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Developing Targeted Therapy Against Pancreatic Cancer, Garima Kaushik

Theses & Dissertations

Not available.

Discovery Of Glycerol Phosphate Modification On Streptococcal Rhamnose Polysaccharides., Rebecca J Edgar, Vincent P Van Hensbergen, Alessandro Ruda, Andrew G Turner, Pan Deng, Yoann Le Breton, Najib M El-Sayed, Ashton T Belew, Kevin S Mciver, Alastair G Mcewan, Andrew J Morris, Gérard Lambeau, Mark J Walker, Jeffrey S. Rush, Konstantin V Korotkov, Göran Widmalm, Nina M Van Sorge, Natalia Korotkova

Molecular and Cellular Biochemistry Faculty Publications

Cell wall glycopolymers on the surface of Gram-positive bacteria are fundamental to bacterial physiology and infection biology. Here we identify gacH, a gene in the Streptococcus pyogenes group A carbohydrate (GAC) biosynthetic cluster, in two independent transposon library screens for its ability to confer resistance to zinc and susceptibility to the bactericidal enzyme human group IIA-secreted phospholipase A

The Dna Damage Response Gene Ddr48 Regulates Sterol Synthesis Genes To Confer Antifungal Resistance To The Pathogenic Fungus Histoplasma Capsulatum, Gabriella Reyes

Honors Theses

Histoplasma capsulatum is a dimorphic fungal pathogen that is endemic to the Ohio, Missouri, and Mississippi river valley regions. The fungus grows as a mold at environmental temperatures (25C) and transforms into a unicellular yeast upon inhalation by a mammalian host (37C). The mold to yeast shift is required for pathogenicity in host organisms, where the potentially fatal disease, histoplasmosis, can present. This study aims to characterize the DNA damage response protein DDR48 and the role that it plays in combating cellular stressors in H. capsulatum. We found that DDR48 is expressed strongly in the mold phase but expressed only …

Development Of A Lectin-Fc Fusion Protein With Antiviral And Anti-Cancer Activity., Matthew William Dent

Electronic Theses and Dissertations

This thesis describes the development of a novel lectin-Fc fusion protein and its antiviral and anti-cancer activity. The molecule, Avaren-Fc (AvFc), is a fusion of a variant of the actinomycete lectin actinohivin (Avaren) and the Fc region of human IgG1, and is selective for the terminal α1,2-mannose residues found at the ends of high-mannose-type glycans that can be found on the surface of certain heavily glycosylated viruses and cancer cells. Here, AvFc was found to be able to neutralize simian immunodeficiency virus as well as Hepatitis C virus with nanomolar IC₅₀ values. Furthermore, AvFc recognizes a number of cell …

Spatial Reorganization Of Histone-Like Nucleoid Structuring Proteins Caused By Silver Nanoparticles, Meaad Alqahtany

Graduate Theses and Dissertations

Silver nanoparticles (AgNPs) and ions (Ag+) can be the new generation of antibiotics due to their antimicrobial effects against bacteria and other microbes. Many studies have shown that AgNPs and suppress the growth of bacteria and damage the cell walls of the microbes; therefore, treating bacterial cells with AgNPs may be a promising method to terminate multi-resistant bacteria. In this work, the effect of AgNPs with two different surface coatings on the spatial reorganization of histone-like nucleoid structuring (H-NS) proteins in Escherichia coli bacteria was investigated using quantitative super-resolution fluorescence microscopy to understand the toxicity and antimicrobial mechanism of AgNPs. …

The One Health Approach To Toxoplasmosis: Epidemiology, Control, And Prevention Strategies, A. Alonso Aguirre, Travis Longcore, Michelle Barbieri, Haydee Dabritz, Dolores Hill, Patrice N. Klein, Christopher Lepczyk, Emily L. Lilly, Rima Mcleod, Judith Milcarsky, Caroline E. Murphy, Chunlei Su, Elizabeth Vanwormer, Robert Yolken, Grant C. Sizemore

School of Veterinary and Biomedical Sciences: Faculty Publications

One Health is a collaborative, interdisciplinary effort that seeks optimal health for people, animals, plants, and the environment. Toxoplasmosis, caused by Toxoplasma gondii, is an intracellular protozoan infection distributed worldwide, with a heteroxenous life cycle that practically affects all homeotherms and in which felines act as definitive reservoirs. Herein, we review the natural history of T. gondii, its transmission and impacts in humans, domestic animals, wildlife both terrestrial and aquatic, and ecosystems. The epidemiology, prevention, and control strategies are reviewed, with the objective of facilitating awareness of this disease and promoting transdisciplinary collaborations, integrative research, and capacity building among universities, …

Transposon Mutagenesis In Mycobacterium Avium Subspecies Paratuberculosis, John P. Bannantine, Denise K. Zinniel, Raul G. Barletta

School of Veterinary and Biomedical Sciences: Faculty Publications

While transposon mutagenesis has been developed for Mycobacterium avium subspecies paratuberculosis (Map), relatively few laboratories have adopted this important genetic tool to examine gene function and essentiality. Here we describe the construction of a Map transposon library using the Himar1 mariner transposon, but concepts can also be applied to the Tn5367 transposon, which has also been used by our group. Delivery of the transposon is by a temperature-sensitive phagemid, ϕMycoMarT7, and plating transductants requires patience and specialized media due to length of incubation required to observe colonies. Several transposon mutants obtained from these libraries have been tested in vaccine and …

Design And Synthesis Of Ceragenins–Cationic Steroid Antimicrobial Compounds, Structural Improvement And Synthesis Of Cyclopentenone Prostaglandins And Modification And Synthesis Of Derivatives Of Ribityllumazines: Potential Antigens For Activation Of Mait Cells, Yubo Li

Theses and Dissertations

Antimicrobial peptides (AMPs) are ubiquitous and display broad-spectrum antimicrobial activity that can control bacterial colonization of surfaces. Ceragenins are small-molecule mimics of AMPs and have several advantages over AMPs, including cost of manufacture and stability. A ceragenin, CSA-120, modified with an acrylamide group was directly incorporated into fluoropolymer coatings as a means of inhibiting bacterial biofilm formation. The ceragenin-containing coatings displayed improved performance. By conjugating a copper chelating group to the ceragenin, chelation of 64Cu by the conjugate was effective and provided a stable complex that allowed in vivo imaging. This conjugate may provide a means of identifying infection sites …

Regulation Of Immune Cell Activation And Functionby The Nbmpp2 Protein Andthe Cd5 Co-Receptor, Claudia Mercedes Freitas

Theses and Dissertations

According to the centers for disease control and prevention (CDC) and the world healthorganization (WHO), heart disease and immune related diseases such as diabetes and cancer areamong the leading causes of death around the world. Thus, the regulation of the function ofimmune cell plays a key role in health and disease. Calcium (Ca2+) ions play a critical role inimmune cell activation, function and in a robust immune response. Defects in Ca2+ signalinginfluences the development of cardiac disease, Alzheimer disease, immune cell metabolism,muscle dysfunction, and cancer. Each immune cell is unique in its activation and function,making it relevant to understand how …

Arthropod Organic Anion Transporting Polypeptides In Tick-Borne Bacterial And Viral Infections, Vikas Kumar Taank

Biomedical Sciences Theses & Dissertations

Vector-borne diseases (VBDs) are human illness transmitted by an arthropod vector. World Health Organization (WHO) estimates that VBD has a huge impact worldwide that is responsible for affecting a billion people and causes 700,000 deaths annually. In recent years, there has been a continuous increase in the incidences of tick-borne diseases such as Lyme diseases and human anaplasmosis as reported by Center for Disease Control and Prevention. Very few reliable VBD control strategies have emerged till now. Transmission-blocking vaccines can provide effective management of VBDs but requires identification and characterization of novel vector-pathogen conserved molecules that play a significant role …

Environmental Transmission Of Toxoplasma Gondii: Oocysts In Water, Soil And Food, Karen Shapiro, Lillian Bahia-Oliveira, Brent Dixon, Aurélien Dumètre, Luz A. De Wit, Elizabeth Vanwormer, Isabelle Villena

School of Veterinary and Biomedical Sciences: Faculty Publications

Toxoplasma gondii is a zoonotic protozoan parasite that can cause morbidity and mortality in humans, domestic animals, and terrestrial and aquatic wildlife. The environmentally robust oocyst stage of T. gondii is fundamentally critical to the parasite's success, both in terms of its worldwide distribution as well as the extensive range of infected intermediate hosts. Despite the limited definitive host species (domestic and wild felids), infections have been reported on every continent, and in terrestrial as well as aquatic environments. The remarkable resistance of the oocyst wall enables dissemination of T. gondii through watersheds and ecosystems, and long-term persistence in diverse …

Improving Coupled Enzyme Assays With Capillary Electrophoresis, Thu Hoai Nguyen

LSU Doctoral Dissertations

The goal of this project is to address limitations of coupled enzyme assays using capillary electrophoresis (CE). In some enzyme assays, it is ineffective to directly detect products and substrates spectroscopically (absorption or fluorescence). Coupling the enzyme-catalyzed reaction of interest with another enzyme-catalyzed reaction allows for indirect detection of product formation or substrate depletion for the target enzyme. While conventional coupled enzyme assays are facile for kinetic measurements, they can be problematic for inhibition screening due to spectral and inhibitor interferences. To address these limitations of coupled assays, CE has been used to develop enzyme assays for acetyl-coenzyme A carboxylase …

Mechanisms To Regulate Genes Encoding Clinically Relevant Multidrug Transporters At The Crossroads Of Antibiotic Resistance And Oxidative Stress Detection, Afsana Sabrin

LSU Doctoral Dissertations

Multiple Antibiotic Resistance Regulators (MarRs) are DNA binding proteins involved in bacterial survival and pathogenesis. My PhD dissertation focuses on a MarR homolog, OstR, which regulates genes encoding major multidrug transporters, a resistance-nodulation-division (RND) and an E. coli multidrug resistance B (EmrB) efflux pump homolog in Burkholderia thailandensis. The ostR gene is divergently oriented from genes encoding a hypothetical protein (Hyp) and an RND transporter and adjacent to a gene encoding an EmrB transporter. OstR binds to the promoters of each gene (K_d = 64.9 ± 8.0 nM, K_d = 126.1 ± 10.9 nM and K …

Targeted Therapy For The Future: The Use Of Novel Antimicrobial Peptides Against P. Aeurginosa, Matthew Froid

UNO Student Research and Creative Activity Fair

Pathogenic bacteria, such as the gram-negative bacterium Pseudomonas aeruginosa, are becoming resistant to our current arsenal of antibiotics at an alarming rate. P. aeruginosa is a leading cause of nosocomial acquired infections and is a primary co-morbidity in patients with compromised immune systems. One potential source of new antibiotic agents is antimicrobial peptides. Antimicrobial peptides (AMPs) are small proteins, and some have shown a high degree of efficacy and broad-spectrum activity against both Gram-positive and Gram-negative bacteria. An experimental AMP that has been developed by Dr. Wang at UNMC, DASamp2, has shown to be effective against virulent bacteria, including P. …

Large Scale Dynamical Model Of Macrophage/Hiv Interactions, Matthew M. Froid

UNO Student Research and Creative Activity Fair

Properties emerge from the dynamics of large-scale molecular networks that are not discernible at the individual gene or protein level. Mathematical models - such as probabilistic Boolean networks - of molecular systems offer a deeper insight into how these emergent properties arise. Here, we introduce a non-linear, deterministic Boolean model of protein, gene, and chemical interactions in human macrophage cells during HIV infection. Our model is composed of 713 nodes with 1583 interactions between nodes and is responsive to 38 different inputs including signaling molecules, bacteria, viruses, and HIV viral particles. Additionally, the model accurately simulates the dynamics of over …

Ribosomally Synthesized And Post-Translationally Modified Peptides As Potential Scaffolds For Peptide Engineering, Devan Bursey

Theses and Dissertations

Peptides are small proteins that are crucial in many biological pathways such as antimicrobial defense, hormone signaling, and virulence. They often exhibit tight specificity for their targets and therefore have great therapeutic potential. Many peptide-based therapeutics are currently available, and the demand for this type of drug is expected to continue to increase. In order to satisfy the growing demand for peptide-based therapeutics, new engineering approaches to generate novel peptides should be developed. Ribosomally synthesized and post-translationally modified peptides (RiPPs) are a group of peptides that have the potential to be effective scaffolds for in vivo peptide engineering projects. These …

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 …

Bisthioether Stapled Peptides Targeting Polycomb Repressive Complex 2 Gene Repression, Gan Zhang

Dissertations, Theses, and Capstone Projects

Interactions between proteins play a key role in nearly all cellular process, and therefore, disruption of such interactions may lead to many different types of cellular dysfunctions. Hence, pathologic protein-protein interactions (PPIs) constitute highly attractive drug targets and hold great potential for developing novel therapeutic agents for the treatment of incurable human diseases. Unfortunately, the identification of PPI inhibitors is an extremely challenging task, since traditionally used small molecule ligands are mostly unable to cover and anchor on the extensive flat surfaces that define those binary protein complexes. In contrast, large biomolecules such as proteins or peptides are ideal fits …

Split Probe Detection Of The Influenza A Virus For Improved Diagnostics In A Point Of Care System, Tamar Yishay

Honors Undergraduate Theses

A group of Influenza viruses, RNA containing viruses of the Orthomyxoviridae family, consists of Influenza virus types A-D and has been known to cause the Flu, a respiratory illness associated with numerous detrimental symptoms that can lead to death. Influenza A virus (IAV) is constantly changing and is capable of causing pandemics. Currently used diagnostic methods include virus culturing, immunoassays including rapid influenza detection tests (RIDTs), and molecular assays including those based on RT-PCR. Most of the methods can be only performed in the certified diagnostic laboratories equipped with sophisticated instrumentation and/or special biosafety facilities. The results using these methods …

Host Restriction Factors In The Replication Of Tombusviruses: From Rna Helicases To Nucleocytoplasmic Shuttling, Cheng-Yu Wu

Theses and Dissertations--Plant Pathology

Positive-stranded (+)RNA viruses replicate inside cells and depend on many cellular factors to complete their infection cycle. In the meanwhile, (+)RNA viruses face the host innate immunity, such as cell-intrinsic restriction factors that could block virus replication.

Firstly, I have established that the plant DDX17-like RH30 DEAD-box helicase conducts strong inhibitory function on tombusvirus replication when expressed in plants and yeast surrogate host. This study demonstrates that RH30 blocks the assembly of viral replicase complex, the activation of RNA-dependent RNA polymerase function of p92pol and viral RNA template recruitment.

In addition, the features rendering the abundant plant DEAD-box helicases either …

Imbalance Of Uracil Dna Glycosylase And Activation-Induced Cytidine Deaminase Expression In Folate Depleted Human Lymphoblastoids, Elizabeth Zanley

Wayne State University Theses

Background: The DNA base excision repair (BER) pathway is responsible for processing of genomic uracil lesions however, in some tissue types the excisional and gap-filling steps performed by UNG2 and POLβ, respectively, are impaired by folate deficiency in human and murine models in vitro. Genomic uracil damage can be acquired by inadequate conversion of uracil to thymine nucleotide precursors resulting from insufficient folate cofactors, or through activation induced cytosine deaminase (AID) activity during antibody diversification in B-cells in the context of adaptive immunity. The immunoglobulin (Ig) diversification methods in B-cells depend on the coordinated interaction between AID and UNG2, and …

Transcriptional Regulation Of Dksa In E. Coli, Daniel Thomas Woods

Legacy Theses & Dissertations (2009 - 2024)

DksA is a global transcription factor that binds RNAP directly to regulate the expression of many genes and operons, including ribosomal RNA, in a ppGpp-dependent or ppGpp–independent manner. It is also involved in facilitating the process of DNA replication by removing stalled transcription elongation complexes that could block the progress of the replication fork. In addition, DksA is important for colonization, establishment of biofilms, and pathogenesis. In order to sustain these various functions, an adequate level of cellular DksA is required. This work tested the hypothesis that the E. coli dksA is substantially regulated at the level of transcription. Using …

Sers For Protein Detection At A Single Molecule Level For Developing A New Medical Diagnostics Platform, Lamyaa Almehmadi

Legacy Theses & Dissertations (2009 - 2024)

A two-step process of protein detection at a single molecule level using Surface Enhanced Raman Spectroscopy (SERS) was developed as a new platform for medical diagnostics in this proof-of-concept study. First, a protein molecule was bound to a linker in the bulk solution and then this adduct was chemically reacted with the SERS substrate. Traut’s Reagent (TR) was used to thiolate Bovine serum albumin (BSA) in solution followed by chemical cross linking to a gold surface through a sulfhydryl group. A Glycine-TR adduct was used as a control sample to identify the protein contribution to the SER spectra. Gold SERS …

Novel Amphiphilic Cyclobutene And Cyclobutane Cis-C18 Fatty Acid Derivatives Inhibit Mycobacterium Avium Subsp. Paratuberculosis Growth, Denise K. Zinniel, Wantanee Sittiwong, Darrell D. Marshall, Govardhan Rathnaiah, Isin T. Sakallioglu, Robert Powers, Patrick H. Dussault, Raul G. Barletta

School of Veterinary and Biomedical Sciences: Faculty Publications

Mycobacterium avium subspecies paratuberculosis (Map) is the etiologic agent of Johne’s disease in ruminants and has been associated with Crohn’s disease in humans. An effective control of Map by either vaccines or chemoprophylaxis is a paramount need for veterinary and possibly human medicine. Given the importance of fatty acids in the biosynthesis of mycolic acids and the mycobacterial cell wall, we tested novel amphiphilic C₁₀ and C₁₈ cyclobutene and cyclobutane fatty acid derivatives for Map inhibition. Microdilution minimal inhibitory concentrations (MIC) with 5 or 7 week endpoints were measured in Middlebrook 7H9 base broth media. We compared the …

Investigation Of Congestive Heart Failure In Beef Cattle In A Feedyard At A Moderate Altitude In Western Nebraska, Rodney A. Moxley, David R. Smith, Dale M. Grotelueschen, Tom Edwards, David Steffen

School of Veterinary and Biomedical Sciences: Faculty Publications

Right-sided congestive heart failure (brisket disease) commonly occurs in cattle raised at elevations >2,500– 3,500 m. We investigated clinical cases resembling brisket disease at a western Nebraska feedyard at a moderate altitude (1,369 m). Over a 15-mo period (2009–2010), we examined 17 cases (16 steers and 1 heifer), all purebred Angus. All animals had clinical right-sided heart failure: brisket and ventral abdominal edema, and severe chronic passive congestion of the liver. Gross examination confirmed right ventricular hypertrophy (left ventricle plus septum: right ventricle weight ratio mean: 1.33 vs. 2.8–4.0 reference interval). Microscopically, all 17 cases had interstitial fibrosis (mean score: …

Island Invasion: The Silent Crisis In Hawaii, Sophia Janssen

Pomona Senior Theses

Keeping out invasive species may, upon first review, seem like a trivial environmental cry from ecologists and deep environmentalists; a belated wish to return to an undeveloped world where nature was pristine. However invasive species create problems that impact all of us and can have far more severe consequences than changing a stunning landscape. These problems are heightened in islands like Hawaii, where the fragile ecosystems have developed over centuries of evolution and adaptation. The introduction of a disease-carrying mosquito can put the people of Hawaii at risk to many vector-born illnesses and create an epidemic, taking human life. The …

The Effects Of Heat-Killed Echinostomatid Parasites On Mice Treated With Dextran Sodium Sulfate (Dss), Natalie Gooder

All Graduate Theses, Dissertations, and Other Capstone Projects

Objective: Autoimmune diseases are chronic, incurable, and affect approximately 50 million Americans. This is a strong need for better ways to treat autoimmune diseases. Parasites and parasite proteins have been observed to protect mice from symptoms of induced colitis in mice treated with dextran sodium sulfate (DSS), a model for inflammatory bowel disease (IBD). I hypothesize that non-living echinostomatid parasites, given during DSS treatment, can decrease intestinal inflammation and weight loss, providing a possible novel treatment for IBD.

Methods: A range of DSS concentrations (0.5%-3%) were delivered to female C57BL/6 mice in their drinking water in order to determine the …

Characterizing The Cellulose-Modifying Enzyme Bcsg From Escherichia Coli, Alexander Anderson, Joel T. Weadge

Theses and Dissertations (Comprehensive)

Microbial biofilms are communities of microorganisms that exhibit co-operative behaviour, producing a matrix of exopolysaccharide that enmeshes the community. The well-studied human pathogens Escherichia coli and Salmonella entericaproduce a biofilm matrix comprised chiefly of the biopolymer cellulose, along with amyloid protein fibers termed curli. This biofilm matrix confers surface adherence and acts as a protective barrier to disinfectants, antimicrobials, environmental stressors, and host immune responses. Pertaining to this research, the bcsEFG operon, conserved in the Enterobacteriaceae, encodes an inner membrane-spanning complex responsible for the addition of a phosphoethanolamine (pEtN) modification to microbial cellulose, essential for extracellular matrix assembly and …

Anti-Tumor Activities Of Auricularia Polytricha Extracts In Hepatocellular Carcinoma Cell Line (Hepg2) And Breast Cancer Cell Lines (Mcf-7 And Mda-Mb-231), Sunita Nilkhet

Chulalongkorn University Theses and Dissertations (Chula ETD)

Cancer is the disease that happens to occur in a high number of new cases each year. Even the choice of treatment is developing, but the adverse effects on cancer therapeutic drugs still challenging. To investigate the antitumor activities of Auricularia polytricha (AP) mushroom extract and active compounds, human cancer cell lines such as Hepatocellcular (HepG2) and Breast cancer cell lines (MCF-7 and MDA-MB-231) were interested. The crude hexane extract of AP (APH) and crude ethanol extract of AP (APE) were prepared by maceration and Soxhlet extraction, respectively. Both APE and APH were investigated for their compound compositions by GC-MS. …

Ehdv-2 Infection Prevalence Varies In Culicoides Sonorensis After Feeding On Infected White-Tailed Deer Over The Course Of Viremia, Sandra Y. Mendiola, Mary K. Mills, Elin Maki, Barbara S. Drolet, William C. Wilson, Roy D. Berghaus, David E. Stallknecht, Jonathan Breitenbach, D. Scott Mcvey, Mark G. Ruder

School of Veterinary and Biomedical Sciences: Faculty Publications

Epizootic hemorrhagic disease viruses (EHDVs) are arboviral pathogens of white-tailed deer and other wild and domestic ruminants in North America. Transmitted by various species of Culicoides, EHDVs circulate wherever competent vectors and susceptible ruminant host populations co-exist. The impact of variation in the level and duration of EHDV viremia in white-tailed deer (Odocoileus virginianus) on Culicoides infection prevalence is not well characterized. Here we examined how infection prevalence in a confirmed North American vector of EHDV-2 (Culicoides sonorensis) varies in response to fluctuations in deer viremia. To accomplish this, five white-tailed deer were experimentally infected with EHDV-2 and colonized C. …