Digital Commons Network^™

Mitochondrial Division: Synergizing In Mitochondrial Divisome, Ao Liu

Dartmouth College Ph.D Dissertations

Mitochondria are the energy factories of the cell. The dynamic nature of cells demands routine changes in mitochondrial morphology by fusion and division. The dynamin GTPase Drp1 is a central mitochondrial division protein, driving constriction of the outer mitochondrial membrane via oligomerization. At least four regulatory factors control Drp1 activity on the outer mitochondrial membrane (OMM): 1) receptor proteins (Mff, MiD49, MiD51, and Fis1); 2) actin filaments; 3) the mitochondrial phospholipid cardiolipin (CL); and 4) Drp1 post-translational modifications, of which two phosphorylation sites (S579 and S600) are the most well studied. However, the molecular mechanism of how these factors work …

Identification Of A Dna Polymerase Alpha Gene Sequence In Thermomyces Lanuginosus Fungus, Nathan Williams

Honors Program Theses

With cell growth being the main focus of our research, we chose to study DNA polymerase alpha. DNA polymerase alpha is likely to be involved in cell growth as it is the enzyme that starts DNA replication. Control of this enzyme might lead to decreased cell growth in cancer or increased cell growth in damaged spinal cord tissue. We chose the thermophilic fungus Thermomyces lanuginosus for the study of the enzyme due to the ability to compare the enzyme’s activity during fungal growth at different temperatures. Thermomyces exhibits rapid growth at high temperatures and slow growth at low temperatures. Studying …

Recent Insights On The Conformational Changes, Functionality, And Physiological Properties Of Plant-Based Protein–Polyphenol Conjugates, Mehnaza Manzoor, Zaria Fozonne Ngabou Tchameni, Zuhaib F. Bhat, Amit K. Jaiswal, Sundeep Jaglan

Articles

Plant proteins are promising sources of nutrition with enhanced health benefits due to their interaction with bioactive compounds like polyphenols. These interactions can form protein–polyphenol complexes with diverse properties and applications in the food, nutraceutical, and pharmaceutical industries. To exploit the potential of these conjugates, it is essential to understand how they are formed, characterized, and delivered. Various techniques such as spectroscopy, thermodynamics, and molecular docking simulations can reveal the mechanism and outcomes of protein–polyphenol binding. Moreover, the surface modification of protein–polyphenol conjugation can enhance the pharmacological effects of different drug molecules and enable their targeted delivery to specific tissues …

Biogeography Of Special Metabolites Produced By Ant-Associated Bacteria, Katherine Hansen

Scripps Senior Theses

There is an urgent and growing need for novel antibiotics with the growing prevalence of antibiotic-resistant pathogens. Ecologically-guided discovery is a strategy that focuses on how and where specially evolved metabolites such as antibiotics are used in nature. This strategy reveals unique active molecules with potential for human use. An unexplored niche with great potential for antibiotic discovery exists with Southwestern fungus-farming Trachymyrmex ants and their Actinobacteria symbionts. In exchange for nutrients from the ant, the ants’ bacterial symbiont produces antifungal molecules that protect the ants’ fungal cultivar from invasion by pathogenic microorganisms. They also produce antibacterial molecules to protect …

Determination Of The Effects Of Added Methionine On The Toxicity Of Platinum Drugs In Saccharomyces Cerevisiae, Kassidy Owens, Jonathan White

Longwood Senior Thesis Proposal

Platinum (Pt) drugs are used in about half of all anticancer treatments. A common way to study Pt drugs is by using S. cerevisiae (brewer’s yeast) as a model cellular organism. One of the most commonly-used strains of yeast is BY4741, which is auxotrophic for (cannot synthesize) several small-molecule nutrients, including the amino acid methionine. Therefore, methionine must be supplemented in the cell culture medium. Interestingly, it is known that methionine can react with Pt compounds, including Pt drugs. Methionine-supplemented media continues to be used to study Pt drugs in yeast, especially BY4741, yet the potential for methionine to interfere …

Investigating Visinin-Like Protein 1 And Ubiquitinated Visinin-Like Protein 1 As Mild Traumatic Brain Injury Biomarkers, Yueming Wu

Theses and Dissertations--Chemistry

Traumatic brain injury (TBI) continues to be a significant cause of morbidity and mortality worldwide. Despite significant progress in understanding the complex pathophysiology of TBI, the underlying mechanisms remain poorly understood. The primary brain damage is acute and irreversible. However, secondary brain injuries often develop gradually over months to years, creating an opportunity for critical therapeutic interventions. In the past decade, research on TBI biomarkers has seen significant progress. This progress has been driven by the diverse nature of TBI pathologies and the challenges they present for evaluation, management, and prognosis. TBI biomarker proteins resulting from axonal, neuronal, or glial …

College Of Natural Sciences 2022 Year-End Publication, College Of Natural Sciences

College of Natural Sciences Newsletters and Reports

This is the 2022 issue of the annual College of Natural Sciences year-end publication.

Contents:
[Page] 2 Dean's message
[Page] 3 Department highlights
[Page] 4 Overview of Bold & Blue Campaign
[Page] 5 Dr. Edward Hogan recognition & endowment
[Page] 6 Career milestones
[Page] 7 Student travel and research
[Page] 8 $11 million COBRE grant
[Page] 9 Professional Science Masters & Research highlights
[Page]10 Outreach highlights throughout the state
[Page] 11 2022 events recap – join us in 2023!
[Page] 12 Updates on our VR initiative
[Page] 14 Overview of awards and recognitions from 2022

The Effects Of Age On Working Memory Capacity And Neural Function, Jasmin P. Joshi

CMC Senior Theses

Do age-related differences in working memory capacities predict specific neural responses? Theories of working memory (WM) suggest that there are different types of WM processes that are associated with specific neural networks and WM declines with age. Event-related potentials (ERPs) evoked by certain tasks are also associated with specific cognitive functions. This study investigates whether specific types of working memory capacities are related to corresponding neural indices of attention and context updating (P3; visual oddball task) or semantic (N400; word-pair paradigm task) processes. In addition, it examines whether age affects this relationship. Younger adults (n=30; ages 18-23) and older adults …

Identification And Functional Characterization Of Mads-Box Proteins And Ccos Involved In Carotenoid Metabolism In Durian Durio Zibethinus L. Pulps, Kittiya Tantisuwanichkul

Chulalongkorn University Theses and Dissertations (Chula ETD)

Durian (Durio zibethinus L.), known as the "King of fruits," holds significant economic importance in Thailand. Apart from its unique odor and sweet taste, durian pulp exhibits a yellow color, which is an important aspect of fruit quality. Carotenoids are essential compounds responsible for the yellow, orange, and red coloration in many fruits and vegetables. During durian fruit development and ripening processes, its pulp changes from white to yellow due to increased carotenoid accumulation. The carotenoid biosynthetic pathway, responsible for carotenoid production, is controlled by ethylene. However, the mechanism underlying this process in durian fruit is still unknow. Notably, the …

Producing Grnas For Use In Crispr-Cas9 Dna Editing Applications Via In Vivo T7 Rna Polymerase Transcription In Escherichia Coli., Christian A. Santiago

Honors Program Theses

The development of the CRISPR-Cas9 system is widely considered to be a breakthrough advancement in gene editing. Compared to traditional technologies, CRISPR is generally regarded as the most accessible, effective, and precise tool for inducing stable and inheritable gene edits in vivo. The CRISPR-Cas9 gene editing complex relies on the complementary binding of guide RNAs to specifically target a DNA sequence for endonuclease cleavage and mutagenesis. The production of gRNAs for use in CRISPR applications can become exceedingly complex and costly, as in vivo methodologies generally require the use of RNA polymerases that interfere with gRNA sequence identity and in …

Creating Meaningful Connections With The Electr Eating Meaningful Connections With The Electron Transport Chain Beyond A Virtual Classroom, Lesley Ann Giddings

Chemistry: Faculty Publications

At the center of feminist pedagogy is community. Creating community within the classroom and between the class and local communities increases student engagement and access to knowledge. Communities can be a source of solidarity and further decenter authority in the classroom, empowering students, teachers, and the surrounding community to be co-learners. Amid the COVID-19 pandemic, remote teaching posed challenges to student engagement. Here, I describe an assignment used to build an inclusive community of co-learners within a virtual biochemistry class and our local communities. Oxidative phosphorylation is a cellular process used to create energy that depends on the electron transport …

Detection Of Sars-Cov-2 Neutralizing Antibodies In Retropharyngeal Lymph Node Exudates Of White-Tailed Deer (Odocoileus Virginianus) From Nebraska, Usa, Korakrit Poonsuk, Duan S. Loy, Rachael Birn, Bryan Buss, Matthew Donahue, Todd Nordeen, Kylie Sinclair, Luke Meduna, Bruce Brodersen, John Dustin Loy

School of Veterinary and Biomedical Sciences: Faculty Publications

Disease surveillance testing for emerging zoonotic pathogens in wildlife is a key component in understanding the epidemiology of these agents and potential risk to human populations. Recent emergence of SARS-CoV-2 in humans, and subsequent detection of this virus in wildlife, highlights the need for developing new One Health surveillance strategies. We used lymph node exudate, a sample type that is routinely collected in hunter-harvested white-tailed deer (WTD, Odocoileus virginianus) for surveillance of chronic wasting disease, to assess anti-SARS-CoV-2 neutralizing antibodies. A total of 132 pairs of retropharyngeal lymph nodes collected from Nebraska WTD harvested in Nebraska, US, in 2019 …

Lead Induced Differences In Bone Properties In Osteocalcin +/+ And −/− Female Mice, G. Yildirim, W. C. Budell, O. Berezovska, S. Yagerman, S. S. Maliath, P. Mastrokostas, S. Tommasini, T. L. Dowd

Publications and Research

Lead (Pb) toxicity is a major health problem and bone is the major reservoir. Lead is detrimental to bone, affects bone remodelingand is associated with elderly fractures. Osteocalcin (OC) affects bone remodeling, improves fracture resistance and decreases with age and in some diseases. The effect of lead in osteocalcin depleted bone is unknown and of interest. We compared bone mineral properties of control and Pb exposed (from 2 to 6 months) femora from female adult C57BL6 OC+/+ and OC−/− mice using Fourier Transform Infrared Imaging (FTIRI), Micro-computed tomography (uCT), bone biomechanical measurements and serum turnover markers (P1NP, CTX). Lead significantly …

Characterizing Cellular Injury And Inflammation With Aldob-/-Mouse Model Of Mafld, Andy Rashid

All Master's Theses

Metabolic-associated fatty liver disease (MAFLD) affects 1 in 3 people in the US and is a healthcare burden on the order of billions of dollars. MAFLD is characterized by pathological lipid accumulation in the liver, excess production of triglycerides and cholesterol, and export of LDL particles that raise serum lipid levels. These metabolic perturbations can lead to the development of liver fibrosis, chronic inflammation, and insulin resistance. Diagnosing MAFLD prior to fibrosis is crucial for successful intervention and prevention of advanced liver disease and other metabolic complications. Fructose-1Phospahte (F1P) accumulation from fructose overconsumption can drive hepatic lipogenesis and MAFLD progression. …

Room-Temperature Crystallography Reveals Altered Binding Of Small-Molecule Fragments To Ptp1b, Tamar Skaist Mehlman, Justin T. Biel, Syeda Maryam Azeem, Elliot R. Nelson, Sakib Hossain, Louise Dunnett, Neil G. Paterson, Alice Douangamath, Romain Talon, Danny Axford, Helen Orins, Frank Von Delft, Daniel A. Keedy

Advanced Science Research Center

Much of our current understanding of how small-molecule ligands interact with proteins stems from X-ray crystal structures determined at cryogenic (cryo) temperature. For proteins alone, room-temperature (RT) crystallography can reveal previously hidden, biologically relevant alternate conformations. However, less is understood about how RT crystallography may impact the conformational landscapes of protein-ligand complexes. Previously, we showed that small-molecule fragments cluster in putative allosteric sites using a cryo crystallographic screen of the therapeutic target PTP1B (Keedy et al., 2018). Here, we have performed two RT crystallographic screens of PTP1B using many of the same fragments, representing the largest RT crystallographic screens of …

Diversification Of Ergot Alkaloid Biosynthesis In Natural And Engineered Fungi, Kyle Austin Davis

Graduate Theses, Dissertations, and Problem Reports (ETD)

Ergot alkaloids are a complex family of tryptophan-derived mycotoxins produced by a diverse range of fungi that occupy a wide variety of ecological niches including soil saprotrophs, plant endophytes, pathogens of plants or insects, and opportunistic pathogens of humans and other mammals. Ergot alkaloids are a similarly diverse family of chemicals that elicit a variety of pharmacological activities in animals due to their resemblance to neurotransmitters and high binding affinity for neurological receptors, including those that bind adrenaline, dopamine, and 5-hydroxytryptamine receptors. These structural similarities allow us to create medicines aimed at treating a range of neurological diseases and disorders …

Lipid Binding Properties Of Huntingtin As A Novel Therapeutic Target, Chathuranga Siriwardhana

Graduate Theses, Dissertations, and Problem Reports (ETD)

As protein aggregation is the defining hallmark of all amyloid diseases, a common therapeutic strategy is to develop molecules that inhibit aggregation. However, this approach has yielded limited success. Many amyloid proteins directly interact with lipid membranes. These interactions promote distinct aggregation pathways and often result in membrane damage leading to toxicity. As a result, directly targeting the ability of amyloids to bind lipid membranes represents a novel therapeutic strategy. As a proof of principle, the interaction between lipid membranes and mutant huntingtin protein (htt) aggregates was used to test this strategy. Mutant htt containing an expanded polygulatmine (polyQ) domain …

Under Ice Photosynthetic Primary Production And Dark Carbon Fixation In A Temperate Freshwater System, Vanessa Cubillos Tellez

Dissertations, Master's Theses and Master's Reports

Ice-covered lakes are vulnerable to environmental change, especially those in the Northern Hemisphere where ice cover is rapidly declining due to global warming. These changes can alter metabolic processes and disrupt carbon cycling driven by primary producers who form the base of the food chain and are key to sustaining ecosystem function. Photosynthetic primary production and dark carbon fixation under the ice in the Keweenaw Waterway, a temperate freshwater system that is ice-covered for ~3 months out of the year, were studied using a carbon isotopic labeling (14C-bicarbonate) technique. Water samples were collected weekly during ice cover and monthly during …

Generation Of Chimeric Rhinoviruses Presenting Sars-Cov-2 Broadly Neutralizing Epitopes And Their Antigenicity Characterization, Danish Ansari

Biotechnology Theses

The global COVID pandemic is not yet fully under control as there were over 21 million new cases of SARS-CoV-2 infections and over 50,000 deaths globally as of January of 2022. A heavily mutated variant of concern, Omicron is responsible for most of these cases which demands an urgency for a new vaccine. NIH reports over 180 vaccine candidates that use various strategies currently in development. However, a recurring concern with these vaccines is that the continuous viral mutations decrease the efficacy of vaccines. Therefore, we proposed to construct a human rhinovirus (HRV) based chimeric virus containing highly conserved, broadly …

Development Of Novel Cellular Assay Model And Therapeutic Deep Eutectic Solvents To Optimize The Activity Of Anticancer Agents, Nizam Uddin

Electronic Theses and Dissertations

Multidrug resistance (MDR) is the major burden behind chemotherapeutic treatment failure. It is the principal mechanism by which cancer cells evade chemotherapeutic treatment. As a result, aggressive cancer cells survive and continue uncontrolled cell division. Multidrug resistance affects survival rate of almost all types of cancer patients and death toll rises at an alarming rate. There are seven different mechanisms for evolving MDR. The most common mechanism in efflux activity of overexpressed ABC transporters. MRP1 is a prominent ABC transporter that pumps out a wide variety of anticancer drugs from the cells and thereby reduces intracellular drug concentrations and develops …

Reconstructing The Germination Pathway From The Rafflesia Seed Transcriptome, Venkata Siva Sankar Maddu

Selected Full-Text Master Theses 2021-

Rafflesia (Rafflesiaceae) produces the largest flowers in the world but has no stems, roots, or leaves. It is a holoparasitic angiosperm that derives all its nutrients from its host vine, Tetrastigma. All species are also threatened with extinction, but propagating it has been incredibly challenging. Its germination from seed has never been observed. The thesis aims to reconstruct the germination pathway of Rafflesia from its published seed transcriptome to gain insight into its molecular genetics and understand what germination genes can be stimulated to facilitate infection of its host for ex-situ propagation. The published seed transcriptome of Rafflesia speciosa was …

Vinyl Chloride Accident Unleashes A Toxic Legacy, Chengjun Li, Peng Gao, Riqing Yu, Huan Zhong, Mengjie Wu, Su Shiung Lam, Christian Sonne

Biology Faculty Publications and Presentations

A railroad accident on February 3, 2023, led to the release and combustion of 115,580 gallons, equivalent to over 437,000 L, of vinyl chloride monomer (VCM) in East Palestine, Ohio [1]. This monomer is used in polyvinyl chloride (PVC) production, and its burning produces additional toxins such as hydrochloric acid and lethal phosgene, known as a notorious chemical weapon during World War I

Of Transcription Factor And Transformation: Elucidating Gene Function In The Common Ice Plant, Mesembryanthemum Crystallinum, Chinenye Lilian Izuegbunam

Dissertations and Theses

Abiotic stresses negatively affect plant growth and development across the globe, which also affect the production of food, feed, biofuel, and fiber to meet the demands of a growing population. Thus, developing novel strategies to increase abiotic stress tolerance in crops is necessary. One of these strategies is exploring transcription factors (TFs) in Crassulacean Acid Metabolism (CAM) plants to improve plant abiotic stress tolerances. Therefore, the first objective of this dissertation determine the abiotic stress tolerance function of a CAM TF, McHB7opt in Arabidopsis. This study found that McHB7opt increased stress-responsive pathways related to seed germination and early seedling development. …

Csi Botany: Dna Barcode “Fingerprints” Identify Cryptic Urban Flora, Luis R. Vega

Theses and Dissertations

As short genomic markers, DNA barcodes can play a role in conservation by identifying cryptic species and hybrids when morphological approaches fall short. Here we present our application of barcodes to the identities of two wetland taxa as part of an ongoing floristic inventory of Van Cortlandt Park (VCP), Bronx, NY. Previous barcode data by Marriott et al. (2018) identified the VCP lake water lily as the exotic Nymphaea alba, rather than the native N. odorata as historically described. In addition, cattails in the park were historically identified as the native Typha latifolia and the exotic T. angustifolia …

Nitrogen Isotopes In Deep Sea Corals; A Potential Tracer Of Paleoceanographic Conditions, Sylvia Bergerud

Scripps Senior Theses

Abstract

In the face of anthropogenic climate change, increasing pressure is being mounted on contextualizing current climate altercations compared to those of the past. One key tracer of climate variation is the isotopic ratio of 15N compared to 14N, which tracks biological and chemical reactions throughout the N cycle. However, it is difficult to find accurate palaeoceanographic records of N isotope fractionation, as most sedimentary and organic samples are subject to extensive diagenesis, degradation, and erosive processes. Scleractinian corals present a potential solution to this lack of accurate data. Multiple studies indicate that, due to their protective aragonite skeletons and …

Comparison Of Bone Robustness Between Fore- And Hindlimb In Neonatal And Infant Galago, Jeremy Busken

Williams Honors College, Honors Research Projects

According to Wolff’s law, bone is constantly subject to change based on loading patterns (Ruff et al., 2006). Those subjected to greater stress become more robust by increasing bone mineral density and often changing geometric properties. Previous studies of primate anatomy have found significant differences in bone robustness between the fore- and hindlimbs in adult leaping primates. Because leaping primates, such as Galago senegalensis and Galago moholi, subject their hindlimbs to much greater stress, this difference in robustness may come as a result of bone functional adaptation/Wolff’s law. This study sought to investigate this possibility by testing neonatal and infant …

Mammalian Dihydropyrimidine Dehydrogenase: Employing Transient State Kinetic Methods To Determine Catalytic And Inhibitory Mechanisms, Dariush Forouzesh

Dissertations

Dihydropyrimidine dehydrogenase (DPD) catalyzes the two-electron reduction of pyrimidine bases uracil and thymine as the first step in pyrimidine catabolism. The enzyme achieves this simple chemistry using a complex cofactor set including two flavins and four Fe4S4 centers. The flavins, FAD and FMN, interact with respective NADPH and pyrimidine substrates and the iron-sulfur centers form an electron transfer wire that links the two active sites that are separated by 56 Å. DPD accepts the common antineoplastic agent 5-fluorouracil (5FU) as a substrate and so undermines the establishment of efficacious toxicity. Though studied for multiple decades, a precise description of the …

The Affect Of Dha Concentration On Lipid Membrane Fluidity, Elise Rezabeck

Williams Honors College, Honors Research Projects

My proposed project will be creating large unilaminar vesicles with varying concentrations of DHA in the vesicles. The diffusion in and out of these vesicles will be tracked by using singular lipid molecules. These singular lipid molecules will be tagged with fluorescence and viewed using an internal reflection fluorescence microscope. The data collected over the course of this project will then be analyzed using Matlab. The result of the project will be to find the specific lipid diffusion constant of these unilaminar vesicles. The relationship between the concentration of DHA and lipid diffusion and membrane fluidity will be found as …

Dual Mechanisms Contributing To Pyruvate Dehydrogenase Activity Deficiency In A Barth Syndrome Cell Model, Zhuqing Liang

Wayne State University Dissertations

Barth syndrome (BTHS) is a rare genetic disease that results from mutations in the TAFAZZIN gene, which encodes the cardiolipin (CL) remodeling enzyme tafazzin (Taz). The mechanisms linking perturbation of CL remodeling and the pathological features of BTHS are not understood. We have recently reported that intermediary metabolism is perturbed in BTHS, and activity of the metabolic gatekeeper enzyme pyruvate dehydrogenase (PDH) is deficient in BTHS models. The mechanism whereby PDH is regulated by Taz is unknown, and this knowledge gap represents an obstacle to the development of therapeutics to treat BTHS. Using an established C2C12 myoblast model of BTHS, …

Biological Adaptations Leading To Metastatic Potential In Ovarian Cancer, Hussein Chehade

Wayne State University Dissertations

Ovarian cancer induces most deaths from gynecological cancers. Patients succumb due to heavy metastatic tumor burden, which accounts for 90% of cancer related deaths and is characterized by the dissemination of malignant cells from primary tumor to secondary site(s), partaking in cancer progression. Ovarian cancer progression is an extremely demanding process that requires cancer cells to be able to survive anoikis conditions and be metabolically flexible to survive microenvironmental changes during transit to a secondary site. Mitochondrial Nuclear Retrograde Regulator 1 (MNRR1) is a bi-organellar protein primarily present in the mitochondria by which it can prevent apoptosis and/or enhance mitochondrial …