Biochemistry, Biophysics, and Structural Biology Commons^™

Effects Of Mono- And Di- Saccharide Osmolytes On The Stability And Folding Dynamics Of Src Sh3, Mahmoud Abouelkheir, Emily Guinn

Annual Student Research Poster Session

Osmolytes are small molecules that stabilize protein’s native structures in living systems. In order to better understand this process, we investigate how changes in specific structural properties of osmolytes affect folding dynamics and stability of proteins. This study focuses on one common structural property that varies in quantity, linkage, and arrangement amongst some osmolytes: glucose subunits. Comparing the effects of osmolytes with varying quantities of cyclic glucose subunits, varying types of glycosidic linkages of cyclic glucose subunits, and a linear glucose analogue on the stability and folding dynamics of proteins may reveal the potential role of these structures on osmolyte-protein …

Synthesis Of Ether Alcohols With Varying Catalysts, Hannah Grady, Frida Li, Jeffrey A. Hansen

Annual Student Research Poster Session

It has previously been found that acids and bases are effective catalysts in the opening of epoxides into ether alcohols. Our first goal for this summer was to determine which of the acids and bases available were the most effective. After figuring out which of the acids and bases are the optimal catalysts, our second goal was producing ether alcohols in the shortest amount of time with higher yields. Our final goal was to see how biologically reactive the ether alcohols we produced were.

Opening Of An Epoxide Ring Using Azide To Form A Triazole, Emily Hufnagel, Jeffrey A. Hansen

Annual Student Research Poster Session

The purpose of this research project is to identify and synthesize biologically active compounds that could potentially aid in pharmaceutical research. Once a compound is correctly identified and purified, the sample can be diluted and added to a Brine Shrimp Lethality Assay in order to determine the toxicity of the compound. This experiment was designed using an epoxide compound to form an azide that would eventually form a triazole. In carrying out this project, two main procedures were used in order to create two different compounds that would eventually create the final result. The triazole was not successful in the …

Leaving Ligand Effects On Reactivity And Solubility Of Monofunctional Platinum(Ii) Anticancer Complexes, Heidi Linn Hruska Millay

Masters Theses & Specialist Projects

Monofunctional platinum(II) complexes, such as phenanthriplatin and pyriplatin, have notably different characteristics from the bifunctional anticancer complexes, such as cisplatin and oxaliplatin, which have detrimental toxicities and resistance associated with them. The unique properties of the monofunctional complexes may be exploited to target cancer cells without producing the toxic side effects associated with the current FDA-approved platinum-based anticancer drugs. To advance the understanding of these monofunctional platinum(II) complexes, this study replaced the chloride leaving ligand with an acetate group, which should increase solubility and alter the rate of reactivity with key amino acid and nucleotide targets. Phenanthriplatin and pyriplatin compounds …

Acute Systemic Inflammatory Response To Lipopolysaccharide Stimulation In Pigs Divergently Selected For Residual Feed Intake, Haibo Liu, Kristina M. Feye, Yet T. Nguyen, Anoosh Rakhshandeh, Crystal L. Loving, Jack C. M. Sekkers, Nicholas K. Gabler, Christopher K. Tuggle

Mathematics & Statistics Faculty Publications

Background: It is unclear whether improving feed efficiency by selection for low residual feed intake (RFI) compromises pigs’ immunocompetence. Here, we aimed at investigating whether pig lines divergently selected for RFI had different inflammatory responses to lipopolysaccharide (LPS) exposure, regarding to clinical presentations and transcriptomic changes in peripheral blood cells.

Results: LPS injection induced acute systemic inflammation in both the low-RFI and high-RFI line (n = 8 per line). At 4 h post injection (hpi), the low-RFI line had a significantly lower (p= 0.0075) mean rectal temperature compared to the high-RFI line. However, no significant differences in complete blood count …

The Essential Role Of Carbon Metabolism In The Virulence Of Cryptococcus Neoformans, Mara Weigner

Senior Honors Theses

Cryptococcus neoformans infections are a major cause of meningoencephalitis in immunosuppressed patients worldwide. Inhaled as spores or desiccated yeast cells, C. neoformans can undergo metabolic changes in response to the new host environment that allow it to cross the blood brain barrier and cause deadly central nervous system (CNS) infections. Nutrient acquisition, and specifically carbon metabolism, is critical for survival and proliferation within the host. Notably, efficient carbon metabolism is necessary to produce the polysaccharide capsule, which is arguably C. neoformans’ most important and well-studied virulence factor. As such, a better understanding of carbon acquisition and regulation is essential for …

Insect Population Dynamics, Varietal Preference And Performance Of Organic Bio-Pesticides, Anitha Chitturi, Jeanine Davis, Margaret Bloomquist, Franklin Quarcoo, Kokoasse Kpomblekou-A, Desmond Mortley

Professional Agricultural Workers Journal

Abstract

Organic farming prohibits use of synthetic agrochemicals and encourages use of Integrated Pest Management (IPM) methods. States in the Southeastern US generally lag behind the rest of the country in organic vegetable production partly because of high insect pressures that make it difficult to grow vegetables without pesticides. This study on summer squash (Cucurbita pepo), grown using organic management practices, was conducted at a research station located in Mills River, North Carolina. The objectives of the study were to assess insect population dynamics and to evaluate performance of three OMRI-approved bio-pesticides: Azadirachtin, Pyrethrin and Spinosad against major …

Standing To Challenge Familial Searches Of Commercial Dna Databases, Hillary L. Kody

William & Mary Law Review

In April 2018, police officers arrested Joseph James DeAngelo. DeAngelo, the officers claimed, was the “Golden State Killer,” a man who committed dozens of murders and over fifty sexual assaults in California in the 1970s and 1980s. The Golden State Killer had long eluded police, even though his DNA profile linked him to dozens of violent crimes. While law enforcement officials from several jurisdictions in California had collected his DNA from crime scenes, the Golden State Killer’s crimes predated modern DNA analysis. Police found little use for the profile without a suspect’s profile to compare to it.

Nearly forty years …

The Effect Of Calcium Alginate Entrapment On The Stability Of Novel Lipases From P. Reinekei And P. Brenneri, Priyanka Priyanka, Gemma K. Kinsella, Gary T. Henehan, Barry J. Ryan

Articles

The high cost of soluble enzymes can limit their use for commercial and industrial purposes. Immobilization can enhance enzyme reusability, thereby reducing product isolation costs and overcoming this economic barrier. In the current study, two novel, purified lipases from Pseudomonas sp. (Pseudomonas reinekei and Pseudomonas brenneri) were entrapped in a calcium alginate matrix, with the aim of simultaneously enhancing enzyme reusability and stability. Following entrapment, the retained activity of the enzyme-alginate composite was verified by an enzymatic hydrolysis reaction of a p-nitrophenol palmitate substrate. The effect of the enzyme-alginate entrapment against various physiochemical parameters such as pH, temperature, metal ions, …

Inclusion Of Enclosed Hydration Effects In The Binding Free Energy Estimation Of Dopamine D3 Receptor Complexes, Rajat Kumar Pal, Satishkumar Gadhiya, Steven Ramsey, Pierpaolo Cordone, Lauren Wickstrom, Wayne W. Harding, Tom Kurtzman, Emilio Gallicchio

Publications and Research

Confined hydration and conformational flexibility are some of the challenges encountered for the rational design of selective antagonists of G-protein coupled receptors.We present a set of C3-substituted (-) -stepholidine derivatives as potent binders of the dopamine D3 receptor.The compounds are characterized biochemically, as well as by computer modeling using a novel molecular dynamics-based alchemical binding free energy approach which incorporates the effect of the displacement of enclosed water molecules from the binding site.The free energy of displacement of specific hydration sites is obtained using the Hydration Site Analysis method with explicit solvation. This work underscores the critical role of confined …

Bright Green Biofluorescence In Sharks Derives From Bromo-Kynurenine Metabolism, Hyun Bong Park, Yick Chong Lam, Jean P. Gaffney, James C. Weaver, Sara Rose Krivoshik, Randy Hamchand, Vincent Pieribone, David F. Gruber, Jason M. Crawford

Publications and Research

Although in recent years there has been an increased awareness of the widespread nature of biofluorescence in the marine environment, the diversity of the molecules responsible for this luminescent phenotype has been mostly limited to green fluorescent proteins (GFPs), GFP-like proteins, and fluorescent fatty acid-binding proteins (FABPs). In the present study, we describe a previously undescribed group of brominated tryptophan-kynurenine small molecule metabolites responsible for the green biofluorescence in two species of sharks and provide their structural, antimicrobial, and spectral characterization. Multi-scale fluorescence microscopy studies guided the discovery of metabolites that were differentially produced in fluorescent versus non-fluorescent skin, as …

The Fitness Landscape Of The African Salmonella Typhimurium St313 Strain D23580 Reveals Unique Properties Of The Pbt1 Plasmid, Rocío Canals, Roy R. Chaudhuri, Rebecca E. Steiner, Siân V. Owen, Natalia Quinones-Olvera, Melita A. Gordon, Michael Baym, Michael Ibba, Jay C. D. Hinton

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

We have used a transposon insertion sequencing (TIS) approach to establish the fitness landscape of the African Salmonella enterica serovar Typhimurium ST313 strain D23580, to complement our previous comparative genomic and functional transcriptomic studies. We used a genome-wide transposon library with insertions every 10 nucleotides to identify genes required for survival and growth in vitro and during infection of murine macrophages. The analysis revealed genomic regions important for fitness under two in vitro growth conditions. Overall, 724 coding genes were required for optimal growth in LB medium, and 851 coding genes were required for growth in SPI-2-inducing minimal medium. These …

Case 64: Alkalosis In A Patient With A Brain Tumor: A Link Between The Cns And Blood Ph, Dr. Kathleen Cornely

Chemistry & Biochemistry Case Studies

The response of the carbonic acid/bicarbonate buffering system to a patient’s hyperventilation–presumably caused by CNS abnormalities following surgery to remove a brain tumor–is examined.

Cellular Distribution Of The Prion Protein In Palatine Tonsils Of Mule Deer (Odocoileus Hemionus) And Rocky Mountain Elk (Cervus Elaphus Nelsoni), Matthew M. Hille, Jean E. Jewell, E. Lee Belden

School of Veterinary and Biomedical Sciences: Faculty Publications

Chronic wasting disease (CWD) is a transmissible spongiform encephalopathy (TSE) that affects members of the Cervidae family, including deer (Odocoileus spp.), elk (Cervus Canadensis spp.), and moose (Alces alces spp.). While CWD is a neurodegenerative disease, lymphoid accumulation of the abnormal isoform of the prion protein (PrPSc) is detectable early in the course of infection. It has been shown that a large portion of the PrPSc lymphoid accumulation in infected mule deer takes place on the surface of follicular dendritic cells (FDCs). In mice, FDC expression of PrPC has been shown to be essential for PrPSc accumulation. …

Immediate-Early Genes And Delayed Primary Response Genes Regulated By Nmu In Skbr3 Her-2 Positive Breast Cancer Cell Line, Jessica Murphy, Sweta Rani

SURE Journal: Science Undergraduate Research Experience Journal

Background
Breast cancer is a heterogeneous disease that consists of varying genetic, cellular and molecular subtypes with unique characteristics. Due to the multiple subtypes and molecular markers of breast cancer, successful clinical treatment is hampered by the lack of reliable biomarkers. HER2-positive breast cancer is an aggressive subtype associated with poor patient prognosis. Although survival rates have dramatically increased due to the development of Trastuzumab in 1997, many patients develop a resistance to this therapeutic treatment and relapse over time. Rani et al. (2014), have associated the acquirement of resistance to HER2-treatment with Neuromedin U, but the mechanisms by …

Developmental And Molecular Changes Underlying The Vernalization-Induced Transition To Flowering In Aquilegia Coerulea (James), Bharti Sharma, Timothy A. Batz, Rakesh Kaundal, Elena M. Kramer, Uriah R. Sanders, Valerie J. Mellano, Naveen Duhan, Rousselene B. Larson

Center for Integrated Biosystems Publications

Reproductive success in plants is dependent on many factors but the precise timing of flowering is certainly among the most crucial. Perennial plants often have a vernalization or over-wintering requirement in order to successfully flower in the spring. The shoot apical meristem undergoes drastic developmental and molecular changes as it transitions into inflorescence meristem (IM) identity, which then gives rise to floral meristems (FMs). In this study, we have examined the developmental and gene expression changes underlying the transition from the vegetative to reproductive phases in the basal eudicot Aquilegia coerulea, which has evolved a vernalization response independently relative …

Creating A Molecular Map Of The Pediatric Lung, Quinlen F. Marshall

Forum Lectures

The newborn lung undergoes vast biochemical and physiological changes during adaptation from the intrauterine to the extrauterine environment. Lung morphogenesis continues from birth into early childhood, mediated by dynamic gene expression and a diversity of pulmonary cell types that exhibit remarkable heterogeneity. (Whitsett, JA. et al. Physiol. Rev, 2019). Surprisingly, few studies have solely focused on human lung development during this critical period, and many current studies of lung maturation rely on adult, murine, or diseased samples, limiting their insights and applicability to longitudinal pediatric lung development. Understanding the molecular and physiological nuances of pulmonary development has important clinical relevance, …

The Alfalfa Insecticide Management (Aim) Toolkit: Linking Insecticide Fate Modelling With Alfalfa Pest And Beneficial Insect Toxicity Endpoints, Kimberly J. Hageman

Funded Research Records

No abstract provided.

Endoglin Protein Interactome Profiling Identifies Trim21 And Galectin-3 As New Binding Partners, Eunate Gallardo-Vara, Lidia Ruiz-Llorente, Juan Casado-Vela, María J. Ruiz-Rodríguez, Natalia López-Andrés, Asit K. Pattnaik, Miguel Quintanilla

School of Veterinary and Biomedical Sciences: Faculty Publications

Endoglin is a 180-kDa glycoprotein receptor primarily expressed by the vascular endothelium and involved in cardiovascular disease and cancer. Heterozygous mutations in the endoglin gene (ENG) cause herediatry hemorrhagic telangiectasia type 1, a vascular disease that presents with nasal and gastrointestinal bleeding, skin and mucosa telangiectase, and arteriovenous malformations in internal organs. A circulating form of endoglin (alias soluble endoglin, sEng), proteolytically released from the membrane-bound protein, has been observed in several inflammation-related pathological conditions and appears to contribute to endothelial dysfunction and cancer development through unknown mechanisms. Membrane-bound endoglin is an auxiliary component of the TGF-B receptor complex and …

Theoretical Studies Of Ir And Nmr Spectral Changes Induced By Sigma-Hole Hydrogen, Halogen, Chalcogen, Pnicogen, And Tetrel Bonds In A Model Protein Environment, Mariusz Michalczyk, Wiktor Zierkiewicz, Rafał Wysokiński, Steve Scheiner

Chemistry and Biochemistry Faculty Publications

Various types of σ-hole bond complexes were formed with FX, HFY, H₂FZ, and H₃FT (X = Cl, Br, I; Y = S, Se, Te; Z = P, As, Sb; T = Si, Ge, Sn) as Lewis acid. In order to examine their interactions with a protein, N-methylacetamide (NMA), a model of the peptide linkage was used as the base. These noncovalent bonds were compared by computational means with H-bonds formed by NMA with XH molecules (X = F, Cl, Br, I). In all cases, the A–F bond, which lies opposite the base and is responsible for …