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Cdo Patterns The Musculature Of The Esophagus And Is Required For Esophageal Motility In Mice, Anthony I. Romera, Jagmohan Singhb, Satish Rattan, Robert S. Krauss

Department of Medicine Faculty Papers

Introduction:

Cdo is a multifunctional cell surface co-receptor that promotes Hedgehog signaling during rostroventral midline development and cadherin-mediated signaling during skeletal myogenesis. We report here novel roles for Cdo in patterning of the murine esophageal musculature and esophageal motility disorders such as achalasia.

Effect Of Age And Vaccination On Extent And Spread Of Chlamydia Pneumoniae Infection In C57bl/6 Mice, Taylor Eddens, Sarah Beaudoin, Amanda Steinberger, Christopher Scott Little, Dawn Shell, Benjamin Wizel, Brian J. Balin Phd, Kerin L. Fresa-Dillon

PCOM Scholarly Works

BACKGROUND: Chlamydia pneumoniae is an obligate intracellular respiratory pathogen for humans. Infection by C. pneumoniae may be linked etiologically to extra-respiratory diseases of aging, especially atherosclerosis. We have previously shown that age promotes C. pneumoniae respiratory infection and extra-respiratory spread in BALB/c mice.

FINDINGS: Aged C57BL/6 mice had a greater propensity to develop chronic and/or progressive respiratory infections following experimental intranasal infection by Chlamydia pneumoniae when compared to young counterparts. A heptavalent CTL epitope minigene (CpnCTL7) vaccine conferred equal protection in the lungs of both aged and young mice. This vaccine was partially effective in protecting against C. …

Scavenger Receptor Cd36 Expression Contributes To Adipose Tissue Inflammation And Cell Death In Diet-Induced Obesity, Lei Cai, Zhen Wang, Ailing Ji, Jason M. Meyer, Deneys R. Van Der Westhuyzen

Internal Medicine Faculty Publications

OBJECTIVE: The enlarged adipose tissue in obesity is characterized by inflammation, including the recruitment and infiltration of macrophages and lymphocytes. The objective of this study was to investigate the role of the scavenger receptor CD36 in high fat diet-induced obesity and adipose tissue inflammation and cell death.

EXPERIMENTAL APPROACH: Obesity and adipose tissue inflammation was compared in CD36 deficient (CD36 KO) mice and wild type (WT) mice fed a high fat diet (60% kcal fat) for 16 weeks and the inflammatory response was studied in primary adipocytes and macrophages isolated from CD36 KO and WT mice.

RESULTS: Compared to WT …

Polyamidoamine Dendrimer Nanoparticle Cytotoxicity, Oxidative Stress, Caspase Activation And Infammatory Response: Experimental Observation And Numerical Simulation, Sourav Prasanna Mukherjee, Hugh Byrne

Articles

Mechanisms underlying the in vitro cytotoxicity of Polyamidoamine nano-dendrimers in human keratinocytes are explored. Previous studies demonstrated a systematic, dendrimer-generation-dependent cytotoxicity, oxidative stress, and genotoxicity. The emerging picture is of dendrimer endocytosis, endosomal rupture and subsequent mitochondrial attack and cell death. To understand the underlying mechanisms, the evolution of reactive oxygen species, intracellular glutathione, caspase activation, mitochondrial membrane potential decay, and inflammatory responses have been examined. Early-stage responses are associated with endosomal encapsulation, later-stage with mitochondrial attack. In all cases, the magnitude and evolution of responses depend on dendrimer generation and dose. The early-stage response is modelled using a rate …

Reduction Of Na/K-Atpase Potentiates Marinobufagenin-Induced Cardiac Dysfunction And Myocyte Apoptosis, Changxuan Liu, Yan Bai, Yiliang Chen, Yu Wang, Yoann Sottejeau, Lijun Liu, Xiaomei Li, Jerry B. Lingrel, Deepak Malhorta, Christopher Cooper, Joseph I. Shapiro M.D., Zi-Jian Xie, Jiang Tian

Biochemistry and Microbiology

Background: Na/K-ATPase decrease has been reported in patients with heart failure and is related to cardiac dysfunction.

Results: Reducing Na/K-ATPase activates caspase 9 and induces cardiac dilation when treated with marinobufagenin.

Conclusion: Reduction of Na/K-ATPase potentiates marinobufagenin-induced cardiac myocyte apoptosis.

Significance: Decreased Na/K-ATPase content together with increased cardiotonic steroids levels is a novel mechanism that may account for cardiac dysfunction.

Deciphering Mechanisms Of Staphylococcal Biofilm Evasion Of Host Immunity., Mark L. Hanke, Tammy Kielian

Journal Articles: Pathology and Microbiology

Biofilms are adherent communities of bacteria contained within a complex matrix. Although host immune responses to planktonic staphylococcal species have been relatively well-characterized, less is known regarding immunity to staphylococcal biofilms and how they modulate anti-bacterial effector mechanisms when organized in this protective milieu. Previously, staphylococcal biofilms were thought to escape immune recognition on the basis of their chronic and indolent nature. Instead, we have proposed that staphylococcal biofilms skew the host immune response away from a proinflammatory bactericidal phenotype toward an anti-inflammatory, pro-fibrotic response that favors bacterial persistence. This possibility is supported by recent studies from our laboratory using …

Function Of Insulin-Like Growth Factor Binding Protein 7 (Igfbp7) In Hepatocellular Carcinoma, Dong Chen

Theses and Dissertations

Title of Dissertation: FUNCTION OF INSULIN-LIKE GROWTH FACTOR BINDING PROTEIN 7(IGFBP7) IN HEPATOCELLULAR CARCINOMA By Dong Chen. Purpose: Hepatocellular carcinoma (HCC) is a highly virulent malignancy with no effective treatment, thus requiring the development of innovative and effective targeted therapies. The oncogene Astrocyte Elevated Gene-1 (AEG-1) plays a seminal role in hepatocarcinogenesis and profoundly downregulates Insulin-like Growth Factor Binding Protein-7 (IGFBP7). The present study focuses on analyzing potential tumor suppressor functions of IGFBP7 in HCC and the relevance of IGFBP7 downregulation in mediating AEG-1 function. Experimental Design: IGFBP7 expression was detected by immunohistochemistry in HCC tissue microarrays by real-time PCR …

Generating Induced Pluripotent Stem Cells From Human Fibroblast Utilizing Controlled Expression Of Transcription Factors, Ju-Sung Song

Honors Scholar Theses

Human Embryonic stem cells (hESCs) represent a pluripotent cell population derived from the inner cell mass (ICM) of the blastocyst stage of the developing embryo. Ethical concerns have been raised regarding the derivation process, as the procedure ultimately results in the destruction of the embryos. Recently, alternative approach has been devised that encompasses reprogramming of terminally differentiated cells into an hESC-like state. This process relies on the over-expression of four pluripotency-associated factors, and successfully reprogrammed cells are termed induced pluripotent stem cells (iPSCs). These cells hold great promise for the use in future cell-based therapeutics such as evaluating drug induced …

Eating And Physical Activity Habits Of College Students., Crystal D. D. West

Undergraduate Honors Theses

No abstract.

Effects Of Burn Injury On Biological Ethanol And Ethyl Glucuronide Concentrations, Trista Haupt Wright

Electronic Theses and Dissertations

Alcohol is the most abused drug in the United States and most frequently performed assay in forensic laboratories. Alcohol is routinely present in biological specimens from fatal residential fires and forensic toxicologists must interpret if these individuals are impaired by determination of their blood alcohol concentrations on post-incineration blood collected at autopsy. There is no known data available to confirm or refute blood alcohol concentrations and impairment in fire-related deaths. Ethyl glucuronide (EtG), a non-volatile minor ethanol metabolite, may provide a better biomarker for ethanol consumption prior to burn injury. The literature does not address the possibility that ethanol or …

Synaptic And Intrinsic Activation Of Gabaergic Neurons In The Cardiorespiratory Brainstem Network, Julie G. Frank, David Mendelowitz

Pharmacology and Physiology Faculty Publications

GABAergic pathways in the brainstem play an essential role in respiratory rhythmogenesis and interactions between the respiratory and cardiovascular neuronal control networks. However, little is known about the identity and function of these GABAergic inhibitory neurons and what determines their activity. In this study we have identified a population of GABAergic neurons in the ventrolateral medulla that receive increased excitatory post-synaptic potentials during inspiration, but also have spontaneous firing in the absence of synaptic input. Using transgenic mice that express GFP under the control of the Gad1 (GAD67) gene promoter, we determined that this population of GABAergic neurons is in …

Pv1 Down-Regulation Via Shrna Inhibits The Growth Of Pancreatic Adenocarcinoma Xenografts, Sophie J. Deharvengt, Dan Tse, Olga Sideleva, Caitlin Mcgarry, Jason R. Gunn, Daniel S. Longnecker, Catherine Carriere, Radu V. Stan

Dartmouth Scholarship

PV1 is an endothelial-specific protein with structural roles in the formation of diaphragms in endothelial cells of normal vessels. PV1 is also highly expressed on endothelial cells of many solid tumours. On the basis of in vitro data, PV1 is thought to actively participate in angiogenesis. To test whether or not PV1 has a function in tumour angiogenesis and in tumour growth in vivo, we have treated pancreatic tumour-bearing mice by single-dose intratumoural delivery of lentiviruses encoding for two different shRNAs targeting murine PV1. We find that PV1 down-regulation by shRNAs inhibits the growth of established tumours derived from two …

Radiation Sensitization Of Breast Cancer Cells By Vitamin D Through The Promotion Of Autophagic Cell Death, Eden Wilson

Theses and Dissertations

Radiation therapy is a widely used tool in cancer therapy and is frequently offered as the first line of treatment for cancers of the breast. While radiotherapy is often initially effective in killing tumor cells or suppressing their growth, there are factors that confer tumor cell resistance to irradiation. Development of resistance may lead to disease recurrence despite the use of surgery, chemotherapy and radiation therapy. A primary goal of the studies in Dr. Gewirtz’s laboratory is to develop strategies to overcome resistance to radiation (and chemotherapy) in breast cancer, with the ultimate goal of preventing or attenuating disease recurrence. …

Corneal Replication Is An Interferon Response-Independent Bottleneck For Virulence Of Herpes Simplex Virus 1 In The Absence Of Virion Host Shutoff, Tracy J. Pasieka, Vineet D. Menachery, Pamela C. Rosato, David A. Leib

Dartmouth Scholarship

Herpes simplex viruses lacking the virion host shutoff function (Δvhs) are avirulent and hypersensitive to type I and type II interferon (IFN). In this study, we demonstrate that even in the absence of IFN responses in AG129 (IFN-αβγR^−/−) mice, Δvhs remains highly attenuated via corneal infection but is fully virulent via intracranial infection. The data demonstrate that the interferon-independent inherent replication defect of Δvhs has a significant impact upon peripheral replication and neuroinvasion.

Elevated Plasma Il-6 Associates With Increased Risk Of Advanced Fibrosis And Cholangiocarcinoma In Individuals Infected By Opisthorchis Viverrini, Banchob Sripa, Bandit Thinkhamrop, Eimorn Mairiang, Thewarach Laha, Sasithorn Kaewkes, Paiboon Sithithaworn, Maria V. Periago, Vajarabhongsa Bhudhisawasdi, Ponlapat Yonglitthipagon, Jason Mulvenna, Paul J. Brindley, Alex Loukas, Jeffrey M. Bethony

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Opisthorchis viverrini is considered among the most important of the food-borne trematodes due to its strong association with advanced periductal fibrosis and bile duct cancer (cholangiocarcinoma). We investigated the relationship between plasma levels of Interleukin (IL)-6 and the risk of developing advanced fibrosis and bile duct cancer from chronic Opisthorchis infection. We show that IL-6 circulates in plasma at concentrations 58 times higher in individuals with advanced fibrosis than age, sex, and nearest-neighbor matched controls and 221 times higher in individuals with bile duct cancer than controls. We also observed a dose-response relationship between increasing levels of plasma IL-6 and …

Environmental Friendly Synthesis, Characterization Of Surface Modifiable Starch Encapsulated Gold Nanoparticles With Bactericidal And Catalytic Activity, Dillon Pender

Mahurin Honors College Capstone Experience/Thesis Projects

In the present study, we report the green synthesis of gold nanoparticles (GNPs), using potato starch as a reducing as well as a stabilizing agent in an aqueous buffer medium. The resulting starch-GNPs (St-GNPs) were near spherical in shape with an average diameter of 15 ± 5 nm. In this approach, St-GNPs were characterized and investigated for their antibacterial properties against both gram negative (Escherichia coli) and gram positive (Staphylococcus epidermidis) bacteria. These St-GNPs were found to possess significant dose dependent antibacterial activity against bacteria. Also, St-GNPs showed a significant catalytic activity and can easily be …

The Prevalence Of Essential Hypertension In Kasigau, Kenya, Lindsay Williams

Mahurin Honors College Capstone Experience/Thesis Projects

Hypertension is the leading cause of cardiovascular disease worldwide. Cardiovascular disease (CVD) is a widespread chronic non-communicable disease (NCD) which is on the rise in developing countries. Evidence based on extensive research studies on risk factors for NCDs suggests that they could be easily significantly decreased by simply controlling their risk factors. Although high blood pressure has been recognized as a leading risk factor for CVD, little research has been done to document the prevalence and incidence of essential hypertension (EH) in lower socioeconomic developing countries. One such country is Kenya. It was found in our research study that Kasigau …

Screening Mammograms In Alzheimer’S Disease Patients, George M. Yousef, Piyush Sovani, Sirisha Devabhaktuni, Lynne J. Goebel

Internal Medicine

Very little guidance exists to help clinicians and families decide whether mammograms are useful in elderly women with Alzheimer’s Disease (AD). We present a case of a patient with moderate AD who had a positive mammogram and discuss the dilemma faced by the family and clinician in deciding what was best to do for the patient. In this case, the family opted for breast conserving surgery (BCS) followed by palliative care which brought up the question of whether screening was appropriate with this treatment goal in mind. We reviewed the literature on AD and breast cancer screening and summarize these …

Genetic Ablation Of Cav1 Differentially Affects Melanoma Tumor Growth And Metastasis In Mice: Role Of Cav1 In Shh Heterotypic Signaling And Transendothelial Migration., Franco Capozza, Casey Trimmer, Remedios Castello-Cros, Sanjay Katiyar, Diana Whitaker-Menezes, Antonia Follenzi, Marco Crosariol, Gemma Llaverias, Federica Sotgia, Richard G Pestell, Michael P Lisanti

Department of Cancer Biology Faculty Papers

Both cell-autonomous and non-cell-autonomous factors contribute to tumor growth and metastasis of melanoma. The function of caveolin-1 (Cav1), a multifunctional scaffold protein known to modulate several biologic processes in both normal tissue and cancer, has been recently investigated in melanoma cancer cells, but its role in the melanoma microenvironment remains largely unexplored. Here, we show that orthotopic implantation of B16F10 melanoma cells in the skin of Cav1KO mice increases tumor growth, and co-injection of Cav1-deficient dermal fibroblasts with melanoma cells is sufficient to recapitulate the tumor phenotype observed in Cav1KO mice. Using indirect coculture experiments with fibroblasts and melanoma cells …

Uptake And Toxic Effects Of Surface Modified Nanomaterials In Freshwater Aquatic Organisms, Brandon Seda

All Dissertations

Nanomaterials are a class of materials with unique properties due to their size, and the association of these properties with the toxicity of nanomaterials is poorly understood. The present study assessed the toxic effects of stable aqueous colloidal suspensions of three distinctly different classes of nanomaterials in aquatic organisms. The fullerene, C70, was stabilized through non-covalent surface modification with gallic acid. Toxicity of C70-gallic acid was confirmed to exhibit similar toxic effects as C60-fullerene, including changes in antioxidative processes in Daphnia magna. Daphnia magna fecundity was significantly reduced in 21d bioassays at C70-gallic concentrations below quantifiable limits (0.03 mg/L C70). …

Racemization Of Amino Acids In Teeth For The Determination Of Age, Andrea Lee Toll

Masters Theses & Specialist Projects

Instrumental to forensic investigations is the ability to identify unknown human remains providing key evidence to criminal cases, resolution to missing persons, and assistance in mass or natural disasters. Identification of remains in an effort to determine age is an area of forensics that has received considerable attention. Traditional methods in age determination such as morphology are often biased, antiquated, and frequently result in a large margin of error. Conversely, the emergence of new forensic techniques provide promise to reduce the margin of error in determining age. One such technique has focused on relating the extent of amino acid racemization …

Effects Of Moderate Swim Exercise On Adiposity And Metabolic Function In Mice, Roberta L. Pohlman, Ana Carneiro, Vera Farah, Lynn K. Hartzler, Mariana Morris

Biological Sciences Faculty Publications

No abstract provided.

The Use Of Infliximab In Older Inflammatory Bowel Disease Patients, Stephanie M. Moleski, Christina C. Lindenmeyer, Patricia L. Kozuch

Department of Medicine Faculty Papers

Limited data suggest anti-tumor necrosis factor (TNF) antibodies have equal efficacy but higher morbidity and mortality in older compared to younger inflammatory bowel disease (IBD) patients(1).

Development Of A Microfluidic Device Coupled To Microdialysis Sampling For The Pre-Concentration Of Cytokines, Randy Francisco Espinal Cabrera

Graduate Theses and Dissertations

A proof-of-concept microfluidic device combined with heparin-immobilized magnetic beads was created to concentrate cytokine proteins collected from microdialysis samples. Cytokines are known to be related to several diseases such as cancer, and Parkinson's diseases, so to be able to develop more effective diseases treatments their interactions have to be well understood. Amine-functionalized polystyrene and carboxyl-functionalized magnetic microspheres of ~6.0 ìm in diameter were used to immobilize heparin. The amount of heparin immobilized on polystyrene beads was 5.82 x 10-8 ± 0.36 x 10-8 M per 1.0 x 106 beads and for magnetic beads was 0.64 x 10-8 ± 0.01 x …

Novel Napi-Iic Mutations Causing Hhrh And Idiopathic Hypercalciuria In Several Unrelated Families: Long-Term Follow-Up In One Kindred., Y Yu, S R. Sanderson, M Reyes, A Sharma, N Dunbar, Tarak Srivastava, H Jüppner, C Bergwitz

Manuscripts, Articles, Book Chapters and Other Papers

Homozygous and compound heterozygous mutations in SLC34A3, the gene encoding the sodium-dependent co-transporter NaPi-IIc, cause hereditary hypophosphatemic rickets with hypercalciuria (HHRH), a disorder characterized by renal phosphate-wasting resulting in hypophosphatemia, elevated 1,25(OH)(2) vitamin D levels, hypercalciuria, rickets/osteomalacia, and frequently kidney stones or nephrocalcinosis. Similar albeit less severe biochemical changes are also observed in heterozygous carriers, which are furthermore indistinguishable from those encountered in idiopathic hypercalciuria (IH). We now searched for SLC34A3 mutations (exons and introns) in two previously not reported HHRH kindreds, which resulted in the identification of three novel mutations. The affected members of kindred A were compound heterozygous …

Isolation And Characterization Of A Novel Substrate For The Pro-Apoptotic Omi/Htra2 Protease, Nathan Ward

HIM 1990-2015

Omi, also known as HtrA2, is a mammalian pro-apoptotic mitochondrial protein and a member of the HtrA (high temperature requirement A) family of serine proteases. Omi promotes the caspase-dependent apoptotic pathway through cleavage of IAPs (inhibitor of apoptosis proteins); this cleavage inactivates IAPs and facilitates caspase activity. Omi's proteolytic activity is necessary and essential for its pro-apoptotic function. This study is aimed to further understand the role of Omi in the cytoplasm by using the yeast two-hybrid system to identify novel Omi interactors/substrates. A HeLa (cervical carcinoma cell line) cDNA library was screened using Omi as a "bait" protein. One …

Effects Of Hyperthermia On Photochemical Internalization-Mediated Delivery Of Bleomycin, Christina Schlazer

UNLV Theses, Dissertations, Professional Papers, and Capstones

Standard treatment protocols for high-grade gliomas, such as glioblastoma multiforme (GBM), are highly ineffective due to their inability to eradicate infiltrating tumor cells. Improvements in overall survival are likely to be realized only with the development of more effective localized therapies capable of eradicating tumor cells in the surgical resection margin and beyond. Photochemical internalization (PCI) is a localized light-based therapeutic modality that enhances the efficacy of therapeutic macromolecules including chemotherapeutic agents such as bleomycin. A number of studies have shown that this photodynamic therapy (PDT) - based modality may prove effective in the treatment of high-grade gliomas.

Three-dimensional multicell …

Biomass Assisted Synthesis Of Antibacterial Gold Nanoparticles And Commentary On Its Future Potential And Applications In Medicine, Chad Willis

Mahurin Honors College Capstone Experience/Thesis Projects

Xylose is a natural monosaccharide found in biomass such as straw, pecan shells, cottonseed hulls, and corncobs. Using this monosaccharide, we report the green synthesis and characterization of biocompatible, biodegradable xylose encapsulated gold nanoparticles (Xyl-GNPs) with potential antibacterial activity. GNPs were synthesized using the bioreduction property of xylose on the chloroaurate anions in an aqueous solution at room temperature and at atmospheric pressure. The characterization of synthesized GNPs was examined by UV-vis spectroscopy; transmission electron microscopy (TEM), energy-dispersive x-ray spectroscopy (EDS) and fourier transform infrared spectroscopy (FTIR). Results indicate that the particles were stable; near spherical in shape with an …

A Mathematical Model For Dengue Fever In A Virgin Environment, Jason K. Bowman

Senior Honors Projects

Dengue is a mosquito-borne viral infection found in tropical and subtropical regions around the world. The disease was named in 1779 and the first recorded epidemic of it occurred simultaneously on three continents within the following decade. Dengue is characterized by flu-like symptoms and, while its symptoms are generally reported as quite unpleasant, is rarely fatal. However, in some cases patients can contract a more serious form of the disease, known as Dengue Hemorrhagic Fever, which is far more dangerous. The World Health Organization estimates that today over 2.5 billion people are at risk for Dengue (over 40% of the …

Prelamin A Influences A Program Of Gene Expression In Regulation Of Cell Cycle Control, Christina N. Bridges

Electronic Theses and Dissertations

The A-type lamins are intermediate filament proteins that constitute a major part of the eukaryotic nuclear lamina—a tough, polymerized, mesh lining of the inner nuclear membrane, providing shape and structural integrity to the nucleus. Lamin A (LA) filaments also permeate the nucleoplasm, providing additional structural support, but also scaffolding numerous tethered molecules to stabilize, organize, and facilitate molecular interactions to accomplish critical functions of cellular metabolism. Over the past 2 decades, much attention has been focused on roles of LA in maintenance of nuclear structural integrity. Only since the late 1990s have scientists discovered the devastating effects of LA gene …