Biochemistry, Biophysics, and Structural Biology Commons^™

Studies On Luminescent Gold And Platinum Nanoclusters For Biological Sensing And Catalysis, Richard Covington

Honors Theses

Nanoclusters are small nanoparticles that usually range around a micrometer in diameter. Gold Nanoclusters are known for their unique size and surface qualities and do not share metallic properties with nanoparticles or their respective bulk material. Some metal nanoclusters show high fluorescence and can be synthesized with protein mediation. Nanocluster formation depends on a number of variables, including temperature, pH, and type of reducing agent. This experiment was done to begin to understand how these variables may affect synthesis and what exactly they are. Pure Wild Type CSP-1 protein was induced, transformed, and purified in order to mediate gold and …

Assessing The Potential Impact Of Nanotechnology On The Purification Of Water, Noor Khan

Quest

Independent Research Paper

Research in progress for PHYS 2426: University Physics II

Faculty Mentor: Raji Kannampuzha, Ph.D.

The following paper represents research work done by students in a University Physics 2426 class, the second half of a two-semester introductory course in physics. It is a calculus-based physics course, intended primarily for physics, chemistry, math, and engineering majors. Students are introduced to the concept of academic research by learning to ask research-focused questions and then use the library resources to pursue outside research to find answers. For this assignment, students are asked to investigate a physical science, biological science, or technology …

Development Of A Sonically Powered Biodegradable Nanogenerator For Bone Regeneration, Avi S. Patel

University Scholar Projects

Background: Reconstruction of bone fractures and defects remains a big challenge in orthopedic surgery. While regenerative engineering has advanced the field greatly using a combination of biomaterial scaffolds and stem cells, one matter of difficulty is inducing osteogenesis in these cells. Recent works have shown electricity’s ability to promote osteogenesis in stem cell lines when seeded in bone scaffolds; however, typical electrical stimulators are either (a) externally housed and require overcomplex percutaneous wires be connected to the implanted scaffold or (b) implanted non-degradable devices which contain toxic batteries and require invasive removal surgeries.

Objective: Here, we establish a biodegradable, piezoelectric …

Development Of A Sonically Powered Biodegradable Nanogenerator For Bone Regeneration, Avi Patel

Honors Scholar Theses

Background: Reconstruction of bone fractures and defects remains a big challenge in orthopedic surgery. While regenerative engineering has advanced the field greatly using a combination of biomaterial scaffolds and stem cells, one matter of difficulty is inducing osteogenesis in these cells. Recent works have shown electricity’s ability to promote osteogenesis in stem cell lines when seeded in bone scaffolds; however, typical electrical stimulators are either (a) externally housed and require overcomplex percutaneous wires be connected to the implanted scaffold or (b) implanted non-degradable devices which contain toxic batteries and require invasive removal surgeries.

Objective: Here, we establish a biodegradable, piezoelectric …

Decrypting Female Attractivity In Garter Snakes, Holly Rucker

Senior Honors Projects, 2010-2019

Pheromones are utilized by many species as sexual signals driving mate choice, and pheromone production in vertebrates hinges on sex hormone action. Female red-sided garter snakes (Thamnophis sirtalis parietalis) produce a skin-based sex pheromone used by males for mate detection and selection. Estradiol is necessary for pheromone production, yet the specific mechanisms within the skin are unknown. Central to this is the metabolism of testosterone to estradiol via the enzyme aromatase. It is hypothesized that female garter snakes synthesize estradiol locally in the skin and maintain pheromone production via tissue-specific regulation of aromatase. Further, I hypothesize that female …

Investigations Of The Mechanism Of Action For Lung Cancer Cell Death By A 4-Trifluoromethoxy Substituted Chalcone, Trevor M. Stantliff

Undergraduate Theses

Chalcones are a diphenyl compound that serves as a natural precursor to flavonoids in plants. Chalcones have been shown to have anticancer and antimicrobial activities. Chemoprevention activity of chalcones are of high interest in medicinal chemistry because of the simple laboratory synthesis and modification via Claisen-Schmidt condensation. Previously this lab created and screened a library of synthetic chalcones against A549 lung adenocarcinoma cell line for antiproliferation properties. We identified a strong drug candidate (4-trifluoromethoxy substituted chalcone) for A549 growth inhibition. However, the cause of inhibition by the substituted chalcone remains to be identified We began to explore the mechanism of …

Identification Of Pathways Required For The Survival Of Inversion(16) Acute Myeloid Leukemia, Yiqian Wang

Theses & Dissertations

Inversion of chromosome 16 [inv(16)] acute myeloid leukemia (AML) generates a fusion gene CBFB-MYH11. Approximately half of inv(16) AML patients eventually relapse mainly due to the existence of leukemia stem cells (LSCs). Previous work using a Cbfb-MYH11 knockin mouse model showed that the LSCs are enriched within CSF2RB^- population. Another gene upregulated by Cbfb-MYH11 encodes the cytokine receptor IL1RL1. Using Cbfb-MYH11 knockin mice, we showed that LSCs exist in multiple sub-populations defined by their immunophenotype, and IL1RL1 is expressed by cell populations with high LSC activity. We also found that treatment of IL-33, the ligand for IL1RL1, promoted …

The Role Of Ros In The Progression And Treatment Of Castration-Resistant Prostate Cancer, Dannah R. Miller

Theses & Dissertations

Prostate cancer is the second leading cause of cancer-related deaths in U.S. men, primarily due to the development of castration-resistant (CR) prostate cancer (PCa), of which there are no effective treatment options. Reactive oxygen species (ROS) plays a critical role in prostate carcinogenesis, including the progression of the CR PCa phenotype. ROS regulates both cell proliferation and apoptosis; a moderate increase in ROS can promote proliferation; however, a substantial rise in ROS levels will result in apoptosis. Oxidase p66Shc is elevated in clinical PCa cells and has been associated with a metastatic phenotype of CR PCa cells, promoting PCa cell …

Developing Targeted Therapy Against Pancreatic Cancer, Garima Kaushik

Theses & Dissertations

Not available.

One Amino Acid Change Of Angiotensin Ii Diminishes Its Effects On Abdominal Aortic Aneurysm, Ya Wang, Yinchuan Xu, Congqing Wu, Hongguang Xia, Yingchao Wang, Jinliang Nan, Jinghai Chen, Hong Yu, Wei Zhu, Peng Shi, Alan Daugherty, Hong S. Lu, Jian'an Wang

Saha Cardiovascular Research Center Faculty Publications

Angiotensin (Ang) A is formed by the decarboxylation of the N terminal residue of AngII. The present study determined whether this one amino acid change impacted effects of AngII on abdominal aortic aneurysm (AAA) formation in mice. Computational analyses implicated that AngA had comparable binding affinity to both AngII type 1 and 2 receptors as AngII. To compare effects of these two octapeptides in vivo, male low-density lipoprotein receptor (Ldlr) or apolipoprotein E (Apoe) deficient mice were infused with either AngII or AngA (1 μg/kg/min) for 4 weeks. While AngII infusion induced AAA consistently in …

Experimental Evidence Supportive Of The Quantum Dna Model, F. Matthew Mihelic

Faculty Publications

The DNA molecule can be modeled as a quantum logic processor in which electron spin qubits are held coherently in each nucleotide in a logically and thermodynamically reversible enantiomeric symmetry, and can be coherently conducted along the pi-stacking interactions of aromatic nucleotide bases, while simultaneously being spin-filtered via the helicity of the DNA molecule. Entangled electron pairs can be separated by that spin-filtering, held coherently at biological temperatures in the topologically insulated nucleotide quantum gates, and incorporated into separate DNA strands during DNA replication. Two separate DNA strands that share quantum entangled electrons can be mitotically divided into individual cells, …

When Life Gives You Lemons: Comparing Two Diffusion Methods For A Psychological Screening Tool In The Medical Field, Jessica Tran

Honors Theses

E.M. Rogers’ Diffusion of Innovation Theory is used to explain the process of how an idea or technology gains momentum and spreads through a particular population. The result of the diffusion is called adoption, meaning that over time the group has changed their initial behavior (i.e. using the new technology, purchasing and performing new behavior, etc.). There is considerable evidence for successful use of this theory in various fields. The study investigates the theory using a new psychological screening technology. A solicitation to hear information about the tool was presented to 19 physicians who were separated into two randomized groups, …

Anti-Crispr Vs. Crispr: The Evolutionary Arms Race Between Microorganisms, Rachael M. St. Jacques

Masters Theses, 2010-2019

CRISPR arrays are a defense mechanism employed by bacteria against viral invaders. Cas proteins do the work in detecting, capturing, and integrating the viral DNA into the CRISPR array (Barrangou et al., 2007). Anti-CRISPR proteins are produced by phages, viruses that infect bacteria, to stop the bacterial host’s CRISPR-Cas complex from interrupting the phage life cycle (Bondy-Denomy, et al., 2015).

SEA-PHAGES is a course-based bacteriophage research network composed of 120 colleges and known at James Madison University as Viral Discovery. JMU uses the unsequenced Streptomyces griseus ATCC10137 as a host for bacteriophage discovery and propagation, and in this study we …

Assessing The Contribution Of Multiple Ascorbate Pathways To Abiotic Stress Tolerance Using Phenomic Approaches, Lucia Margarita Acosta Gamboa

Student Theses and Dissertations

L-Ascorbic acid (AsA, vitamin C) is an essential molecule that humans cannot synthesize; therefore, it must be acquired through dietary sources. Vitamin C has an important role in protecting organelles and cells against the damage caused by reactive oxygen species (ROS). In plants, AsA is synthesized by a complex metabolic network. Although progress has been made in the characterization of genes involved in some of these pathways, there is a gap in understanding which pathway(s) is/are activated in response to different stresses. The long term goal of this project is to assess the contribution of multiple ascorbate pathways to abiotic …

Biotransformation Of Natural Antioxidants Osajin And Pomiferin By Cunninghamella Elegans (Atcc® 9245tm), Stephen Luis

Theses & Dissertations

Osajin and pomiferin, prenylated isoflavones extracted from the fruit of the osage orange tree (Maclura pomifera) have been reported as antioxidant compounds. The purpose of this study is to analyze the metabolization of osajin and pomiferin by the fungi Cunninghamella elegans (ATCC 9245) and supporting strains Umbelopsis ramanniana and Aspergillus fumigatus fresnius.

HPLC analysis of the extracts showed new, more polar compounds were formed, evidenced by peaks at lower retention times for each strain of fungi. To further investigate the metabolites produced, HPLC-guided chromatographic purification will be performed, and the pure metabolites will be analyzed through nuclear magnetic resonance and …

Disruption Of Valosin-Containing Protein Activity Causes Cardiomyopathy And Reveals Pleiotropic Functions In Cardiac Homeostasis, Matthew J. Brody, Davy Vanhoutte, Chinmay V. Bakshi, Ruijie Liu, Robert N. Correll, Michelle A. Sargent, Jeffery D. Molkentin

Peer Reviewed Articles

Valosin-containing protein (VCP), also known as p97, is an ATPase with diverse cellular functions, although the most highly characterized is targeting of misfolded or aggregated proteins to degradation pathways, including the endoplasmic reticulum–associated degradation (ERAD) pathway. However, how VCP functions in the heart has not been carefully examined despite the fact that human mutations in VCP cause Paget disease of bone and frontotemporal dementia, an autosomal dominant multisystem proteinopathy that includes disease in the heart, skeletal muscle, brain, and bone. Here we generated heart-specific transgenic mice overexpressing WT VCP or a VCP^K524A mutant with deficient ATPase activity. Transgenic mice …

A Dedicated Chaperone Mediates The Safe Transfer Of Mitoribosomal Proteins To Their Site Of Assembly, Gabrielle Ashley Hillman

Graduate School of Biomedical Sciences Theses and Dissertations

Mitochondrial ribosomes are functionally specialized for the synthesis of several essential inner membrane proteins of the respiratory chain. While remarkable progress has recently been made towards understanding the structure of mitoribosomes, the unique pathways and factors that facilitate their biogenesis remain largely unknown. This dissertation defines the physiological role of an evolutionarily conserved yeast protein called Mam33 in mitochondrial ribosome assembly. The biomedical relevance of this finding stems from the fact that mutations or changes in its expression of the human ortholog p32 result in mitochondrial dysfunction. In human patients, bi-allelic mutations cause severe multisystemic defects in mitochondrial energy metabolism, …

Bamorc: A Software Package For Accurate And Robust 13C Reference Correction Of Protein Nmr Spectra, Xi Chen, Andrey Smelter, Hunter N. B. Moseley

Molecular and Cellular Biochemistry Faculty Publications

We describe Bayesian Model Optimized Reference Correction (BaMORC), a software package that performs ¹³C chemical shifts reference correction for either assigned or unassigned peak lists derived from protein NMR spectra. BaMORC provides an intuitive command line interface that allows non-nuclear magnetic resonance (NMR) experts to detect and correct ¹³C chemical shift referencing errors of unassigned peak lists at the very beginning of NMR data analysis, further lowering the bar of expertise required for effective protein NMR analysis. Furthermore, BaMORC provides an application programming interface for integration into sophisticated protein NMR data analysis pipelines, both before and after the …

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

Determining Therapeutic Efficacy Of Low-Frequency Ultrasound In Targeting In-Vitro Human Attached Cell Lines With Adjuvant Chemotherapy, Charles Schauer

Renée Crown University Honors Thesis Projects - All

Research in the Fondy laboratory at Syracuse University has shown that in free-moving cancer cell lines, such as leukemia and lymphoma, larger cells are preferentially targeted by ultrasound therapy and have reduced viability as a result. Little time with respect to ultrasound, however, has been dedicated to the study of cell lines such as colorectal carcinoma and glioblastoma, which require connective tissue to grow.

Our research involves the low-frequency ultrasound treatment of attached carcinoma cell lines with adjuvant chemotherapy to evaluate an effective regimen for reducing viability of cancer cells. Prior research with human glioblastoma has shown that cells attached …

The Effects Of Eicosapentaenoic Acid (Epa) And Docosahexaenoic Acid (Dha) On Brown Adipogenesis In Stem Cell Culture, Darynne Dahlem

Animal Science Undergraduate Honors Theses

Polyunsaturated fatty acids (PUFAs), especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are major maternal dietary supplements due to their positive benefits on neurological tissue growth during the first 12 weeks of gestation. Previous studies show that EPA and DHA inhibit muscle formation but promote adipogenesis. However, no research has addressed the question whether high intake of EPA and DHA affects brown fat development during gestation. The objective of this study was to measure the effect of EPA and DHA supplement on brown adipogenesis and potential pathways related to mitochondrial biosynthesis using fibroblasts as in vitro model. Using Oil-Red-O staining …

Relationships Of Protein Biomarkers Of The Urokinase Plasminogen Activator System With Expression Of Their Cognate Genes In Primary Breast Carcinomas., Seth B. Sereff

College of Arts & Sciences Senior Theses

Background: Urokinase plasminogen activator (uPA), its receptor uPAR and serine protease inhibitors PAI-1 or PAI-2 play key roles in tissue membrane remodeling and invasion of basement membranes by induction of a fibrinolytic pathway. Earlier studies reported that uPA and PAI-1 protein levels in breast carcinomas assist in prediction of response to chemotherapy. Our goal is to develop molecular signatures of candidate genes and identify novel relationships with these four protein biomarkers that demonstrate clinical utility for assessment of breast carcinoma outcomes.

Methods: This retrospective study used de-identified biomarker results and clinical outcomes from primary breast cancers that were stored in …

Dom Control Of Mercury Methylation In The Water Column Of A Meromictic Lake, Madalyn Bozinski

Renée Crown University Honors Thesis Projects - All

The trophic transfer and bioaccumulation of methyl mercury (MeHg) in aquatic ecosystems is a substantial concern, resulting in fish consumption advisories worldwide. Aquatic ecosystems have been identified as the critical environments that breed production of MeHg and low levels of initial accumulation in biota. MeHg production is a microbially-mediated process, occurring primarily at the transition between oxic and anoxic environments. This research aimed to assess the extent to which dissolved organic matter (DOM) affects methylation of mercury in the oligotrophic meromictic lake, Green Lake, in Fayetteville, NY and the warm monomictic lake, Seneca Lake, in Geneva, NY. General physical parameters …

An Exploration Of Ruthenium Catalyzed Alder-Ene Reactions, Emily Bonner

Renée Crown University Honors Thesis Projects - All

This project focuses on expanding the reaction scope of the ruthenium (Ru) catalyzed Alder-ene reaction with both exocyclic enol ethers and simple alkenes. Knowledge gained from these reactions may be applied to the development of efficient methods for the synthesis of both oxygen heterocycles and acyclic compounds that incorporate a 1,4-diene unit. Each of the two double bonds in the diene possesses different reactivity which increases the utility of these products as synthetic intermediates by allowing for greater versatility in synthesizing natural product targets. A breadth of alkyne and alkene couplings were attempted in this project via the Ru catalyzed …

Reactive Glutamines And A Binding Site Region Contribute To Fxiii Substrate Specificity For Fibrinogen Αc, Mohammed Hindi

College of Arts & Sciences Senior Theses

The reaction between transglutaminase factor XIII (FXIII) and fibrin is a key process in the final stages of blood coagulation. The αC region of fibrin contains three reactive glutamines (Q237, Q328, and Q366) which are crosslinked by FXIII, as well as a FXIII anchoring site (E396). Previous work has helped elucidate the FXIII-αC interaction, but much is still unknown about the key residues in the αC region.

Four crosslinking assays were carried out to characterize the contribution of the αC anchoring site and reactive glutamines in crosslinking by FXIII. The effects of individual E396A, Q366N, and Q328P (Fibrinogen Seoul II …

Autofluorescence To Study The Effects Of Acid Concentration On Cellular Metabolism In Vitro, Robin L. Raley

Chemistry & Biochemistry Undergraduate Honors Theses

Ultraviolet (UV) radiation-induced sunburns and their accompanying afflictions are a growing public health concern in the United States. There is a need for techniques that can accurately and non-invasively characterize the physiology of sunburned skin tissue directly after UV-damage and applying a topical skin treatment to relieve pain and promote healing. Two-photon excited fluorescence (TPEF) microscopy and fluorescence lifetime imaging (FLIM) can be used to investigate metabolic processes in live cells through endogenous fluorescence of the cofactors, NADH and FAD. These methods employ the optical redox ratio of FAD/(NADH+FAD), mean NADH lifetime, and the separation of the free and bound …

Protein Engineering For Biomedical Applications, Claudia Heritage

Renée Crown University Honors Thesis Projects - All

The Korendovych lab recently demonstrated for the first time that short peptides can selfassemble in the presence of metal ions to produce efficient catalysts in a variety of chemical reactions ranging from ester hydrolysis to oxygen activation. Original catalysts were produced by solid phase peptide synthesis. Solid phase synthesis can become the limiting factor for an experiment because it takes over two days to make and purify one peptide. Depending on characteristics of a peptide, the purification process can become a challenge involving a tedious process of protocol optimization. Screening of several peptides is time-consuming as it involves analysis of …

The Synthesis, Purification, And Characterization Of The P3 Peptoid, Myles Joyce

Chemical Engineering Undergraduate Honors Theses

The relatively young field of nano-systems has vast applications over various different fields. Peptoids (peptide analogues) and their uses are consistently investigated components of these nano-studies. A particularly interesting group of peptoids are able to self-assemble into secondary structures under the right conditions. The P3 peptoid is able to form microspheres if properly synthesized and purified. Microspheres are frequently studied due to their low surface area to volume ratios. This unique aspect of microspheres makes them an excellent candidate for drug delivery systems; however, these systems must also be robust so that the desired compound can be encapsulated within the …

The Chelation Of Metal Ions By Vicibactin, A Siderophore Produced By Rhizobium Leguminosarum Atcc 14479, Joshua Stinnett

Undergraduate Honors Theses

Vicibactin is a small, high-affinity iron chelator produced by Rhizobium leguminosarum ATCC 14479. Previous work has shown that vicibactin is produced and secreted from the cell to sequester ferric iron from the environment during iron-deplete conditions. This ferric iron is then transported into the cell to be converted into ferrous iron. This study uses UV-Vis spectroscopy as well as ion trap-time of flight mass spectroscopy to determine that vicibactin does form a complex with copper(II) ions, however, at a much lower affinity than for iron(III). Stability tests have shown that the copper(II)-vicibactin complex is stable over time. The results of …

Transformation Of Model Organisms With Munc13-1 For Subcloning And Protein Harvesting, Grace Dittmar

Honors Theses

Exocytosis is the process by which cells release various molecules into the extracellular space. This mechanism is accomplished by membrane fusion, in which the membrane of the transport vesicle and that of the cell itself fuse to create one continuous membrane, allowing the release of the molecules inside the vesicle. A family of proteins, known as SNARE proteins, is responsible for facilitating membrane fusion. SNARE proteins form a complex between the vesicle membrane and the plasma membrane. For various cells, such as mast cells and neurons, exocytosis is essential to carry out their vital functions. Various accessory proteins are known …