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Complex Mental Health Sequelae Of Psychological Trauma Among Women In Prenatal Care, Julian D. Ford

UCHC Articles - Research

Pregnancy is a critical time to identify and address maternal mental health problems, for the health of both mother and child. Pregnant women with histories of exposure to interpersonal psychological trauma may experience a range of mental health problems including but not limited to posttraumatic stress disorder (PTSD). In a community sample of 1,581 pregnant women, 25% reported symptoms consistent with at least one of six syndromes, including PTSD, major depressive disorder (MDD), generalized anxiety disorder (GAD), or clinically significant dissociation, somatization, or affect dysregulation. Six sub-groups with distinct mental health problem profiles were identified by cluster analysis. Controlling for …

Toward A Robust Computational Screening Strategy For Identifying Glycosaminoglycan Sequences That Display High Specificity For Target Proteins, Nehru Viji Sankaranarayanan, Umesh R. Desai

Medicinal Chemistry Publications

Glycosaminoglycans (GAGs) interact with many proteins to regulate processes such as hemostasis, cell adhesion, growth and differentiation and viral infection. Yet, majority of these interactions remain poorly understood at a molecular level. A major reason for this state is the phenomenal structural diversity of GAGs, which has precluded analysis of specificity of their interactions. We had earlier presented a computational protocol for predicting “high-specificity” GAG sequences based on combinatorial virtual library screening (CVLS) technology. In this work, we expand the robustness of this technology through rigorous studies of parameters affecting GAG recognition of proteins, especially antithrombin and thrombin. The CVLS …

Associations Between U.S. Adult Obesity And State And County Economic Conditions In The Recession, Qi Zhang, Rajan Lamichhane, Youfa Wang

Community & Environmental Health Faculty Publications

This study examines the association between state and county unemployment rates and individuals' body weight status during the latest recession in the U.S. We used the U.S. Behavioral Risk Factor Surveillance System (BRFSS) data in 2007, 2009 and 2011, which were collected from 722,692 American adults aged 18 or older. Overweight and obesity were defined as body mass index (BMI) ≥25, and ≥30, respectively. Multivariate linear and logistic regressions were applied to assess the association between BMI, risks of overweight and obesity, and state and county unemployment rates. State unemployment rates were negatively associated with individual BMI across years, while …

Mapping Genes With Longitudinal Phenotypes Via Bayesian Posterior Probabilities, Anthony Musolf, Alejandro Q. Nato Jr., Douglas Londono, Lisheng Zhou, Tara C. Matise, Derek Gordon

Biochemistry and Microbiology

Most association studies focus on disease risk, with less attention paid to disease progression or severity. These phenotypes require longitudinal data. This paper presents a new method for analyzing longitudinal data to map genes in both population-based and family-based studies. Using simulated systolic blood pressure measurements obtained from Genetic Analysis Workshop 18, we cluster the phenotype data into trajectory subgroups. We then use the Bayesian posterior probability of being in the high subgroup as a quantitative trait in an association analysis with genotype data. This method maintains high power (>80%) in locating genes known to affect the simulated phenotype …

Cranberry Metabolites With Urinary Anti-Adhesion Activity, Christina M. Coleman

Electronic Theses and Dissertations

The fruit of the American cranberry (Vaccinium macrocarpon Aiton, Ericaceae) is a comfood and a top selling dietary supplement in the U.S. Cranberry juice is traditionally used for the prevention of urinary tract infections (UTIs), many of which are caused by P-fimbriated Escherichia coli. Human urine produced after cranberry juice consumption can prevent E. coli adhesion, but the urinary metabolites responsible for this activity are currently not known. High-molecular weight components of cranberry juice, specifically proanthocyanidin oligomers (PACs), are currently believed to be responsible for the ability of cranberry juice to prevent UTIs. Cranberry PACs can prevent the adherence of …

Structure, Synthesis And Biological Activity Of Harmful Algal Bloom Toxins From Karlodinium Sp. And Exploration Of Microbial Derived Natural Products, Amanda Leigh Waters

Electronic Theses and Dissertations

This work features natural products isolated from both the marine and microbial environments. Part I focuses on the elucidation of toxins from harmful algal blooms (HAB). The HAB dinoflagellate Karlodinium veneficum produces a harmful suite of molecules identified as the karlotoxins (KmTx) that have been implicated in massive fish kills pan-globally. Nine new karlotoxin congeners were isolated from various Karlodinium blooms around the world and utilizing the structure of KmTx2 were characterized using overlaid 2D NMR techniques. Due to the contrasting conformational differences between KmTx and the closely related amphidinols, the absolute configuration of KmTx was further evaluated by extensive …

Isolation And Characterization Of Multipotent Lung Stem Cells From P53 Mutant Mice Models, Venkat Sundar Gadepalli

Theses and Dissertations

Recent advances in understanding lung biology have shown evidence for the existence of resident lung stem cells. Independent studies in identifying and characterizing these somatic lung stem cells have shown the potential role of these cells in lung repair and regeneration. Understanding the functional characteristics of these tissue resident stem/progenitor cells has gained much importance with increasing evidence of cancer stem cells, cells in a tumor tissue with stem cell characteristics. Lung cancer is most commonly characterized by loss of p53 function which results in uncontrolled cell divisions. Incidence of p53 point mutations is highest in lung cancer, with a …

Characterization Of A Putative Tonb Deficient Porphyromonas Gingivalis Mutant, Soheil Rostami

Theses and Dissertations

Porphorymonas gingivalis is one of the major bacterial pathogens responsible for the initiation and progression of periodontal disease. The bacterium requires hemin uptake for its growth and has developed sophisticated mechanisms to extract hemin from hemin containing proteins in the oral cavity. Hemin first binds to receptors on the surface of P. gingivalis and is then taken up in an energy dependent manner. TonB is an inner membrane bound protein that spans the periplasm and is believed to be involved in the passage of hemin through the double membrane of P. gingivalis. However, the TonB protein in P. gingivalis is …

Molecular Profiling In Cervical Carcinogenesis And Progression, Kathryn Elizabeth Royse

All ETDs from UAB

Coexisting lesions can reduce genomic heterogeneity in precancer progression analysis by reducing variation and bias that can mask gene effects. Our goal was to use novel methodologies to depict the neoplastic stage effect (Normal v. LSIL v. HSIL) in cervical precancer. We analyzed the neoplastic stage effect via in silico and in vivo methodologies. For in silico analyses, we calculated differential expression (DE) estimates from a systematic review of DNA methylation and gene expression literature. Significant genes (FC≤2.0 or p-value≥0.05) were grouped by histology for pathway analysis. For in vivo analyses, we performed RNA-seq on microdissected FFPE coexisting cervical tissue …

The Increasing Weight Of Regulation: Countries Combat The Global Obesity Epidemic, Allyn L. Taylor, Emily W. Parento, Laura A. Schmidt

Georgetown Law Faculty Publications and Other Works

Obesity is a global epidemic, exacting an enormous human and economic toll. In the absence of a comprehensive global governance strategy, states have increasingly employed a wide array of legal strategies targeting the drivers of obesity. This article identifies recent global trends in obesity-related legislation and makes the normative case for an updated global governance strategy.

National governments have responded to the epidemic both by strengthening traditional interventions and by developing novel legislative strategies. This response consists of nine important trends: (1) strengthened and tailored tax measures; (2) broader use of counter-advertising and health campaigns; (3) expanded food labeling; (4) …

Expression And Clinical Implications Of P53, P63, And P73 Protein In Malignant Tumor Of The Parotid Gland, Mei Yong, Ling Yang, Qimuge Suyila, Wenyan Han, Hongwei Yuan, Cheng Zhao, Xiulan Su

Turkish Journal of Medical Sciences

To investigate the expression of P53, P63, and P73 proteins in malignant parotid gland tumors and adjacent nonneoplastic tissues and the association between the 3 proteins and their clinical characteristics. Materials and methods: A total of 40 pairs of paraffin-embedded malignant parotid gland tumors and adjacent nonneoplastic tissues were collected. We detected P53, P63, and P73 protein expression by immunohistochemistry. Statistical analysis was performed by using the chi-square test. Results: P53, P63, and P73 protein expression in malignant parotid gland tumors was higher than their expression in adjacent nonneoplastic tissue (P = 0.030, 0.001, and 0.001, respectively). Expression of P53, …

Biomarkers Of Alzheimer's Disease Risk In Peripheral Tissues; Focus On Buccal Cells, Maxime François, Wayne Leifert, Ralph Martins, Philip Thomas, Michael Fenech

Research outputs 2014 to 2021

Alzheimer's disease (AD) is a progressive degenerative disorder of the brain and is the most common form of dementia. To-date no simple, inexpensive and minimally invasive procedure is available to confirm with certainty the early diagnosis of AD prior to the manifestations of symptoms characteristic of the disease. Therefore, if population screening of individuals is to be performed, more suitable, easily accessible tissues would need to be used for a diagnostic test that would identify those who exhibit cellular pathology indicative of mild cognitive impairment (MCI) and AD risk so that they can be prioritized for primary prevention. This need …

Bismuth Nanoparticles As Medical X-Ray Contrast Agents: Synthesis, Characterization And Applications, Anna Laura Brown

Dissertations and Theses

Bismuth based nanomaterials have recently attracted attention as heavy element X-ray contrast agents because of the high atomic number and predicted biological compatibility of bismuth. Nanoparticle X-ray contrast agents may enable a number of novel medical imaging applications, including blood pool and site-directed imaging. However these hypothetical applications are hindered by lack of suitable synthetic methods for production of imaging agents. This dissertation describes synthesis of a novel class of bismuth nanoparticles that are aqueously stabilized using poly and monosaccharides. These particles are synthesized using highly biologically compatible reagents and are oxidatively stable in water and in moderately basic buffered …

Layered Long Term Co-Culture Of Hepatocytes And Endothelial Cells On A Transwell Membrane: Toward Engineering The Liver Sinusoid, Young Bok (Abraham) Kang, Siddhartha Rawat, Joseph Cirillo, Michael Bouchard, Hongseok (Moses) Noh

Faculty Publications - Biomedical, Mechanical, and Civil Engineering

This paper presents a novel liver model that mimics the liver sinusoid where most liver activities occur. A key aspect of our current liver model is a layered co-culture of primary rat hepatocytes (PRHs) and primary rat liver sinusoidal endothelial cells (LSECs) or bovine aortic endothelial cells (BAECs) on a transwell membrane. When a layered co-culture was attempted with a thin matrigel layer placed between hepatocytes and endothelial cells to mimic the Space of Disse, the cells did not form completely separated monolayers. However, when hepatocytes and endothelial cells were cultured on the opposite sides of a transwell membrane, PRHs …

Cell-Based Multi-Parametric Model Of Cleft Progression During Submandibular Salivary Gland Branching Morphogenesis, Shayoni Ray, Daniel Yuan, Nimit Dhulekar, Basak Oztan, Bu¨Lent Bu¨Lent Yener, Melinda Larsen

Biological Sciences Faculty Scholarship

Cleft formation during submandibular salivary gland branching morphogenesis is the critical step initiating the growth and development of the complex adult organ. Previous experimental studies indicated requirements for several epithelial cellular processes, such as proliferation, migration, cell-cell adhesion, cell-extracellular matrix (matrix) adhesion, and cellular contraction in cleft formation; however, the relative contribution of each of these processes is not fully understood since it is not possible to experimentally manipulate each factor independently. We present here a comprehensive analysis of several cellular parameters regulating cleft progression during branching morphogenesis in the epithelial tissue of an early embryonic salivary gland at a …

Bdnf In The Dentate Gyrus Is Required For Consolidation Of "Pattern-Separated" Memories., Pedro Bekinschtein, Brianne A Kent, Charlotte A Oomen, Gregory D Clemenson, Fred H Gage, Lisa M Saksida, Timothy J Bussey

Brain and Mind Institute Researchers' Publications

Successful memory involves not only remembering information over time, but also keeping memories distinct and less confusable. The computational process for making representations for similar input patterns more distinct from each other has been referred to as "pattern separation." In this work, we developed a set of behavioral conditions that allowed us to manipulate the load for pattern separation at different stages of memory. Thus, we provide experimental evidence that a brain-derived neurotrophic factor (BDNF)-dependent pattern separation process occurs during the encoding/storage/consolidation, but not the retrieval stage of memory processing. We also found that a spontaneous increase in BDNF in …

Evidence For Finely-Regulated Asynchronous Growth Of Toxoplasma Gondii Cysts Based On Data-Driven Model Selection, Adam M. Sullivan, Xiaopeng Zhao, Yasuhiro Suzuki, Eri Ochiai, Stephen Crutcher, Michael A. Gilchrist

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Toxoplasma gondii establishes a chronic infection by forming cysts preferentially in the brain. This chronic infection is one of the most common parasitic infections in humans and can be reactivated to develop life-threatening toxoplasmic encephalitis in immunocompromised patients. Host-pathogen interactions during the chronic infection include growth of the cysts and their removal by both natural rupture and elimination by the immune system. Analyzing these interactions is important for understanding the pathogenesis of this common infection. We developed a differential equation framework of cyst growth and employed Akaike Information Criteria (AIC) to determine the growth and removal functions that best describe …

Disruption Of Drosophila Melanogaster Lipid Metabolism Genes Causes Tissue Overgrowth Associated With Altered Developmental Signaling., Takeshi Sasamura, Kenji Matsuno, Mark E Fortini

Department of Biochemistry and Molecular Biology Faculty Papers

Developmental patterning requires the precise interplay of numerous intercellular signaling pathways to ensure that cells are properly specified during tissue formation and organogenesis. The spatiotemporal function of many developmental pathways is strongly influenced by the biosynthesis and intracellular trafficking of signaling components. Receptors and ligands must be trafficked to the cell surface where they interact, and their subsequent endocytic internalization and endosomal trafficking is critical for both signal propagation and its down-modulation. In a forward genetic screen for mutations that alter intracellular Notch receptor trafficking in Drosophila melanogaster, we recovered mutants that disrupt genes encoding serine palmitoyltransferase and acetyl-CoA carboxylase. …

Altered Cholesterol Metabolism In Human Cancers Unraveled By Label-Free Spectroscopic Imaging, Shuhua Yue

Open Access Dissertations

Despite tremendous scientific achievements, cancer remains the second leading cause of death in the United States. Metabolic reprogramming has been increasingly recognized as a core hallmark of cancer. My dissertation work identified novel diagnostic markers and therapeutic targets for human cancers through the study of cholesterol in cancer cells.

Enabled by label-free Raman spectromicroscopy, we performed the first quantitative analysis of lipogenesis at single cell level in human patient cancerous tissues. Our imaging data revealed an unexpected, aberrant accumulation of esterified cholesterol in lipid droplets of high-grade prostate cancer and metastases, but not in normal prostate, benign prostatic hyperplasia, or …

Small Molecule Antagonists Of Melanopsin-Mediated Phototransduction, Kenneth A. Jones, Megumi Hatori, Ludovic S. Mure, Jayne R. Bramley, Roman Artymyshyn, Sang-Phyo Hong, Mohammad Marzabadi, Huailing Zhong, Jeffrey Sprouse, Quansheng Zhu, Andrew T. E. Hartwick, Patricia J. Sollars, Gary E. Pickard, Satchidananda Panda

School of Veterinary and Biomedical Sciences: Faculty Publications

Melanopsin, expressed in a subset of retinal ganglion cells, mediates behavioral adaptation to ambient light and other non-image forming photic responses. This has raised the possibility that pharmacological manipulation of melanopsin can modulate several CNS responses including photophobia, sleep, circadian rhythms and neuroendocrine function. Here we describe the identification of a potent synthetic melanopsin antagonist with in vivo activity. Novel sulfonamide compounds inhibiting melanopsin (opsinamides) compete with retinal binding to melanopsin and inhibit its function without affecting rod/cone mediated responses. In vivo administration of opsinamides to mice specifically and reversibly modified melanopsin-dependent light responses including the pupillary light reflex and …

Solvent Dependency Of The Uv-Vis Spectrum Of Indenoisoquinolines: Role Of Keto-Oxygens As Polarity Interaction Probes., Andrea Coletta, Silvia Castelli, Giovanni Chillemi, Nico Sanna, Mark S. Cushman, Yves Pommier, Alessandro Desideri

Borch Department of Medicinal Chemistry and Molecular Pharmacology Faculty Publications

Indenoisoquinolines are the most promising non-campthotecins topoisomerase IB inhibitors. We present an integrated experimental/computational investigation of the UV-Vis spectra of the IQNs parental compound (NSC314622) and two of its derivatives (NSC724998 and NSC725776) currently undergoing Phase I clinical trials. In all the three compounds a similar dependence of the relative absorption intensities at 270 nm and 290 nm on solvent polarity is found. The keto-oxygens in positions 5 and 11 of the molecular scaffold of the molecule are the principal chromophores involved in this dependence. Protic interactions on these sites are also found to give rise to absorptions at wavelengthsolution, …

Adoptive T Cell Therapy For Metastatic Colorectal Cancer, Shauna Ebanks

Summer Training Program in Cancer Immunotherapy

Colorectal cancer is the second leading cause of cancer-related death in US (1). Most of the mortality reflects local, regional and distant metastatic tumors. Cancers that are confined within the wall of the colon are often curable with surgery while tumor cells that have spread into other organs like liver and lung has low curable possibility, even though the chemotherapies and monoclonal antibodies can extend the person's life and improve quality of life(2, 3). Surgery is the main treatment for primary colorectal tumors but recurrence can happen and develop into metastasis. In addition, colorectal cancer …

Enhanced Nicotine Self-Administration And Suppressed Dopaminergic Systems In A Rat Model Of Diabetes, Laura O'Dell

Departmental Papers (Psych)

Patients with diabetes display a heightened propensity to use tobacco; however, it is unclear whether they experience enhanced rewarding effects of nicotine. Thus, this study examined the reinforcing effects of nicotine in a rodent model of diabetes involving administration of streptozotocin (STZ), a drug that is toxic to pancreatic insulin-producing cells. The first study compared STZ- and vehicle-treated rats that had 23-hour access to intravenous self-administration (IVSA) of nicotine or saline and concomitant access to food and water. In order to examine the contribution of dopamine to our behavioral effects, dopamine transporter (DAT), D1 and D2 receptor levels were compared …

Conformational Dynamics Of K-Ras And H-Ras Proteins: Is There Functional Specificity At The Catalytic Domain?, Nandini Rambahal

Dissertations and Theses (Open Access)

Ras proteins serve as crucial signaling modulators in cell proliferation through their ability to hydrolyze GTP and exist in a GTP “on” state and GTP “off” state. There are three different human Ras isoforms: H-ras, N-ras and K-ras (4A and 4B). Although their sequence identity is very high at the catalytic domain, these isoforms differ in their ability to activate different effectors and hence different signaling pathways. Much of the previous work on this topic has attributed this difference to the hyper variable region of Ras proteins, which contains most of the sequence variance among the isoforms and encodes specificity …

Transcription Factor Binding Profiles Reveal Cyclic Expression Of Human Protein-Coding Genes And Non-Coding Rnas, Chao Cheng, Matthew Ung, Gavin D. Grant, Michael L. Whitfield

Dartmouth Scholarship

Cell cycle is a complex and highly supervised process that must proceed with regulatory precision to achieve successful cellular division. Despite the wide application, microarray time course experiments have several limitations in identifying cell cycle genes. We thus propose a computational model to predict human cell cycle genes based on transcription factor (TF) binding and regulatory motif information in their promoters. We utilize ENCODE ChIP-seq data and motif information as predictors to discriminate cell cycle against non-cell cycle genes. Our results show that both the trans- TF features and the cis- motif features are predictive of cell cycle genes, and …

Relationship Between Serum And Brain Carotenoids, Α-Tocopherol, And Retinol Concentrations And Cognitive Performance In The Oldest Old From The Georgia Centenarian Study, Elizabeth J. Johnson, Rohini Vishwanathan, Mary Ann Johnson, Dorothy B. Hausman, Adam Davey, Tammy M. Scott, Robert C. Green, L. Stephen Miller, Marla Gearing, John Woodard, Peter T. Nelson, Hae-Yun Chung, Wolfgang Schalch, Jonas Wittwer, Leonard W. Poon

Sanders-Brown Center on Aging Faculty Publications

Oxidative stress is involved in age-related cognitive decline. The dietary antioxidants, carotenoids, tocopherols, and vitamin A may play a role in the prevention or delay in cognitive decline. In this study, sera were obtained from 78 octogenarians and 220 centenarians from the Georgia Centenarian Study. Brain tissues were obtained from 47 centenarian decedents. Samples were analyzed for carotenoids, α-tocopherol, and retinol using HPLC. Analyte concentrations were compared with cognitive tests designed to evaluate global cognition, dementia, depression and cognitive domains (memory, processing speed, attention, and executive functioning). Serum lutein, zeaxanthin, and β-carotene concentrations were most consistently related to better cognition …

Proteomic Studies Of The Influenza Virus-Human Cell Interactions: The Responses Of Host Cell Protein Expression To Viral Infection And The Novel Host Proteins That Interact With Virus Protein Ns1, Yimeng Wang

Graduate Theses and Dissertations

Influenza A viruses (IAVs) continue to be a threat to human health. Despite extensive studies, the mechanisms underlying the IAVs-host interactions during IAV infection remain elusive. We employed quantitative proteomic methods to systematically explore the host cell protein expression responses to IAV infection and examine the function of a critical IAV protein called NS1 by identifying its host binding partners. Specifically, we used a 2-dimentional gel electrophoresis (2-DE) based proteomic method to screen host proteins whose expression was substantially altered by IAV. One critical protein named IκB kinase-gamma (IKKγ) was found to be significantly down-regulated during IAV infection. Functional studies …

Ovarian Modifications In Mice Exposed To Whole-Body Irradiation., Jacob Marion Poole

Undergraduate Honors Theses

This experiment was designed to determine the involvement of varying levels of whole-body irradiation on ovarian follicular and corpora luteal development in mice. Previous research has indicated reduced counts of ovarian follicles and corpora lutea in mice flown in space. These differences may be the result of microgravity, increased exposure to radiation, or some combination of both. Fifty-six mice were divided into three groups (apocynin-treated, nox2 knockout, and wild-type control) before exposure to 0 Gy, 0.5 Gy, or 2.0 Gy radiation. The tissues were harvested, preserved, run through the appropriate paraffin embedding procedures, serially sectioned, mounted on microscope slides, and …

A Key New Ally In The Search For Huntington’S Disease Treatments, Kenneth P. Serbin

At Risk for Huntington's Disease

No abstract provided.

Fertile Lands And Bodies: Connecting The Green Revolution, Pesticides, And Women’S Reproductive Health, Sarah M.K. Cycon

Pitzer Senior Theses

Environmentalists, social scientists, and economists have long critiqued the enduring impacts of the Green Revolution’s diffusion of agricultural technologies throughout the Global South. However, largely missing from the myriad analyses is the relationship between those technologies, namely pesticides, and health outcomes. This thesis explores the social and biological mechanisms through which excessive pesticide use culminated into adverse reproductive health outcomes for rural women in the Global South. Drawing together the history of the Green Revolution’s use of DDT, its social and economic impacts, and the biology of pesticide contamination in women’s bodies exposes how the Green Revolution situated women in …