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Biological And Computational Studies Of The Structure And Function Of Pul103, A Human Cytomegalovirus Tegument Protein, Ashley N. Anderson

Wayne State University Dissertations

Human cytomegalovirus (HCMV) is an enveloped, single segment, double-stranded DNA virus. HCMV infection causes disease in immunocompromised (HIV patients, transplant recipients) and immunodeficient (fetuses, neonates) populations. Current treatments are effective but are either limited in use or can lead to organ damage and/or antiviral resistance, and no vaccines are available. Additional antiviral targets are needed. HCMV pUL103 is a potential antiviral target. pUL103 is a conserved herpesvirus protein present in the tegument, layer of proteins and RNA between the envelope and capsid of HCMV virions. pUL103 helps reorganize cellular secretory machinery (Golgi, endosomes) to form the cytoplasmic virion assembly compartment …

Novel Hiv Adaptation Strategy Against Host Cd8 T Cell Immunity, Kai Qin

All ETDs from UAB

Since the 1980s, HIV infection has caused millions of death and tremendous economic losses worldwide. Despite great scientific advances, the only effective therapy to date, antiretroviral therapy (ART), merely delays disease progression yet cannot eradicate viral infection. Therefore, an effective HIV vaccine that can prevent the acquisition of infection would be a desirable alternative. The critical role of CD8 T-cell immunity in HIV infection has been well documented and therefore not surprisingly a great deal of effort has been focused on developing an effective CD8 T-cell based HIV vaccine. However, by far, such CD8 T-cell based HIV vaccine trials have …

An Investigation Of The Potentials Of 2-[(2-Hydroxyphenyl) Methylidene] Hydrazine-1-Carbothioamide And Its Mn(Ii) And Zn(Ii) Complexes As Antimicrobial Agents, Umar Sani, Musbahu Yahaya, Dailami S. Adam

Tanzania Journal of Science

Antibiotic resistance as a result of misuse, overuse or abuse of drugs is an issue of serious concern world over. The quest for more active and robust antimicrobial agents remains a scientific challenge and requires multimillion-dollar investment in the area of drug design and development. Here in, we report the synthesis and characterisation of a tridentate thiosemicarbazone (2-[(2-hydroxyphenyl)methylidene]hydrazine-1-carbothioamide) (HL) from salicylaldehyde and thiosemicarbazide. Its complexes with Mn(II) and Zn(II) were prepared following similar technique and characterised by melting point, FT-IR, UV –visible spectrophotometry, and elemental analysis. The Mn(II) complex showed paramagnetism with a magnetic moment value of 5.80 BM while …

9th Annual Postdoctoral Science Symposium, University Of Texas Md Anderson Cancer Center Postdoctoral Association

Annual Postdoctoral Science Symposium Abstracts

The mission of the Annual Postdoctoral Science Symposium (APSS) is to provide a platform for talented postdoctoral fellows throughout the Texas Medical Center to present their work to a wider audience. The MD Anderson Postdoctoral Association convened its inaugural Annual Postdoctoral Science Symposium (APSS) on August 4, 2011.

The APSS provides a professional venue for postdoctoral scientists to develop, clarify, and refine their research as a result of formal reviews and critiques of faculty and other postdoctoral scientists. Additionally, attendees discuss current research on a broad range of subjects while promoting academic interactions and enrichment and developing new collaborations.

Comparative Transcriptomic Analysis And Structure Prediction Of Novel Newt Proteins, Abijeet Singh Mehta, Agustin Luz-Madrigal, Jian-Liang Li, Panagiotis A. Tsonis, Amit Singh

Biology Faculty Publications

Notophthalmus viridescens (Red-spotted Newt) possess amazing capabilities to regenerate their organs and other tissues. Previously, using a de novo assembly of the newt transcriptome combined with proteomic validation, our group identified a novel family of five protein members expressed in adult tissues during regeneration in Notophthalmus viridescens. The presence of a putative signal peptide suggests that all these proteins are secretory in nature. Here we employed iterative threading assembly refinement (I-TASSER) server to generate three-dimensional structure of these novel Newt proteins and predicted their function. Our data suggests that these proteins could act as ion transporters, and be involved …

Isolation, Analysis, And Partial Characterization Of An Inhibitor Of Neisseria Gonorrhoeae, Natania Paul

Undergraduate Honors Theses

There is an emerging threat of Neisseria gonorrhoeae strains that are resistant to all antibiotics. Because of this, the purpose of this research is to isolate, analyze, and partially characterize a new inhibitor(s) of N. gonorrhoeae. Since there is an unknown molecule secreted by Candida albicans that inhibits N. gonorrhoeae, this molecule can be partially characterized using ¹H NMR Spectroscopy to assist in the development of a new antibiotic compound. It was hypothesized that quorum-sensing molecules, trans, trans- farnesol, tyrosol, phenylethyl alcohol, and tryptophol, could be possible candidates for the inhibitor. Because of this, ¹H …

P53 Phosphomimetics Preserve Transient Secondary Structure But Reduce Binding To Mdm2 And Mdmx, Robin Levy, Emily Gregory, Wade Borcherds, Gary W. Daughdrill

Molecular Biosciences Faculty Publications

The disordered p53 transactivation domain (p53TAD) contains specific levels of transient helical secondary structure that are necessary for its binding to the negative regulators, mouse double minute 2 (Mdm2) and MdmX. The interactions of p53 with Mdm2 and MdmX are also modulated by posttranslational modifications (PTMs) of p53TAD including phosphorylation at S15, T18 and S20 that inhibits p53-Mdm2 binding. It is unclear whether the levels of transient secondary structure in p53TAD are changed by phosphorylation or other PTMs. We used phosphomimetic mutants to determine if adding a negative charge at positions 15 and 18 has any effect on the transient …

Antibiotic-Resistant Escherichia Coli From Retail Poultry Meat With Different Antibiotic Use Claims, Gregg S. Davis, Kara Waits, Lora Nordstrom, Heidi Grande, Brett Weaver, Katerina Papp, Joseph Horwinski, Benjamin Koch, Bruce A. Hungate, Cindy M. Liu, Lance B. Price

Civil and Environmental Engineering and Construction Faculty Research

Background We sought to determine if the prevalence of antibiotic-resistant Escherichia coli differed across retail poultry products and among major production categories, including organic, “raised without antibiotics”, and conventional. Results We collected all available brands of retail chicken and turkey—including conventional, “raised without antibiotic”, and organic products—every two weeks from January to December 2012. In total, E. coli was recovered from 91% of 546 turkey products tested and 88% of 1367 chicken products tested. The proportion of samples contaminated with E. coli was similar across all three production categories. Resistance prevalence varied by meat type and was highest among E. …

Tof-Sims Analysis Of Plant Seed Interactions With Plant Growth-Promoting Bacteria, Tammy Pheuphong, Rachel Komorek, Xiao-Ying Yu

STAR Program Research Presentations

The use of time-of-flight secondary ion mass spectrometry (ToF-SIMS) in plant biology is a relatively unexplored and quickly developing field. The majority of research in plant SIMS involves the application of ToF-SIMS to study dried wood tissues, and only a handful of studies apply SIMS on plant stems, roots, and/or seeds. Our project provides a brief description and review of previous work using SIMS on plant stems, roots, and/or seeds, along with an emphasis on the sample preparation in each study. Additionally, the use of Brachypodium distachyon (Brachypodium) as a model system for research on grasses has also become more …

The Diversity Found Among Carbapenem-Resistant Bacteria, Galen Edward Card

Theses and Dissertations

This work will look at two factors that add to the diversity of carbapenem resistant bacteria. First, it focuses on the diversity of carbapenemase resistance plasmids. 446 plasmids were characterized by size, gene content and replicon groups. We identified that on average, over 30% of the encoded proteins on each plasmid have an unknown function. Plasmid sizes ranged from 1.6kb to 500kb, with an average of around 100kb and median of 80kb. Additionally, six replicon groups account for 80% of all the carbapenemase resistance plasmids. We also highlight the lack of data available for carbapenemase carrying plasmids from bacterial genera …

Gesture: An Online Hand-Drawing Tool For Gene Expression Pattern Search, Chunyan Wang, Yiqing Xu, Xuelin Wang, Li Zhang, Suyun Wei, Qiaolin Ye, Youxiang Zhu, Hengfu Yin, Manoj Nainwal, Luis Tanon-Reyes, Feng Cheng, Tongming Yin, Ning Ye

Molecular Biosciences Faculty Publications

Gene expression profiling data provide useful information for the investigation of biological function and process. However, identifying a specific expression pattern from extensive time series gene expression data is not an easy task. Clustering, a popular method, is often used to classify similar expression genes, however, genes with a ‘desirable’ or ‘user-defined’ pattern cannot be efficiently detected by clustering methods. To address these limitations, we developed an online tool called GEsture. Users can draw, or graph a curve using a mouse instead of inputting abstract parameters of clustering methods. GEsture explores genes showing similar, opposite and time-delay expression patterns with …

A Cure For Salmonella: Engaging Students In Pathogen Microbiology And Bioinformatics, Sophie Jurgensen

Senior Honors Projects, 2010-2019

Advances in Next Generation Sequencing (NGS) technology have generated a vast amount of publicly available genomic data, creating a need for students with training in computational analysis. This laboratory lesson is a course-based undergraduate research experience (CURE) focusing on environmental Salmonella, a common foodborne pathogen that is of great interest to public health laboratories but is relatively less virulent than most other such pathogens. As discovery is a central tenet of CUREs, students isolate novel Salmonella enterica and related strains from stream sediment, poultry litter, or other sources in the first half of the lesson (Module 1). They also …

Universal Swine Influenza Antigen And Vaccine, Zhao Wang

Electronic Theses and Dissertations

Swine influenza A viruses pose a serious concern for global health and worldwide swine industry considering their evasion from vaccine-induced immune responses. Formulation of effective influenza vaccines can be complicated by both antigenic shift to a different subtype of hemagglutinin (HAs) and antigenic drift within a particular HA subtype. To address these concerns, we employed a systematic approach to determine the antigenic determinants of swine influenza A viruses by focusing on H1 and H3 subtypes. In parallel, we used a cross-disciplinary approach including structural biology and modeling, virology, and immunology to identify swine influenza A virus-derived HA fusion intermediates broadly …

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 …

A Comparative Analysis Of Stress Responses In Diverse Acanthamoeba Isolates, Mallory Jean Douthitt

Theses, Dissertations and Capstones

Acanthamoeba are free-living amoebae which can differentiate from vegetative, trophozoite forms into dormant cysts upon encountering unfavorable conditions. Acanthamoeba isolates FLA9, BP, and FLA22 are known to have unusual tolerance to environmental conditions which would promote encystment in the type strain, Neff. To facilitate further research into the behavior of these isolates, the phenotypic variables of instantaneous growth rate (μ), mean exponential encystment rate (Ԑ), and overall encystment success are calculated for the study isolates a variety of environmental conditions. Results indicate that BP and FLA22 may prefer growth conditions that are intolerable to the Neff strain. Findings suggest genomic …

Review Of The Algal Biology Program Within The National Alliance For Advanced Biofuels And Bioproducts, Clifford J. Unkefer, Richard T. Sayre, Jon K. Magnuson, Daniel B. Anderson, Ivan Baxter, Ian K. Balby, Judith K. Brown, Michael Carleton, Rose Ann Cattolico, Taraka Dale, Timothy P. Devarenne, C. Meghan Downes, Susan K. Dutcher, David T. Fox, Ursula Goodenough, Jan Jaworski, Jonathan E. Holladay, David M. Kramer, Andrew T. Koppisch, Mary S. Lipton, Babetta L. Marrone, Margaret Mccormick, István Molnár, John B. Mott, Kimberly L. Ogden, Ellen A. Panisko, Matteo Pellegrini, Juergen Polle, James W. Richardson, Martin Sabarsky, Shawn R. Starkenburg, Gary D. Stormo, Munehiro Teshima, Scott N. Twary, Pat J. Unkefer, Joshua S. Yuan, José A. Olivares

Publications and Research

In 2010,when the National Alliance for Advanced Biofuels and Bioproducts (NAABB) consortiumbegan, littlewas known about themolecular basis of algal biomass or oil production. Very fewalgal genome sequenceswere available and efforts to identify the best-producing wild species through bioprospecting approaches had largely stalled after the U.S. Department of Energy's Aquatic Species Program. This lack of knowledge included how reduced carbon was partitioned into storage products like triglycerides or starch and the role played bymetabolite remodeling in the accumulation of energy-dense storage products. Furthermore, genetic transformation and metabolic engineering approaches to improve algal biomass and oil yields were in their infancy. Genome …

Frequency Of Colistin And Fosfomycin Resistance In Carbapenem-Resistant Enterobacteriaceae From A Tertiary Care Hospital In Karachi, Salima Qamar, Najma Shaheen, Sadia Shakoor, Joveria Farooqi, Kauser Jabeen, Rumina Hasan

Department of Pathology and Laboratory Medicine

Introduction:
Management of infections with carbapenem-resistant Enterobacteriaceae (CRE) is challenging. In recent times, agents such as colistin and fosfomycin have been used in combination with other antibiotics to treat such infections. In this study, we aim to seek frequency of colistin and fosfomycin resistance in CRE from Pakistan.
Methods:
This study was conducted at clinical laboratories, Aga Khan University Hospital. In total, 251 CRE were included in the study. Colistin minimum inhibitory concentrations (MICs) were performed using broth microdilution (BMD) method and VITEK 2 system, whereas fosfomycin susceptibility was performed using Kirby-Bauer method. MIC50 and MIC90 were calculated for colistin …

Affinity Cryo-Electron Microscopy: Methods Development And Applications, Guimei Yu

Open Access Dissertations

Single particle cryo-electron microscopy (cryo-EM) is an emerging powerful tool for structural studies of macromolecular assemblies. Although less concentrated and smaller amounts of samples are required for single particle cryo-EM compared to X-ray crystallography, it remains challenging to study specimens that are low-abundance, low-yield, or short-lived. The recent development of affinity grid techniques holds great promise to tackle these challenging samples by combining the sample purification and freezing on TEM grids steps in cryo-EM grid preparation into a single step, revolutionize the grid preparation of cryo-EM, and extend single particle cryo-EM to a routine structural biology tool to characterize structures …

Insights Into Determinants That Contribute To Colonization, Virulence And Antibiotic Resistance In Enterococci, Maria Camila Montealegre

Dissertations and Theses (Open Access)

Enterococcus faecalis and Enterococcus faecium are increasingly common as causative agents of human infections, many of which are very difficult to treat due to multi-drug resistance. The work presented in the first part of this dissertation elucidates a mechanism for the regulation of pilus expression. I showed that ATT is the initiation codon of ebpA, the first gene of an operon that codes for the endocarditis and biofilm-associated pili (Ebp), a recognized virulence factor in E. faecalis. The presence of this rare start codon downregulates EbpA translation and protein levels, diminishing biofilm and binding abilities of …

Interactomics-Based Functional Analysis: Using Interaction Conservation To Probe Bacterial Protein Functions, J. Harry Caufield

Theses and Dissertations

The emergence of genomics as a discrete field of biology has changed humanity’s understanding of our relationship with bacteria. Sequencing the genome of each newly-discovered bacterial species can reveal novel gene sequences, though the genome may contain genes coding for hundreds or thousands of proteins of unknown function (PUFs). In some cases, these coding sequences appear to be conserved across nearly all bacteria. Exploring the functional roles of these cases ideally requires an integrative, cross-species approach involving not only gene sequences but knowledge of interactions among their products. Protein interactions, studied at genome scale, extend genomics into the field of …

Suitability Of Great South Bay, New York To Blooms Of Pfiesteria Piscicida And P. Shumwayae Prior To Superstorm Sandy, October 29, 2012, Pawel Tomasz Zablocki

Theses and Dissertations

Pfiesteria piscicida and P. shumwayae are toxic dinoflagellates implicated in massive fish kills in North Carolina and Maryland during 1990s. A set of physical, chemica l, and biological factors influence population dynamics of these organisms. This study employs i nformation gathered from relevant literature on temperature, salinity, dissolved oxygen, pH, turbulent mixing, and dissolved nutrients, bacteria, algae, microzooplankton, mesozooplankton, bivalve m ollusks, finfish, and other toxic dinoflagellates, which influence Pfiesteria population dynamics. The research focused on whether conditions in the Great South Bay, Long Island, New York were suitable to blooms of Pfiesteria species prior to the passage of superstorm …

Exploring The Physiological Role Of Vibrio Fischeri Pepn, Sally L. Cello

Master's Theses

The primary contributor to Vibrio fischeri aminopeptidase activity is aminopeptidase N, PepN. Colonization assays revealed the pepN mutant strain to be deficient at forming dense aggregates and populating the host’s light organ compared to wildtype within the first 12 hours of colonization; however the mutant competed normally at 24 hours. To address the role of PepN in colonization initiation and establish additional phenotypes for the pepN mutant strain, stress response and other physiological assays were employed. Marked differences were found between pepN mutant and wildtype strain in response to salinity, acidity, and antibiotic tolerance. This study has provided a foundation …

On Individual, Sex And Age Differentiation Of Indian House Crow (Corvus Splendens) Call: A Preliminary Study In Potohar, Pakistan, Waqas Hameed, Inayat Ullah, Safia Janjua, Fakhar -I- Abbas, Afsar Mian

Journal of Bioresource Management

Considering importance of acoustics studies in population biology, 500 calls of the Indian House Crow (Corvus splendens) were recorded in morning - mid-afternoon hours (January-February, 2009) from 23 sites of urban areas of Potahar (Punjab, Pakistan). Calls were recorded using Sony CFS 1030 S sound records (sampling rate = 48 KHz) and edited using Sound Analysis Pro (Version 1.02). software using FFT method rate 50%, data window 9.27 ms, advanced window 1.36 ms. Through editing of calls, we selected 60 (37 ♂♂, 17 ♀♀, 6 Juvenile ♂♂) good quality spectrograms for detailed analysis. Spectrograms were characterized by rapid frequency modulations …

Analysis Of Human Papillomavirus Capsid Proteins: Insights Into Capsid Assembly, Willie A. Hughes

School of Biological Sciences: Dissertations, Theses, and Student Research

Papillomaviruses (PVs) are double stranded (ds)-DNA viruses (~8-kbp), which infect mucosal and cutaneous epithelial cells from various mammalian species, causing tumors in both epithelial cell-types. During the late-phase, the capsid proteins (L1 and L2), are expressed to encapsidate the viral genome generating infectious virion particles required for PV. Natural PV infections produce morphologically homogenous progeny virions 55-nm in diameter. Transient transfection systems allow individual expression of the capsid proteins, which are able to produce low-levels of infectious virion-like particles (VLPs) and non-infectious VLPs that have the capacity to resemble and function as wild-type virions.

Results: The research herein demonstrates …

Proteomic Studies Of The Influenza Virus-Human Cell Interactions: The Responses Of Host Cell Protein Expression To Viral Infection And The Novel Host Proteins That Interact With Virus Protein Ns1, Yimeng Wang

Graduate Theses and Dissertations

Influenza A viruses (IAVs) continue to be a threat to human health. Despite extensive studies, the mechanisms underlying the IAVs-host interactions during IAV infection remain elusive. We employed quantitative proteomic methods to systematically explore the host cell protein expression responses to IAV infection and examine the function of a critical IAV protein called NS1 by identifying its host binding partners. Specifically, we used a 2-dimentional gel electrophoresis (2-DE) based proteomic method to screen host proteins whose expression was substantially altered by IAV. One critical protein named IκB kinase-gamma (IKKγ) was found to be significantly down-regulated during IAV infection. Functional studies …

Cytokine Signaling In The Microenvironment May Aid In Tumor Development And Progression, Dr. Kim O'Neill

Journal of Undergraduate Research

Studies have indicated that in breast tumors a high number of tumor associated macrophages (TAM’s) is indicative of a poor prognosis. TAM’s in the breast tumor microenvironment generally have a compromised immune response and focus their energy toward tissue repair which leads to angiogenesis, tumor growth, and metastasis. These macrophages have been termed M2 macrophages. Conversely, studies also indicate that in the microenvironment of some colon cancers, M1 phenotypic macrophages are present and that a high number of TAM’s is associated with a good prognosis.

Antony Van Leeuwenhoek: Creation “Magnified” Through His Magnificent Microscopes, Alan L. Gillen, Douglas Oliver

Faculty Publications and Presentations

Although van Leeuwenhoek was not the inventor of the microscope, he advanced it more than anyone else for seeing living things.

Antony van Leeuwenhoek1 (Fig. 1) found great joy in God’s smallest creatures. He first discovered protozoans in his youth. The Dutch haberdasher retained a child-like joy of discovery from his youth until his death at age 90. He lived to see tiny microbes though his homemade microscopes. He loved to grind and focus a new lens in order to see the unseen world. Leeuwenhoek spent countless hours grinding tiny lenses and looking through them. This Christian lay biologist …

Toward The History Of Study Of Symbiogenesis: On The English Translation Of B. M. Kozo-Polyansky’S A New Principle Of Biology (1924), Victor Fet

Biological Sciences Faculty Research

We reproduce the text by Victor Fet, which was read on 6 October 2011 at the Moscow Society of Naturalists during the presentation of new book translation (B.M. Kozo- Polyansky. Symbiogenesis: A New Principle of Evolution / transl. by Victor Fet; ed. by Victor Fet & Lynn Margulis. Cambridge, Mass.: Harvard University Press, 2010. 138 p.) This half- forgotten book by Boris M. Kozo-Polyansky was known only by name to Western biologists. Victor Fet gives a brief history of this new translation, enthusiastically initiated and supported by Lynn Margulis (1938–2011), a famous naturalist who was always eager to gave credit …

Estimating The Impact Of Human Papillomavirus (Hpv) Vaccination On Hpv Prevalence And Cervical Cancer Incidence In Mali, Leree Tracy, Holly Gaff, Colleen Burgess, Samba Sow, Patti E. Gravitt, J. Kathleen Tracy

Biological Sciences Faculty Publications

Human papillomavirus vaccines have potential to reduce cervical cancer incidence and mortality; however, cultural and economic barriers may hinder success in developing countries. We assessed impact of a single vaccine campaign in Mali with use of mathematical modeling. Our model shows that decreases in the prevalence of Human papillomavirus infection are proportional to achieved vaccination coverage.

Pleiotropic Regulatory Function Of The Lysr Family Transcriptional Regulator Cpsy During Streptococcus Iniae Systemic Infection, Jonathan Paul Allen

Wayne State University Dissertations

The ability of a pathogen to metabolically adapt to the local environment for optimal expression of virulence determinants is a continued area of research. Orthologs of the Streptococcus iniae LysR family regulator CpsY have been shown to regulate methionine biosynthesis and uptake pathways, but appear to influence expression of several virulence genes as well. A S. iniae mutant with an in-frame deletion of cpsY is highly attenuated in a zebrafish infection model. The cpsY deletion mutant displays a methionine-independent growth defect in serum, which differs from the methionine-dependent defect observed for orthologous mutants of S. mutans and S. agalactiae. …