Molecular Biology Commons^™

Loss Of Carnitine Palmitoyltransferase 1a Reduces Docosahexaenoic Acid-Containing Phospholipids And Drives Sexually Dimorphic Liver Disease In Mice, Mikala M. Zelows, Corissa Cady, Nikitha Dharanipragada, Anna E. Mead, Zachary A. Kipp, Evelyn A. Bates, Venkateshwari Varadharajan, Rakhee Banerjee, Se-Hyung Park, Nathan R. Shelman, Harrison A. Clarke, Tara R. Hawkinson, Terrymar Medina, Ramon C. Sun, Todd A. Lydic, Terry D. Hinds, Jr., J. Mark Brown, Samir Softic, Gregory A. Graf, Robert N. Helsley

Saha Cardiovascular Research Center Faculty Publications

Background and aims: Genome and epigenome wide association studies identified variants in carnitine palmitoyltransferase 1a (CPT1a) that associate with lipid traits. The goal of this study was to determine the role of liver-specific CPT1a on hepatic lipid metabolism.

Approach and results: Male and female liver-specific knockout (LKO) and littermate controls were placed on a low-fat or high-fat diet (60% kcal fat) for 15 weeks. Mice were necropsied after a 16 h fast, and tissues were collected for lipidomics, matrix-assisted laser desorption ionization mass spectrometry imaging, kinome analysis, RNA-sequencing, and protein expression by immunoblotting. Female LKO mice had increased serum alanine …

On The Origin And Evolution Of The Mosquito Male-Determining Factor Nix, James K. Biedler, Azedah Aryan, Yumin Qi, Aihua Wang, Ellen O. Martinson, Daniel A. Hartman, Fan Yang, Atashi Sharma, Katherine S. Morton, Mark Potters, Chujia Chen, Stephen L. Dobson, Gregory D. Ebel, Rebekah C. Kadling, Sally Paulson, Rui-De Xue, Michael R. Strand, Zhijian Tu

Entomology Faculty Publications

The mosquito family Culicidae is divided into 2 subfamilies named the Culicinae and Anophelinae. Nix, the dominant male-determining factor, has only been found in the culicines Aedes aegypti and Aedes albopictus, 2 important arboviral vectors that belong to the subgenus Stegomyia. Here we performed sex-specific whole-genome sequencing and RNAseq of divergent mosquito species and explored additional male-inclusive datasets to investigate the distribution of Nix. Except for the Culex genus, Nix homologs were found in all species surveyed from the Culicinae subfamily, including 12 additional species from 3 highly divergent tribes comprising 4 genera, suggesting Nix originated at least 133 to …

A Cancer-Specific Study On The Differentially Expressed Protein-Protein Interactions Of Fumarate Hydratase, Sydney Lac

Dissertations and Theses (Open Access)

Fumarate hydratase (FH) is an enzyme used in the Krebs Cycle to convert fumarate to malate, and it is controlled by the FH gene. In this paper, we will investigate its role in Uterine Corpus Endometrial Carcinoma (UCEC) and how FH-deficient cells affect tumorigenesis. It is well-established that FH has been extensively studied in connection with renal cell carcinoma, skin and uterine leiomyomas, pheochromocytoma, and paraganglioma. However, we aim to construct an interaction network of significant genes related to the FH gene under conditions of FH deficiency in the Kreb Cycle. Creating an interactive network that illustrates the interconnectedness of …

Amyloid Fibrils Of Human Fgf-1 Induced By Different Detergents, Zeina Ismael Ibrahem Alraawi

Graduate Theses and Dissertations

Nature achieves molecular self-assembly through the ordered growth of nanoscale building blocks with high efficiency to fabricate macromolecular architectures. One example of self- assembly is peptides folding onto protein is one of the most astounding biological self-assembly processes. When proteins aggregate to form amyloid fibers, the secondary structure of the protein converts from its native state to a cross-beta-sheet. Fibroblast growth factors (FGFs) possess an essential role in neuronal survival during development. In addition, they are involved in neural stem cell (NSC) proliferation. Fibroblast growth factors (FGFs) are well known to be synthesized in the central nervous system (CNS) and …

Characterization Of Human Fibroblast Growth Factor 2 Variant To Determine Effects On Structure, Stability, And Cell Proliferation, Ryan Layes

Graduate Theses and Dissertations

Fibroblast growth factors (FGFs) are a family of cell signaling proteins conserved across multiple species. Each individual FGF elicits different cellular functions including, but not limited to, proliferation, migration, differentiation, angiogenesis, and wound healing. One of the most studied members, fibroblast growth factor 2 (FGF2), has demonstrated substantial wound healing capacity in a wide range of tissues including skeletal, muscular, neural, respiratory, epithelial, and cardiovascular. This ability makes FGF2 a potential therapeutic for a wide range of conditions and injuries. However, due to a short half-life at room temperature, therapeutic use of FGF2 is limited. It has been demonstrated that …

Repositioning Propranolol To Block Mitogenic Signaling In Breast Cancer, Alexa Noel Montoya

Open Access Theses & Dissertations

Breast cancer is the second most diagnosed cancer among women and is about 30% of all new cases of female cancers each year. It is projected that 1 in 8 every U.S. woman (about 13%) develop invasive breast cancer over the course of her lifetime. While advances in cancer research have made it possible to elucidate several breast cancer genomic subtypes, and develop new novel therapies, many of these agents are associated with significant toxicity, as well as high costs. A retrospective cross-sectional study of 404 breast cancer patients was performed to determine the effect of β-blocker usage on tumor …

Overexpression Of Ubtf Correlates With Aggressive Phenotypes Of Prostate Cancer Cells, Guillermo Andres Saldana

Theses and Dissertations

Prostate cancer (PrCa) is one of the most common malignancies in men globally and the second leading cause of cancer associated deaths in developed countries. Accumulating evidence have demonstrated involvement of various molecular and cellular factors in the development, progression and chemoresistance of PrCa and many of them were successfully established as potential molecular targets for therapy. Despite these advancements, the underlying mechanisms of PrCa occurrence is still unclear, which limits the diagnosis and therapy. Therefore, it is an urgent need to discover potential molecular targets which can be used in rational design of new strategies for the prevention and …

Cyclin D1 Extensively Reprograms Metabolism To Support Biosynthetic Pathways In Hepatocytes, Heng Wu, Betsy T. Kren, Andrew N. Lane, Teresa A. Cassel, Richard M. Higashi, Teresa Whei-Mei Fan, George S. Scaria, Laurie L. Shekels, Mark A. Klein, Jeffrey H. Albrecht

Markey Cancer Center Faculty Publications

Cell proliferation requires metabolic reprogramming to accommodate biosynthesis of new cell components, and similar alterations occur in cancer cells. However, the mechanisms linking the cell cycle machinery to metabolism are not well defined. Cyclin D1, along with its main partner cyclindependent kinase 4 (Cdk4), is a pivotal cell cycle regulator and driver oncogene that is overexpressed in many cancers. Here, we examine hepatocyte proliferation to define novel effects of cyclin D1 on biosynthetic metabolism. Metabolomic studies reveal that cyclin D1 broadly promotes biosynthetic pathways including glycolysis, the pentose phosphate pathway, and the purine and pyrimidine nucleotide synthesis in hepatocytes. Proteomic …

Md_Harmonize: A Python Package For Atom-Level Harmonization Of Public Metabolic Databases, Huan Jin, Hunter N. B. Moseley

Markey Cancer Center Faculty Publications

A major challenge to integrating public metabolic resources is the use of different nomenclatures by individual databases. This paper presents md_harmonize, an open-source Python package for harmonizing compounds and metabolic reactions across various metabolic databases. The md_harmonize package utilizes a neighborhood-specific graph coloring method for generating a unique identifier for each compound via atom identifiers based on a compound’s chemical structure. The resulting harmonized compounds and reactions can be used for various downstream analyses, including the construction of atom-resolved metabolic networks and models for metabolic flux analysis. Parts of the md_harmonize package have been optimized using a variety of computational …

Design And Characterization Of A Novel Eef2k Degrader With Potent Therapeutic Efficacy Against Triple-Negative Breast Cancer, Changxin Zhong, Rongfeng Zhu, Ting Jiang, Sheng Tian, Xiaobao Zhao, Xiaoya Wan, Shilong Jiang, Zonglin Chen, Rong Gong, Linhao He, Jin-Ming Yang, Na Ye, Yan Cheng

Markey Cancer Center Faculty Publications

Dysregulated eEF2K expression is implicated in the pathogenesis of many human cancers, including triple-negative breast cancer (TNBC), making it a plausible therapeutic target. However, specific eEF2K inhibitors with potent anti-cancer activity have not been available so far. Targeted protein degradation has emerged as a new strategy for drug discovery. In this study, a novel small molecule chemical is designed and synthesized, named as compound C1, which shows potent activity in degrading eEF2K. C1 selectively binds to F8, L10, R144, C146, E229, and Y236 of the eEF2K protein and promotes its proteasomal degradation by increasing the interaction between eEF2K and the …

Flavonol Glucosylation: A Structural Investigation Of The Flavonol Specific 3-O Glucosyltransferase Cp3gt, Aaron S. Birchfield

Electronic Theses and Dissertations

Flavonoid glycosyltransferases (GTs), enzymes integral to plant ecological responses and human pharmacology, necessitate rigorous structural elucidation to decipher their mechanistic function and substrate specificity, particularly given their role in the biotransformation of diverse pharmacological agents and natural products. This investigation delved into a comprehensive exploration of the flavonol 3-O GT from Citrus paradisi (Cp3GT), scrutinizing the impact of a c-terminal c-myc/6x histidine tag on its enzymatic activity and substrate specificity, and successfully achieving its purification to apparent homogeneity. This established a strong foundation for potential future crystallographic and other structure/function analyses. Through the strategic implementation of site-directed mutagenesis, a thrombin …

The Interplay Between Lung Adenocarcinoma, Nutrient Availability, And The Microbiome., Alexis A. Vega

Electronic Theses and Dissertations

Lung cancer is one of the most common forms of cancer diagnosed, and has the highest lethality rate across all other forms of cancer in the U.S. While current therapeutic options include chemo-, immuno-, and radio-therapy, the benefits of caloric or nutrient restriction on cancer cells has also been investigated. Due to the many biological functions associated with methionine, many have proposed a methionine restricted diet would lead to favorable outcomes when combating cancer. Although our cells are incapable of synthesizing methionine, the bacteria found in our microbiome can. Furthermore, recent discoveries suggest an independent microbiome found within tumors that …

Doxorubicin-Induced Changes To The Tgf-Β Signaling Pathway And Autophagic Flux In Fibroblasts: Implications For Cardiotoxicity, Conner Patricelli

Boise State University Theses and Dissertations

Doxorubicin is a commonly used chemotherapeutic used to treat many different types of cancer. However, its clinical use is limited due to its cardiotoxic adverse effects. While multiple mechanisms have been shown to be responsible for doxorubicin-induced cardiotoxicity, it is generally accepted that the principle mechanism is oxidative stress induction through the production of reactive oxygen species and free radicals in the myocardium. However, efforts to reduce/prevent doxorubicin toxicity using antioxidants have largely failed in pre-clinical and clinical trials. The targeted approach using a liposome delivery of doxorubicin significantly reduced the risk of cardiotoxicity; however, this approach is limited to …

Development Of Novel Methods To Study Host-Microbe Interactions In The Larval Zebrafish Gastrointestinal Tract, Anh K. Trinh Nguyen

Dissertations and Theses (Open Access)

The dynamic nature and inaccessible location of the intestine pose significant challenges to the study of intestinal physiology and pathology. Zebrafish larvae, possessing optical transparency and genetic tractability, offer an accessible and clinically relevant model for investigating dynamic events in the intestine via time-lapse imaging. In the first part of this work, I discuss our efforts to optimize the parameters of a foodborne infection assay using paramecia as a vehicle. This method provides an effective, high-throughput alternative to infection via immersion or oral gavage, and replicates the most common route of transmission of gastrointestinal (GI) infection in humans. The foodborne …

A Signal To Divide: Apoptotic Extracellular Vesicles As Carriers Of Mitogenic And Immunogenic Signals, Safia Essien, Safia Essien

Dissertations and Theses (Open Access)

Efficient replacement of dead cells in epithelial tissue is crucial for maintaining barrier function and tissue homeostasis. Apoptotic cells can signal to neighboring cells to stimulate proliferation and compensate for cell loss and maintain overall cell numbers in normal physiology and cancer. While dying cells can transmit instructive cues to neighboring cells, the molecular mechanisms that induce cell division are not well understood. Recent evidence suggests that apoptotic bodies (ABs) or apoptotic extracellular vesicles (AEVs) mediate cell-to-cell communication and carry diverse biologically active cellular cargo which can influence cell proliferation. This dissertation visualizes and characterizes AEVs in larval zebrafish and …

Biochemical And Kinetic Analysis Of Phosphofructokinase In The Eukaryotic Human Pathogen Entamoeba Histolytica, Jin Cho

All Dissertations

Entamoeba histolytica is a water- and food-borne intestinal parasite that causes amoebiasis and liver abscess in ~100 million people each year leading to ~100,000 deaths. This amitochondriate parasite lacks many metabolic pathways including the tricarboxylic acid cycle and oxidative phosphorylation, and cannot synthesize purines, pyrimidines, or most amino acids. As a result, E. histolytica is presumed to rely on its modified pyrophosphate (PP_i)-dependent glycolytic pathway for ATP production during growth on glucose. This pathway relies on a PP_i-dependent rather than ATP-dependent phosphofructokinase (PFK) and thus has a net production of three ATP per glucose. However, in …

Delineating The Impact Of Vascular Smooth Muscle Cell Abca1/G1 And Mir-33a Expression On Atherosclerosis, Olanrewaju Oladosu

All Dissertations

Atherosclerotic cardiovascular disease is the leading cause of mortality worldwide due to being the predominant factor in heart attack and stroke deaths. Atherosclerotic cardiovascular disease is caused by cholesterol accumulating in arteries. It is historically thought that the cell type most responsible for causing atherosclerosis via excessive cholesterol accumulation is intimal monocyte-derived macrophages. However, macrophage-like cells (MLC) of vascular smooth muscle cell (VSMC) origin have now been proposed as another cell type to trigger atherosclerosis, since VSMC cholesterol accumulation results in these cells to trans-differentiate into a MLC phenotype. Three major genes involved in cholesterol metabolism are ABCA1, ABCG1, and …

Characterization Of The Effects Of The Pyrazolopyrimidine Inhibitor Grassofermata (Nav-2729) In The Eukaryotic Pathogen Trypanosoma Brucei, Kristina Marie Parman

All Dissertations

The protozoan pathogen, Trypanosoma brucei, is the causative agent of sleeping sickness in humans and nagana in livestock in sub-Saharan Africa. T. brucei cycles between tsetse fly and mammalian hosts, and it is adapted to survive in diverse host tissues. Variant Surface Glycoprotein (VSG) plays a key role in immune evasion in the mammalian host. The VSG membrane anchor requires two myristates, 14-carbon saturated fatty acids (FAs) that are scarce in the host. T. brucei can synthesize FAs de novo, but also readily takes up exogenous FAs, despite lacking homologs to fatty acid uptake proteins found in other …

Effect Of Plant Genotype On Plant-Microbe Interactions And Multi-Generation Ecosystem Selection Of Microbial Communities Associated With Plant Biomass In Arabidopsis Thaliana, Nachiket Shankar

Graduate Doctoral Dissertations

The microbiome's role in shaping host phenotypes is a critical area of investigation, with implications for ecology, evolution, and host health. Dynamic plant-microbe interactions are influenced by factors like soil type, environment, and genotype. Understanding their impact on microbial communities is key for tailored plant benefits. An artificial ecosystem selection experiment was done for eight generations with Arabidopsis thaliana Ler and Cvi. This revealed distinct microbial communities shaped by genotypes and biomass treatments. Initially, environment dominated, but over time, genotype and biomass gained influence, explaining ~40% of the variation. Moreover, genotype-specific rhizobacterial associations were observed, enhancing understanding of community dynamics …

Exploring The Interactions Of Copper High Aspect Ratio Structures (Cuhars), A Novel Metal-Organic Biohybrid Nanocomposite, With Chondrocytes, Tasneem Khasru

Master's Theses

Osteoarthritis (OA) is a prevalent degenerative joint disorder characterized by cartilage lesions and subchondral bone destruction (1). Addressing OA is challenging due to cartilage's avascular and aneural nature, unique cellular arrangement, and dense extracellular matrix (ECM). Current pharmacological treatments are mainly symptomatic and are unable to halt disease progression or reverse cartilage damage . Surgical interventions also come with complications. Tissue-engineered grafts using biomaterials and molecular manipulation have emerged as potential treatments for cartilage regeneration. Copper-containing scaffolds have shown promise in bone and cartilage regeneration. Nanotechnology offers new avenues, with nanoparticles and nanofibers being used in tissue engineering research. However, …