Microbiology Commons^™

Yap1-Lats2 Feedback Loop Dictates Senescent Or Malignant Cell Fate To Maintain Tissue Homeostasis, Chunbo He, Xiangmin Lv, Cong Huang, Guohua Hua, Bowen Ma, Xingcheng Chen, Peter C. Angeletti, Jixin Dong, Jin Zhou, Zhengfeng Wang, Bo R. Rueda, John S. Davis, Cheng Wang

Nebraska Center for Virology: Faculty Publications

Dysfunction of the homeostasis-maintaining systems in specific cell types or tissues renders the organism susceptible to a range of diseases, including cancers. One of the emerging mechanisms for maintaining tissue homeostasis is cellular senescence. Here, we report that the Hippo pathway plays a critical role in controlling the fate of ovarian cells. Hyperactivation of Yes-associated protein 1 (YAP1), the major effector of the Hippo pathway, induces senescence in cultured primary human ovarian surface epithelial cells (hOSEs). Large tumor suppressor 2 (LATS2), the primary upstream negative regulator of YAP1, is elevated in both YAP1-induced and natural replicative-triggered senescence. Deletion of LATS2 …

Characterization Of Immunomodulatory Microbial Factors In Medicinal Plants, Kriti Kalpana

Dissertations, Theses, and Capstone Projects

Medicinal plants are one of the biggest sources of natural products with therapeutic importance. There are currently over 28,000 plants with putative medicinal values. Plant-derived compounds have been explored extensively for various biological activities ranging from anti-cancer, immune-boosting to anti-inflammatory and anti-oxidant. Some of the most important therapeutic agents are of plant-origin, such as paclitaxel from Pacific yew (Taxus brevifolia) and artemisinin from qinghao su (a Chinese medicinal herb; a.k.a. Artemisia annua) to name a few.

The study presented in this thesis started out as classical pharmacognosy research, which focused on the identification of immunostimulatory factors in …

A Review Of Asthma Treatments: Monoclonal Antibody, Corticosteroid, Leukotriene Modifier, And Bronchodilator, Alec Williams

Biology and Microbiology Graduate Students Plan B Research Projects

Medical research has created multitudes of medications to help control the symptoms of asthma. Asthmas effects the respiratory system in different ways, creating unique challenges to researchers and doctors alike to create or a manage the symptoms of asthma. Identifying the common treatment methods and understanding their effect on the human physiology can aid in treating patients. The goal of this review is to identify the common medications used to treat asthma, how these medications work on the human’s physiology, as well as bring to light a new upcoming medication with greater asthma control. As asthma research continues, the need …

Design And Characterization Of A Consensus Hemagglutinin Vaccine Immunogen Against H3 Influenza A Viruses Of Swine, Haiyan Sun, Jung-Hyang Sur, Sarah Vitosh-Sillman, David J. Steffen, Hiep Vu

Nebraska Center for Virology: Faculty Publications

The substantial genetic diversity exhibited by influenza A viruses of swine (IAV-S) represents the main challenge for the development of a broadly protective vaccine against this important pathogen. The consensus vaccine immunogen has proven an effective vaccinology approach to overcome the extraordinary genetic diversity of RNA viruses. In this project, we sought to determine if a consensus IAV-S hemagglutinin (HA) immunogen would elicit broadly protective immunity in pigs. To address this question, a consensus HA gene (designated H3-CON.1) was generated from a set of 1,112 H3 sequences of IAV-S recorded in GenBank from 2011 to 2015. The consensus HA gene …

Development And Evaluation Of Vaccine Candidates For Senecavirus A, Bishwas Sharma

Electronic Theses and Dissertations

Senecavirus A (SVA) has been associated with several outbreaks of vesicular disease (VD) since 2014 in major swine-producing countries around the world. The virus causes VD that is clinically indistinguishable from foot-and-mouth disease (FMD) in pigs. Currently there are no commercial vaccines available for SVA. Here, we developed a live attenuated SVA strain by mutating a wild type SVA strain SD15-26 (wt SVA). The live attenuated virus, rSVA mSacII, replicated less efficiently in cell cultures in vitro and expressed lower amounts of VP1 and VP2 capsid proteins than wt SVA. Most importantly, the rSVA mSacII virus failed to induce clinical …

Comparative Characteristics Of Antibacterial Activity Of Plants Growing In The Central Part Of The Republic Of Tajikistan., Saidbeg Satorov, F. Mirzoeva, Sh. Satorov, M. Vakhidova, Vyacheslav Dushenkov

Publications and Research

Objective: To evaluate the spectrum of antibacterial activity of plants growing in the central part of the Republic of Tajikistan.
Methods: The antibacterial properties of 18 plant species from the 14 families were studied. The extract samples on dry filter discs were prepared according to the method developed at Rutgers University. Screens-to-Nature (STN) and disc diffusion (DD) methods were used to assess antimicrobial properties of the extracts. The antimicrobial activity of plant extracts was determined against four types of pathogenic standard museum strains of Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae, as well as …

Development Of A Biosafety Level-2 Facility For Irradiation Of Biological Cells Using Mev Ions, Jay D. Diaz, Naresh T. Deoli, Deborah Rogers, Armin De Vera, Karen M. Smith, Robin Schmeider-Broussard, Harry J. Whitlow

Louisiana Accelerator Center

The development of a facility for irradiation of murice and primate tissue presents several challenges. First, extremely low fluences (10⁶-10¹¹ ions cm⁻²) are required to deliver doses of 1 mGy - 50 Gy using MeV proton. Second,the tissues, particularly from non-human primate, may be infectious to humans. Third, protection of irradiated tissue samples from contamination by mold and bacteria is critical. Here we present an ultra-low flux irradiation facility and associated fluence control for biological cell and tissue irradiation under sterile biosafety level 2 (BSL-2) conditions suitable for use with low energy (1-3.4 MeV) protons. The operation is demonstrated using …

Bovine Cellular And Innate Immune Response To Hemostatic Polysaccharides, Brian Kobylkevich

Electronic Theses and Dissertations

Chronic wounds are longstanding dermal wounds that do not heal in a normal amount of time and can commonly last for over a year. These wounds plague humans and farm animals alike. Wounds are characterized by chronic inflammation and are often painful, difficult to heal, have a high recurrence rate, and are potentially debilitating. Long term wounds that do not fully heal are distressing for both humans and animals, but understandably more resources have been directed towards humans. Some treatment options for humans may be suitable for adaptation into the field of animal care. Chronic lesions such as bovine digital …

Comparative Optic Nerve Head Physiology: Glaucoma Induced Retinal Ganglion Cell Apoptosis By Disruption Of The Translaminar Pressure Gradient And Reduced Neurotrophic Signaling, Cassidy Christopherson

Biology and Microbiology Graduate Students Plan B Research Projects

Glaucoma is the leading cause of irreversible blindness, and the second leading vision loss neurodegenerative disease affecting millions worldwide. Glaucoma is characterized as a group of eye disorders which are initially asymptomatic but may progress to significant optic nerve head damage and vision loss with time. Early stages of glaucoma often go undetected, leading to irreversible damage to the optic nerve head prior to patients seeking medical care. Glaucoma leads to vision loss via death of retinal ganglion cells. Retinal ganglion cell apoptosis is thought to begin due to interference with the normal transmission of neurotrophic signals that arrive by …

Irritable Bowel Syndrome With Constipation (Ibs-C) Treatment Efficacy And The Emerging Importance Of Serotonin, Meghan Schenk

Biology and Microbiology Graduate Students Plan B Research Projects

Irritable bowel syndrome with constipation (IBS-C) affects a large proportion of the population. It decreases quality of life for the patient both physically and mentally. Patients report higher levels of mental health issues and other gastrointestinal maladies compared to the normal population, in addition to an IBS diagnosis. Patients have increased healthcare visits and costs, raising insurance rates for all, and also results in more missed time from work. There are limited treatments available for IBS-C, and medicinal and non-medicinal modalities are differentially prescribed to patients throughout the country. Recently, serotonin has emerged as a key mediator of normal gut …

A Review: The Association Of Asthma And The Microbiome, Kathleen Olson

Biology and Microbiology Graduate Students Plan B Research Projects

The microbiome gut-lung axis has been associated with asthma. Asthma is a respiratory disease that presents itself in many different ways. The microbiome is the bacteria, fungi, protozoa, and viruses found in a particular environment. The association of the microbiome gutlung axis in an asthmatic individual compared to a healthy individual has shown that different types and/or concentrations of bacterial genera are present in an asthmatic individual compared to a healthy individual. A causal relationship between the microbiome and asthma has not yet been identified. The aim of this review is to present the association of asthma and the microbiome …

Pathogenesis Of Cte: A Review Of Ptau, Lewy Bodies, And Cytokine Involvement In Cte, Karter Keefer

Biology and Microbiology Graduate Students Plan B Research Projects

Chronic Traumatic Encephalopathy (CTE) is a neuropathological disease that develops years after experiencing repetitive traumatic brain injuries. In recent years, this disease has been gaining recognition from professional, college, and high school teams that participate in contact sports. The purpose of this paper is to review available information about this neurodegenerative disease. Only limited published experiments are available on this disease. Research on CTE has been limited by the fact that patients can only be diagnosed with the disease by a post mortem autopsy. Many experiments were analyzed regarding different CTE pathologies, symptoms, and treatments. Articles used in this paper …

Serosurvey For Evidence Of Dengue And West Nile Virus Human Infections In El Paso, Texas, Veronica Suarez

Open Access Theses & Dissertations

Dengue viruses (DENV), including the 4 serotypes are the cause of dengue fever and dengue hemorrhagic fever. The viruses are transmitted by Aedes aegypti mosquitoes in urban communities in tropical, sub-tropical, and temperate regions and are the cause of the highest rate of infection and death of all known Flaviviruses. DENV are endemic in United States (US) -Mexico (MX) border communities in the Rio Grande Valley and suspected of being endemic in Ciudad Juarez, a sister city to El Paso, TX. To determine if DENV were endemic in the El Paso community, cord-blood samples from mothers were tested for antibody …

Nurse Practitioner Attitudes, Perceptions And Knowledge About Antimicrobial Stewardship, Evelyn C. Fabian

Walden Dissertations and Doctoral Studies

Resistance to antibiotics has increased dramatically in the United States, with serious associated medical, social, and economic consequences. The purpose of this project was to assess nurse practitioners' attitudes, perceptions, and knowledge about antimicrobial stewardship and knowledge in the management of anaerobic infections as well as resistant gram-negative bacteremia. Data were collected using a web-based survey in a hospital facility. The practice question explored whether nurse practitioners' attitudes, perceptions, and knowledge about antimicrobial stewardship significantly increased after an education program on antimicrobial stewardship. The project was framed by Knowles's adult learning theory. A 16-item survey was administered before and after …

Pyocyanin, A Virulence Factor Produced By Sepsis-Causing Pseudomonas Aeruginosa, Promotes Adipose Wasting And Cachexia, Nika Larian

Theses and Dissertations--Pharmacology and Nutritional Sciences

Sepsis is a leading cause of death among critically ill patients that results in metabolic alterations including hypercatabolism, lipoatrophy, and muscle wasting, contributing to the development of cachexia. Septic cachexia is associated with loss of body weight, fat mass, and lean mass and dysregulated immune function. There are currently no efficacious treatment strategies for septic cachexia, and nutritional interventions have limited success in preventing hypercatabolic wasting. Pyocyanin is a virulence factor produced by sepsis-causing Pseudomonas aeruginosa that has been shown to activate the aryl hydrocarbon receptor (AhR), increase inflammation, and produce reactive oxygen species. Thus, pyocyanin represents a novel mechanistic …

Monocytes And Monocyte-Derived Antigen-Presenting Cells Have Distinct Gene Signatures In Experimental Model Of Multiple Sclerosis, Kelly L. Monaghan, Wen Zheng, Gangqing Hu, Edwin C. K. Wan

Faculty & Staff Scholarship

Multiple sclerosis (MS) is a chronic inflammatory disease mediated by a complex interaction between the autoreactive lymphocytes and the effector myeloid cells within the central nervous system (CNS). In a murine model of MS, experimental autoimmune encephalomyelitis (EAE), Ly6Chi monocytes migrate into the CNS and further differentiate into antigen-presenting cells (APCs) during disease progression. Currently, there is no information about gene signatures that can distinguish between monocytes and the monocyte-derived APCs. We developed a surface marker-based strategy to distinguish between these two cell types during the stage of EAE when the clinical symptoms were most severe, and performed transcriptome analysis …

Incidentally Found Metastatic Prostatic Carcinoma In A Therapeutic Orchiectomy Specimen, Zeeshan Uddin, Muhammad Bilal, Mohammad Ayaz Khan

Department of Pathology and Laboratory Medicine

Metastatic tumour involving the testis is a rare event. Incidental discovery of metastatic cancer in a therapeutic orchiectomy is even rarer. We report a case of metastatic adenocarcinoma prostate found incidentally in one of the bilateral therapeutic orchiectomy specimens. The patient was a 55-year-old man presenting with back ache and generalized body aches. Clinical examination showed malignant feel of prostate. Bone scan revealed metastatic disease and a serum PSA level of >100 ng/ml. Clinical diagnosis of carcinoma prostate was established and subsequent bilateral orchiectomy for hormonal deprivation was performed. On gross examination of left testis, there was a small 0.7 …

The Microbiomes Of Pancreatic And Duodenum Tissue Overlap And Are Highly Subject Specific But Differ Between Pancreatic Cancer And Non-Cancer Subjects, Erika Del Castillo, Richard Meier, Mei Chung, Devin C. Koestler, Tsute Chen, Bruce J. Paster, Kevin P. Charpentier, Karl T. Kelsey, Jacques Izard, Dominique S. Michaud

Department of Food Science and Technology: Faculty Publications

Background: In mice, bacteria from the mouth can translocate to the pancreas and impact pancreatic cancer progression. In humans, oral bacteria associated with periodontal disease have been linked to pancreatic cancer risk. It is not known if DNA bacterial profiles in the pancreas and duodenum are similar within individuals.

Methods: Tissue samples were obtained from 50 subjects with pancreatic cancer or other conditions requiring foregut surgery at the Rhode Island Hospital (RIH), and from thirty-four organs obtained from the National Disease Research Interchange. 16S rRNA gene sequencing was performed on 189 tissue samples (pancreatic duct, duodenum, pancreas), 57 …

A Poxvirus Pseudokinase Represses Viral Dna Replication Via A Pathway Antagonized By Its Paralog Kinase, Annabel T. Olson, Zhigang Wang, Amber B. Rico, Matthew S. Wiebe

Nebraska Center for Virology: Faculty Publications

Poxviruses employ sophisticated, but incompletely understood, signaling pathways that engage cellular defense mechanisms and simultaneously ensure viral factors are modulated properly. For example, the vaccinia B1 protein kinase plays a vital role in inactivating the cellular antiviral factor BAF, and likely orchestrates other pathways as well. In this study, we utilized experimental evolution of a B1 deletion virus to perform an unbiased search for suppressor mutations and identify novel pathways involving B1. After several passages of the ΔB1 virus we observed a robust increase in viral titer of the adapted virus. Interestingly, our characterization of the adapted viruses reveals that …

Persistent Viral Reservoirs In Lymphoid Tissues In Siv-Infected Rhesus Macaques Of Chinese-Origin On Suppressive Antiretroviral Therapy, Summer Siddiqui, Stefanie Perez, Yong Gao, Lara Doyle-Meyers, Brian T. Foley, Qingsheng Li, Binhua Ling

Nebraska Center for Virology: Faculty Publications

Understanding HIV latent reservoirs in tissues is essential for the development of new strategies targeting these sites for eradication. Here, we assessed the size of latent reservoirs and the source of residual viruses in multiple lymphoid tissues of SIV-infected and fully suppressed rhesus macaques of Chinese-origin (cRMs). Eight cRMs were infected with SIVmac251 and treated with tenofovir and emtricitabine daily for 24 weeks initiated 4 weeks post-infection. Four of the eight animals reached sustained full viral suppression with undetectable viremia. The levels of cell-associated SIV DNA varied in peripheral blood mononuclear cells (PBMCs) and multiple lymphoid tissues, but with higher …

Relationship Between The Cervical Microbiome, Hiv Status, And Precancerous Lesions, Cameron Klein, Daniela Gonzalez, Kandali Samwel, Crispin Kahesa, Julius Mwaiselage, Nirosh Aluthge, Samodha Fernando, John T. West, Charles Wood, Peter C. Angeletti

Nebraska Center for Virology: Faculty Publications

Nearly all cervical cancers are causally associated with human papillomavirus (HPV). The burden of HPV-associated dysplasias in sub-Saharan Africa is influenced by HIV. To investigate the role of the bacterial microbiome in cervical dysplasia, cytobrush samples were collected directly from cervical lesions of 144 Tanzanian women. The V4 hypervariable region of the 16S rRNA gene was amplified and deep sequenced. Alpha diversity metrics (Chao1, PD whole tree, and operational taxonomic unit [OTU] estimates) displayed significantly higher bacterial richness in HIV-positive patients (P = 0.01) than in HIV-negative patients. In HIV-positive patients, there was higher bacterial richness in patients with …

Near-Atomic Structure Of A Giant Virus, Qianglin Fang, Dongjie Zhu, Irina Agarkova, Jagat Adhikari, Thomas Klose, Yue Liu, Zhenguo Chen, Yingyuan Sun, Michael L. Gross, James L. Van Etten, Xinzheng Zhang, Michael G. Rossmann

Nebraska Center for Virology: Faculty Publications

Although the nucleocytoplasmic large DNA viruses (NCLDVs) are one of the largest group of viruses that infect many eukaryotic hosts, the near-atomic resolution structures of these viruses have remained unknown. Here we describe a 3.5 Å resolution icosahedrally averaged capsid structure of Paramecium bursaria chlorella virus 1 (PBCV-1). This structure consists of 5040 copies of the major capsid protein, 60 copies of the penton protein and 1800 minor capsid proteins of which there are 13 different types. The minor capsid proteins form a hexagonal network below the outer capsid shell, stabilizing the capsid by binding neighboring capsomers together. The size …

A Single-Cycle Adenovirus Type 7 Vaccine For Prevention Of Acute Respiratory Disease, Brianna L. Bullard, Brigette N. Corder, Eric A. Weaver

Nebraska Center for Virology: Faculty Publications

Adenovirus type 7 (Ad7) infection is associated with acute respiratory disease (ARD), especially in military recruits living in close quarters. Recently, several outbreaks of Ad7 infections have occurred in civilian populations, with some cases leading to death. However, the current Ad7 vaccine is licensed for use only in military recruits because it utilizes an orally delivered wild type virus which is shed in the stool for 28 days after immunization. This poses a safety risk due to the possibility of virus spread to vulnerable populations. To address the need for a safer Ad7 vaccine for use in civilian populations, we …

A Double Humanized Blt-Mice Model Featuring A Stable Human-Like Gut Microbiome And Human Immune System, Lance Daharsh, Jianshui Zhang, Amanda E. Ramer-Tait, Qingsheng Li

Nebraska Center for Virology: Faculty Publications

Humanized mice (hu-mice) that feature a functional human immune system have fundamentally changed the study of human pathogens and disease. They can be used to model diseases that are otherwise difficult or impossible to study in humans or other animal models. The gut microbiome can have a profound impact on human health and disease. However, the murine gut microbiome is very different than the one found in humans. There is a need for improved pre-clinical hu-mice models that have an engrafted human gut microbiome. Therefore, we created double hu-mice that feature both a human immune system and stable human-like gut …

The Vaccinia Virus (Vacv) B1 And Cellular Vrk2 Kinases Promote Vacv Replication Factory Formation Through Phosphorylation-Dependent Inhibition Of Vacv B12, Annabel T. Olson, Zhigang Wang, Annabel Olson, Alexandria C. Linville, Brianna L. Bullard, Eric A. Weaver, Clinton Jones, Matthew S. Wiebe

Nebraska Center for Virology: Faculty Publications

Comparative examination of viral and host protein homologs reveals novel mechanisms governing downstream signaling effectors of both cellular and vi- ral origin. The vaccinia virus B1 protein kinase is involved in promoting multiple facets of the virus life cycle and is a homolog of three conserved cellular enzymes called vaccinia virus-related kinases (VRKs). Recent evidence indicates that B1 and VRK2 mediate a com- mon pathway that is largely uncharacterized but appears independent of previous VRK substrates. Interestingly, separate studies described a novel role for B1 in inhibiting vac- cinia virus protein B12, which otherwise impedes an early event in the …

Adaptation Of The Streptococcal Collagen-Like Protein 1, Scl1, Of Group A Streptococcus To Recognize Fibronectin Type Iii Repeats, Dudley H. Mcnitt

Graduate Theses, Dissertations, and Problem Reports (ETD)

Background: Group A Streptococcus (GAS) is responsible more than 700 million infections worldwide each year. Most of these infections start with initial colonization of the throat and skin, which is augmented by surface adhesins. The streptococcal collagen-like protein 1 (Scl1) is a major adhesin expressed by GAS that contains an N-terminal sequence-variable (V) domain, protruded away from the cell surface by the collagen domain. The Scl-V domain is comprised of three pairs of anti-parallel α-helices interconnected by surface-exposed loops. For attachment, GAS adhesins require a portal of entry, such as a wound or breach in the epithelium, to enter …

Modeling Disease Impact Of Vibrio-Phage Interactions, Christopher Botelho

Electronic Theses and Dissertations

Since the work of John Snow, scientists and medical professionals have understood that individuals develop cholera by means of consuming contaminated water. Despite the knowledge of cholera's route of infection, many countries have experienced and still experience endemic cholera. Cholera is caused by the Vibrio cholerae (V. cholerae) bacterium and presents with acute diarrhea and vomiting. If untreated, infected individuals may die due to dehydration. Cholera is a disease that most commonly affects countries with poor infrastructure and water sanitation. Despite efforts to control cholera in such countries, the disease persists. One such example is Haiti which has been experiencing …

Best Practices In Patellar Tendinopathy Management: An Evidence To Practice Review, Christopher J. Burcal, Adam B. Rosen, Tony Taylor, Mike Nicola

Clinical Practice in Athletic Training

Patellar tendinopathy (PT) is a degenerative condition that is common in sporting populations due to the loads placed on the tendon during dynamic activity. PT often occurs in overtraining situations; however, it may also occur in conjunction with and/or worsen through poor biomechanics, persistent inflammation, and altered movement patterns. Although sports medicine practitioners have evidence to support the prevalence of this injury, we do not have a strong base of evidence surrounding the contributing factors and pathophysiology that lead the pain and disability reported in patients with PT. The purpose of this evidence to practice review was to summarize a …

Value Of Dedicated Research Time For Imgs In Obtaining Surgical Residency Training Positions: A 10-Year Review Of Applicants From A Medical College In Pakistan, Mohammad Raheel Jajja, Marvi Tariq, Salila Shoaib Hashmi, Thomas F. Dodson, Rashida Ahmed

Department of Pathology and Laboratory Medicine

Objective: International Medical Graduates (IMGs) secured greater than 10% of all general surgery (GS) residency positions in the US during the past decade. The Match process remains competitive, with a significant number of IMGs performing dedicated research before residency application. The impact of such research remains largely unknown. We aimed to provide an objective analysis of the impact of dedicated research time on obtaining a categorical GS residency position.
Design: Data for National Resident Matching Program Match results from 2008-2017 was compiled from annual Match lists of the Aga Khan University, Medical College (Karachi, Pakistan). Medical graduates provided this information …

Illumination Of The Golgi Apparatus Of Pathogenic And Nonpathogenic Naegleria Species, Tyler M. Poe

Theses and Dissertations

In this study, Naegleria fowleri, a pathogenic amoeba and the causative agent of Primary Amebic Meningoencephalitis (PAM), was utilized to determine the presence or absence of classically conserved Golgi molecules featured in the expression of a Golgi apparatus. Previous studies concluded no Golgi expression via light microscopy and transmission electron microscopy, but a recent report on Naegleria gruberi indicated the presence of dispersed Golgi tubules. Non-pathogenic species of the Naegleria genus such as Naegleria gruberi 30540 and Naegleria lovaniensis 30569 were utilized in Western immunoblot analysis compared to reduced whole-cell lysate proteins of two strains of N. fowleri and …