Digital Commons Network^™

An Autism-Linked Missense Mutation In Shank3 Reveals The Modularity Of Shank3 Function, Li Wang, Kaifang Pang, Kihoon Han, Carolyn J Adamski, Wei Wang, Lingjie He, Jason K Lai, Vitaliy V Bondar, Joseph G Duman, Ronald Richman, Kimberley F Tolias, Patrick Barth, Timothy Palzkill, Zhandong Liu, J Lloyd Holder, Huda Y Zoghbi

Faculty, Staff and Students Publications

Genome sequencing has revealed an increasing number of genetic variations that are associated with neuropsychiatric disorders. Frequently, studies limit their focus to likely gene-disrupting mutations because they are relatively easy to interpret. Missense variants, instead, have often been undervalued. However, some missense variants can be informative for developing a more profound understanding of disease pathogenesis and ultimately targeted therapies. Here we present an example of this by studying a missense variant in a well-known autism spectrum disorder (ASD) causing gene SHANK3. We analyzed Shank3's in vivo phosphorylation profile and identified S685 as one phosphorylation site where one ASD-linked variant has …

Usability Testing Of A Sensor-Controlled Digital Game To Engage Older Adults With Heart Failure In Physical Activity And Weight Monitoring, Kavita Radhakrishnan, Christine Julien, Matthew O'Hair, Thomas Baranowski, Grace Lee, Catherine Allen, Atami Sagna, Edison Thomaz, Miyong Kim

Faculty, Staff and Students Publications

BACKGROUND: Poor self-management of heart failure (HF) has contributed to poor health outcomes. Sensor-controlled digital games (SCDGs) integrates data from behavior-tracking sensors to trigger progress, rewards, content, and positive feedback in a digital game to motivate real-time behaviors.

OBJECTIVES: To assess the usability of an SCDG prototype over a week of game-playing among 10 older adults with HF in their homes.

METHODS: During initial play, participants' SCDG experiences were observed in their homes using a checklist based on the seven-item Serious Game User Evaluator (SeGUE) instrument. After a week of game-playing, participants completed a survey guided by the Intrinsic Motivation …

Mir-30a Targets Gene Networks That Promote Browning Of Human And Mouse Adipocytes, Pradip K Saha, Mark P Hamilton, Kimal Rajapakshe, Vasanta Putluri, Jessica B Felix, Peter Masschelin, Aaron R Cox, Mandeep Bajaj, Nagireddy Putluri, Cristian Coarfa, Sean M Hartig

Faculty, Staff and Students Publications

MicroRNA-30a (miR-30a) impacts adipocyte function, and its expression in white adipose tissue (WAT) correlates with insulin sensitivity in obesity. Bioinformatic analysis demonstrates that miR-30a expression contributes to 2% of all miRNA expression in human tissues. However, molecular mechanisms of miR-30a function in fat cells remain unclear. Here, we expanded our understanding of how miR-30a expression contributes to antidiabetic peroxisome proliferator-activated receptor-γ (PPARγ) agonist activity and metabolic functions in adipocytes. We found that WAT isolated from diabetic patients shows reduced miR-30a levels and diminished expression of the canonical PPARγ target genes ADIPOQ and FABP4 relative to lean counterparts. In human adipocytes, …

Application Of Human Factors Methods To Understand Missed Follow-Up Of Abnormal Test Results, Deevakar Rogith, Tyler Satterly, Hardeep Singh, Dean F Sittig, Elise Russo, Michael W Smith, Don Roosan, Viraj Bhise, Daniel R Murphy

Faculty, Staff and Students Publications

OBJECTIVE: This study demonstrates application of human factors methods for understanding causes for lack of timely follow-up of abnormal test results ("missed results") in outpatient settings.

METHODS: We identified 30 cases of missed test results by querying electronic health record data, developed a critical decision method (CDM)-based interview guide to understand decision-making processes, and interviewed physicians who ordered these tests. We analyzed transcribed responses using a contextual inquiry (CI)-based methodology to identify contextual factors contributing to missed results. We then developed a CI-based flow model and conducted a fault tree analysis (FTA) to identify hierarchical relationships between factors that delayed …

Atrial Myocyte Nlrp3/Camkii Nexus Forms A Substrate For Postoperative Atrial Fibrillation, Jordi Heijman, Azinwi Phina Muna, Tina Veleva, Cristina E Molina, Henry Sutanto, Marcel Tekook, Qiongling Wang, Issam H Abu-Taha, Marcel Gorka, Stephan Künzel, Ali El-Armouche, Hermann Reichenspurner, Markus Kamler, Viacheslav Nikolaev, Ursula Ravens, Na Li, Stanley Nattel, Xander H T Wehrens, Dobromir Dobrev

Faculty, Staff and Students Publications

RATIONALE: Postoperative atrial fibrillation (POAF) is a common and troublesome complication of cardiac surgery. POAF is generally believed to occur when postoperative triggers act on a preexisting vulnerable substrate, but the underlying cellular and molecular mechanisms are largely unknown.

OBJECTIVE: To identify cellular POAF mechanisms in right atrial samples from patients without a history of atrial fibrillation undergoing open-heart surgery.

METHODS AND RESULTS: Multicellular action potentials, membrane ion-currents (perforated patch-clamp), or simultaneous membrane-current (ruptured patch-clamp) and [Ca

CONCLUSIONS: Preexisting Ca

Loss Of Speg Inhibitory Phosphorylation Of Ryanodine Receptor Type-2 Promotes Atrial Fibrillation, Hannah M Campbell, Ann P Quick, Issam Abu-Taha, David Y Chiang, Carlos F Kramm, Tarah A Word, Sören Brandenburg, Mohit Hulsurkar, Katherina M Alsina, Hui-Bin Liu, Brian Martin, Dennis Uhlenkamp, Oliver M Moore, Satadru K Lahiri, Eleonora Corradini, Markus Kamler, Albert J R Heck, Stephan E Lehnart, Dobromir Dobrev, Xander H T Wehrens

Faculty, Staff and Students Publications

BACKGROUND: Enhanced diastolic calcium (Ca

METHODS: Western blotting was performed with right atrial biopsies from patients with paroxysmal AF. SPEG atrial knockout mice were generated using adeno-associated virus 9. In mice, AF inducibility was determined using intracardiac programmed electric stimulation, and diastolic Ca

RESULTS: Western blotting revealed decreased SPEG protein levels in atrial biopsies from patients with paroxysmal AF in comparison with patients in sinus rhythm. SPEG atrial-specific knockout mice exhibited increased susceptibility to pacing-induced AF by programmed electric stimulation and enhanced Ca

CONCLUSIONS: Unlike other kinases (PKA, CaMKII) that increase RyR2 activity, SPEG phosphorylation reduces RyR2-mediated sarcoplasmic reticulum Ca

In Vitro Susceptibility Of Treponema Pallidum Subsp Pallidum To Doxycycline, Diane G Edmondson, Gary P Wormser, Steven J Norris

Faculty, Staff and Student Publications

Doxycycline is regarded as an effective therapy for early syphilis, and there is increasing interest in using doxycycline for prophylaxis of this infection. However, the MIC of doxycycline for Treponema pallidum subsp. pallidum has not been reported previously. In this study, an in vitro culture system was utilized to determine that the MIC of doxycycline is 0.06 to 0.10 μg/ml for four strains of T. pallidum subsp. pallidum (Nichols, SS14, UW231B, and UW249B). The Nichols strain cultured in vitro with doxycycline was also tested for infectivity in rabbits, and the minimum bactericidal concentration (MBC) was found to be ≤0.1 μg/ml …

Structural Characterization Of A Clinically Described Heparin-Like Substance In Plasma Causing Bleeding, Yanlei Yu, Karen Bruzdoski, Vadim Kostousov, Lisa Hensch, Shiu-Ki Hui, Fakiha Siddiqui, Amber Farooqui, Ahmed Kouta, Fuming Zhang, Jawed Fareed, Jun Teruya, Robert J Linhardt

Faculty, Staff and Students Publications

Heparin-like substances (HLS) have been described in various clinical situations, including in settings of liver disease associated with infection, transplant, and metastasis. HLS are generally attributed to circulating glycosaminoglycans. Initial results for this patient showed coagulopathy due to liver disease without HLS. Two weeks after liver transplantation, a 10 year-old female with liver failure patient began to bleed from catheter insertion sites, mouth, and nares and HLS was suspected. The patient subsequently died and these clinical samples resulted in the isolation of a single heparan sulfate (HS) present at high concentrations in the plasma. Analysis of this HS showed it …

Early Transplantation In Acute On Chronic Liver Failure: Who And When, Nadim Mahmud, Ruben Hernaez, Tiffany Wu, Vinay Sundaram

Faculty, Staff and Students Publications

PURPOSE OF REVIEW: Acute on chronic liver failure (ACLF) is a unique syndrome that afflicts patients with chronic liver disease and results in high short-term mortality, > 50% at 28 days in patients with severe ACLF (grade 3, ACLF-3). Given this prognosis, there is an urgent need to understand risk factors for this condition, as well as selection criteria for patients who may benefit from liver transplantation (LT).

RECENT FINDINGS: Several studies have identified risk factors for developing ACLF, including higher model for end-stage liver disease score, anemia, and morbid obesity, as well ACLF mortality, such as infection, increasing organ failures, …

Characterization Of Retinal Biomechanical Properties Using Brillouin Microscopy, Yogeshwari S Ambekar, Manmohan Singh, Giuliano Scarcelli, Elda M Rueda, Benjamin M Hall, Ross A Poché, Kirill V Larin

Faculty, Staff and Students Publications

SIGNIFICANCE: The retina is critical for vision, and several diseases may alter its biomechanical properties. However, assessing the biomechanical properties of the retina nondestructively is a challenge due to its fragile nature and location within the eye globe. Advancements in Brillouin spectroscopy have provided the means for nondestructive investigations of retina biomechanical properties.

AIM: We assessed the biomechanical properties of mouse retinas using Brillouin microscopy noninvasively and showed the potential of Brillouin microscopy to differentiate the type and layers of retinas based on stiffness.

APPROACH: We used Brillouin microscopy to quantify stiffness of fresh and paraformaldehyde (PFA)-fixed retinas. As further …

Mtor-Initiated Metabolic Switch And Degeneration In The Retinal Pigment Epithelium, Young-Mi Go, Jing Zhang, Jolyn Fernandes, Christopher Litwin, Rui Chen, Theodore G Wensel, Dean P Jones, Jiyang Cai, Yan Chen

Faculty, Staff and Students Publications

The retinal pigment epithelium (RPE) is a particularly vulnerable tissue to age-dependent degeneration. Over the life span, the RPE develops an expanded endo-lysosomal compartment to maintain the high efficiency of phagocytosis and degradation of photoreceptor outer segments (POS) necessary for photoreceptor survival. As the assembly and activation of the mechanistic target of rapamycin complex 1 (mTORC1) occur on the lysosome surface, increased lysosome mass with aging leads to higher mTORC1 activity. The functional consequences of hyperactive mTORC1 in the RPE are unclear. In the current study, we used integrated high-resolution metabolomic and genomic approaches to examine mice with RPE-specific deletion …

Long Noncoding Rna H19x Is A Key Mediator Of Tgf-Β-Driven Fibrosi, Elena Pachera, Shervin Assassi, Gloria A Salazar, Mara Stellato, Florian Renoux, Adam Wunderlin, Przemyslaw Blyszczuk, Robert Lafyatis, Fina Kurreeman, Jeska De Vries-Bouwstra, Tobias Messemaker, Carol A Feghali-Bostwick, Gerhard Rogler, Wouter T Van Haaften, Gerard Dijkstra, Fiona Oakley, Maurizio Calcagni, Janine Schniering, Britta Maurer, Jörg Hw Distler, Gabriela Kania, Mojca Frank-Bertoncelj, Oliver Distler

Faculty, Staff and Student Publications

TGF-β is a master regulator of fibrosis, driving the differentiation of fibroblasts into apoptosis-resistant myofibroblasts and sustaining the production of extracellular matrix (ECM) components. Here, we identified the nuclear long noncoding RNA (lncRNA) H19X as a master regulator of TGF-β-driven tissue fibrosis. H19X was consistently upregulated in a wide variety of human fibrotic tissues and diseases and was strongly induced by TGF-β, particularly in fibroblasts and fibroblast-related cells. Functional experiments following H19X silencing revealed that H19X was an obligatory factor for TGF-β-induced ECM synthesis as well as differentiation and survival of ECM-producing myofibroblasts. We showed that H19X regulates DDIT4L gene …

The Impact Of Narratives And Active Video Games On Long-Term Moderate-To-Vigorous Physical Activity: A Randomized Controlled Trial Protocol, Dar Alon, Caio Victor Sousa, Tom Baranowski, Tiago V Barreira, Romina Cabrera-Perez, Kelly Chiu, Austin Fernandez, Amy Fleischman, Shirley Huang, Jungyun Hwang, Melanie C Green, I-Min Lee, Kelly Lee, Sarah Lessard, Lynne L Levitsky, Aika Misawa, Farzad Noubary, Ronald Samuels, Kyung Jin Sun, Debbe Thompson, Amy S Lu

Children’s Nutrition Research Center Staff Publications

Background: Although physical activity (PA) has been shown in helping prevent and treat obesity, current PA interventions are still not effective in ameliorating the obesity epidemic. Additional forms of PA need to be investigated to improve PA engagement and outcomes. We hypothesize that pairing a narrative (i.e., story) with an active video game (AVG), a less traditional form of PA, will increase participant engagement in PA. This paper presents the rationale, implementation, and pilot results of a study assessing the effect of narrative's impact on PA and a series of other health outcomes.

Objective: This paper presents the rationale, implementation, …

Loss Of Uncoupling Protein 3 Attenuates Western Diet-Induced Obesity, Systemic Inflammation, And Insulin Resistance In Rats, Tyler M Lomax, Sadia Ashraf, Gizem Yilmaz, Romain Harmancey

Faculty, Staff and Student Publications

OBJECTIVE: Uncoupling protein 3 (UCP3) is a mitochondrial carrier related to fatty acid metabolism. Although gene variants of UCP3 are associated with human obesity, their contribution to increased adiposity remains unclear. This study investigated the impact that loss of UCP3 has on diet-induced obesity in rats.

METHODS: Male UCP3 knockout rats (ucp3

RESULTS: Loss of UCP3 decreased fat mass gain, white adipocytes size, and systemic inflammation. The ucp3

CONCLUSIONS: Loss of UCP3 partially protects rats from diet-induced obesity. This phenotype is related to induction of a compensatory antioxidant mechanism and prevention of iBAT whitening.

Structure And Mechanism Of A Unique Diiron Center In Mammalian Stearoyl-Coa Desaturase, Jiemin Shen, Gang Wu, Ah-Lim Tsai, Ming Zhou

Faculty, Staff and Students Publications

Stearoyl-CoA desaturase 1 (SCD1) is a membrane-embedded metalloenzyme that catalyzes formation of a double-bond on a saturated acyl-CoA. SCD1 has a diiron center and its proper function requires an electron transport chain composed of NADH (or NADPH), cytochrome b5 reductase (b5R), and cytochrome b5 (cyt b5). Since SCD1 is a key regulator in fat metabolism and is required for survival of cancer cells, there is intense interest in targeting SCD1 for various metabolic diseases and cancers. Crystal structures of human and mouse SCD1 were reported recently, however, both proteins have two zinc ions instead of two iron ions in the …

Modulation Of Lymphocyte Potassium Channel Kv13 By Membrane-Penetrating, Joint-Targeting Immunomodulatory Plant Defensin, Seow Theng Ong, Saumya Bajaj, Mark R Tanner, Shih Chieh Chang, Bankala Krishnarjuna, Xuan Rui Ng, Rodrigo A V Morales, Ming Wei Chen, Dahai Luo, Dharmeshkumar Patel, Sabina Yasmin, Jeremy Jun Heng Ng, Zhong Zhuang, Hai M Nguyen, Abbas El Sahili, Julien Lescar, Rahul Patil, Susan A Charman, Edward G Robins, Julian L Goggi, Peng Wen Tan, Pragalath Sadasivam, Boominathan Ramasamy, Siddana V Hartimath, Vikas Dhawan, Janna Bednenko, Paul Colussi, Heike Wulff, Michael W Pennington, Serdar Kuyucak, Raymond S Norton, Christine Beeton, K George Chandy

Faculty, Staff and Students Publications

We describe a cysteine-rich, membrane-penetrating, joint-targeting, and remarkably stable peptide, EgK5, that modulates voltage-gated KV1.3 potassium channels in T lymphocytes by a distinctive mechanism. EgK5 enters plasma membranes and binds to KV1.3, causing current run-down by a phosphatidylinositol 4,5-bisphosphate-dependent mechanism. EgK5 exhibits selectivity for KV1.3 over other channels, receptors, transporters, and enzymes. EgK5 suppresses antigen-triggered proliferation of effector memory T cells, a subset enriched among pathogenic autoreactive T cells in autoimmune disease. PET-CT imaging with 18F-labeled EgK5 shows accumulation of the peptide in large and small joints of rodents. In keeping with its arthrotropism, EgK5 treats disease in a rat …

Dendritic Cell Derived Exosomes Loaded With Immunoregulatory Cargo Reprogram Local Immune Responses And Inhibit Degenerative Bone Disease In Vivo, Mahmoud Elashiry, Mohamed M Elashiry, Ranya Elsayed, Mythily Rajendran, Carol Auersvald, Rana Zeitoun, Mohammad H Rashid, Roxan Ara, Mohamed M Meghil, Yutao Liu, Ali S Arbab, Roger M Arce, Mark Hamrick, Mohammed Elsalanty, Marshall Brendan, Rafal Pacholczyk, Christopher W Cutler

Faculty, Staff and Student Publications

Chronic bone degenerative diseases represent a major threat to the health and well-being of the population, particularly those with advanced age. This study isolated exosomes (EXO), natural nano-particles, from dendritic cells, the "directors" of the immune response, to examine the immunobiology of DC EXO in mice, and their ability to reprogram immune cells responsible for experimental alveolar bone loss

Metabolism Of Jq1, An Inhibitor Of Bromodomain And Extra Terminal Bromodomain Proteins, In Human And Mouse Liver Microsomes†, Feng Li, Kevin R Mackenzie, Prashi Jain, Conrad Santini, Damian W Young, Martin M Matzuk

Faculty, Staff and Students Publications

JQ1 is a small-molecule inhibitor of the bromodomain and extra terminal (BET) protein family that potently inhibits the bromodomain testis-specific protein (BRDT), which is essential for spermatogenesis. JQ1 treatment produces a reversible contraceptive effect by targeting the activity of BRDT in mouse male germ cells, validating BRDT as a male contraceptive target. Although JQ1 possesses favourable physical properties, it exhibits a short half-life. Because the details of xenobiotic metabolism play important roles in the optimization of drug candidates and in determining the role of metabolism in drug efficacy, we investigated the metabolism of JQ1 in human and mouse liver microsomes. …

A Global Slc7a7 Knockout Mouse Model Demonstrates Characteristic Phenotypes Of Human Lysinuric Protein Intolerance, Bridget M Stroup, Ronit Marom, Xiaohui Li, Chih-Wei Hsu, Cheng-Yen Chang, Luan D Truong, Brian Dawson, Ingo Grafe, Yuqing Chen, Ming-Ming Jiang, Denise Lanza, Jennie Rose Green, Qin Sun, J P Barrish, Safa Ani, Audrey E Christiansen, John R Seavitt, Mary E Dickinson, Farrah Kheradmand, Jason D Heaney, Brendan Lee, Lindsay C Burrage

Faculty, Staff and Students Publications

Lysinuric protein intolerance (LPI) is an inborn error of cationic amino acid (arginine, lysine, ornithine) transport caused by biallelic pathogenic variants in SLC7A7, which encodes the light subunit of the y+LAT1 transporter. Treatments for the complications of LPI, including growth failure, renal disease, pulmonary alveolar proteinosis, autoimmune disorders and osteoporosis, are limited. Given the early lethality of the only published global Slc7a7 knockout mouse model, a viable animal model to investigate global SLC7A7 deficiency is needed. Hence, we generated two mouse models with global Slc7a7 deficiency (Slc7a7em1Lbu/em1Lbu; Slc7a7Lbu/Lbu and Slc7a7em1(IMPC)Bay/em1(IMPC)Bay; Slc7a7Bay/Bay) using CRISPR/Cas9 technology by introducing a deletion of exons …

Cellular And Circuit Properties Of Slow Oscillations In The Thalamic Reticular Nucleus, John O'Malley

Dissertations and Theses (Open Access)

During sleep, neurons in the thalamic reticular nucleus (TRN) generate distinct types of oscillatory activity. While the reciprocal synaptic circuits between TRN and sensory thalamic nuclei underlie the generation of sleep spindles, the mechanisms regulating slow (<1 >Hz) forms of thalamic oscillations are poorly understood. Under in vitro conditions, in the absence of synaptic inputs, TRN neurons can generate slow oscillations in a cell-intrinsic manner. Activation of postsynaptic Group 1 metabotropic glutamate receptors (mGluR) leads to long-lasting plateau potentials thought to be mediated by both T-type calcium currents and calcium-activated nonselective cation currents (I_CAN). However, the identity of …

Longitudinal Clonal Lineage Dynamics And Functional Characterization Of Pancreatic Cancer Chemo-Resistance And Metastasization, Chieh-Yuan Li

Dissertations and Theses (Open Access)

In recent years, technological advancements, such as next-generation sequencing and single-cell interrogation techniques, have enriched our understanding in tumor heterogeneity. By dissecting tumors and characterizing clonal lineages, we are better understanding the intricacies of tumor evolution. Tumors are represented by the presence of and dynamic interactions amongst clonal lineages. Each lineage and each cell contributes to tumor dynamics through intrinsic and extrinsic mechanisms, and the variable responses of clones to perturbations in the environment, especially therapeutics, underlie disease progression and relapse. Thus, there exists a pressing need to understand the molecular mechanisms that determine the functional heterogeneity of tumor sub-clones …

Atitiudes Tow Ards Computer Games For Learning And Pl.A Yer Archetypes: An Exploration Of Measures On Preintervention Player Characteristics For Serious Game-Based Interventions, Benjamin Lee

Dissertations and Theses (Open Access)

Serious game-based interventions offer promising health outcome results with the aid of pre-intervention player tailoring and the development of measurements that evaluate pre-intervention player characteristics and subgroups. Video gaming measures can potentially provide helpful tailoring information that discerns individual video gaming preferences which could influence their overall user experience. It is critical that measures that target adolescent video gaming be psychometrically validated. There is a gap in the literature with psychometrically validated measures evaluating adolescent attitudes towards computer games for learning and gaming archetypes. Therefore the aims of this dissertation were to 1) evaluate the psychometric properties (i.e., reliability and …

Determining The Racial And Ethnic Differences In Neonatal Intensive Care Unit Admission Rates, Youngran Kim

Dissertations and Theses (Open Access)

Background: Recent trends show that the utilization of neonatal intensive care unit (NICU) has extended beyond severely ill infants and increased substantially across all birth weights. However, little is known about what drives the growth of NICU admission rates and whether these trends differ by race/ethnicity. Methods: The study used 2008-2018 Natality Files with restricted use of state and county-level information. Crude and risk-adjusted NICU admission rates, overall and stratified by birth weight group, were compared between black and white infants and between Hispanic and white infants. Kitagawa decomposition and Oaxaca-Blinder decomposition analyses were conducted for the temporal increase in …

Heat Stress Related Symptoms And Pulmonary Function In Oil Spill Response And Cleanup Workers Following The Deepwater Horizon Disaster, Yiyou Li

Dissertations and Theses (Open Access)

The objective of this study was to estimate the relationship between heat stress and pulmonary function among OSRC workers following the Deepwater Horizon (DWH) disaster. Methods: Pulmonary function test results were analyzed from a cohort of oil spill response and cleanup workers 1-3 years following the DWH disaster (N=5,131). Proxies for heat stress was employed by using information on heat stress-related symptoms as well as a questionnaire on stopping work due to heat reported during a structured telephone enrollment questionnaire. Associations between heat stress proxies and lung function were estimated using multivariable linear models and binomial logistic regression models while …

Heat Stress Related Symptoms And Pulmonary Function In Oil Spill Response And Cleanup Workers Following The Deepwater Horizon Disaster, Yiyao Li

Dissertations and Theses (Open Access)

Objective: The objective of this study was to estimate the relationship between heat stress and pulmonary function among OSRC workers following the Deepwater Horizon (DWH) disaster. Methods: Pulmonary function test results were analyzed from a cohort of oil spill response and cleanup workers 1-3 years following the DWH disaster (N=5,131). Proxies for heat stress was employed by using information on heat stress-related symptoms as well as a questionnaire on stopping work due to heat reported during a structured telephone enrollment questionnaire. Associations between heat stress proxies and lung function were estimated using multivariable linear models and binomial logistic regression models …

Area-Level Landfill Density And Asthma Prevalence In Urban Texas Areas, Jessica Meighan Herrin

Dissertations and Theses (Open Access)

Environmental exposures, especially air pollutants, pose a threat for an increase in asthma prevalence. In particular, hydrogen sulfide (H2S) gas can cause severe health effects closely resembling asthmatic symptoms. Ambient concentrations of H2S gas correlates with the amount of solid waste found in landfills. The potential for adverse health risks associated with H2S emitted from landfills is of concern for those populations living in close proximity to landfills. Asthma is one of the adverse health effects that can occur due to H2S exposure. However, there is a lack of detailed studies characterizing possible associations between the density of landfills and …

Impact Of Substance Use In Social Networks On Antiretroviral Therapy Adherence For Hiv-Positive Younger Men Who Have Sex With Men, Natascha Del Vecchio

Dissertations and Theses (Open Access)

The community of young men who have sex with men (YMSM) has higher rates of substance use than the general population and the use of alcohol, cannabis, and illicit drugs has been shown to have a negative impact on the HIV care continuum. Our first aim was to understand the prevalence of substance use in the community through the use of self-reported, RDS-II, and RDS-SS estimates. We used multivariable logistic and negative binomial GEE with QIC selection to determine the factors important to having a prescription and staying adherent, respectively. Selected variables were included with a subset of substance use …

Astrocytes Rescue Neuronal Health After Cisplatin Treatment Through Mitochondrial Transfer., Krystal English, Krystal English

Dissertations and Theses (Open Access)

Abstract

Astrocytes rescue neuronal health after cisplatin treatment through mitochondrial transfer.

Author: Krystal English

Advisory Professor: Dr. Cobi J. Heijnen, Ph.D.

Chemotherapy-induced cognitive impairments are associated with neuronal mitochondrial dysfunction. Cisplatin, a commonly used chemotherapeutic, induces neuronal mitochondrial dysfunction in vivo and in vitro. Astrocytes are key players in supporting neuronal development, synaptogenesis, axonal growth, metabolism and, potentially, mitochondrial health. We tested the hypothesis that astrocytes transfer healthy mitochondria to neurons after cisplatin treatment to restore neuronal health.

We used an in vitro system in which astrocytes with Mito-mCherry-labeled mitochondria were co-cultured with primary cortical neurons or neuronal stem …

Identification Of Trim24 Domain Essentiality In Primary Trim24coe Carcinosarcoma Cell Lines, Cem Dede

Dissertations and Theses (Open Access)

Regulation of transcriptional control is a critical feature for organismal development and survival. Because of its effects on chromatin-controlled expression, disruptions of this delicately tuned mechanism are an important factor in development of tumorigenesis. Therefore, there is a growing interest in targeting these control mechanisms for their potential therapeutic values.

Our lab previously discovered the epigenetic regulator function of Tripartite motif protein 24 (TRIM24) through its H3K4me0 and H3K23ac dual histone signature reader function, its negative regulatory effect on the p53 tumor suppressor, in addition to its shown oncogenic driving capacity on immortalized mammary epithelial cells when overexpressed. Although TRIM24 …

Aging Lowers Pex5 Levels In Cortical Neurons In Male And Female Mouse Brains, Ndidi-Ese Uzor

Dissertations and Theses (Open Access)

Peroxisomes are small organelles with critical functions: lipid synthesis, breakdown of reactive oxygen species by antioxidant enzymes, and amino acid degradation. In the brain, peroxisomal lipids make up the myelin sheath. Brain peroxisomal dysfunction leads to lipid disruption or neurological consequences if key peroxisomal proteins are absent. Still, it is unclear how peroxisomes are affected in neurodegenerative diseases and in normal brain aging. This work examines peroxisomal markers in three settings: 1) in a neuronal and 2) animal model of Huntington disease (HD), where mutant huntingtin (mHtt), the causative protein in Huntington disease pathogenesis is expressed, and 3) in the …