Biochemistry, Biophysics, and Structural Biology Commons^™

Investigating The Roles Of Dapk, P53/Cep-1, And Mitochondrial Damage In Necrotic Neurodegeneration In C. Elegans, Anil Singh

Dissertations and Theses

Stroke is one of the leading causes of death in the U.S., with minority groups, suffering higher fatality rates. Stroke is caused by ischemia, where occlusion of blood supply to the brain results in neurodegeneration. Most of the damage is attributed to excitotoxicity, where an accumulation of the neurotransmitter glutamate in the synapse overstimulates postsynaptic neurons and ultimately leads to cell death (largely by necrosis). Stroke treatments are often ineffective, due to the delay between the onset of stroke and the delivery of effective treatment. To address this, we focus our study on putative later-acting mediators of excitotoxicity such as …

Climate Change And Coastal Development Impacts On Oyster Abundances In Mosquito Lagoon, Fl, Emily Suchonic

Graduate Thesis and Dissertation 2023-2024

Live eastern oyster (Crassostrea virginica) reefs have declined by 62.6% in Mosquito Lagoon (ML) along the eastern Florida coast since 1943. While this species creates reefs by successive generations of oysters recruiting to conspecific shells, C. virginica can also attach to non-reef substrates including mangrove roots and armoring (e.g., seawalls), which may help counteract reef habitat loss. In recent decades, warmer winters have enabled red (Rhizophora mangle) and black (Avicennia germinans) mangrove expansion in subtropical salt marshes and temperate estuaries where oyster reefs occur. Additionally, 11.8% of ML's shorelines have been armored as of …

Uracil Landscape Of Mouse B Cell Genome Undergoing Class-Switch Recombination, Fathima Rukshana Mohamad Ramshan

Wayne State University Dissertations

Activation-induced cytosine deaminase (AID) is required for both somatic hypermutation (SHM) and class switch recombination (CSR) within mammalian antibody genes. Uracils created by AID in the Ig loci are recognized and processed by base-excision and mismatch repair pathways leading to antibody diversification. This involves a hypermutation process restricted to the V(D)J segments of the immunoglobulin genes, SHM, and an error-prone end-joining process that causes isotype switching, CSR, but the molecular details of these processes have remained obscure for the past 20+ years. Most studies of SHM and CSR have used AID-promoted mutations as a proxy for the uracils, but their …

A New Model For Polar Growth In Mycobacteria: The Role Of Wag31 And Mmpl3 In Cell Wall Synthesis, Neda Habibi Arejan

Biology Dissertations - Archive

The disease Tuberculosis (TB) is caused by the pathogen Mycobacterium tuberculosis and was the cause of over one million deaths worldwide in 2023 (World Health Organization, 2023). TB treatment is difficult due to antibiotic tolerance and emerging resistance in Mtb strains. Mycobacterial cells have different regulatory mechanisms that allow them to adjust to myriad environmental stressors: these responses often lead to antibiotic tolerance. Therefore, studying responses to stress will lead to insights about antibiotic tolerance and treatment failure. Here, we specifically study two essential mycobacterial proteins, Wag31 and MmpL3, involved in cell wall metabolism. We show that Wag31 has distinct …

Osteohistological Assessment Of Edmontosaurus Radii From The Liscomb Bonebed, Prince Creek Formation, North Slope, Alaska, Emma Griffin

Student Research Poster Presentations 2024

Hadrosaurs were one of the most diverse dinosaur groups in the Late Cretaceous period and are known for their numerous articulated skeletons and monodominant bonebeds (Wosik et al., 2020). They are more commonly known as duck-billed dinosaurs and are found globally including latitudinal extremes such as the artic and Antarctica. Edmontosaurus, a genus of hadrosaur, are herbivores and are very large growing up to 8,000 pounds. Edmontosaurus were known to travel in herds as a defense mechanism and were one of the last non-avian dinosaurs living during the late Campanian stage through the end of the Maastrichtian stage, right up …

Rhizophora Mangle (Red Mangrove) Seedling Success In Different Habitats In Mosquito Lagoon, Florida, Usa, Mekail N. Negash

Graduate Thesis and Dissertation 2023-2024

Mangroves provide many ecosystem services in coastal environments around the world. These include water quality improvement, creating habitats for terrestrial and aquatic species, and stabilizing shorelines. In central Florida, the red mangrove Rhizophora mangle is a common species in coastal wetlands, and recently the number of individuals successfully recruiting to intertidal oyster reefs has greatly increased, possibly because biogeochemical hot spots are present on oyster reefs due to nutrient-rich biodeposits from the live oysters. To understand how well R. mangle responds in terms of survival and growth to the suite of variables associated within these two unique habitats, I tracked …

Synthesis Of Dihydro-Β-Carbolines By Tandem C-H Activation And Aza-Michael Reaction In The Presence Of Rh(Ii)/Squaramide Catalysis: Investigation Of The Mechanism Via Computational Methods, Syed Wasiuddin

Senior Honors Theses and Projects

N-heterocycles are the major component of various bioactive natural products, pharmaceuticals, and their precursors. In particularly, β-carbolines are examples of substituted indole and its derivatives that serve as the basic structures of diverse, therapeutically important molecules with broad pharmacological properties. Rajasekar and Anbarasan have suggested a novel one-pot synthesis for dihydro-β-carbolines involving more than one catalytic system: a rhodium acetate dimer for C-H insertion on the indole and a basic organo-catalyst for the subsequent aza-Michael addition. The product can be obtained enantioselectively by using a chiral squaramide as the organo-catalyst. Since the mechanism of this reaction, including the rate determining …

Feeding Systems And Fresh Lamb Color Stability, Koushik Mondal

Theses and Dissertations--Animal and Food Sciences

Consumers consider the surface color of fresh lamb as the indicator of freshness and wholesomeness, which affects their purchase decisions. The redox chemistry of myoglobin (Mb) determines the color of fresh lamb. Artificial raising on milk replacer (a pre-weaning strategy) as well as red clover supplementation are management strategies used in lamb production. This thesis focuses on the effects of artificial raising on milk replacer and red clover supplementation on the color and oxidative stability of fresh lamb.

In the first experiment, the effect of pre-weaning with milk replacer on the carcass attributes, color stability and lipid oxidation of lamb …

Malate Dehydrogenase In Parasitic Protozoans: Roles In Metabolism And Potential Therapeutic Applications, Amy L. Springer, Swati Agrawal, Eric P. Chang

Biological Sciences Research

The role of malate dehydrogenase (MDH) in the metabolism of various medically significant protozoan parasites is reviewed. MDH is an NADH-dependent oxidoreductase that catalyzes interconversion between oxaloacetate and malate, provides metabolic intermediates for both catabolic and anabolic pathways, and can contribute to NAD+/NADH balance in multiple cellular compartments. MDH is present in nearly all organisms; isoforms of MDH from apicomplexans (Plasmodium falciparum, Toxoplasma gondii, Cryptosporidium spp.), trypanosomatids (Trypanosoma brucei, T. cruzi) and anaerobic protozoans (Trichomonas vaginalis, Giardia duodenalis) are presented here. Many parasitic species have complex life cycles and depend on the environment …

Fxr Agonism With Bile Acid Mimetic Reduces Pre-Clinical Triple-Negative Breast Cancer Burden, Sydney Joseph, Samson Eugin Simon, Margaret S. Bohm, Minjeong Kim, Madeline E. Pye, Boston W. Simmons, Dillon G. Graves, Stacey M. Thomas-Gooch, Ubaid A. Tanveer, Jeremiah R. Holt, Suriyan Ponnusamy, Laura M. Sipe, Et Al.

Biological Sciences Research

Bariatric surgery is associated with improved outcomes for several cancers, including breast cancer (BC), although the mechanisms mediating this protection are unknown. We hypothesized that elevated bile acid pools detected after bariatric surgery may be factors that contribute to improved BC outcomes. Patients with greater expression of the bile acid receptor FXR displayed improved survival in specific aggressive BC subtypes. FXR is a nuclear hormone receptor activated by primary bile acids. Therefore, we posited that activating FXR using an established FDA-approved agonist would induce anticancer effects. Using in vivo and in vitro approaches, we determined the anti-tumor potential of bile …

Why Should Early-Career Scientists Publish In Society Journals, Stephen K. Dolan, Lori D. Banks, Wenqi Yu

Molecular Biosciences Faculty Publications

In this editorial, written by early-career scientists, we advocate for the invaluable role of society journals in our scientific community. By choosing to support these journals as authors, peer reviewers, and as editors, we can reinforce our academic growth and benefit from their re-investment back into the scientific ecosystem. Considering the numerous clear merits of this system for future generations of microbiologists and more broadly, society, we argue that early-career researchers should publish our high-quality research in society journals to shape the future of science and scientific publishing landscape.

The Inaugural Mbio Junior Editorial Board—Lessons Learned And The Path Forward Toward Improving The Peer Review Process, Cynthia Ayefoumi Adinortey, Stephen K. Dolan, Sarah Doore, Rebeccah Lijek, Diana Priscila Pires, Wenqi Yu, Elizabeth B. Draganova, Lennart Schada Von Borzyskowski

Molecular Biosciences Faculty Publications

The inaugural Junior Editorial Board (JEB) of mBio consisted of 64 early-career researchers active from 2022 to 2023. The goal of the JEB was to train early-career researchers in the art of peer review under the guidance of experienced editors. JEB members gained hands-on experience in peer review by participating in modules detailing the publishing process through the lenses of the journal, editor, and reviewer. Ultimately, JEB members applied this new knowledge by reviewing mBio manuscripts. Here, we summarize the background, the mission, and the achievements of the first mBio JEB. We also include possible trajectories for the future editions …

Developing Partnerships For Academic Data Science Consulting And Collaboration Units, Marianne Huebner, Laura Bond, Felesia Stukes, Joel Herndon, David J. Edwards, Gina-Maria Pomann

Biomedical Research Institute Publications and Presentations

Data science consulting and collaboration units (DSUs) are core infrastructure for research at universities. Activities span data management, study design, data analysis, data visualization, predictive modelling, preparing reports, manuscript writing and advising on statistical methods and may include an experiential or teaching component. Partnerships are needed for a thriving DSU as an active part of the larger university network. Guidance for identifying, developing and managing successful partnerships for DSUs can be summarized in six rules: (1) align with institutional strategic plans, (2) cultivate partnerships that fit your mission, (3) ensure sustainability and prepare for growth, (4) define clear expectations in …

Revolutionizing Our Understanding Of Specific Platelet-Pathogen Interactions, Hammodah Rawhi Hammodah Alfar

Theses and Dissertations--Molecular and Cellular Biochemistry

Aside from their classical role in maintaining hemostasis, platelets are considered first-line vascular guardians that influence both the innate and adaptive immune systems. This is mediated by either direct interactions with immune cells or through the release of pre-stored cytokines and chemokines upon interacting with pathogens such as viruses. While this establishes platelets as potential players in the response to pathogens, it remains unclear what platelets can do with pathogens and how important that is to immune responses, especially against viruses. Most systemic viremias, such as HIV-1, present with mild thrombocytopenia, which is mediated through several mechanisms such as a …

Calcium And Proteasomal Regulation Of Er-To-Golgi Protein Transport In Neurons, Samuel A. Galindo

Undergraduate Theses, Professional Papers, and Capstone Artifacts

Regulatory mechanisms of protein trafficking from the endoplasmic reticulum (ER) are critical to understand since neurodegenerative diseases involve defects in this process leading to chronic ER stress and cell death. This study aimed to better understand the calcium regulatory mechanisms of ER-to-Golgi trafficking in hybrid neuroglioblastoma cells (NG108). Specifically, we asked whether proteasomal degradation of transport machinery was involved in the previously demonstrated upregulation of ER-to-Golgi transport evoked by calcium signaling. Based upon previous literature, we believe that the calcium induced increase in transport is due to the activation of the calcium sensitive regulatory protein apoptosis linked gene 2 (ALG-2) …

Characterization And Evolutionary Analysis Of Poly(Aspartic Acid) Degrading Enzymes: Exploring Enzymes-Dna Interactions And Expanding The Enzyme Family, Thi Ho

College of Graduate Studies: Theses & Dissertations

Poly(aspartic acid) (PAA) has emerged as a biodegradable and environmentally friendly alternative to non- biodegradable polycarboxylates. This thesis aims to further advance the understanding of PAA degradation by exploring multiple facets focusing on PAA-DNA interactions, particularly those involving the enzyme PahZ1 from Pedobacter sp. KP-2, and to investigate their physiological relevance and potential role in the evolution of PAA biodegradation enzymes. Additionally, the research characterizes PahZ1 homologs from various bacterial species, including Brevifollis gellanilyticus, Erythrobacter insulae, Sphingomonadales, and Sphingopyxis sp. Root 1497. These efforts have identified four novel homologs capable of degrading PAA. Synthetic oligopeptides were employed to identify potential …

The Multifunctional Catalytic Hemoglobin Fromamphitrite Ornata: Protocols On Isolation, Taxonomic Identification, Protein Extraction, Purification, And Characterization, Anna L. Husted, Lauren A. Presnar, R. Kevin Blackburn, Joseph L. Staton, Stephen A. Borgiani, Edward L. D'Antonio

Natural Sciences Faculty Publications

The multifunctional catalytic hemoglobin from the terebellid polychaete Amphitrite ornata, also named dehaloperoxidase (AoDHP), utilizes the typical oxygen transport function in addition to four observed activities involved in substrate oxidation. The multifunctional ability of AoDHP is presently a rare observation, and there exists a limitation for how novel dehaloperoxidases can be identified from macrobenthic infauna. In order to discover more infaunal DHP-bearing candidates, we have devised a facilitated method for an accurate taxonomic identification that places visual and molecular taxonomic approaches in parallel. Traditional visual taxonomic species identification by the non-specialist, at least for A. ornata or even for other …

Sphingosine Kinase 2 Depletion Dysregulates Hepatic Redox Metabolism And Enhances Inflammation In Early Metabolic Dysfunction-Associated Steatohepatitis (Mash), Kaitlyn Georgene Jackson

Theses and Dissertations

Metabolic dysfunction-associated steatotic liver disease (MASLD) currently affects one in three people worldwide; its prevalence is growing alongside other cardiometabolic disorders. Aberrations to redox and sphingolipid metabolism contribute to MASLD pathologic progression. Sphingosine-1-phosphate (S1P) is an active lipid, meaning that S1P participates in biochemical processes within the cell. S1P is generated by two distinct isoenzymes, sphingosine kinase (SphK)1 and SphK2. The localization of the SphK enzyme dictates S1P function. While cytosolic SphK1-generated S1P is well-characterized, nuclear and mitochondrial SphK2-generated S1P is less known. Moreover, SphK2 depletion effects on cellular redox processes and inflammation are not well-defined.

This study defines the …

Primary Cilia And Intraflagellar Transport Are Essential Regulators Of Lymphangiogenesis And Modulate Cellular Trafficking Of Ve-Cadherin, Delayna Paulson

Electronic Theses and Dissertations

No abstract provided.

Iron–Sulfur Cluster Assembly Scaffold Protein Iscu Is Required For Activation Of Ferric Uptake Regulator (Fur) In Escherichia Coli, Huangen Ding

Faculty Publications

No abstract provided.

Development Of Innovative Flocculation Technologies For Agricultural Water Treatment, Noor Haleem

Electronic Theses and Dissertations

The development of innovative flocculation technologies is essential for addressing the challenges of agricultural water treatment. These technologies play a crucial role in removing contaminants such as suspended solids and nutrients, thereby ensuring safer water for irrigation and livestock consumption. By enhancing water quality and wastewater management, they contribute significantly to environmental sustainability and public health in agricultural communities. This comprehensive thesis extensively explores various dimensions of flocculation, with a focused effort on methodologies and resources aimed at strengthening sustainability and efficiency. A pivotal aspect of the research involves synthesizing cationic starch (CS), a flocculant derived from an underutilized resource, …

Advancing Biological Applications Through Microfluidic-Based Tool Development, K.M. Taufiqur Rahman

Electronic Theses and Dissertations

This research undertook an interdisciplinary approach, integrating bioengineering, microbiology, molecular biology, and systems biology to investigate bacterial dynamics behavior. Specifically, it delved into the development of microfluidic devices for biological applications such as bacterial cell counts, real-time observation of plant roots (here, specialized lectin-coated microbeads are used that mimic root characteristics), and soil microbe interactions. Furthermore, Next-Generation Sequencing and systems biology methodologies were employed to explore the intricate, multifaceted survival mechanisms of Escherichia coli persister population. Studying and quantifying persisters or testing for the existence of VBNC (viable but nonculturable) is challenging. These experiments require precise counts. It has been …

Design, Synthesis, And Evaluation Of Class Iia Histone Deacetylase (Hdac) Inhibitors, Lauren Nicole Kotsull

Wayne State University Dissertations

Histone deacetylase (HDAC) proteins are linked to disease states, including cancer, and have become important targets for therapeutic development. Many inhibitors have been developed to target HDAC proteins, including FDA-approved inhibitors Vorinostat (SAHA), Belinostat, Romidepsin, and Panobinostat. These inhibitors non-specifically influence most of the 11 metal-dependent HDAC isoforms, which might contribute to the side effects that patients experience during treatment. The lack of selectivity also diminishes the use of HDAC inhibitors as biomedical research tools. To address these drawbacks, the development of selective inhibitors has been heavily studied. Yet, reported inhibitors are predominantly selective for class I HDAC isoforms (HDACs …

Utilizing Plasmid Dna Hydrogels For Cell-Free Protein Production, Tinotenda Duche

Honors Theses and Capstones

Proteins play an important role in various biological processes and are crucial components in biomedical research and therapeutics. Cell-free protein synthesis (CFPS) has provided a valuable approach for rapid protein production outside living cells, involving both transcription and translation processes. However, traditional CFPS methods encounter challenges such as high cost, relatively low yields, and scalability. The end goal of our project is to incorporate our template into the hydrogel. In this work, we report advancements towards that by trying to optimize our solution of CFPS. Unfortunately, the standards for pDNA hydrogel synthesis are not met by the pDNA production and …

Targeting Bcl6 Transcription Factor In Ovarian Cancer, Allison F. Mackey

Honors Theses and Capstones

Ovarian cancer is the most fatal female reproductive cancer, with most cases being diagnosed in late stages, after metastasis has become widespread. This can make ovarian cancer challenging to successfully treat, especially with its high rate of recurrence. The use of small molecule compounds to inhibit overexpressed transcription factors may provide an effective method for treatment. BCL6 is a transcription factor that is abnormally overexpressed in patients with recurring and late-stage ovarian cancer and has been implicated in proliferation and metastatic behavior. The identification of multiple potential inhibitors of BCL6 could improve chances for the further testing of these compounds, …

Assessing Lipid Composition Of Cell Membrane In Escherichia Coli Under Aerobic And Anaerobic Conditions, Isabelle Johnson

Undergraduate Theses, Professional Papers, and Capstone Artifacts

Escherichia coli is a highly studied model organism that is tightly tied to the mammalian gastrointestinal system. This microorganism has the capability to be a beneficial gut microbe or a life-threatening pathogen. In this study, the lipid membrane of Escherichia coli was investigated using Matrix-Assisted Laser Desorption/Ionization-Time of Flight Mass Spectrometry (MALDI-TOF MS) to observe the change in its composition in aerobic and anaerobic conditions. Evidence of desaturation was discovered in the spectra, though more investigation is needed to understand the metabolic processes and drives that result in this change. Elucidation of these pathways in the future could result in …

Discovery Of Dna Aptamers As Probes For Detecting Ranavirus Mcp, Corbin Hudson

Theses, Dissertations and Culminating Projects

Global amphibian populations have been declining since the late 20th century; one of the most significant contributors to these declines is a genus of viral pathogens known as Ranavirus (Rv). Frog virus 3 is one of these viral agents and is currently found affecting frog populations throughout NJ, MD, PA, DE, and VA. While Frog virus 3 is most known for afflicting frogs, the Ranavirus genus can also infect bony fish species as well as reptiles, allowing for a wide vector of transmission and making its spread a danger both locally and globally. In the absence of a cure, it …

Chemical Biology Approach To Study Rna Modifications, Ya Ying Zheng

Legacy Theses & Dissertations (2009 - 2024)

Nucleic acid modifications have gained compelling interest for their pivotal roles in cellular and biological processes. These modifications introduced a new layer of regulation without altering the original genetic sequence. In this burgeoning field of epitranscriptomics, many of the chemical modifications have emerged as potential biomarkers in therapeutic applications. Inosine is an essential post-transcriptional RNA modification that has functional roles in modulating the fate of all RNAs. The enzyme ADAR catalyzes the deamination of adenosine to inosine. This can also lead to change in the eukaryotic transcriptome due to A-G miscoding since inosine preferentially base pairs with cytosine. Moreover, hyper-editing …

Rps6kb1 Is A Critical Target For Overcoming Tumor Lineage Plasticity And Therapy Resistance, Saptadwipa Ganguly

Theses and Dissertations--Toxicology and Cancer Biology

Most tumors initially respond to treatment, yet refractory clones subsequently develop owing to resistance mechanisms which can be classified as intrinsic or extrinsic resistance. The intrinsic resistance is usually present prior to any treatment whereas the extrinsic resistance develops as a result of exposure to some kind of therapy. In order to target these “therapy resistant” tumor cells an unbiased screen of an FDA-approved drug library against cancer cells was performed. This was followed by synthesis of chemical analogs of the most effective drug.

The studies led to the identification of a derivative of the antihistamine drug ebastine, designated Super-ebastine …

An Rnai-Based Approach To Ips Calligraphus Management: A Promising Strategy For Forest Protection, Mary Wallace

Theses and Dissertations--Entomology

As climate change leads to more frequent and severe extreme weather, host tree stress is increasing the occurrence of large-scale bark beetle outbreaks. One such beetle, Ips calligraphus (Germar), a native bark beetle in the southeastern United States, has traditionally been considered a secondary pest of pine trees. Management has relied on silvicultural practices that enhance forest resilience, enabling host trees to effectively use natural defenses to deter beetle infestation. However, during periods of forest stress caused by storms, droughts, human disturbance, and other factors, beetle outbreaks can cause considerable ecological and economic damage.

Addressing worsening I. calligraphus outbreaks will …