Biochemistry, Biophysics, and Structural Biology Commons^™

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 …

Submarine Groundwater Discharge At A Mega-Tidal Beach, Raymond D. Craddock, Aaron A. Mohammed, Joseph J. Tamborski, Barret L. Kurylyk

OES Faculty Publications

Tidally influenced groundwater systems in coastal environments represent important mixing zones of fresh groundwater and circulating seawater, manifesting as submarine groundwater discharge (SGD). Water circulation induced by tidal pumping enhances the exchange of chemicals between aquifers and coastal waters and thereby influences the biogeochemistry of coastal zones. Here, we report the results of an SGD field study conducted at a steep, mega-tidal sand and gravel beach along the Canadian coast of the Bay of Fundy, a region with the world's highest tides (semi-diurnal tidal ranges exceeding 10 m). Several physical and geochemical measurement techniques were employed to document the spatiotemporal …

Heterogeneity Of Nitrogen Fixation In The Mesopelagic Zone Of The South China Sea, Siqi Wu, Xianhui Sean Wan, Moge Du, Xirong Chen, Corday R. Selden, Mar Benavides, Sophie Bonnet, Carolin R. Löscher, M. Robert Hamersley, Margaret R. Mulholland, Xiuli Yan, Shuh-Ji Kao

OES Faculty Publications

Biological dinitrogen (N₂) fixation, the energetically expensive conversion of N₂ gas to ammonia, plays an essential role in balancing the nitrogen budget in the ocean. Accumulating studies show detectable N₂ fixation rates below the euphotic zone in various marine systems, revealing new insights of marine N₂ fixation. However, the reported rates are highly variable and frequently fall close to detection limits, raising the question of the ubiquity and significance of N₂ fixation in the global dark ocean. Using highly sensitive isotopic labeling incubation including a set of control incubations, we confirm the occurrence of mesopelagic N₂ fixation in the South …

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 …