Life Sciences Commons^™

Evaluation Of Extracellular Matrix Composition And Rheology As Determinants Of Growth, Invasion, And Response To Photodynamic Therapy In 3d Cell Culture Models Of Pancreatic Ductal Adenocarcinoma, Gwendolyn M. Cramer

Graduate Doctoral Dissertations

Pancreatic ductal adenocarcinoma (PDAC) is a notoriously lethal disease characterized by prominent stromal involvement, which plays complex roles in regulating tumor growth and therapeutic response. The extracellular matrix (ECM)-rich stroma has been implicated as a barrier to drug penetration, although stromal depletion strategies have had mixed clinical success. It remains less clear how biophysical interactions with the ECM regulate invasive progression and susceptibilities to specific therapies. Here, an integrative approach combining 3D cell culture and quantitative imaging techniques is used to evaluate invasive behavior and motility as determinants of response to classical chemotherapy and photodynamic therapy (PDT), in which light …

Discovery Of Novel, Orally Bioavailable, Antileishmanial Compounds Using Phenotypic Screening, Diana Ortiz, W. Armand Guiguemde, Jared T. Hammill, Angela K. Carrillo, Yizhe Chen, Michele Connelly, Kayla Stalheim, Carolyn Elya, Alex Johnson, Jaeki Min, Anang Shelat, David C. Smithson, Lei Yang, Fangyi Zhu, R. Kiplin Guy, Scott M. Landfear

Pharmaceutical Sciences Faculty Publications

Leishmaniasis is a parasitic infection that afflicts approximately 12 million people worldwide. There are several limitations to the approved drug therapies for leishmaniasis, including moderate to severe toxicity, growing drug resistance, and the need for extended dosing. Moreover, miltefosine is currently the only orally available drug therapy for this infection. We addressed the pressing need for new therapies by pursuing a two-step phenotypic screen to discover novel, potent, and orally bioavailable antileishmanials. First, we conducted a high-throughput screen (HTS) of roughly 600,000 small molecules for growth inhibition against the promastigote form of the parasite life cycle using the nucleic acid …

Immune Checkpoint Inhibitors In Neuroendocrine Tumors: A Single Institution Experience With Review Of Literature, Aman Chauhan, Millicent Horn, Gray Magee, Kurt Hodges, B. Mark Evers, Susanne Arnold, Lowell B. Anthony

Markey Cancer Center Faculty Publications

This unique case series and review of literature suggests that immune checkpoint inhibitors may have clinical activity in neuroendocrine tumors.

Objective: Summarize advances of immuno-oncology in neuroendocrine tumors with the help of a case series.

Design: Case series and review of literature.

Intervention or Exposure: The patients were treated with immune checkpoint inhibitors (pembrolizumab or nivolumab).

Main Outcome(s) and Measures(s): Life expectancy, quality of life, disease progression.

Results: Maximum durable response of 16 months in one of the patients so far. All patients showed improvement in quality of life before disease progression. Two out of four are still on therapy. …

Nuclear Spindles Pave The Way To Metastasis, Patrick J. Hensley, Natasha Kyprianou

Urology Faculty Publications

No abstract provided.

Neurofeedback With Fmri: A Critical Systematic Review, Robert T. Thibault, Amanda Macpherson, Michael Lifshitz, Raquel R. Roth, Amir Raz

Psychology Faculty Articles and Research

Neurofeedback relying on functional magnetic resonance imaging (fMRI-nf) heralds new prospects for self-regulating brain and behavior. Here we provide the first comprehensive review of the fMRI-nf literature and the first systematic database of fMRI-nf findings. We synthesize information from 99 fMRI-nf experiments—the bulk of currently available data. The vast majority of fMRI-nf findings suggest that self-regulation of specific brain signatures seems viable; however, replication of concomitant behavioral outcomes remains sparse. To disentangle placebo influences and establish the specific effects of neurofeedback, we highlight the need for double-blind placebo-controlled studies alongside rigorous and standardized statistical analyses. Before fMRI-nf can join the …

Tfpiα Interacts With Fva And Fxa To Inhibit Prothrombinase During The Initiation Of Coagulation, Jeremy P. Wood, Helle H. Petersen, Bingke Yu, Xiaoai Wu, Ida Hilden, Alan E. Mast

Gill Heart & Vascular Institute Faculty Publications

Tissue factor pathway inhibitor α (TFPIα) inhibits prothrombinase, the thrombin-generating complex of factor Xa (FXa) and factor Va (FVa), during the initiation of coagulation. This inhibition requires binding of a conserved basic region within TFPIα to a conserved acidic region in FXa-activated and platelet-released FVa. In this study, the contribution of interactions between TFPIα and the FXa active site and FVa heavy chain to prothrombinase inhibition were examined to further define the inhibitory biochemistry. Removal of FXa active site binding by mutation or by deletion of the second Kunitz domain (K2) of TFPIα produced 17- or 34-fold weaker prothrombinase inhibition, …

Urologist Burnout: Frequency, Causes, And Potential Solutions To An Unspoken Entity, Julie Franc-Guimond, Brian Mcneil, Steven M. Schlossberg, Amanda C. North, Alp Sener

Anatomy and Cell Biology Publications

Physician burnout has been linked to decreased job performance, increased medical errors, interpersonal conflicts, and depression. Recent multispecialty studies suggest that urologists have higher rates (up to 63.6%) of burnout compared to physicians in other specialties; however, these reports were limited by low sample sizes.1 We aimed to evaluate the prevalence of urologist burnout, verify risk factors, and recommend preventative measures and solutions for colleagues at risk or suffering from burnout. Urologist burnout is a true entity that transcends level of training and nationality. Its roots appear to be deep-seated in our tireless efforts to strive for excellence in care …

Survival Advantage Of Both Human Hepatocyte Xenografts And Genome-Edited Hepatocytes For Treatment Of Alpha-1 Antitrypsin Deficiency, Florie Borel, Qiushi Tang, Gwladys Gernoux, Cynthia Greer, Ziqiong Wang, Adi Barzel, Mark A. Kay, Leonard D. Shultz, Dale L. Greiner, Terence R. Flotte, Michael A. Brehm, Christian Mueller

Christian Mueller

Hepatocytes represent an important target for gene therapy and editing of single-gene disorders. In alpha-1 antitrypsin (AAT) deficiency, one missense mutation results in impaired secretion of AAT. In most patients, lung damage occurs due to a lack of AAT-mediated protection of lung elastin from neutrophil elastase. In some patients, accumulation of misfolded PiZ mutant AAT protein triggers hepatocyte injury, leading to inflammation and cirrhosis. We hypothesized that correcting the Z mutant defect in hepatocytes would confer a selective advantage for repopulation of hepatocytes within an intact liver. A human PiZ allele was crossed onto an immune-deficient (NSG) strain to create …

Acute Resistance Exercise Induces Sestrin2 Phosphorylation And P62 Dephosphorylation In Human Skeletal Muscle, Nina Zeng, Randall F. D'Souza, Vandre C. Figueiredo, James F. Markworth, Llion A. Roberts, Jonathan M. Peake, Cameron J. Mitchell, David Cameron-Smith

Center for Muscle Biology Faculty Publications

Sestrins (1, 2, 3) are a family of stress-inducible proteins capable of attenuating oxidative stress, regulating metabolism, and stimulating autophagy. Sequestosome1 (p62) is also a stress-inducible multifunctional protein acting as a signaling hub for oxidative stress and selective autophagy. It is unclear whether Sestrin and p62^Ser403 are regulated acutely or chronically by resistance exercise (RE) or training (RT) in human skeletal muscle. Therefore, the acute and chronic effects of RE on Sestrin and p62 in human skeletal muscle were examined through two studies. In Study 1, nine active men (22.1 ± 2.2 years) performed a bout of single-leg strength …

Atomistic Simulations And Network-Based Modeling Of The Hsp90-Cdc37 Chaperone Binding With Cdk4 Client Protein: A Mechanism Of Chaperoning Kinase Clients By Exploiting Weak Spots Of Intrinsically Dynamic Kinase Domains, John Czemeres, Kurt Buse, Gennady M. Verkhivker

Mathematics, Physics, and Computer Science Faculty Articles and Research

A fundamental role of the Hsp90 and Cdc37 chaperones in mediating conformational development and activation of diverse protein kinase clients is essential in signal transduction. There has been increasing evidence that the Hsp90-Cdc37 system executes its chaperoning duties by recognizing conformational instability of kinase clients and modulating their folding landscapes. The recent cryo-electron microscopy structure of the Hsp90-Cdc37- Cdk4 kinase complex has provided a framework for dissecting regulatory principles underlying differentiation and recruitment of protein kinase clients to the chaperone machinery. In this work, we have combined atomistic simulations with protein stability and network-based rigidity decomposition analyses to characterize dynamic …

Prevalence And Incidence Of Health Risk Factors Among Adolescent Girls, Kylah Pollard, Mohammed Chowdhury, Sarai Bauguess

The Kennesaw Journal of Undergraduate Research

Heart Disease has many different risk factors, including hypertension (high blood pressure) and high cholesterol. Research has shown that hypertension can be identified as early as adolescence, and preventative measures can be instilled in this age. However, the relationship between hypertension, high cholesterol, race, and income have not been studied in detail among adolescents. The present study analyzed the effects of different health factors on blood pressure and cholesterol levels in Caucasian and African-American girls ages 9-21 years old, the prime of adolescence. The dataset was part of a larger study completed by the National Heart, Blood, and Lung Institute …

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

University of 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 …

Pde8 Is Expressed In Human Airway Smooth Muscle And Selectively Regulates Camp Signaling By Β 2 Ar-Ac6, Timothy B. Johnstone, Kaitlyn H. Smith, Cynthia J. Koziol-White, Fengying Li, Austin G. Kazarian, Maia L. Corpuz, Maya Shumyachter, Frederick J. Ehlert, Bianca E. Himes, Reynold A. Pannettieri Jr., Rennolds S. Ostrom

Pharmacy Faculty Articles and Research

Two cAMP signaling compartments centering around adenylyl cyclase (AC) exist in human airway smooth muscle (HASM) cells, one containing ß2AR-AC6 and another containing E prostanoid receptors (EPR)-AC2. We hypothesized that different phosphodiesterase (PDE) isozymes selectively regulate cAMP signaling in each compartment. According to RNA-seq data, 18 of 24 PDE genes were expressed in primary HASM cells derived from age- and gender-matched donors with and without asthma. PDE8A was the third most abundant of the cAMP-degrading PDE genes, after PDE4A and PDE1A. Knockdown of PDE8A using shRNA evoked 2-fold greater cAMP responses to 1 DM forskolin in the presence of IBMX. …

Virtual Reality As A Training Tool To Treat Physical Inactivity In Children, Adam W. Kiefer, David Pincus, Michael J. Richardson, Gregory D. Myer

Psychology Faculty Articles and Research

Lack of adequate physical activity in children is an epidemic that can result in obesity and other poor health outcomes across the lifespan. Physical activity interventions focused on motor skill competence continue to be developed, but some interventions, such as neuromuscular training (NMT), may be limited in how early they can be implemented due to dependence on the child’s level of cognitive and perceptual-motor development. Early implementation of motor-rich activities that support motor skill development in children is critical for the development of healthy levels of physical activity that carry through into adulthood. Virtual reality (VR) training may be beneficial …

Comparison Between Listeria Sensu Stricto And Listeria Sensu Lato Strains Identifies Novel Determinants Involved In Infection, Jakob Schardt, Grant Jones, Stefanie Müller-Herbst, Kristina Schauer, Sarah E. F. D'Orazio, Thilo M. Fuchs

Microbiology, Immunology, and Molecular Genetics Faculty Publications

The human pathogen L. monocytogenes and the animal pathogen L. ivanovii, together with four other species isolated from symptom-free animals, form the "Listeria sensu stricto" clade. The members of the second clade, "Listeria sensu lato", are believed to be solely environmental bacteria without the ability to colonize mammalian hosts. To identify novel determinants that contribute to infection by L. monocytogenes, the causative agent of the foodborne disease listeriosis, we performed a genome comparison of the two clades and found 151 candidate genes that are conserved in the Listeria sensu stricto species. Two factors were …

Evaluation Of A Field-Deployable Reverse Transcription-Insulated Isothermal Pcr For Rapid And Sensitive On-Site Detection Of Zika Virus, Mariano Carossino, Yanqiu Li, Pei-Yu A. Lee, Chuan-Fu Tsai, Pin-Hsing Chou, Dennis Williams, Ashley Skillman, R. Frank Cook, Grayson Brown, Hsiao-Fen G. Chang, Hwa-Tang T. Wang, Udeni B. R. Balasuriya

Maxwell H. Gluck Equine Research Center Faculty Publications

Background: The recent emergence of Zika virus (ZIKV) in Brazil and its precipitous expansion throughout the Americas has highlighted the urgent need for a rapid and reliable on-site diagnostic assay suitable for viral detection. Such point-of-need (PON), low-cost diagnostics are essential for ZIKV control in vulnerable areas with limited resources.

Methods: We developed and evaluated a ZIKV-specific field-deployable RT-iiPCR reagent set targeting the E gene for rapid detection of ZIKV in ZIKV-spiked human and mosquito specimens, and compared its performance to the Center for Disease Control and Prevention (CDC) and Pan American Health Organization (PAHO) RT-qPCR assays targeting the E …

A Gut Pathobiont Synergizes With The Microbiota To Instigate Inflammatory Disease Marked By Immunoreactivity Against Other Symbionts But Not Itself, João Carlos Gomes-Neto, Hatem Kittana, Sara Mantz, Rafael R. Segura Munoz, Robert J. Schmaltz, Laure B. Bindels, Jennifer L. Clarke, Jesse M. Hostetter, Andrew K. Benson, Jens Walter, Amanda Ramer-Tait

Department of Food Science and Technology: Faculty Publications

Inflammatory bowel diseases (IBD) are likely driven by aberrant immune responses directed against the resident microbiota. Although IBD is commonly associated with a dysbiotic microbiota enriched in putative pathobionts, the etiological agents of IBD remain unknown. Using a pathobiont-induced intestinal inflammation model and a defined bacterial community, we provide new insights into the immune-microbiota interactions during disease. In this model system, the pathobiont Helicobacter bilis instigates disease following sub-pathological dextran sulfate sodium treatment. We show that H. bilis causes mild inflammation in mono-associated mice, but severe disease in the presence of a microbiota, demonstrating synergy between the pathobiont and microbiota …

Survey Instrument: Data Challenges Of Biomedical Researchers In The Age Of Omics, Rolando Garcia-Milian, Denise Hersey, Milica Vukmirovic

Rolando Garcia-Milian

No abstract provided.

Interview Questionaire: Data Challenges Of Biomedical Researchers In The Age Of Omics, Rolando Garcia-Milian, Denise Hersey, Milica Vukmirovic

Rolando Garcia-Milian

No abstract provided.

Of Rats And Men, Thomas S. Walsh

Capstones

This capstone is a data-driven investigation into New York City's rat problem. By using publicly available government data to map rat activity in NYC, I identified several socio-economic variables that correlate with rat populations at the community district, borough, and city-scale. I used these findings (mainly that rat problems are linked to lower incomes) as the basis of an investigation, which includes interviews with residents, experts, and city officials. Prof. Bobby Corrigan, urban rodentologist and formerly with the NYC Department of Health criticizes the city's efforts for the first time on the record.

https://thomasseiyawalsh.wixsite.com/ratstone

Injury And Illness In Marching Band And Color Guard Members And The Need For Athletic Trainers: A Critically Appraised Topic, Alissa C. Rhode

Journal of Sports Medicine and Allied Health Sciences: Official Journal of the Ohio Athletic Trainers Association

Purpose: To determine the prevalence, incidence, risk, rate, and type of injury and illness suffered by collegiate and high school marching band (MB) and color guard (CG) members and determine if there is a need for medical coverage. Methods: Articles were identified from: PubMed, CINAHL, MEDLINE, Physical Therapy and Sports Medicine Collection, ScienceDirect, and single-citation matching using search string, ["marching band" OR "color guard" OR "marching athlete" AND injury] from January 1990-to-October 2016, resulting in 141 articles. Following screening (title, abstract), six articles were reviewed. Four met these inclusion criteria: (1) peer-reviewed, cross-sectional studies, (2) high school or collegiate-aged members, …

The Head Shake Sensory Organization Test (Hs-Sot): Normative Data And Correlation With Dynamic Visual Acuity Testing, Andrea E. Cripps, Scott C. Livingston

Journal of Sports Medicine and Allied Health Sciences: Official Journal of the Ohio Athletic Trainers Association

Background: Among healthy (asymptomatic) subjects and patients, the relationship between performance on the Head Shake Sensory Organization Test (HS-SOT) and performance on the Dynamic Visual Acuity (DVA) testing has not been reported. The purpose of this study was to establish normative data for the HS-SOT and compare performance on the HS-SOT and the DVA test. Hypothesis: A strong positive correlation would exist between the DVA and the HS-SOT. Study Design: A cross-sectional design was used. Level of Evidence: Level 3. Methods: Sixty asymptomatic subjects (34 females, 26 males, ages 20 to 26 years, 23.7±1.6) participated. Each subject’s dynamic balance …

Utilization Of Cupping Therapy In The Treatment Of Vascular Thoracic Outlet Syndrome In A Collegiate Pitcher: A Case Study, Stephen A. Cage, Diana M. Gallegos, Brandon J. Warner

Journal of Sports Medicine and Allied Health Sciences: Official Journal of the Ohio Athletic Trainers Association

Objective: Present a clinical case detailing the effectiveness of dry cupping therapy in treating thoracic outlet syndrome. The utilization of dry cupping therapy on a 20-year-old collegiate baseball pitcher with diagnosed thoracic outlet syndrome is presented. Background: Thoracic outlet syndrome is a relatively rare musculoskeletal condition affecting 1/100,000 patients annually. Dry cupping therapy is an ancient therapeutic modality that utilizes various means of suction with the goal of decompressing myofascial layers. Treatment: Following diagnosis, patient was successfully treated in two weeks using dry cupping therapy. The patient experienced no further incidence of thoracic outlet syndrome symptoms and was able …

Athletic Trainers’ Knowledge Of Legal Practice Within Information Technology And Social Media, Elizabeth R. Neil, Zachary K. Winkelmann, Lindsey E. Eberman

Journal of Sports Medicine and Allied Health Sciences: Official Journal of the Ohio Athletic Trainers Association

Purpose: As healthcare and technology continue to connect in daily practice, athletic trainers (ATs) must be knowledgeable of the governing acts for ethical and legal clinical practice. This is vital to ensure ethical and legal practice as a clinician and protection of confidential protected health information (PHI). The objective of this study was to assess certified athletic trainers’ knowledge of regulations within technology and social media (SoMe). Methods: Certified ATs were recruited from the National Athletic Trainers’ Association membership database. Respondents completed an instrument of 28 questions, including 16 participant demographics, clinical site demographics, SoMe usage and general questions, and …

Metabolic Dysregulation And Cancer Mortality In A National Cohort Of Blacks And Whites, Tomi Akinyemiju, Justin Xavier Moore, Suzanne Judd, Susan Lakoski, Michael Goodman, Monika M. Safford, Maria Pisu

Epidemiology and Environmental Health Faculty Publications

Background: We examined the association between metabolic dysregulation and cancer mortality in a prospective cohort of Black and White adults.

Methods: A total of 25,038 Black and White adults were included in the analysis. Metabolic dysregulation was defined in two ways: 1) using the joint harmonized criteria for metabolic syndrome (MetS) and 2) based on factor analysis of 15 variables characterizing metabolic dysregulation. We estimated hazards ratios (HRs) and 95% confidence intervals (CIs) for the association of MetS and metabolic dysregulation with cancer mortality during follow-up using Cox proportional hazards models.

Results: About 46% of Black and 39% of White …

The Role Of Yes-Associated Protein 1 In Ovarian Physiology And Pathology, Xiangmin Lv

Theses & Dissertations

Ovarian granulosa cells are the major somatic components of the ovarian follicle. Proper proliferation and differentiation of ovarian granulosa cells are essential for successful follicle development. Accumulating evidence indicates that the Hippo-YAP signaling pathway plays critical roles in both development and tumorigenesis of several organs. The present study aims to investigate the role of Yes-associated protein 1 (YAP) in ovarian granulosa cell proliferation, differentiation, and malignant transformation. At first, we found that nuclear YAP (active) was highly expressed in proliferative granulosa cells, whereas cytoplasmic YAP (inactive) was detected mainly in terminally-differentiated luteal cells. Further studies suggested that endogenous YAP activity …

Understanding Huntington's Disease Using Machine Learning Approaches, Sonali Lokhande

KGI Theses and Dissertations

Huntington’s disease (HD) is a debilitating neurodegenerative disorder with a complex pathophysiology. Despite extensive studies to study the disease, the sequence of events through which mutant Huntingtin (mHtt) protein executes its action still remains elusive. The phenotype of HD is an outcome of numerous processes initiated by the mHtt protein along with other proteins that act as either suppressors or enhancers of the effects of mHtt protein and PolyQ aggregates. Utilizing an integrative systems biology approach, I construct and analyze a Huntington’s disease integrome using human orthologs of protein interactors of wild type and mHtt protein. Analysis of this integrome …

Type 2 Neural Progenitor Cell Activation Drives Reactive Neurogenesis After Binge-Like Alcohol Exposure In Adolescent Male Rats, Chelsea Rhea Geil Nickell, Hui Peng, Dayna M. Hayes, Kevin Y. Chen, Justin A. Mcclain, Kimberly Nixon

Pharmaceutical Sciences Faculty Publications

Excessive alcohol consumption during adolescence remains a significant health concern as alcohol drinking during adolescence increases the likelihood of an alcohol use disorder in adulthood by fourfold. Binge drinking in adolescence is a particular problem as binge-pattern consumption is the biggest predictor of neurodegeneration from alcohol and adolescents are particularly susceptible to the damaging effects of alcohol. The adolescent hippocampus, in particular, is highly susceptible to alcohol-induced structural and functional effects, including volume and neuron loss. However, hippocampal structure and function may recover with abstinence and, like in adults, a reactive burst in hippocampal neurogenesis in abstinence may contribute to …

Identification Of Prognostic Cancer Biomarkers Through The Application Of Rna-Seq Technologies And Bioinformatics, Nathan Wong

McKelvey School of Engineering Theses & Dissertations

MicroRNAs (miRNAs) are short single-stranded RNAs that function as the guide sequence of the post-transcriptional regulatory process known as the RNA-induced silencing complex (RISC), which targets mRNA sequences for degradation through complementary binding to the guide miRNA. Changes in miRNA expression have been reported as correlated with numerous biological processes, including embryonic development, cellular differentiation, and disease manifestation. In the latter case, dysregulation has been observed in response to infection by human papillomavirus (HPV), which has also been established as both oncogenic in cervical cancers and oropharyngeal cancers and favorable for overall patient survival after tumor formation. The identification of …

In Memoriam 2017, Stephen J. Langendorfer Ph.D.

International Journal of Aquatic Research and Education

In Memoriam 2017 - Adolph Kiefer, Louise Priest, Terry Laughlin