Diseases Commons^™

Temporal Changes In Cortical And Hippocampal Expression Of Genes Important For Brain Glucose Metabolism Following Controlled Cortical Impact Injury In Mice, June Zhou, Mark Burns, Linda Huynh, Sonia Villapol, Daniel D. Taub, Juan M. Saavedra, Marc R. Blackman

Pharmacology and Physiology Faculty Publications

Traumatic brain injury (TBI) causes transient increases and subsequent decreases in brain glucose utilization. The underlying molecular pathways are orchestrated processes and poorly understood. In the current study, we determined temporal changes in cortical and hippocampal expression of genes important for brain glucose/lactate metabolism and the effect of a known neuroprotective drug telmisartan on the expression of these genes after experimental TBI. Adult male C57BL/6J mice (n = 6/group) underwent sham or unilateral controlled cortical impact (CCI) injury. Their ipsilateral and contralateral cortex and hippocampus were collected 6 h, 1, 3, 7, 14, 21, and 28 days after injury. …

Cross-Reactive Immunity To Porcine Reproductive And Respiratory Syndrome Virus And Its Contribution To Protection, Ignacio Correas

School of Veterinary and Biomedical Sciences: Dissertations, Theses, and Student Research

Due to the vast geographical distribution and significant economic losses generated, porcine reproductive and respiratory syndrome virus (PRRSV) can be considered the most important swine pathogen of contemporary times. Current control and eradication strategies against PRRSV have difficulty succeeding because of their complex nature and the absence of an effective vaccine. A major obstacle for PRRSV vaccine development is the broad heterogeneity of the virus, both at the genetic and antigenic level, its rapid evolution, and an incomplete knowledge of the immune responses responsible for clearing the virus from the host. Specifically, how known correlates of protection against PRRSV—neutralizing antibodies …

Reduced Ability Of Calcitriol To Promote Augmented Dopamine Release In The Lesioned Striatum Of Aged Rats, Wayne A. Cass, Laura E. Peters

Neuroscience Faculty Publications

Parkinson’s disease (PD) is a progressive and debilitating neurodegenerative disorder that affects over one million people in the United States. Previous studies, carried out in young adult rats, have shown that calcitriol, the active metabolite of vitamin D, can be neuroprotective in 6-hydroxydopamine (6-OHDA) models of PD. However, as PD usually affects older individuals, the ability of calcitriol to promote dopaminergic recovery was examined in lesioned young adult (4 month old), middle-aged (14 month old) and aged (22 month old) rats. Animals were given a single injection of 12 μg 6-OHDA into the right striatum. Four weeks later they were …

Challenges And Considerations Related To Studying Dementia In Blacks/African Americans, Eseosa T. Ighodaro, Peter T. Nelson, Walter A. Kukull, Frederick A. Schmitt, Erin L. Abner, Allison M. Caban-Holt, Shoshana H. Bardach, Derrick C. Hord, Crystal M. Glover, Gregory A. Jicha, Linda J. Van Eldik, Alexander X. Byrd, Anita Fernander

Neuroscience Faculty Publications

Blacks/African Americans have been reported to be ~2–4 times more likely to develop clinical Alzheimer’s disease (AD) compared to Whites. Unfortunately, study design challenges (e.g., recruitment bias), racism, mistrust of healthcare providers and biomedical researchers, confounders related to socioeconomic status, and other sources of bias are often ignored when interpreting differences in human subjects categorized by race. Failure to account for these factors can lead to misinterpretation of results, reification of race as biology, discrimination, and missed or delayed diagnoses. Here we provide a selected historical background, discuss challenges, present opportunities, and suggest considerations for studying health outcomes among racial/ethnic …

Anti-Herv-K (Hml-2) Capsid Antibody Responses In Hiv Elite Controllers., Miguel De Mulder, Devi Sengupta, Steven G Deeks, Jeffrey N Martin, Christopher D Pilcher, Frederick M Hecht, Jonah B Sacha, Douglas F Nixon, Henri-Alexandre Michaud

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Background

Human endogenous retroviruses (HERVs) comprise approximately 8% of the human genome and while the majority are transcriptionally silent, the most recently integrated HERV, HERV-K (HML-2), remains active. During HIV infection, HERV-K (HML-2) specific mRNA transcripts and viral proteins can be detected. In this study, we aimed to understand the antibody response against HERV-K (HML-2) Gag in the context of HIV-1 infection.

Results

We developed an ELISA assay using either recombinant protein or 164 redundant “15mer” HERV-K (HML-2) Gag peptides to test sera for antibody reactivity. We identified a total of eight potential HERV-K (HML-2) Gag immunogenic domains: two on …

Inhibition Of Post-Transcriptional Steps In Ribosome Biogenesis Confers Cytoprotection Against Chemotherapeutic Agents In A P53-Dependent Manner, Russell T Sapio, Anastasiya N Nezdyur, Matthew Krevetski, Leonid Anikin, Vincent J Manna, Natalie Minkovsky, Dimitri G Pestov

Rowan-Virtua School of Osteopathic Medicine Departmental Research

The p53-mediated nucleolar stress response associated with inhibition of ribosomal RNA transcription was previously shown to potentiate killing of tumor cells. Here, we asked whether targeting of ribosome biogenesis can be used as the basis for selective p53-dependent cytoprotection of nonmalignant cells. Temporary functional inactivation of the 60S ribosome assembly factor Bop1 in a 3T3 cell model markedly increased cell recovery after exposure to camptothecin or methotrexate. This was due, at least in part, to reversible pausing of the cell cycle preventing S phase associated DNA damage. Similar cytoprotective effects were observed after transient shRNA-mediated silencing of Rps19, but not …

Investigation Of The Safety Of Focused Ultrasound-Induced Blood-Brain Barrier Opening In A Natural Canine Model Of Aging, Meaghan Anne O'Reilly, Ryan Matthew Jones, Edward Barrett, Anthony P. Schwab, Elizabeth Head, Kullervo Hynynen

Sanders-Brown Center on Aging Faculty Publications

Rationale: Ultrasound-mediated opening of the Blood-Brain Barrier(BBB) has shown exciting potential for the treatment of Alzheimer's disease(AD). Studies in transgenic mouse models have shown that this approach can reduce plaque pathology and improve spatial memory. Before clinical translation can occur the safety of the method needs to be tested in a larger brain that allows lower frequencies be used to treat larger tissue volumes, simulating clinical situations. Here we investigate the safety of opening the BBB in half of the brain in a large aged animal model with naturally occurring amyloid deposits.

Methods: Aged dogs naturally accumulate plaques and show …

Autoantibodies As Diagnostic Biomarkers For The Detection And Subtyping Of Multiple Sclerosis, Cassandra Demarshall, Eric Goldwaser, Abhirup Sarkar, George Godsey, Nimish Acharya, Umashanger Thayasivam, Benjamin Belinka, Robert Nagele

Rowan-Virtua School of Osteopathic Medicine Departmental Research

The goal of this preliminary proof-of-concept study was to use human protein microarrays to identify blood-based autoantibody biomarkers capable of diagnosing multiple sclerosis (MS). Using sera from 112 subjects, including 51 MS subjects, autoantibody biomarkers effectively differentiated MS subjects from age- and gender-matched normal and breast cancer controls with 95.0% and 100% overall accuracy, but not from subjects with Parkinson's disease. Autoantibody biomarkers were also useful in distinguishing subjects with the relapsing-remitting form of MS from those with the secondary progressive subtype. These results demonstrate that autoantibodies can be used as noninvasive blood-based biomarkers for the detection and subtyping of …

Symptoms, Infectious Pathway, Treatment, And History Of Rabies In The United States, Paul Beckman-Ellenwood

Honors Theses

Rabies is a virus of the Lyssavirus family that is endemic to almost all parts of the world and claims over 55,000 lives every year. The virus is capable of being vectored through any warm-blooded animal and has a variable incubation time in its hosts. Once the disease finishes incubating and symptoms appear in the host, the disease is always fatal to humans. To prevent this there are several treatments available, but they can be expensive or difficult to obtain in parts of the world that have the most problems with rabies. To solve this vaccines have been created to …

Finding Human Proteins That Bind To A Lassa Virus Protein, Maria Alejandra Pardo Ruge, Veronica J. Heintz, Douglas J. Lacount

The Summer Undergraduate Research Fellowship (SURF) Symposium

Viral hemorrhagic fevers are severe illnesses caused by many different viruses. Lassa Virus is one of these important pathogens in Western Africa, causing hemorrhagic fever and eventually death without early medical treatment. There is no vaccine and there is little information on host-pathogen interactions. Therefore, the interaction between viral proteins and host targets is useful to understand Lassa virus’s lifecycle and pathology, and to develop ways to prevent infection. In this project, we study the nucleoprotein of Lassa virus (NP), which has been reported to have anti-interferon (IFN) activity through elimination of double stranded RNA (dsRNA). These features could be …

Computational Drug Design: A Multitargeted Approach In Bladder Cancer, Travis C. Lantz, Joydeb Majumder, Gaurav Chopra

The Summer Undergraduate Research Fellowship (SURF) Symposium

Cancer is a complex, robust disease with multiple redundant disease pathways which lead to tumor development, growth, and eventually even death. Despite known redundancies, cancer therapeutics continue to be developed against a single protein target. Initial disease regression occurs followed by relapse in a drug resistant disease state. In response, combinational drug clinical trial targeting multiple pathways began, and have failed due to increased toxicity caused by adverse drug interactions. Development of a single drug that differentially targets multiple disease pathways will result in a more potent therapeutic while inducing minimal toxicity. This was done computationally through in-lab software packages, …

Molecular Mechanisms Of Dna Replication Initiation In Hpvs With Genetic Variations Leading To Cellular Carcinogenesis, Gulden Yilmaz

Graduate School of Biomedical Sciences Theses and Dissertations

Human papillomaviruses are a vast family of double-stranded DNA viruses containing non-carcinogenic and carcinogenic types, whose crucial differences remain unknown, except for the difference in the frequency of DNA replication. The human papillomavirus (HPV) E2 protein regulates the initiation of viral DNA replication and transcription. Its recognition and binding to four 12 bp palindromic sequences in the viral origin is essential for its function. Little is known about the DNA binding mechanism of the E2 protein found in HPV types that have low risk for oncogenicity (low-risk) as well as the roles of various elements of the individual binding sites. …

Advances In Developing Therapies To Combat Zika Virus: Current Knowledge And Future Perspectives, Ashok Munjal, Rekha Khandia, Kuldeep Dharma, Swati Sachan, Kumaragurubaran Karthik, Ruchi Tiwari, Yashpal S. Malik, Deepak Kumar, Raj K. Singh, Hafiz M. N. Iqbal, Sunil K. Joshi

Bioelectrics Publications

Zika virus (ZIKV) remained largely quiescent for nearly six decades after its first appearance in 1947. ZIKV reappeared after 2007, resulting in a declaration of an international “public health emergency” in 2016 by the World Health Organization (WHO). Until this time, ZIKV was considered to induce only mild illness, but it has now been established as the cause of severe clinical manifestations, including fetal anomalies, neurological problems, and autoimmune disorders. Infection during pregnancy can cause congenital brain abnormalities, including microcephaly and neurological degeneration, and in other cases, Guillain-Barré syndrome, making infections with ZIKV a substantial public health concern. Genomic and …

Impact Of Home Visit Capacity On Genetic Association Studies Of Late-Onset Alzheimer's Disease, David W. Fardo, Laura E. Gibbons, Shubhabrata Mukherjee, M. Maria Glymour, Wayne Mccormick, Susan M. Mccurry, James D. Bowen, Eric B. Larson, Paul K. Crane

Biostatistics Faculty Publications

INTRODUCTION—Findings for genetic correlates of late-onset Alzheimer's disease (LOAD) in studies that rely solely on clinic visits may differ from those with capacity to follow participants unable to attend clinic visits.

METHODS—We evaluated previously identified LOAD-risk single nucleotide variants in the prospective Adult Changes in Thought study, comparing hazard ratios (HRs) estimated using the full data set of both in-home and clinic visits (n = 1697) to HRs estimated using only data that were obtained from clinic visits (n = 1308). Models were adjusted for age, sex, principal components to account for ancestry, and additional health indicators.

RESULTS …

Using Neonatal Skin To Study The Developmental Programming Of Aging, Leryn J. Reynolds, Brett J. Dickens, Benjamin B. Green, Carmen J. Marsit, Kevin J. Pearson

Pharmacology and Nutritional Sciences Faculty Publications

Numerous studies have examined how both negative and positive maternal exposures (environmental contaminants, nutrition, exercise, etc.) impact offspring risk for age-associated diseases such as obesity, type 2 diabetes, hypertension, and others. The purpose of this study was to introduce the foreskin as a novel model to examine developmental programming in human neonates, particularly in regard to adipogenesis and insulin receptor signaling, major contributors to age-associated diseases such as obesity and diabetes. Neonatal foreskin was collected following circumcision and primary dermal fibroblasts were isolated to perform adipocyte differentiation and insulin stimulation experiments. Human neonatal foreskin primary fibroblasts take up lipid when …

A Novel Method For Synthesis Of Hydroxytyrosol, Emmanuel Onobun

Electronic Theses and Dissertations

Hydroxytyrosol, 3,4-dihydroxyphenolethanol, a naturally occurring polyphenol most common in olive tree (Olea europaea), is one of the most effective member of the polyphenols family, because of its remarkable antioxidant activity, its ability to inhibit oxidation of low density lipids (LDL), and its protection against DNA oxidative damage. Hydroxytyrosol, which is widely used in cosmetics and food supplements industries, can be purchased as an olive oil extract that contains low concentration of hydroxytyrosol besides other polyphenols. The price and low natural abundance of hydroxytyrosol make alternative synthetic sources very attractive. In this research, a novel method for the synthesis of pure …

Role Of Tlrs, Hippo-Yap1 Signaling, And Micrornas In Cardiac Repair And Regeneration Of Damaged Myocardium During Ischemic Injury, Xiaohui Wang

Electronic Theses and Dissertations

Cardiovascular disease is a leading cause of death in the United States. Toll-like receptor (TLR)-mediated pathways have been demonstrated to play a role in myocardial ischemia/reperfusion (I/R) injury. We and others have shown that PI3K/Akt signaling is involved in regulating cellular survival and protecting the myocardium from I/R induced injury. In this dissertation, we provide compelling evidence that miR-125b serves to “fine tune” TLR mediated NF-kB responses by repressing TNF-a and TRAF6 expression. We constructed lentiviral expressing miR-125b, delivered it into the myocardium. The data showed that delivery of lentivirus expressing miR-125b significantly reduces myocardial infarct size and improves cardiac …

Genetic Divergence Of Influenza A(H3n2) Amino Acid Substitutions Mark The Beginning Of The 2016-2017 Winter Season In Israel, Aharona Glatman-Freedman, Yaron Drori, Sharon Beni, Nehemya Friedman, Rakefet Pando, Hanna Sefty, Ilana Tal, John Mccauley, Galia Rahav, Nathan Keller, Tamy Shohat, Ella Mendelson, Musa Hindiyeh, Michal Mandelboim

NYMC Faculty Publications

BACKGROUND: Influenza vaccine composition is reevaluated each year due to the frequency and accumulation of genetic changes that influenza viruses undergo. The beginning of the 2016-2017 influenza surveillance period in Israel has been marked by the dominance of influenza A(H3N2).

OBJECTIVES: To evaluate the type, subtype, genetic evolution and amino acid substitutions of influenza A(H3N2) viruses detected among community patients with influenza-like illness (ILI) and hospitalized patients with respiratory illness in the first weeks of the 2016-2017 influenza season.

STUDY DESIGN: Respiratory samples from community patients with influenza-like illness and from hospitalized patients underwent identification, subtyping and molecular characterization. Hemagglutinin …

Towards A Personalized Cancer Gene Therapy: A Case Of Clear Cell Renal Cell Carcinoma, Dumitru Iacobas, Sanda Iacobas

NYMC Faculty Publications

No abstract provided.

Comparison Of Chikungunya Virus Strains In Disease Severity And Susceptibility To T-705 (Favipiravir), In Vitro And In Vivo, Makda Gebre

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

Chikungunya is a mosquito-transmitted disease caused by Chikungunya virus (CHIKV). Symptoms of Chikungunya include debilitating joint pain and swelling, fever and rash. CHIKV was first discovered in 1953 in Tanzania, and has since caused periodic outbreaks of disease. The virus reemerged recently in 2004 and has since spread around the world affecting more than 3 million people. The different strains of CHIKV have been grouped into three phylogenetic clades: West African, Asian and East/Central/South African (ECSA). There are no FDA approved medicines or vaccines used to treat or prevent CHIKV infection. The antiviral drug, T-705 (commercially known as Favipiravir), has …

Vorinostat Renders The Replication-Competent Latent Reservoir Of Human Immunodeficiency Virus (Hiv) Vulnerable To Clearance By Cd8 T Cells., Julia A Sung, Katherine Sholtis, Jennifer Kirchherr, Joann D Kuruc, Cynthia L Gay, Jeffrey L Nordstrom, Catherine M Bollard, Nancie M Archin, David M Margolis

Pediatrics Faculty Publications

Latently human immunodeficiency virus (HIV)-infected cells are transcriptionally quiescent and invisible to clearance by the immune system. To demonstrate that the latency reversing agent vorinostat (VOR) induces a window of vulnerability in the latent HIV reservoir, defined as the triggering of viral antigen production sufficient in quantity and duration to allow for recognition and clearance of persisting infection, we developed a latency clearance assay (LCA). The LCA is a quantitative viral outgrowth assay (QVOA) that includes the addition of immune effectors capable of clearing cells expressing viral antigen. Here we show a reduction in the recovery of replication-competent virus from …

Bacterial Communities Associated With Healthy And Diseased Acropora Cervicornis (Staghorn Coral) Using High-Throughput Sequencing, Charles Walton

HCNSO Student Theses and Dissertations

Coral diseases were first noted in the 1960s and 1970s and have had major impacts globally on coral reef community structures. In the Caribbean, a major outbreak of white band disease has been considered responsible for the drastic decline of Caribbean Acroporids since the 1970s. In addition to white band disease, another more recently described condition known as rapid tissue loss (RTL) has had major impacts on Acropora cervicornis populations, specifically offshore Broward County Southeast Florida. While these diseases have contributed to the population decline, determining their etiologies has been elusive.

Coral diseases have been characterized by shifts in their …

The Feoabc Locus Of Yersinia Pestis Likely Has Two Promoters Causing Unique Iron Regulation, Lauren O'Connor, Jacqueline D. Fetherston, Robert D. Perry

Microbiology, Immunology, and Molecular Genetics Faculty Publications

The FeoABC ferrous transporter is a wide-spread bacterial system. While the feoABC locus is regulated by a number of factors in the bacteria studied, we have previously found that regulation of feoABC in Yersinia pestis appears to be unique. None of the non-iron responsive transcriptional regulators that control expression of feoABC in other bacteria do so in Y. pestis. Another unique factor is the iron and Fur regulation of the Y. pestis feoABC locus occurs during microaerobic but not aerobic growth. Here we show that this unique iron-regulation is not due to a unique aspect of the Y. pestis …

Alzheimer's Disease Genetics And Abca7 Splicing, Jared B. Vasquez, James F. Simpson, Ryan Harpole, Steven Estus

Physiology Faculty Publications

Both common and rare polymorphisms within ABCA7 have been associated with Alzheimer’s disease (AD). In particular, the rare AD associated polymorphism rs200538373 was associated with altered ABCA7 exon 41 splicing and an AD risk odds ratio of ∼1.9. To probe the role of this polymorphism in ABCA7 splicing, we used minigene studies and qPCR of human brain RNA. We report aberrant ABCA7 exon 41 splicing in the brain of a carrier of the rs200538373 minor C allele. Moreover, minigene studies show that rs200538373 acts as a robust functional variant in vitro. Lastly, although the ABCA7 isoform with an extended …

A Multiscale Modeling Study Of The Mammary Gland, Joseph D. Butner

Biomedical Engineering ETDs

Multiscale, hybrid computer modeling has emerged as a valuable tool in the fields of computational systems biology and mathematical oncology. In this work, we present an overview of the motivations for, and development and implementation of, three hybrid multiscale models of the mammary gland system and early stage ductal carcinoma in situ (DCIS) in the gland. Pubertal mammary gland development was described first using a two-dimensional, lattice-based hybrid agent-based model description of the mammary terminal end bud (TEB), and then with a three-dimensional lattice-free TEB model. Both models implement a discrete, agent-based description of the cell scale, and a continuum, …

Alternative Interventions For Children Coping With Chronic Conditions: A Critical Review Of The Literature, Nina M. Pelsi, Kim S. Amer

DePaul Discoveries

Reduction of stressors and anxiety levels in adolescents with chronic illnesses is a critical concept in pediatric health care in America today. The many stressors associated with chronic illness include displaying physical and mental differences, social stigma, financial difficulty, and family stress. These stressors may affect the adolescent’s ability to learn and cope in everyday life. The current research was a critical review of the literature examining studies done with adolescents coping with chronic diseases and illnesses. The aim was to analyze the most efficacious non-pharmacological methods for reducing stressors in adolescents with chronic illness. A critical review of the …

Helminth Infection-Induced Malignancy., Paul J Brindley, Alex Loukas

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Infectious diseases cause more than 20% of cancers in the developing world [1]. About a dozen pathogens including Epstein-Barr virus and human T cell lymphocytotropic virus 1 are among the well-known examples. In addition, infection with several trematodes, which are eukaryotes, can cause malignancy. The International Agency for Research on Cancer categorizes infection with the fish-borne trematodes Opisthorchis viverrini and Clonorchis sinensis and the blood fluke Schistosoma haematobium as Group 1 biological carcinogens [2]. In addition to parasitism directly damaging development, health, and prosperity of infected populations, infection with these helminths leads to cholangiocarcinoma (CCA) (bile duct cancer) and squamous …

Praja Is Overexpressed In Glioblastoma And Contributes To Neural Precursor Development, Joshua Shin, Viveka Mishra, Eric Glasgow, Sobia Zaidi, Kazufumi Ohshiro, Lopa Mishra, Shuyun Rao, +Several Additional Authors

Medicine Faculty Publications

PRAJA, a RING-H2 E3 ligase, is abundantly expressed in brain tissues such as the cerebellum and frontal cortex, amongst others, and more specifically in neural progenitor cells as well as in multiple cancers that include glioblastomas. However, the specific role that Praja plays in neural development and gliomas remains unclear. In this investigation, we performed bioinformatic analyses to examine Praja1 and Praja2 expression across 29 cancer types, and observed raised levels of Praja1 and Praja2 in gliomas with an inverse relationship between Praja1 and apoptotic genes and Praja substrates such as Smad3. We analyzed the role of Praja in the …

Is Biological Repair Of Heart On The Horizon?, H R. Ahmad, Satwat Hashmi

Department of Biological & Biomedical Sciences

The stem cells keep us young by endogenously repairing us upon need. They do so bysmartly one step forward towards differentiation while another step backward to nurturethe undifferentiated stem cells. They are building blocks for every organ witha differential rate of repair of worn out tissues. Since stem cells can be cultured with a normal karyo type, they could be the ideal source for heart repair after myocardial infarction. As opposed to lower vertebrates and neonatal mice, cardiac regeneration in adult mammalian heart seems to be difficult to assess with a solid evidence of cytokinesis. It becomes more difficult to …

Induction And Suppression Of Antiviral Rna Silencing By Tomato Spotted Wilt Virus, Sergio M. Gabriel Peralta

Department of Agronomy and Horticulture: Dissertations, Theses, and Student Research

Tomato spotted wilt virus (TSWV) is an emerging pathogen with wide host range and one of the most important viruses of plants. Information regarding processing of negative single stranded RNA viruses such as TSWV in the RNA silencing pathway remains limited. In nature TSWV is only transmitted by thrips as vectors and since infection occurs in both thrips and plants, an experimental system to transmit using thrips and the detection of TSWV were established. In order to understand the processing of TSWV in the RNA silencing pathway, Arabidopsis thaliana as a model plant was used in the genetic analysis against …