Digital Commons Network^™

A Neuronal Network Of Mitochondrial Dynamics Regulates Metastasis., M. Cecilia Caino, Jae Ho Seo, Angeline Aguinaldo, Eric Wait, Kelly G. Bryant, Andrew V. Kossenkov, James E. Hayden, Valentina Vaira, Annamaria Morotti, Stefano Ferrero, Silvano Bosari, Dmitry I. Gabrilovich, Lucia R. Languino, Andrew R. Cohen, Dario C. Altieri

Department of Cancer Biology Faculty Papers

The role of mitochondria in cancer is controversial. Using a genome-wide shRNA screen, we now show that tumours reprogram a network of mitochondrial dynamics operative in neurons, including syntaphilin (SNPH), kinesin KIF5B and GTPase Miro1/2 to localize mitochondria to the cortical cytoskeleton and power the membrane machinery of cell movements. When expressed in tumours, SNPH inhibits the speed and distance travelled by individual mitochondria, suppresses organelle dynamics, and blocks chemotaxis and metastasis, in vivo. Tumour progression in humans is associated with downregulation or loss of SNPH, which correlates with shortened patient survival, increased mitochondrial trafficking to the cortical cytoskeleton, greater …

The Hif/Phf8/Ar Axis Promotes Prostate Cancer Progression., D Tong, Q Liu, G Liu, W Yuan, L Wang, Y Guo, W Lan, Dianzheng Zhang, S Dong, Y Wang, H Xiao, J Mu, C Mao, J Wong, J Jiang

PCOM Scholarly Works

Recent studies provide strong evidence that the androgen receptor (AR) signaling pathway remains active in castration-resistant prostate cancer (CRPC). However, the underlying mechanisms are not well understood. In this study, we demonstrate that plant homeo domain finger protein 8 (PHF8 )interacts with and functions as an essential histone demethylase activity-dependent AR coactivator. Furthermore, we demonstrate that the expression of PHF8 is induced by hypoxia in various prostate cancer cell lines. Knockdown of either hypoxia-inducible factor HIF2α or HIF1α almost completely abolished hypoxia-induced PHF8 expression. Importantly, we observed that PHF8 is highly expressed in clinical androgen deprived prostate cancer samples and …

The Hemostatic Effects Of Acute Exposure To Colored Cornstarch Powder During A 5k Run, Robert C. Allsbrook

Senior Honors Projects, 2010-2019

PURPOSE: To examine the acute hemostatic effects of particulate matter (PM) in the form of colored corn starch powder during a 5 kilometer race. METHODS: 10 recreationally active adults completed two 5k runs, one with color and one without color. 10 mL blood samples were taken 6 hours prior to the trial and immediately following the trial. PAI-1 activity, FVIII antigen, and tPA activity were measured using an ELISA. RESULTS: No significant main effects or interaction effects (P<0.05) were observed among any of the variables although a trend (P = 0.082) was observed for increased PAI-1 activity during exercise in the color condition. CONCLUSIONS: There is a trend towards increased PAI-1 activity levels during exercise during color runs that could be due to increased inflammation. Furthermore, the lack of increased FVIII:ag and tPA activity suggests that the intensity of the exercise may not have been adequate and further research should be conducted in this area.

Selective Suppression Of The Α Isoform Of P38 Mapk Rescues Late-Stage Tau Pathology, Nicole Maphis, Shanya Jiang, Guixiang Xu, Olga N. Kokiko-Cochran, Saktimayee M. Roy, Linda J. Van Eldik, D. Martin Watterson, Bruce T. Lamb, Kiran Bhaskar

Sanders-Brown Center on Aging Faculty Publications

Background: Hyperphosphorylation and aggregation of tau protein are the pathological hallmarks of Alzheimer’s disease and related tauopathies. We previously demonstrated that the microglial activation induces tau hyperphosphorylation and cognitive impairment via activation of p38 mitogen-activated protein kinase (p38 MAPK) in the hTau mouse model of tauopathy that was deficient for microglial fractalkine receptor CX3CR1.

Method: We report an isoform-selective, brain-permeable, and orally bioavailable small molecule inhibitor of p38α MAPK (MW181) and its effects on tau phosphorylation in vitro and in hTau mice.

Results: First, pretreatment of mouse primary cortical neurons with MW181 completely blocked inflammation-induced p38α MAPK activation and AT8 …

Ca2+/Calmodulin/Mlck Pathway Initiates, And Rhoa/Rock Maintains, The Internal Anal Sphincter Smooth Muscle Tone., Satish Rattan

Division of Gastroenterology and Hepatology Faculty Papers

No abstract provided.

Phytochemicals As Novel Agents For The Induction Of Browning In White Adipose Tissue, Yusra Azhar, Ashish Parmar, Colette N Miller, Janaiya S Samuels, Srujana Rayalam

PCOM Scholarly Works

Obesity and its associated metabolic syndrome continue to be a health epidemic in westernized societies and is catching up in the developing world. Despite such increases, little headway has been made to reverse adverse weight gain in the global population. Few medical options exist for the treatment of obesity which points to the necessity for exploration of anti-obesity therapies including pharmaceutical and nutraceutical compounds. Defects in brown adipose tissue, a major energy dissipating organ, has been identified in the obese and is hypothesized to contribute to the overall metabolic deficit observed in obesity. Not surprisingly, considerable attention has been placed …

Glutathione Species And Metabolomic Prints In Subjects With Liver Disease As Biological Markers For The Detection Of Hepatocellular Carcinoma, Juan R. Sanabria, Rajan S. Kombu, Guo-Fang Zhang, Yana Sandlers, Jizhou Ai, Rafael A. Ibarra, Rime Abbas, Kush Goyal, Henri Brunengraber

Surgery

Background: The incidence of liver disease is increasing in USA. Animal models had shown glutathione species in plasma reflects liver glutathione state and it could be a surrogate for the detection of hepatocellular carcinoma (HCC).

Methods: The present study aimed to translate methods to the human and to explore the role of glutathione/metabolic prints in the progression of liver dysfunction and in the detection of HCC. Treated plasma from healthy subjects (n = 20), patients with liver disease (ESLD, n = 99) and patients after transplantation (LTx, n = 7) were analyzed by GC- or LC/MS. Glutathione labeling profile was …

Baylisascaris Procyonis Exposure Case Study, Andrea M. Lauffer M.D., Patricia Lutz M.D., Susan L. Flesher M.D.

Pediatrics

We report a case of exposure to raccoon feces found to be contaminated with baylisascaris procyonis. The exposure was recognized early enough by the family to allow prophylaxis with albendazole. Because of the potential fatal or neurologically catastrophic effects of this disease immediate treatment is indicated. This is started in advance of environmental studies that are done to determine if the feces is indeed contaminated.

Is Current Evidence That Avoidance Of Inhalation Agents And Opioids May Decrease Metastasis Strong Enough For Crnas To Show A Willingness To Change Practice?, Michael Wesley Tillman

Doctoral Projects

Metastasis following the surgical resection of primary site breast cancer is a medical issue, which plagues mastectomy patients. The intention of this project was to synthesize current literature in order to make a presentation and disseminate it to Certified Registered Nurse Anesthetists (CRNAs) in southern Mississippi and assess the providers' willingness to change practice. CRNAs took part in a Qualtrics survey after viewing a PowerPoint presentation of evidence regarding anesthesia and metastasis. The presentation illustrated the anesthetic techniques and pharmacological agents utilized, which either mitigate or potentiate a patient's risk for metastasis. The survey assessed for a willingness to change …

The Role And Regulation Of Inhibitor Of Kappa B Kinase In The Impaired Monocyte Response., Norman James Galbraith

Electronic Theses and Dissertations

Trauma, major surgery and systemic infection can lead to a subsequent immunosuppressed state which can predispose patients to nosocomial infection and death. Approximately a sixth of patients will have impaired monocyte function, as determined by decreased HLA-DR expression or decreased TNF-α production in response to ex-vivo lipopolysaccharide (LPS) stimulation. This project aimed to develop an in-vitro model of impaired monocyte function using isolated monocytes from healthy volunteers, to study the effect of monocyte impairment on IκK signaling, and determine the role of IκK in the impaired monocyte response. These studies have provided the following results:

1. Monocytes treated with low dose …

The Role Of Nicotine, A7 Nicotinic Acetylcholine Receptors And Extracellular Matrix Remodeling In Pulmonary Fibrosis., Glenn Ward Vicary

Electronic Theses and Dissertations

The median survival for idiopathic pulmonary fibrosis (IPF) patients from diagnosis is a dismal 3 years. This condition is characterized by pulmonary fibroproliferation and excess production and disordered deposition of extracellular matrix (ECM) proteins resulting in obliteration of the original tissue architecture, loss of lung function and eventual death due to respiratory failure. The main hindrance to the development of effective treatments against pulmonary fibrosis is the late detection of its progression and is often of unknown cause. Tobacco smoke represents the most important environmental factor linked to the development of pulmonary fibrosis, with over 60% of IPF patients current …

The Potential Roles Of Long Noncoding Rnas (Lncrna) In Glioblastoma Development, Shuang Liu, Ramkrishna Mitra, Ming-Ming Zhao, Wenhong Fan, Christine M. Eischen, Feng Yin, Zhongming Zhao

Department of Cancer Biology Faculty Papers

Long noncoding RNA (lncRNA) may contribute to the initiation and progression of tumor. In this study, we first systematically compared lncRNA and mRNA expression between glioblastoma and paired normal brain tissues using microarray data. We found 27 lncRNA and 82 mRNA significantly upregulated in glioblastoma, as well as 198 lncRNA and 285 mRNA significantly downregulated in glioblastoma. We identified 138 coexpressed lncRNA–mRNA pairs from these differentially expressed lncRNA and genes. Subsequent pathway analysis of the lncRNA-paired genes indicated that EphrinB–EPHB, p75-mediated signaling, TNFα/NF-κB, and ErbB2/ErbB3 signaling pathways might be altered in glioblastoma. Specifically, lncRNA RAMP2-AS1 had significant decrease of expression …

A Novel Codon-Optimized Siv Gag-Pol Immunogen For Gene-Based Vaccination, Catherine M. Crosby, Eric A. Weaver, Reeti Khare, Michael A. Barry

Nebraska Center for Virology: Faculty Publications

Simian immunodeficiency virus (SIV) is a robust pathogen used in non-human primates to model HIV vaccines. SIV encodes a number of potential vaccine targets. By far the largest and most conserved protein target in SIV is its gag-pol protein that bears many epitopes to drive multivalent immune T cell responses. While gag-pol is an attractive antigen, it is only translated after a frame shift between gag and pol with the effect that gag and pol are expressed at an approximate 10/1 ratio. The codon bias of native lentiviral genes are also mismatched with the abundance of tRNAs in mammalian cells …

The Dynamics Of Adult Neurogenesis In Human Hippocampus, Amadi O. Ihunwo, Lackson H. Tembo, Charles Dzamalala

Brain and Mind Institute

The phenomenon of adult neurogenesis is now an accepted occurrence in mammals and also in humans. At least two discrete places house stem cells for generation of neurons in adult brain. These are olfactory system and the hippocampus. In animals, newly generated neurons have been directly or indirectly demonstrated to generate a significant amount of new neurons to have a functional role. However, the data in humans on the extent of this process is still scanty and such as difficult to comprehend its functional role in humans. This paper explores the available data on as extent of adult hippocampal neurogenesis …

Nanoparticle Toxicity And Molecular Mechanisms In Fish: A Case Study With Silver Nanoparticles, Jiejun Gao

Open Access Dissertations

Nanoparticles (NPs) are widely used in a myriad of commercial and industrial products making their entry to the environment a likely event. NPs have unique physical-chemical properties that result from their small size and high surface area to volume ratio, making them highly reactive and potentially toxic. In Chapter 1, we summarize the effects and mechanisms of metal-based NPs on the vascular system. In vitro studies have shown that NPs are anti-angiogenic because they cause inflammation, oxidative stress, and apoptosis of endothelial cells resulting in increased permeability and decreased proliferation and migration. Whole animal studies examining the effects of NPs …

Gonadal Intersex In Teleosts: Mechanisms, Molecular Biomarkers And Diagnostic Assays, Ahmed M.E. Abdel-Moneim Mohamed

Open Access Dissertations

Natural and synthetic estrogenic and androgenic compounds are continuously released into aquatic ecosystems. Exposure of teleost fishes to these contaminants can negatively impact sex differentiation and reproductive output. Specifically, development of gonadal intersex in gonochoristic (fixed sex) fish species has been studied extensively in relation to exposure to this class of compounds. The main objectives of this dissertation were to: 1) conduct field and laboratory studies to investigate the molecular signaling pathways behind the development of gonadal intersex; and 2) establish molecular biomarkers and assays for testing the ability of environmental pollutants to develop this condition using a battery of …

Self-Reported Sleep Apnea And Dementia Risk: Findings From The Prevention Of Alzheimer's Disease With Vitamin E And Selenium Trial, Xiuhua Ding, Richard J. Kryscio, Joshua Turner, Gregory A. Jicha, Gregory E. Cooper, Allison M. Caban-Holt, Frederick A. Schmitt, Erin L. Abner

Sanders-Brown Center on Aging Faculty Publications

OBJECTIVES: To investigate the association between baseline sleep apnea and risk of incident dementia in the Prevention of Alzheimer's Disease with Vitamin E and Selenium (PREADViSE) study and to explore whether the association depends on apolipoprotein E (APOE) ɛ4 allele status.

DESIGN: Secondary analysis based on data collected during PREADViSE.

SETTING: Participants were assessed at 128 local clinical study sites during the clinical trial phase and later were followed by telephone from a centralized location.

PARTICIPANTS: Men enrolled in PREADViSE (without dementia or other active neurological conditions that affect cognition such as major psychiatric disorders, including depression; N = …

Ido1 Is An Integral Mediator Of Inflammatory Neovascularization., Arpita Mondal, Courtney Smith, James B. Duhadaway, Erika Sutanto-Ward, George C. Prendergast, Arturo Bravo-Nuevo, Alexander J. Muller

Kimmel Cancer Center Papers, Presentations, and Grand Rounds

The immune tolerogenic effects of IDO1 (indoleamine 2,3-dioxygenase 1) have been well documented and genetic studies in mice have clearly established the significance of IDO1 in tumor promotion. Dichotomously, the primary inducer of IDO1, the inflammatory cytokine IFNγ (interferon-γ), is a key mediator of immune-based tumor suppression. One means by which IFNγ can exert an anti-cancer effect is by decreasing tumor neovascularization. We speculated that IDO1 might contribute to cancer promotion by countering this anti-neovascular effect of IFNγ, possibly through IDO1-potentiated elevation of the pro-tumorigenic inflammatory cytokine IL6 (interleukin-6). In this study, we investigated how genetic loss of IDO1 affects …

Evaluating Cardiovascular Dysfunction During Increased Activity And Exercise Rehabilitation Following Incomplete Thoracic Spinal Cord Injury In The Adult Rat., Kathryn A. Harman

Electronic Theses and Dissertations

Spinal cord injury (SCI) results in whole-body dysfunction. While the majority of SCI research is focused on improving locomotor function after injury, cardiovascular (CV) disease continues to be the leading cause of morbidity in the chronic SCI patient population. The combination of injury-induced destruction of autonomic pathways, maladaptive plasticity within lumbosacral circuits, and the progressive decline in physical fitness contribute to the poor CV status of SCI individuals. Currently, there is little emphasis on implementing appropriately-timed acute rehabilitation techniques aimed to curtail maladaptive remodeling and improve CV outcomes. Furthermore, no pre-clinical or clinical studies have investigated the most appropriate time-course …

Intravenous Ketamine For Subacute Treatment Of Refractory Chronic Migraine: A Case Series., Clinton Lauritsen, Santiago Mazuera, Richard B. Lipton, Sait Ashina

Department of Neurology Faculty Papers

BACKGROUND: Refractory migraine is a challenging condition with great impact on health related quality of life. Intravenous (IV) ketamine has been previously used to treat various refractory pain conditions. We present a series of patients with refractory migraine treated with intravenous ketamine in the hospital setting.

METHODS: Based on retrospective chart review, we identified six patients with refractory migraine admitted from 2010 through 2014 for treatment with intravenous ketamine. Ketamine was administered using a standard protocol starting with a dose of 0.1 mg/kg/hr and increased by 0.1 mg/kg/hr every 3 to 4 h as tolerated until the target pain score …

Nicotinamide Adenine Dinucleotide Phosphate Oxidase 2 Regulates Lps-Induced Inflammation And Alveolar Remodeling In The Developing Lung., Heather Menden, Sheng Xia, Sherry M. Mabry, Angels Navarro, Michael F. Nyp, Venkatesh Sampath

Manuscripts, Articles, Book Chapters and Other Papers

In premature infants, sepsis is associated with alveolar simplification manifesting as bronchopulmonary dysplasia. The redox-dependent mechanisms underlying sepsis-induced inflammation and alveolar remodeling in the immature lung remain unclear. We developed a neonatal mouse model of sepsis-induced lung injury to investigate whether nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2) regulates Toll-like receptor (TLR)-mediated inflammation and alveolar remodeling. Six-day-old NOX2

Interpreting Measurements Of Cardiac Function Using Vendor-Independent Speckle Tracking Echocardiography In Children: A Prospective, Blinded Comparison With Catheter-Derived Measurements., Suma Goudar, G Hamilton Baker, Shahryar M. Chowdhury, Kimberly J. Reid, Girish S. Shirali, Mark A. Scheurer

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Adult studies demonstrate that echocardiographic measurements of cardiac function using speckle tracking correlate with invasive measurements, but such data in the pediatric population are sparse. Our aim was to compare speckle-derived measures of cardiac function to measurements routinely obtained by cardiac catheterization in children.

METHODS: Echocardiograms were performed on the day of cardiac catheterization. Using Tomtec 2D Cardiac Performance Analysis, longitudinal strain (LS), longitudinal strain rate (LSR), early diastolic LSR, and ejection fraction (EF) for the right and left ventricle (RV and LV) were calculated via speckle tracking. Global LS and LSR were calculated for the LV. These results …

Indoor Tobacco Legislation Is Associated With Fewer Emergency Department Visits For Asthma Exacerbation In Children., Christina E. Ciaccio, Tami Gurley-Calvez, Theresa I. Shireman

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: During the past 3 decades, numerous cities and states have adopted laws that ban smoking in public indoor spaces. The rationale for these policies has been to protect nonsmokers from the adverse health effects of secondhand smoke.

OBJECTIVE: To determine whether the implementation of indoor smoking legislation is associated with a decrease in emergency department visits for asthma in children.

METHODS: This retrospective analysis used a natural experiment to estimate the impact of clean indoor air legislation on the rate of emergency department admissions for asthma exacerbation in children. Data were obtained from the Pediatric Health Information System. A …

Plasma Processes And Polymers Third Special Issue On Plasma And Cancer, Mounir Laroussi, Annemie Bogaerts, Nazir Barekzi

Electrical & Computer Engineering Faculty Publications

(First paragraph) This issue of Plasma Processes and Polymers is the third in a series on the applications of low temperature plasma (LTP) against cancer, or “plasma oncology.” The papers in this issue are inspired from the talks given at the third International Workshop on Plasma for Cancer Treatment (IWPCT) which took place on April 11–12, 2016 in Washington, DC, USA. IWPCT is an international workshop that was created in 2014 as a venue to share cutting edge plasma oncology research. The first IWPCT was held in Washington DC, under the co-chairmanship of Prof. Mounir Laroussi (Old Dominion University) and …

Comparative Efficacy Of Nebivolol And Metoprolol To Prevent Tachycardia-Induced Cardiomyopathy In A Porcine Model, Alireza Nazeri, Macarthur A Elayda, Ana Maria Segura, Raymond F Stainback, Joanna Nathan, Vei-Vei Lee, Christina Bove, Luiz Sampaio, Brian Grace, Ali Massumi, Mehdi Razavi

The Texas Heart Institute Journal

Chronic tachycardia is a well-known cause of nonischemic cardiomyopathy. We hypothesized that nebivolol, a β-blocker with nitric oxide activity, would be superior to a pure β-blocker in preventing tachycardia-induced cardiomyopathy in a porcine model.

Fifteen healthy Yucatan pigs were randomly assigned to receive nebivolol, metoprolol, or placebo once a day. All pigs underwent dual-chamber pacemaker implantation. The medication was started the day after the pacemaker implantation. On day 7 after implantation, each pacemaker was set at atrioventricular pace (rate, 170 beats/min), and the pigs were observed for another 7 weeks. Transthoracic echocardiograms, serum catecholamine levels, and blood chemistry data were …

Blood-Brain Barrier Transport Machineries And Targeted Therapy Of Brain Diseases, Jaleh Barar, Mohammad Rafi, Mohamad Mostafa Pourseif, Yadollah Omidi

Department of Neurology Faculty Papers

Introduction: Desired clinical outcome of pharmacotherapy of brain diseases largely depends upon the safe drug delivery into the brain parenchyma. However, due to the robust blockade function of the blood-brain barrier (BBB), drug transport into the brain is selectively controlled by the BBB formed by brain capillary endothelial cells and supported by astrocytes and pericytes. Methods: In the current study, we have reviewed the most recent literature on the subject to provide an insight upon the role and impacts of BBB on brain drug delivery and targeting. Results: All drugs, either small molecules or macromolecules, designated to treat brain diseases …

Epidemiology And Impact Of Campylobacter Infection In Children In 8 Low-Resource Settings: Results From The Mal-Ed Study, Shahida Qureshi, Aneeta Hotwani, Sadia Shakoor, (Mal-Ed) Network Investigators, Imran Ahmed, Didar Alam, Syed Asad Ali, Zulfiqar Ahmed Bhutta, Muneera Rasheed, Sajid Bashir Soofi, Ali Turab, Anita K. M. Zaidi

Department of Paediatrics and Child Health

Background: Enteropathogen infections have been associated with enteric dysfunction and impaired growth in children in low-resource settings. In a multisite birth cohort study (MAL-ED), we describe the epidemiology and impact of Campylobacter infection in the first 2 years of life.
Methods: Children were actively followed up until 24 months of age. Diarrheal and nondiarrheal stool samples were collected and tested by enzyme immunoassay for Campylobacter Stool and blood samples were assayed for markers of intestinal permeability and inflammation.
Results: A total of 1892 children had 7601 diarrheal and 26 267 nondiarrheal stool samples tested for Campylobacter We describe a high …

V-Src Oncogene Induces Trop2 Proteolytic Activation Via Cyclin D1., Xiaoming Ju, Xuanmao Jiao, Adam Ertel, Mathew C. Casimiro, Gabriele Disante, Shengqiong Deng, Zhiping Li, Agnese Di Rocco, Tingting Zhan, Adam Hawkins, Tanya Stoyanova, Sebastiano Andò, Alessandro Fatatis, Michael P. Lisanti, Leonard G. Gomella, Lucia R. Languino, Richard G. Pestell

Department of Cancer Biology Faculty Papers

Proteomic analysis of castration-resistant prostate cancer demonstrated the enrichment of Src tyrosine kinase activity in approximately 90% of patients. Src is known to induce cyclin D1, and a cyclin D1-regulated gene expression module predicts poor outcome in human prostate cancer. The tumor-associated calcium signal transducer 2 (TACSTD2/Trop2/M1S1) is enriched in the prostate, promoting prostate stem cell self-renewal upon proteolytic activation via a γ-secretase cleavage complex (PS1, PS2) and TACE (ADAM17), which releases the Trop2 intracellular domain (Trop2 ICD). Herein, v-Src transformation of primary murine prostate epithelial cells increased the proportion of prostate cancer stem cells as characterized by gene expression, …

Photothermal Therapy Improves The Efficacy Of A Mek Inhibitor In Neurofibromatosis Type 1-Associated Malignant Peripheral Nerve Sheath Tumors., Elizabeth E. Sweeney, Rachel A. Burga, Chaoyang Li, Yuan Zhu, Rohan Fernandes

Pediatrics Faculty Publications

Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive tumors with low survival rates and the leading cause of death in neurofibromatosis type 1 (NF1) patients under 40 years old. Surgical resection is the standard of care for MPNSTs, but is often incomplete and can generate loss of function, necessitating the development of novel treatment methods for this patient population. Here, we describe a novel combination therapy comprising MEK inhibition and nanoparticle-based photothermal therapy (PTT) for MPNSTs. MEK inhibitors block activity driven by Ras, an oncogene constitutively activated in NF1-associated MPNSTs, while PTT serves as a minimally invasive method to ablate …

Download Entire Bodine Journal Volume 1, Issue 1, 2008

Bodine Journal

No abstract provided.