities, Seth Michael Parker

Dissertations and Theses (Open Access)

The use of potentially hazardous physical, chemical, biological, and radiological agents is inherent to the teaching, research, and services missions of any university. To manage the risks associated with these agents, it is common for universities to host environmental health & safety (EH&S) programs to protect the safety of the institution’s students, faculty, staff, and visitors. However, since EH&S programs in universities are primarily focused on prevention, it is difficult to estimate the appropriate “industry average” in terms of budget and staffing resources a particular university needs for such programs. Historically, the Campus Safety, Health, and Environmental Management Association (CSHEMA) …

Evaluation Of Presage® As A 3d Dose Verification To Ol In Proton Beams, Mitchell Carroll

Dissertations and Theses (Open Access)

Radiotherapy techniques have advanced and radiation dose plans have become much more complex over the last decade. This is especially true in proton therapy, which involves extremely steep dose gradients as a result of positioning the Bragg peak to cover the volumes to be treated. The Bragg peak can be shifted significantly in the patient as a result of nonuniformities in the tissue composition in its path, which can result in treatment complications. Some traditional dose verification tools used in proton beam commissioning and treatment plan verification are film, TLD, and ionization chambers. Such 0D and 2D dosimeters are incapable …

Intratumoral Sting Activation Sensitizes Poorly Immunogenic Cancers To Checkpoint Blockade Immunotherapy, Casey Ager

Dissertations and Theses (Open Access)

Unprecedented durable tumor regression can be achieved in patients with checkpoint blockade immunotherapy, yet these responses are rare and are not observed in all tumor types. Castration resistant prostate cancer (CRPC) and pancreatic adenocarcinoma (PDAC) are two common lethal cancers that remain refractory to checkpoint blockade, requiring development of new therapeutic approaches to promote responsivity in patients with these diseases. Both CRPC and PDAC are characterized by an immunosuppressive tumor milieu rich in cells of the myeloid lineage, which regulate T cell activity in many ways independent of the coinhibitory receptor axis. We investigated whether activation of acute inflammatory signaling …

Bayesian Integrative Analysis Of Omics Data, Youyi Zhang

Dissertations and Theses (Open Access)

Technological innovations have produced large multi-modal datasets that range in multiplatform genomic data, pathway data, proteomic data, imaging data and clinical data. Integrative analysis of such data sets have potentiality in revealing important biological and clinical insights into complex diseases like cancer. This dissertation focuses on Bayesian methodology establishment in integrative analysis of radiogenomics and pathway driver detection applied in cancer applications. We initially present Radio-iBAG that utilizes Bayesian approaches in analyzing radiological imaging and multi-platform genomic data, which we establish a multi-scale Bayesian hierarchical model that simultaneously identifies genomic and radiomic, i.e., radiology-based imaging markers, along with the latent …

Insights Into The Reactivation, Regulation And Essentiality Of Oxidative Protein Folding Pathways In Actinobacteria, Belkys Sanchez

Dissertations and Theses (Open Access)

Accurate disulfide bond formation is important for proper folding, stability and function of exported proteins. The process of disulfide bond formation, termed oxidative protein folding, is catalyzed by thiol-disulfide oxidoreductase enzymes. Oxidative protein folding pathways influence processes essential for bacterial physiology and pathogenicity. In the Gram-positive actinobacterial pathogens Actinomyces oris and Corynebacterium diphtheriae oxidative protein folding is catalyzed by the primary thiol-disulfide oxidoreductase MdbA. MdbA is required for assembly of adhesive pilus, which mediate receptor-dependent bacterial interactions, or coaggregation, in A. oris. In the first part of this dissertation, I identify components of the electron transport chain (ETC) required for …

Genetic Evolution And Prognostic Determinants Of Pancreatic Cancer On Longitudinal Liquid Biopsies, Vincent Bernard

Dissertations and Theses (Open Access)

Pancreatic ductal adenocarcinoma (PDAC) has one of the lowest 5-year survival rates amongst solid tumors. As early detection of PDAC is unusual and typically incidental, most patients present with locally advanced and metastatic disease where effective therapeutic strategies remain a significant unmet need. Specifically, surrogate biomarkers for tumor monitoring of PDAC may lead to improved elucidation of clinical actionability and prognostic potential. On the other hand, tumor tissue is rarely sampled in patients presenting with de novo or recurrent metastatic PDAC, apart from a fine needle aspiration or a core needle biopsy performed for diagnosis. This precludes the opportunity for …

The Role Of Tumor Suppressor Dear1 In The Acquisition Of Mammary Stem/Progenitor Cell Properties, Uyen Le

Dissertations and Theses (Open Access)

Breast cancer is the most commonly diagnosed cancer in women in America. Ductal carcinoma in situ (DCIS), one of the earliest pre-invasive forms of invasive ductal carcinoma (IDC), has a 30-50% risk of progressing to IDC. Understanding the mechanisms regulating progression from DCIS to IDC would help identify biomarkers to stratify patients at higher risk of progression or metastasis. Cumulative literature suggests the earliest phase of dissemination from the primary tumor is driven by the epithelial-mesenchymal transition (EMT) program. DEAR1 is a tumor suppressor gene which is mutated, undergoes loss of heterozygosity in breast cancer, and is downregulated in DCIS …

Involvement Of Gdap1 In The Regulation Of Mtorc1 Activity In A Drosophila Mliv Model, Kristen Clemons

Dissertations and Theses (Open Access)

The master regulator of metabolism and growth, mechanistic target of rapamycin complex 1 (mTORC1), is responsible for maintaining metabolic homeostasis by sensing nutrient and energy levels within the cell to promote or inhibit translation and autophagy accordingly. In the childhood neurodevelopmental disorder Mucolipidosis type IV (MLIV), mTORC1 activity is decreased. The underlying mechanism for reduced mTORC1 signaling in MLIV is poorly understood. The gene encoding ganglioside-induced differentiation associated protein 1 (GDAP1) is transcriptionally upregulated in MLIV. This project investigated the involvement of GDAP1 in MLIV disease pathology. Using the UAS/GAL4 system in an established MLIV Drosophila model, we …

A Compressed Sensing Approach To Detect Immobilized Nanoparticles Using Superparamagnetic Relaxometry, Sara Thrower

Dissertations and Theses (Open Access)

Superparamagnetic relaxometry (SPMR) is an emerging technology that leverages the unique properties of biologically targeted superparamagnetic iron oxide nanoparticles to detect cancer. The use of ultra-sensitive sensors enables SPMR to detect tumors ten times smaller than current imaging methods. Reconstructing the distribution of cancer-bound nanoparticles from SPMR measurements is challenging because the inverse problem is ill posed. Current methods of source reconstruction rely on prior knowledge of the number of clusters of bound nanoparticles and their approximate locations, which is not known in clinical applications. In this work, we present a novel reconstruction algorithm based on compressed sensing methods that …

Role Of P300 Zz Domain In Chromatin Association And Histone Acetylation, Yongming Xue

Dissertations and Theses (Open Access)

Transcription is strictly regulated by numerous factors including transcription coactivators. The p300 protein and its close paralogue CREB-binding protein (CREBBP, aka CBP) are well-known transcriptional coactivators that have intrinsic lysine acetyltransferase activity. The functions of p300/CBP largely rely on their capabilities to bind to chromatin and to acetylate the histone substrates. However, the molecular mechanisms underlying the regulation of these processes are not fully understood.

Through combination of various biochemical, biophysical and molecular approaches, we show that the ZZ-type zinc finger (ZZ) domain of p300 functions as a histone reader that specifically binds the N-terminal tail of histone H3. Crystal …

Behavioral Insights Into Nociceptor Function: A Systematic Approach To Understanding Postsurgical And Neuropathic Pain Mechanisms In Rats, Max Odem

Dissertations and Theses (Open Access)

Postsurgical and neuropathic pain are each clinically common, and often associated with ongoing pain. Ongoing pain has been linked to ongoing activity (OA) in human C-fiber nociceptors. Preclinical studies using rodent neuropathic models have concentrated on allodynia driven by OA generated in non-nociceptive Aβ fibers, but little attention has been paid to postsurgical pain in sham controls or to C-fiber nociceptor OA promoting ongoing pain.

Operant assays that reveal negative motivational and cognitive aspects of voluntary pain-related behavior may be particularly sensitive to pain-related alterations. In the mechanical conflict (MC) test, rodents can freely choose to escape from a brightly …

A Role For Epac1 And Epac2 In Nociceptor Hyperexcitability And Chronic Pain After Spinal Cord Injury, Samantha Berkey

Dissertations and Theses (Open Access)

Chronic pain is a major complaint of those living with spinal cord injury (SCI), affecting 65-80% of the SCI population, but the treatment options remain limited or non-existent. The cAMP sensor EPAC has previously been shown to play a key role in chronic inflammatory and neuropathic pain, though the contribution from each of its two main isoforms, EPAC1 and EPAC2, is unclear. Here I test the hypothesis that both EPAC1 and EPAC2 play a key role in the maintenance of persistent nociceptor hyperexcitability and chronic pain after SCI.

Using both a T9 SCI mouse model and a T10 SCI rat …

Adenylyl Cyclase Type 9: Regulation And Cardiac Function, Tanya A. Baldwin, Tanya A. Baldwin

Dissertations and Theses (Open Access)

Abnormalities in cardiac stress signaling underlie a number of cardiovascular diseases (e.g. arrhythmias and heart failure). Cardiac stress signaling pathways normally integrate signals from the sympathetic nervous system to promote efficient contraction and relaxation under stress. Sympathetic control through β-adrenergic stimulation is propagated by adenylyl cyclase (AC). AC synthesizes cyclic AMP (cAMP), an important second messenger that initiates signaling pathways to modulate physiological and pathophysiological functions of the heart, including the activation of PKA and subsequent phosphorylation of ion channels, contractile machinery, and stress response proteins that enhance cardiac function. Alterations of cAMP signaling occur in the failing heart and …

3d Scintillator Detector Quenching Characterization For Scanning Proton Beams, Fahed Alsanea

Dissertations and Theses (Open Access)

Proton pencil beam scanning is becoming the standard treatment delivery technique for proton therapy centers. Scanned proton pencil beams provide a highly conformal dose distribution. The complex dose distribution poses challenges for quality assurance measurements leading to sophisticated detector setups and time consuming measurements. Fast 3D measurements are therefore desirable to verify the complex dose distribution and to enable the utilization of the full potential of proton therapy. The overall objective of this project is to improve volumetric scintillators detectors to provide 3D measurements for applications for beam commissioning, quality assurance program, and patient-specific treatment delivery verification.

Detectors based on …

Integrative Bioinformatics Approaches To Elucidating Prostate Cancer Cell Heterogeneity, Plasticity, And Treatment Response, Hsueh-Ping Chao

Dissertations and Theses (Open Access)

Prostate cancer (PCa) is the most common non-cutaneous tumor in American men, and the second leading cause of cancer-related deaths. PCa-related deaths can be attributed to heterogeneous tumors containing metastatic and therapy-resistant cancer cells. Cancer stem cells (CSC) are an important contributor to this tumor heterogeneity, which are present in primary tumors and become enriched in castration resistant PCa (CRPC). Our lab has demonstrated that the prostate cancer stem cells (PCSCs) are enriched in the phenotypically undifferentiated PCa cell population that lacks the expression of differentiation marker prostate-specific antigen (PSA). Our work has also demonstrated that PCa cells manifest significant …

Investigation Of Novel Virulence Mechanisms In Candida Albicans, Elisa Marie Tafoya Vesely

Dissertations and Theses (Open Access)

Candida albicans is the most important fungal species associated with humans. Normally present in the human microbiome as a commensal colonizer, C. albicans is also the fourth most prevalent organism isolated from bloodstream infections in hospitals. Disseminated infections have an associated mortality rate of around 40%. The results of the work described in this dissertation cover the broad subject of C. albicans adaptation to the host and the mechanisms by which this organism is able to survive and cause infection through a variety of means. A key determinant in disease progression is interaction with innate immune cells, specifically macrophages and …

Improving Dbnsfp, Mingyao Lu

Dissertations and Theses (Open Access)

IMPROVING dbNSFP

Mingyao Lu, B.S.

Advisory Professor: Xiaoming Liu, Ph.D.

The analysis and interpretation of DNA variation are very important for the Whole Exome studies (WES). Genome research has focused on single nucleotide variants (SNVs). Since indels are as important as SNVs, especially indels in coding regions are often candidates of disease-causing variants, thus, it is necessary to expand the focus to include indel mutations.

The goal of my project is to provide an automatic annotation pipeline to the WES based disease studies project by extending the dbNSFP with a tool for automated indel annotation and deleteriousness prediction. The current …

Il-1Α Blockade Reduces Immune Suppression In The Early Tumor Micro-Environment, Brenda Melendez

Dissertations and Theses (Open Access)

IL-1α Blockade Reduces Immune Suppression in the Early Tumor Micro-Environment

Brenda Melendez, B.S.

Advisory Professor: Gregory Lizee, PhD.

Immunotherapy against melanoma has shown great promise in the clinic for treating advanced-stage patients. However, a major barrier against effective T cell mediated cytotoxicity is immunosuppression in the tumor micro-environment. It has been described that tumors secrete pro-inflammatory cytokines capable of modulating immune responses that favors the growth of tumor cells. Specifically, IL-1 plays a critical role in myeloid cell recruitment and activation, which can in turn inhibit T cell activity in vivo. Moreover, IL-1 is also known to up-regulate immune inhibitory …

Heme Peroxidase Hpx-2 Protects Caenorhabditis Elegans From Pathogens, Yi Liu

Dissertations and Theses (Open Access)

Heme-containing peroxidases are important components of innate immunity. Many of them functionally associate with NADPH oxidase (NOX)/dual oxidase (DUOX) enzymes by using the hydrogen peroxide they generate in downstream reactions. In Caenorhabditis elegans, a ShkT-containing peroxidase, SKPO-1, and the dual oxidase, BLI-3, contribute to resistance against the human pathogen Enterococcus faecalis, likely functioning in conjunction with each other. However, the exact mechanism(s) by which peroxidases and NOX/DUOXs contribute to pathogen resistance remain unclear. Here, we demonstrated that another peroxidase, HPX-2 (Heme-PeroXidase 2), is required for resistance against some, but not all pathogens. Tissue specific …

Vaccine Myths: Setting The Record Straight, Julie A. Boom, Rachel M. Cunningham, Lindy U. Mcgee

Journal of Family Strengths

Despite their standing as one of the most remarkable public health achievements, vaccines have been surrounded by dangerous myths since the development of the smallpox vaccine in the 18th century. In recent decades, with the publication of a fraudulent article linking vaccines to autism, the involvement of celebrities in the debate, and the rise of the internet and social media as sources for information for patients, these myths have become more widespread. This paper reviews four common vaccine myths: vaccines cause autism, vaccines are not safe, too many vaccines are given too soon, and the influenza vaccine is not necessary. …

Book Review: The Study Of Violent Crime: Its Correlates And Concerns, Richard Riner

Journal of Family Strengths

Mire, S. and Roberson, C. The Study of Violent Crime: Its Correlates and Concerns. Boca Raton, FL Taylor and Francis. (2011). $90.95 (Hardback), ISBN 9781439807477.

Exome Sequencing Identifies Gene Variants And Networks Associated With Extreme Respiratory Outcomes Following Preterm Birth, Aaron Hamvas, Rui Feng, Yingtao Bi, Fan Wang, Soumyaroop Bhattacharya, Jared Mereness, Madhurima Kaushal, C Michael Cotten, Philip L Ballard, Thomas J Mariani

Faculty, Staff and Student Publications

BACKGROUND: Previous studies have identified genetic variants associated with bronchopulmonary dysplasia (BPD) in extremely preterm infants. However, findings with genome-wide significance have been rare, and not replicated. We hypothesized that whole exome sequencing (WES) of premature subjects with extremely divergent phenotypic outcomes could facilitate the identification of genetic variants or gene networks contributing disease risk.

RESULTS: The Prematurity and Respiratory Outcomes Program (PROP) recruited a cohort of > 765 extremely preterm infants for the identification of markers of respiratory morbidity. We completed WES on 146 PROP subjects (85 affected, 61 unaffected) representing extreme phenotypes of early respiratory morbidity. We tested for …