Digital Commons Network^™

Glial Contributions To Neural Function And Disease, Mn Rasband

Faculty, Staff and Students Publications

The nervous system consists of neurons and glial cells. Neurons generate and propagate electrical and chemical signals, whereas glia function mainly to modulate neuron function and signaling. Just as there are many different kinds of neurons with different roles, there are also many types of glia that perform diverse functions. For example, glia make myelin; modulate synapse formation, function, and elimination; regulate blood flow and metabolism; and maintain ionic and water homeostasis to name only a few. Although proteomic approaches have been used extensively to understand neurons, the same cannot be said for glia. Importantly, like neurons, glial cells have …

Early Rescue Of Interneuron Disease Trajectory In Developmental Epilepsies, Ms Siehr, Jl Noebels

Faculty, Staff and Students Publications

The discovery of over 150 monogenic epilepsies and advances in early genetic diagnoses have launched a search for molecular strategies and developmental timetables to reverse or even prevent the course of these debilitating brain disorders. Orthologous rodent models of key disease genes are providing important examples of the range of targets, and serve as valuable test systems for perinatal therapeutic approaches. While gene-specific analyses of single rare 'orphan' diseases are each narrow in scope, they illuminate downstream pathways converging onto interneurons, and treatments that strengthen inhibition during cortical maturation may provide broad protection against these seemingly disparate gene errors. Several …

Endosteal Biologic Augmentation For Surgical Fixation Of Displaced Femoral Neck Fractures, Lionel E Lazaro, Jacqueline F Birnbaum, Nadja A Farshad-Amacker, David L Helfet, Hollis G Potter, Dean G Lorich

Faculty, Staff and Student Publications

OBJECTIVES: To report outcomes of a cohort with displaced femoral neck fractures (FNFs) treated with a length/angle-stable construct augmented with an endosteal fibular allograft serving as a biologic dowel.

DESIGN: Prospective.

SETTING: Level I Trauma Center.

PATIENTS: The study group consists of 27 patients with isolated FNF surgically treated by a single surgeon.

INTERVENTION: Open reduction of the femoral neck, fixed with a length- and angle-stable construct of 2 fully threaded cannulated screws augmented with an endosteal fibular allograft serving as a biologic dowel.

MAIN OUTCOME MEASUREMENTS: Clinical and radiographic outcomes of the fixation construct and the viability of both …

The Mosaic Mitral Valve Bioprosthesis: A Long-Term Clinical And Hemodynamic Follow-Up, Michele Celiento, Stefania Blasi, Andrea De Martino, Stefano Pratali, Aldo D Milano, Uberto Bortolotti

The Texas Heart Institute Journal

We reviewed the cases of 100 patients (mean age, 73 ± 10 yr; 64 men) who had mitral valve replacement with a Medtronic Mosaic porcine bioprosthesis from 1995 through 2011. The mean New York Heart Association (NYHA) class was 3 ± 0.7, and 52 patients were in atrial fibrillation. Prosthetic sizes were chiefly 27 mm (50 patients) and 29 mm (40 patients). Follow-up ended in December 2012 and is 97% complete, with a cumulative duration of 611 patient-years (mean duration, 6 ± 4.6 yr; maximum, 17.7 yr). The early mortality rate was 10% (6% in elective patients); late deaths occurred …

Caring Minds, University Of Texas Health Science Center At Houston School Of Nursing

Caring Minds

No abstract provided.

Effect Of Two-Year Caloric Restriction On Bone Metabolism And Bone Mineral Density In Non-Obese Younger Adults: A Randomized Clinical Trial, Dt Villareal, L Fontana, Sk Das, Et Al.

Faculty, Staff and Students Publications

Although caloric restriction (CR) could delay biologic aging in humans, it is unclear if this would occur at the cost of significant bone loss. We evaluated the effect of prolonged CR on bone metabolism and bone mineral density (BMD) in healthy younger adults. Two-hundred eighteen non-obese (body mass index [BMI] 25.1?±?1.7?kg/m(2) ), younger (age 37.9?±?7.2 years) adults were randomly assigned to 25% CR (CR group, n?=?143) or ad libitum (AL group, n?=?75) for 2 years. Main outcomes were BMD and markers of bone turnover. Other outcomes included body composition, bone-active hormones, nutrient intake, and physical activity. Body weight (-7.5?±?0.4 versus …

Activation Of Signal Transduction Pathways During Hepatic Oncogenesis, W Chung, M Kim, S De La Monte, L Longato, R Carlson, B L. Slagle, X Dong, J R. Wands

Faculty, Staff and Students Publications

BACKGROUND AND AIMS: Understanding the molecular pathogenesis of hepatocellular carcinoma (HCC) is essential to identify therapeutic targets. A hepatitis B virus (HBV) related double transgenic murine model was developed. METHODS: Liver specific expression of HBV X protein (HBx) and insulin receptor substrate 1 (IRS1) was achieved and transgenic mice were followed from birth to age 21 months. Liver and tumor tissue were assessed for histologic changes as well as activation of signal transduction pathways by qRT-PCR and multiplex ELISA protein assays. RESULTS: Overexpression of HBx and IRS1 stimulates liver cell proliferation in the double transgenic mice. Only the male mice …

Local Corticotropin Releasing Hormone (Crh) Signals To Its Receptor Crhr1 During Postnatal Development Of The Mouse Olfactory Bulb, Isabella Garcia, Paramjit K Bhullar, Burak Tepe, Joshua Ortiz-Guzman, Longwen Huang, Alexander M Herman, Lesley Chaboub, Benjamin Deneen, Nicholas J Justice, Benjamin R Arenkiel

Faculty, Staff and Students Publications

Neuropeptides play important physiological functions during distinct behaviors such as arousal, learning, memory, and reproduction. However, the role of local, extrahypothalamic neuropeptide signaling in shaping synapse formation and neuronal plasticity in the brain is not well understood. Here, we characterize the spatiotemporal expression profile of the neuropeptide corticotropin-releasing hormone (CRH) and its receptor CRHR1 in the mouse OB throughout development. We found that CRH-expressing interneurons are present in the external plexiform layer, that its cognate receptor is expressed by granule cells, and show that both CRH and CRHR1 expression enriches in the postnatal period when olfaction becomes important towards olfactory-related …

Nutritional Status And Tuberculosis Risk In Adult And Pediatric Household Contacts, Omowunmi Aibana, Xeno Acharya, Chuan-Chin Huang, Mercedes C Becerra, Jerome T Galea, Silvia S Chiang, Carmen Contreras, Roger Calderon, Rosa Yataco, Gustavo E Velásquez, Karen Tintaya, Judith Jimenez, Leonid Lecca, Megan B Murray

Faculty, Staff and Student Publications

BACKGROUND: Studies show obesity decreases risk of tuberculosis (TB) disease. There is limited evidence on whether high body mass index also protects against TB infection; how very high body mass indices influence TB risk; or whether nutritional status predicts this risk in children. We assessed the impact of body mass index on incident TB infection and disease among adults and children.

METHODS AND FINDINGS: We conducted a prospective cohort study among household contacts of pulmonary TB cases in Lima, Peru. We determined body mass index at baseline and followed participants for one year for TB infection and disease. We used …

No Sabía Que Tenía Valor”: Uncovering Latina Mothers’ Multiple Literacies, Julia Lopez-Robertson

Journal of Family Strengths

Five Latina mothers were engaged in pláticas literarias/literature discussions about Latino children’s literature at their children’s school. The pláticas served as means to build the links from personal experiences to school learning and to help the mothers recognize that their ways of knowing and making meaning of the world-their multiliteracies-are tools from which their children will and do learn. A community cultural wealth [CCW] framework was employed to identify and make visible the significance of these rich contributions and strengths. Basing the pláticas on texts that interested and were relevant to the mothers and providing them a safe space …

Big Read: Collaborations Between A University And A Community, Chris Birchak, Keri Bell, Rachel Dickson, Vida Robertson, Leigh Van Horn

Journal of Family Strengths

University and community partners write about their collaborations around the reading of Ernest Gaines’ A Lesson Before Dying. When an urban university received a National Endowment of the Arts Big Read Grant, they immediately began making connections to existing key initiatives within the university and in the surrounding community. As the partners collaborated within and among the university and community programs and events created for the Big Read they made multiple discoveries regarding the importance of planning together, analyzing the intended audience for each program and event, including multiple ways to access the text, and considering the ways that readers …

Preventing Thymus Involution In K5.Cyclin D1 Transgenic Mice Sustains The Naïve T Cell Compartment With Age, Michelle L. Bolner

Dissertations and Theses (Open Access)

The thymus maintains T cell receptor (TCR) repertoire diversity through perpetual release of self-MHC restricted naive T cells. However, thymus involution during the aging process reduces naïve T cell output, leading to defective immune responsiveness to newly encountered antigens. We have found that early thymus involution precipitates the age-associated shift favoring memory T cell dominancy in young control mice. Furthermore, we have shown that age-related thymus involution is prevented in mice expressing a keratin 5 promoter-driven Cyclin D1 (K5.D1) transgene in thymic epithelial cells (TECs). Thymopoiesis occurs normally in K5.D1 transgenic thymi and sustains T cell output to prevent the …

Identifying Protein Kinase Tbk1 As A Novel Inhibitor Of Intestinal Tumorigenesis, Amber L. Mathews

Dissertations and Theses (Open Access)

Colorectal cancer (CRC) is the third most common cancer diagnosed in women and men， causing almost 600,000 annual deaths worldwide. There is a clear need to understand how CRC forms and progresses in order to improve the strategies of CRC prevention and therapy. A major factor that drives the development of CRC is genetic mutations that lead to activation of oncogenes and inactivation of tumor suppressor genes in intestinal epithelial cells (IECs). In addition, the initiation and progression of CRC involve environmental and immunological factors. In particular, chronic inflammatory conditions are known as an important risk factor for CRC. Intestinal …

The Role Of Dna Methylation And Hydroxymethylation In Smooth Muscle Cell Phenotypic Change During Atherogenesis, Jason Williams

Dissertations and Theses (Open Access)

Atherosclerosis is a chronic arterial disease which impacts systemically the function of organs and tissues by causing inflammation and disruption of blood supply. During atherogenesis, lipid deposits, inflammation, and cells accumulate within the walls of arteries, ultimately leading to a buildup of fatty plaques and occlusion of the arterial lumen. In a multifactorial disease like atherosclerosis there are complex interplays between environmental, genetic and epigenetic risk factors. The epigenetics of atherosclerosis involving DNA methylation has been progressing from single gene to genome wide analyses. Although these epistudies have provided evidence that DNA methylation exists within certain genes during atherogenesis, the …

Prediction Of Laser Ablation In Brain: Sensitivity, Calibration, And Validation, Samuel J. Fahrenholtz

Dissertations and Theses (Open Access)

The surgical planning of MR-guided laser induced thermal therapy (MRgLITT) stands to benefit from predictive computational modeling. The dearth of physical model parameter data leads to modeling uncertainty. This work implements a well-accepted framework with three key steps for model-building: model-parameter sensitivity analysis, model calibration, and model validation.

The sensitivity study is via generalized polynomial chaos (gPC) paired with a transient finite element (FEM) model. Uniform probability distribution functions (PDFs) capture the plausible range of values suggested by the literature for five model parameters. The five PDFs are input separately into the FEM model to gain a probabilistic sensitivity response …

In Vivo Functional Significance Of Ccat2 Long Non-Coding Rna In Myelodysplastic Syndrome, Maitri Y. Shah

Dissertations and Theses (Open Access)

Long non-coding RNAs form the largest part of the mammalian non-coding transcriptome and control gene expression at various levels including chromatin modification, transcriptional and post-transcriptional processing. Although the underlying molecular mechanisms are not yet entirely understood, lncRNAs are implicated in initiation and progression of several cancers. CCAT2 is a lncRNA that spans the highly conserved 8q24 region associated with increased risk for various cancers. CCAT2 has been shown to play an important role in inducing chromosomal instability and supporting cell proliferation and cell cycle arrest. However, a causal role of CCAT2 in initiation of tumorigenesis and the importance of G/T …

Role Of Stat3 In Human Nk Cell Functions, Prasad V. Phatarpekar

Dissertations and Theses (Open Access)

Natural Killer (NK) cells are cytotoxic lymphocytes, which play a critical role in the immune response against malignant cells and microbial infections. NK cells are equipped with activating receptors, which upon detecting ligands expressed on stressed cells induce cytolytic activity of NK cells. Stimulation of NK cell proliferation and priming of NK cytolytic capability are accomplished by cytokines, which mediate their signals mainly through JAK-STAT signaling pathway. Previously, we found that K562 cells genetically modified to express membrane bound IL-21 (mbIL-21), which predominantly activates STAT3, induce robust expansion and activation of human NK cells. Further investigations revealed role of STAT3 …

Mobilization Of Adipose Stromal Cells In Obesity And Cancer By Sparc And Its Proteolytic Isoforms, Chieh Tseng

Dissertations and Theses (Open Access)

Obesity increases cancer risk and progression as shown by epidemiologic studies. However, the underlying pathophysiology remained unclear. Adipose stromal cells (ASC) are adipose tissue-derived mesenchymal progenitors, abundant in white adipose tissue (WAT). In this study, we show that the ASC pool is expanded in obesity and is associated with promoted tumor growth. Next, by using a chimeric GFP-RFP bone marrow transplant model, we observed higher tumor infiltrating cells with ASC phenotype in obese mice compared to lean. Consistently, systemic circulating ASC frequency is six fold higher in tumor-bearing obese mice compared to lean. The tumor infiltrating cells with ASC phenotype …

Determining The Mechanisms Generating Soluble Il-15 Complexes, Scott Anthony

Dissertations and Theses (Open Access)

A diverse assortment of infectious pathogens and TLR agonists enhance the expression of Interleukin (IL)-15. Additionally, inducing lymphopenia enhances anti-tumor responses in an IL-15-dependent manner. Paradoxically, despite the limited expression of IL-15 during homeostasis, the role of IL-15 during the steady state is well-known, while its roles during inflammation and infections remain largely undefined. IL-15 uses a unique method of production and presentation to support the development and homeostasis of NK and CD8 T cells. IL-15 is produced with its high affinity IL-15Rα and this IL-15Rα/IL-15 complex is shuttled to the cell surface where it is presented in-trans or cleaved …

Normal Glycolytic Enzyme Activity Is Critical For Hypoxia Inducible Factor-1a Activity And Provides Novel Targets For Inhibiting Tumor Growth, Geoffrey Grandjean Phd

Dissertations and Theses (Open Access)

Normal Glycolytic Enzyme Activity is Critical for Hypoxia Inducible Factor-1α Activity and Provides Novel Targets for Inhibiting Tumor Growth

By Geoffrey Grandjean

Advisory Professor: Garth Powis, D. Phil

Unique to proliferating cancer cells is the observation that their increased need for energy is provided by a high rate of glycolysis followed by lactic acid fermentation in a process known as the Warburg Effect, a process many times less efficient than oxidative phosphorylation employed by normal cells to satisfy a similar energy demand ^[1]. This high rate of glycolysis occurs regardless of the concentration of oxygen in the cell and …

Molecular Regulation Of Vascular Calcification In Murine Models Of Atherosclerosis, Shanshan Gao

Dissertations and Theses (Open Access)

Background: Calcification occurs often in the atherosclerotic lesions of patients with coronary heart disease and animals with hypercholesterolemia, such as apolipoprotein-E deficient (ApoE-/-) mice. However, the mechanism(s) underlying the development of calcification in atherosclerosis remains unclear. ApoE acts as a lipid transporter, but also has been recognized as a potential regulator of osteogenesis. Little information is available as to whether ApoE has any direct impact on osteogenesis and calcification in vascular smooth muscle cells (VSMC). Several signal transduction pathways play a role in regulation of calcification, including the Wnt/β-catenin system and potentially GTAP, an ubiquitin-conjugating enzyme responsible for protein …

Effects Of Pharmacological And Genetic Disruption Of Chemokine Receptor Cxcr4 In B-Cell Acute Lymphoblastic Leukemia, Shubhchintan Randhawa

Dissertations and Theses (Open Access)

The CXCR4 chemokine receptor plays a pivotal role in homing and retention of B-cell Acute Lymphoblastic Leukemia cells to bone marrow niches. The bone marrow stromal cells (BMSCs) constitutively secrete the CXCR4 ligand CXCL12, thus attracting leukemia cells and protecting them from cytotoxic drugs, a mechanism that might be responsible for minimal residual disease after conventional chemotherapy against B-ALL. Indeed, in this study we observed that B-ALL cells that had migrated beneath the BMSCs were highly resistant to chemotherapeutic drugs. Inhibition of CXCR4 to disrupt this interaction presents itself as an attractive target to overcome bone marrow derived drug resistance …

Ut Gsbs News, Fall/Winter 2015, Graduate School Of Biomedical Sciences, University Of Texas Health Science Center At Houston/M.D. Anderson Cancer Center

GSBS News

No abstract provided.

The Axillary View Typically Does Not Contribute To Decision Making In Care For Proximal Humeral Fractures, Marschall B Berkes, Joshua S Dines, Jacqueline F Birnbaum, Lionel E Lazaro, Tristan C Lorich, Milton T M Little, Joseph T Nguyen, Dean G Lorich

Faculty, Staff and Student Publications

Background: Convention dictates that an axillary view be obtained when evaluating proximal humerus fractures (PHF). However, the axillary view is frequently omitted because of pain and technical considerations. Furthermore, its diagnostic utility is unclear in this setting.

Questions/purposes: The purpose of this study was to (1) determine the rate of obtaining an adequate axillary X-ray and complete shoulder series at a level I trauma center, (2) understand the cost of ordering and attempting an axillary radiograph, and (3) determine if axillary radiographs influence the management of PHF.

Patients and methods: PHF treated between 2009 and 2011 that were ordered for …

Time From Infection To Disease And Infectiousness For Ebola Virus Disease, A Systematic Review, Gustavo E Velásquez, Omowunmi Aibana, Emilia J Ling, Ibrahim Diakite, Eric Q Mooring, Megan B Murray

Faculty, Staff and Student Publications

We systematically reviewed the literature to estimate the incubation and latent periods of Ebola virus disease. We found limited epidemiological data from individuals with discrete 1-day exposures. Available data suggest that the incubation and latent periods may differ, and mathematical models may be improved by distinguishing between the two periods.

Designing For Practice Development In A Social Learning System: Communicating Norms And Vicarious Experience, Claire Loe

Dissertations and Theses (Open Access)

Over the past quarter century, the United States has experienced an increase in demand for health services. Expanded use of community health workers (CHWs) has been identified as a strategic response for more effective distribution of healthcare resources by alleviating pressures on clinical personnel and infusing prevention education into the community-to-clinical care continuum. Expansion of the CHW workforce poses many challenges. For CHWs to effectively reduce costs and pressures on the healthcare system, ‘expansion’ implies not only increasing their numbers, but also assuring a workforce that has the capacity to perform in diverse settings. I propose a theoretical framework for …

Investigating The Role Of Cholesterol Metabolism And Synthesis In Metastasis And Radiation Response In Aggressive Subtypes Of Breast Cancer, Adam Wolfe

Dissertations and Theses (Open Access)

Aggressive breast cancers, triple-negative breast cancer (TNBC) and inflammatory breast cancer (IBC), metastasize at a high rate and are notoriously resistant to standard treatments. Research has shown diets high in cholesterol increase the incidence of aggressive breast cancers and pre-clinical research has shown cholesterol can fuel the growth of breast cancer in vivo. Studies at MD Anderson have shown that IBC patients taking cholesterol lowering drugs, statins, have improved survival outcomes, and also statins can improve the response to radiation in vitro. Furthermore, statins have been shown to target the cells with stem like-properties called cancer stem cells (CSCs) which …

New Insights On The Role Of Jmjd2a In Cancer Progression, Yuan Gao

Dissertations and Theses (Open Access)

Changes in chromatin architecture are known to be one of the underlying causes of cancer because of its ability to alter gene transcription. Histone methylation is one of the most intricate epigenetic marks because it adds multiple layers of modification on the targeted sites. Therefore, many studies have brought histone methylases and demethylases into focus, hoping to decipher their roles in cancer progression. Among these enzymes, JMJD2A is the first to shown to have demethylation activity against trimethylation, and to regulate gene expression, development, and cancer progression. While many studies have mainly focused on its role in transcriptional regulation, only …

Structure And Composition Of Postsynaptic Densities, Madeline Farley

Dissertations and Theses (Open Access)

Communication between neurons within the brain occurs at chemical synapses and is fundamental for all brain functions. Modulation of the strength of communication is controlled by both presynaptic and postsynaptic mechanisms and is termed synaptic plasticity. One postsynaptic structure postulated to regulate synaptic strength is the postsynaptic density (PSD), a large electron dense protein complex located just below the synaptic membrane. The PSD, which is composed of signaling, scaffold and cytoskeletal proteins, supports and organizes neurotransmitter receptors within the synaptic membrane in addition to bridging signaling with the actin cytoskeletal network. The protein composition and structure of PSDs is known …

Merlin Mediated Regulation Of Hair Follicle Morphogenesis, Megan K. Fentress

Dissertations and Theses (Open Access)

Epidermal homeostasis is paramount for the ongoing function of the skin as the primary barrier between a mammalian organism and the external environment. Homeostasis is achieved through a complex and delicate balance of cell death, cell proliferation and cell differentiation. Critical for regeneration and maintenance of the skin are epidermal stem cells. Within the epidermis two distinct stem cell compartments exist, the bulge and interfollicular/basal stem cell niches, which play a central role in the regeneration of the epidermis through self-renewal and contribution to the differentiated cells of the epidermis. The bulge stem cell niche is established early in epidermal …