Digital Commons Network^™

Cheminformatic Discovery And Characterization Of Copperdependent Bacterial Inhibitors, Alex Dalecki

All ETDs from UAB

Deaths due to antibiotic-resistant bacteria are predicted to exceed 10 million per year by 2050, endangering our ability to conduct fundamental medical procedures such as immunosuppressive therapy or even basic surgery. Unfortunately, we are largely falling behind in the evolutionary arms race against common pathogens. Not only are we in sore need of new antibiotics, we also evidently need altogether new approaches to drug discovery itself, as our familiar avenues are increasingly failing to meet demands. In this dissertation, we describe a promising new source of antibacterials: copper-dependent inhibitors (CDIs), compounds that exert significant antibiotic activity only in the presence …

The Primary Cilium Regulates Interstitial Immune Cells During Renal Cystogenesis, Cheng Song

All ETDs from UAB

Renal cysts are a pathological condition that can lead to end-stage renal failure and death. The mechanisms that underlie renal cyst development are under active investigation, and emerging evidence has revealed defects in a number of proteins required for cilia assembly or signaling, such as intraflagellar transport (IFT) proteins and the polycystins. Characterization of mice harboring conditional IFT mutations suggests that the rate of cyst formation is dependent upon the timing of cilia loss. Induction of cilia loss in juvenile mice results in rapid cyst development, while induction of cilia loss in adult mice leads to a slower progressing form …

The Role Of Pim Kinases In Hepatoblastoma Tumorigenicity, Stem Cell-Like Cancer Cell Maintenance, And Chemoresistance, Laura Lee Stafman

All ETDs from UAB

Hepatoblastoma is the most common primary liver malignancy in children. Despite increasing incidence, treatment has not changed significantly in the past 20 years, making the need for novel therapeutics imperative. Proviral Integration site for Moloney murine leukemia virus (PIM) kinases are a family of serine/threonine kinases that have been implicated in multiple other cancer types including the adult liver cancer, hepatocellular carcinoma. Emerging evidence has begun to elucidate a role for PIM kinases in stem-cell like cancer cells (SCLCCs). This subpopulation of cells is thought tobe responsible for tumor maintenance, recurrence, metastasis, and chemoresistance. Chemoresistance is a significant barrier to …

Analysis Of The Gtp Cyclohydrolase I/Tetrahydrobiopterin Pathway In Glioblastoma Biology, Anh Tran

All ETDs from UAB

Glioblastomas (GBMs) are the most common primary malignant brain tumors in adults and one of the most aggressive cancers with high rates of recurrence and therapeutic resistance. In GBMs, subpopulations of highly tumorigenic cells called brain tumor initiating cells (BTICs) have the unique capacity to promote tumor maintenance, therapeutic resistance, and angiogenesis. Depending on the level, differentiation state, and tumor stage, reactive nitrogen and oxygen species inhibit or increase cancer growth and BTIC maintenance. GTP cyclohydrolase 1 (GCH1) is the rate limiting enzyme in a pathway that can regulate reactive species production but has not been thoroughly investigated in GBM. …

Effects Of Novel Inhibitors Against Wnt/Β-Catenin Signaling In Ovarian And Triple-Negative Breast Cancers, Abhishek Gangrade

All ETDs from UAB

Ovarian and triple-negative breast cancers (TNBC) are aggressive due to their dependence on Wnt/β-catenin signaling. Niclosamide, a strong inhibitor of Wnt/β-catenin signaling, is an efficacious cytotoxic agent for various cancers in vitro, including ovarian and breast cancers. However, it has cross-reactivity with mTOR, STAT3, and Notch pathways. A limitation of using the agent in animal studies involves its poor water solubility and bioavailability. This study investigates novel compounds based on the structure of niclosamide to improve specificity for the Wnt/β-catenin signaling pathway. The investigation evaluates three questions: 1) whether WNT974 inhibits Wnt/β-catenin signaling in ovarian cancer; 2) whether novel analogs …

Epigenetic Regulation Of Stem Cell Fate Determination And Tumorigenesis, Kushani Shah

All ETDs from UAB

It is unclear how H3K4 methylation, an epigenetic modification associated with gene activation, regulates stem cell fate determination and tumorigenesis. DPY30 is one of the core subunits of the SET1/MLL complex in mammals responsible for H3K4me. DPY30 enhances the H3K4me activity of the SET1/MLL complex. Here, I sought to define role of DPY30 and H3K4me3 in postnatal neurogenesis and hematopoietic malignancies. Using a conditional knockout model, I found that Dpy30 deficiency halts the development of postnatal hippocampus, the subventricular zone, and cerebellum. Deficiency in cerebellum is most likely the cause of uncoordinated ataxia-like movements in these mice. By deleting Dpy30 …

Multi-Antigen-Chemiluminescent-Elisa For The Diagnosis Of Trypanosoma Cruzi Infection In Chihuahua, Mexico., Jose Andrei Orozco

Open Access Theses & Dissertations

No abstract provided.

Is Current Fragile X Syndrome Counseling Enough? Expanding The Clinical Phenotype Of Fragile X In Premutation And Intermediate Allele Carriers, Zahra Saadat Girnary

Theses and Dissertations

Fragile X syndrome (FXS) is caused by a triplet repeat expansion on the FMR1 gene. Individuals with >200 repeats have FXS, while individuals between 45-54 and 55- 200 repeats have the FMR1 intermediate allele and premutation, respectively. FXS is characterized by autism and intellectual disability while the premutation is associated with fragile X-associated tremor/ataxia syndrome (FXTAS) and fragile X-associated primary ovarian insufficiency (FXPOI). However, recent research shows that the premutation may be associated with psychiatric manifestations. Currently, there are no established clinical features associated with the intermediate allele. This study sought to 1) study knowledge regarding FXTAS, FXPOI, as well …

Integrating Genetic Counseling And Testing In The Pediatric Oncology Setting: Parental Attitudes And Influencing Factors, Lauren Renee Desrosiers

Theses and Dissertations

Cancer predisposition syndromes (CPS), caused by germline pathogenic variants in tumor suppressor genes and oncogenes, are genetic conditions that put an individual at increased risk to develop cancer. It is estimated that 10-15% of children with cancer have an underlying CPS. Although genetic testing for these conditions has become routine in the adult setting, incorporation of germline genomic technologies into pediatric cancer care has not occurred as rapidly. The purpose of this study is to assess desire for genetic counseling and testing services among parents of children with cancer to provide parental insight in the incorporation of genomic technologies in …

S100b As A Potential Biomarker For Concussion In Male And Female Collegiate Rugby Athletes, Monica L. Ortiz

Cal Poly Humboldt theses and projects

Sport related concussions are among the top ten most common sport injuries. Substantial and mounting evidence points to extensive short and long term negative consequences from mismanaged sport related concussions. Consequently, researchers have called for better diagnostic concussion tests that are rapid, reliable, sensitive, specific and objective. The purpose of this research was to determine the ability of salivary S100B to detect concussions, predict concussion symptom resolution time, and correlate with changes in neurocognitive performance over the course of one athletic season. A repeated measures of salivary S100B and neurocognitive performance using the ImPACT test and a concussion symptom questionnaire …

Evaluation And Adaptation Of Live-Cell Interferometry For Applications In Basic, Translational, And Clinical Research, Kevin A. Leslie

Theses and Dissertations

Cell mass is an important indicator of cell health and status. A diverse set of techniques have been developed to precisely measure the masses of single cells, with varying degrees of technical complexity and throughput. Here, the development of a non-invasive, label-free optical technique, termed Live-Cell Interferometry (LCI), is described. Several applications are presented, including an evaluation of LCI’s utility for assessing drug response heterogeneity in patient-derived melanoma lines and the measurement of CD3+ T cell kinetics during hematopoietic stem cell transplantation. The characterization of mast cells during degranulation, the measurement of viral reactivation kinetics in Kaposi’s Sarcoma, and drug …

Glycosaminoglycan Lyases In The Preparation Of Oligosaccharides, Alhumaidi B. Alabbas

Theses and Dissertations

Glycosaminoglycans are heterogeneous polysaccharides that mediate important biological functions. There has been considerable interest in deciphering the precise GAG sequences that are responsible for protein interactions. In fact, several GAG oligosaccharides have been discovered to date as targeting proteins with higher level of specificity. Yet, it has been difficult to develop GAG oligosaccharides as drugs. One of the key reasons for this state of art is that GAG synthesis is extremely challenging and is highly structure-specific. Thus, much of the biology and pharmacology of GAG remains unknown and unexploited to date.

An alternative approach is to prepare GAG oligosaccharides using …

Advances In Dual-Energy Computed Tomography Imaging Of Radiological Properties, Dong Han

Theses and Dissertations

Dual-energy computed tomography (DECT) has shown great potential in the reduction of uncertainties of proton ranges and low energy photon cross section estimation used in radiation therapy planning. The work presented herein investigated three contributions for advancing DECT applications. 1) A linear and separable two-parameter DECT, the basis vector model (BVM) was used to estimate proton stopping power. Compared to other nonlinear two-parameter models in the literature, the BVM model shows a comparable accuracy achieved for typical human tissues. This model outperforms other nonlinear models in estimations of linear attenuation coefficients. This is the first study to clearly illustrate the …

Understanding The Role Of Phosphoinositide 3-Kinase And Its Function As A Driving Force Behind The Er Stress Response In Fibrostenotic Crohn’S Disease-Affected Ileal Smooth Muscle Cells, Prashant Yadav

Theses and Dissertations

Crohn’s disease (CD) affects about 780,000 people in the United States alone, and it is estimated that 6-15 per 100,000 persons will receive a diagnosis of this disease each year. There currently is no cure for Crohn’s disease, and available medical therapies simply serve to alleviate the inflammation. This does not help treat fibrostenosis that Crohn’s disease patients may develop, which can only be treated surgically. Finding alternatives to treat CD requires an understanding of mechanisms at the biochemical level. In this thesis, we attempted to gain a better understanding of certain pathways found to be active in Crohn’s disease-affected …

The Cryopreservation Of Human Semen, And Subsequent Evaluation Of A Commercially-Available Device To Isolate Motile Sperm, Callum Andrew Robinson

Theses: Doctorates and Masters

The cryopreservation of human semen is a vital asset in assisted reproductive technologies (ART). Although advances have been in the freezing of sperm, further refinement is both necessary and ongoing. Computer-assisted semen analysis (CASA) has been increasingly utilised in both research and diagnostic however there are a range of variables that must first be controlled in order to produce reliable measurements. Following thawing, sperm must be isolated from both the original seminal plasma and the cryoprotectants; the two most used isolation methods include density gradient centrifugation (DGC) and the swim-up method.

The present thesis sought to investigate the following areas …

Faculty Publications 2017, Lsu Health Sciences Center New Orleans

Historical Faculty Publications

This Faculty bibliography contains 947 publications.

A Single-Subject Evaluation Of Facilitated Communication In The Completion Of School-Assigned Homework, Nancy A. Meissner

Antioch University Dissertations & Theses

Few projects have combined quantitative and qualitative approaches in the analysis of facilitated communication as did this study of a 17-year-old nonverbal autistic male responding to homework questions using facilitated communication. Findings were consistent with prior studies: Tim was minimally able to produce correct responses independent of facilitator influence under controlled conditions; whereas, at least some typed messages in the spontaneous narratives appear to be his authentic communications independent of facilitator control.

An overview of the history of facilitated communication, its related research, and the heated debates around its validity are presented. Disparate findings between controlled and non-controlled circumstances are …

Low-Level Cadmium Exposure And Cardiovascular Outcomes In Elderly Australian Women: A Cohort Study, Kane Deering, Anna C. Callan, Richard Prince, Wai Lim, Peter Thompson, Joshua Lewis, Andrea Hinwood, Amanda Devine

Research outputs 2014 to 2021

Background

Cadmium has been associated with increased risk of cardiovascular disease (CVD) in observational studies, however there has been a limited focus on this relationship in women.

Objectives

This study investigated the association of urinary cadmium (UCd) concentrations with CVD outcomes and all-cause mortality in elderly Western Australian (WA) women.

Methods

UCd excretion was measured at baseline in 1359 women, mean age 75.2 ± 2.7 years and 14.5 years of atherosclerotic vascular disease (ASVD) hospitalisations and deaths, including both the principle cause of death and all associated causes of death. Health outcome data were retrieved from the Western Australian Data …

Tellurite Resistance In Shiga Toxin-Producing Escherichia Coli , Gentry L. Lewis, Quentin R. Jorgensen, John Dustin Loy, Rodney A. Moxley

School of Veterinary and Biomedical Sciences: Faculty Publications

Potassium tellurite ( K₂TeO₃) is an effective selective agent for O157:H7 Shiga toxin-producing Escherichia coli (STEC), whereas tellurite resistance in non-O157 STEC is variable with information on O45 minimal. High-level K₂TeO₃ resistance in STEC is attributable to the ter gene cluster with terD an indicator of the cluster’s presence. Polymerase chain reactions for terD and K₂TeO₃ minimum inhibitory concentration (MIC) determinations in broth cultures were conducted on 70 STEC and 40 non-STEC control organisms. Sixty-six STEC strains (94.3%) were terD+ compared to 28 control organisms (70.0%; P < 0.001). The prevalence of terD in …

Development Of A Multiplex Real-Time Pcr Assay Using Two Thermocycling Platforms For Detection Of Major Bacterial Pathogens Associated With Bovine Respiratory Disease Complex From Clinical Samples, John Dustin Loy, Laura Leger, Aspen M. Workman, Michael L. Clawson, Ece Bulut, Bing Wang

School of Veterinary and Biomedical Sciences: Faculty Publications

Bovine respiratory disease complex (BRDC) is one of the most significant diseases of cattle. Bacterial pathogens involved in BRDC include Mannheimia haemolytica, Mycoplasma bovis, Histophilus somni, and Pasteurella multocida. We developed and evaluated a multiplexed real-time hydrolysis probe (rtPCR) assay using block-based Peltier and rotary-based thermocycling on lung tissue, nasal swabs, and deep nasopharyngeal swabs. The rtPCR results were compared to culture or a gel-based M. bovis PCR using statistical analysis to determine optimum quantification cycle (Cq) cutoffs to maximize agreement. The limits of detection were 1.2–12 CFU/reaction for each pathogen. M. haemolytica was the most prevalent organism detected …

Coordinated Regulation Of Transcription By Ccpa And The Staphylococcus Aureus Twocomponent System Hptrs, Joseph M. Reed, Sean Olson, Danielle F. Brees, Caitlin E. Griffin, Ryan A. Grove, Paul J. Davis, Stephen D. Kachman, Jiri Adamec, Greg A. Somerville

School of Veterinary and Biomedical Sciences: Faculty Publications

The success of Staphylococcus aureus as a pathogen is due in part to its ability to adapt to changing environmental conditions using signal transduction pathways, such as metaboliteresponsive regulators and two-component systems. S. aureus has a two-component system encoded by the gene pair sav0224 (hptS) and sav0223 (hptR) that regulate the hexose phosphate transport (uhpT) system in response to extracellular glucose-6-phosphate. Glycolytic intermediates such as glucose-6-phosphate are important carbon sources that also modulate the activity of the global metabolite-responsive transcriptional regulator CcpA. Because uhpT has a putative CcpA binding site in its promoter and …

Novel Docosahexaenoic Acid Ester Of Phloridzin Inhibits Proliferation And Triggers Apoptosis In An In Vitro Model Of Skin Cancer, Theodora Mantso, Dimitrios T. Trafalis, Sotiris Botaitis, Rodrigo Franco, Aglaia Pappa, H. P. Vasantha Rupasinghe, Mihalis I. Panayiotidis

School of Veterinary and Biomedical Sciences: Faculty Publications

Skin cancer is among the most common cancer types accompanied by rapidly increasing incidence rates, thus making the development of more efficient therapeutic approaches a necessity. Recent studies have revealed the potential role of decosahexaenoic acid ester of phloridzin (PZDHA) in suppressing proliferation of liver, breast, and blood cancer cell lines. In the present study, we investigated the cytotoxic potential of PZDHA in an in vitro model of skin cancer consisting of melanoma (A375), epidermoid carcinoma (A431), and non-tumorigenic (HaCaT) cell lines. Decosahexaenoic acid ester of phloridzin led to increased cytotoxicity in all cell lines as revealed by cell viability …

Mucosal Antibody Responses To Vaccines Targeting Siv Protease Cleavage Sites Or Fulllength Gag And Env Proteins In Mauritian Cynomolgus Macaques, Hongzhao Li, Yan Hai, So-Yon Lim, Nikki Toledo, Jose Crecente-Campo, Dane Schalk, Lin Li, Robert W. Omange, Tamara G. Dacoba, Lewis R. Liu, Mohammad Abul Kashem, Yanmin Wan, Binhua Liang, Qingsheng Li, Eva Rakasz, Nancy Schultz-Darken, Maria J. Alonso, Francis A. Plummer, James B. Whitney, Ma Luo

Nebraska Center for Virology: Faculty Publications

HIV mutates rapidly and infects CD4⁺ T cells, especially when they are activated. A vaccine targeting conserved, essential viral elements while limiting CD4⁺ T cell activation could be effective. Learning from natural immunity observed in a group of highly HIV-1 exposed seronegative Kenyan female sex workers, we are testing a novel candidate HIV vaccine targeting the 12 viral protease cleavage sites (PCSs) (the PCS vaccine), in comparison with a vaccine targeting full-length Gag and Env (the Gag/Env vaccine) in a Mauritian cynomolgus macaque/SIV model. In this study we evaluated these vaccines for induction of mucosal antibodies to SIV …

Contribution Of The Gp120 V3 Loop To Envelope Glycoprotein Trimer Stability In Primate Immunodeficiency Viruses, Dane Bowder, Haley Hollingsead, Kate Durst, Duoyi Hu, Wenzhong Wei, Joshua Wiggins, Halima Medjahed, Andrés Finzi, Joseph Sodroski, Shi-Hua Xiang

Nebraska Center for Virology: Faculty Publications

The V3 loop of the human immunodeficiency virus type 1 (HIV-1) gp120 exterior envelope glycoprotein (Env) becomes exposed after CD4 binding and contacts the coreceptor to mediate viral entry. Prior to CD4 engagement, a hydrophobic patch located at the tip of the V3 loop stabilizes the non-covalent association of gp120 with the Env trimer of HIV-1 subtype B strains. Here, we show that this conserved hydrophobic patch (amino acid residues 307, 309 and 317) contributes to gp120-trimer association in HIV-1 subtype C, HIV-2 and SIV. Changes that reduced the hydrophobicity of these V3 residues resulted in increased gp120 shedding and …

Plasma Medicine: A Brief Introduction, Mounir Laroussi

Electrical & Computer Engineering Faculty Publications

This mini review is to introduce the readers of Plasma to the field of plasma medicine. This is a multidisciplinary field of research at the intersection of physics, engineering, biology and medicine. Plasma medicine is only about two decades old, but the research community active in this emerging field has grown tremendously in the last few years. Today, research is being conducted on a number of applications including wound healing and cancer treatment. Although a lot of knowledge has been created and our understanding of the fundamental mechanisms that play important roles in the interaction between low temperature plasma and …

Interpretive Phenomenological Analysis: Exploring The Experiences Of Eye Bank Coordinators When Approaching Families Of Decedents For Eye Donation, Concetta Triglia

Health Sciences Program Student Theses, Dissertations and Capstones

This dissertation was used to addresses a group of individuals who work as eye bank coordinators. These individuals call families and approach them for eye donations from a loved one who has just passed away. An interpretative phenomenological analysis (IPA) was used to explain the lived experience of eye bank coordinators who call families for consent of eye tissue. The focus was to understand the dedication of the coordinators to giving the gift of sight and exploring the positive and negative experiences of eye bank coordinators. IPA is used for a keen understanding of eye bank coordinators, and the investigator …

Cks1 Expression In Melanocytic Nevi And Melanoma, Anna A. Brożyna, Andrew Aplin, Cynthia Cohen, Grant Carlson, Andrew Joseph Page, Michael Murphy, Andrzej T. Slominski, J. Andrew Carlson

Department of Cancer Biology Faculty Papers

Cyclin-dependent kinase subunit 1 (Cks1) regulates the degradation of p27, an important G1-S inhibitor, which is up regulated by MAPK pathway activation. In this study, we sought to determine whether Cks1 expression is increased in melanocytic tumors and correlates with outcome and/or other clinicopathologic prognostic markers. Cks1 expression was assessed by immunohistochemistry in 298 melanocytic lesions. The frequency and intensity of cytoplasmic and nuclear expression was scored as a labeling index and correlated with clinico-pathological data. Nuclear Cks1 protein was found in 63% of melanocytic nevi, 89% primary and 90% metastatic melanomas with mean labeling index of 7 ± 16, …

Possible Breakdown Of Dopamine Receptor Synergism In A Mouse Model Of Huntington's Disease, Samantha F. Kennedy

LSU New Orleans Theses and Dissertations

The model of basal ganglia function proposed by Albin, Young and Penney (1989) describes two anatomically independent motor pathways, the direct and indirect. However, under normal conditions striatal dopamine (DA) is required for the expression of motor behavior, and DAergic control of the two pathways (via D1 and D2 receptors, respectively) is dependent on co-activation. We tested for a possible breakdown of D1/D2 synergism using transgenic R6/1 mice bearing the human huntingtin allele (Htt). Motor stereotypy, observed prior to the onset of HD-related symptoms, was rated on a 5-point scale following activation of: A) D1 receptors alone, B) D2 receptors …

Week Of December 18, 2017, New York Medical College

InTouch

• Prominent Trauma Surgeon Addresses 14th Annual Louis R.M. DelGuercio Professorship and Research Day
• GSA Organizes Successful Second Annual Snowman Project
• SOM P2P Committee Recognizes Role Models at NYMC

Medical Sciences 4300: London-Middlesex Suicide Prevention Council, Harshith Bhaskar, Adnan Husein, Ramin Javaheri-Poya, Sabrina Jetly, Christopher Nguyen, Serena Tejpar

Community Engaged Learning Final Projects

Suicide is an issue that affects people of all backgrounds, and takes the lives of many individuals every year. The London-Middlesex Suicide Prevention Council (LMSPC), an organization established in 1990, seeks to provide suicide prevention training to members of the community. They seek to engage community members in prevention and intervention by recognizing warning signs that may exist among the London-Middlesex region. The three main programs that strive to deliver these skills are ASIST, ASK, and safeTALK, each with a slightly different focus. LMSPC’s current goal is to increase access to these services through external grants and potential partnerships. Our …