Biology Commons^™

Towards A New Role Of Mitochondrial Hydrogen Peroxide In Synaptic Function, Cliyahnelle Z. Alexander

Student Theses and Dissertations

Aerobic metabolism is known to generate damaging ROS, particularly hydrogen peroxide. Reactive oxygen species (ROS) are highly reactive molecules containing oxygen that have the potential to cause damage to cells and tissues in the body. ROS are highly reactive atoms or molecules that rapidly interact with other molecules within a cell. Intracellular accumulation can result in oxidative damage, dysfunction, and cell death. Due to the limitations of H₂O₂ (hydrogen peroxide) detectors, other impacts of ROS exposure may have been missed. HyPer7, a genetically encoded sensor, measures hydrogen peroxide emissions precisely and sensitively, even at sublethal levels, during …

Pipecolic Acid And Novel Insights Into Cerebral Malaria, Akua E. Mensah

Theses

Cerebral malaria (CM), a severe manifestation of Plasmodium infection, prompts our investigation into the nuanced role of pipecolic acid in its pathophysiology. To unravel the molecular intricacies, we conducted in vitro lysine labeling techniques of mice infected with P. berghei ANKA parasites, and human P. falciparum grown in vitro, aiming to discern the impact of Plasmodium on pipecolic acid production. Previous observations indicated an elevation in pipecolic acid levels correlating with neurological decline in children with CM. In our study, confirming elevated pipecolic acid presence in the plasma and brain tissues of CM patients and the animal model of CM, …

Inhibiting Glutamine Utilization Creates A Synthetic Lethality For Suppression Of Atp Citrate Lyase In Kras-Driven Cancer Cells, Ahmet Hatipoglu, Deepak Menon, Talia Levy, Maria A. Frias, David A. Foster

Publications and Research

Metabolic reprogramming is now considered a hallmark of cancer cells. KRas-driven cancer cells use glutaminolysis to generate the tricarboxylic acid cycle intermediate α -ketoglutarate via a transamination reaction between glutamate and oxaloacetate. We reported previously that exogenously supplied unsaturated fatty acids could be used to synthesize phosphatidic acid–a lipid second messenger that activates both mammalian target of rapamycin (mTOR) complex 1 (mTORC1) and mTOR complex 2 (mTORC2). A key target of mTORC2 is Akt–a kinase that promotes survival and regulates cell metabolism. We report here that mono- unsaturated oleic acid stimulates the phosphoryla tion of ATP citrate lyase (ACLY) at …

Three Lc-Ms Plant Metabolomics Studies Of Hop (Humulus) Species: Wild H. Neomexicanus, Drought Stress, And Agricultural Terroir, Taylan Morcol

Dissertations, Theses, and Capstone Projects

The hop plant (Humulus L., Cannabaceae) is a dioecious, perennial, twining vine with a long history of human use. Nowadays, hop plants are generally grown for their inflorescences (“cones”), which are used in brewing for their phytochemical metabolites. Many of these metabolites are involved in plant stress response and communication. Genetics and environment are two major factors that affect plant metabolism. In three separate metabolomics studies, this project examined the effects of both genetic and environmental factors on hop phytochemistry.

In the first study, 23 hop genotypes were grown in two different locations in the Pacific Northwest region of …

The Structural And Functional Role Of Photosensing In Rgs-Lov Proteins, Zaynab Jaber

Dissertations, Theses, and Capstone Projects

Light provides organisms with energy and spatiotemporal information. To survive and adapt, organisms have developed the ability to sense light to drive biochemical effects that underlie vision, entrainment of circadian rhythm, stress response, virulence, and many other important molecularly driven responses. Blue-light sensing Light-Oxygen-Voltage (LOV) domains are ubiquitous across multiple kingdoms of life and modulate various physiological events via diverse effector domains. Using a small molecule flavin chromophore, the LOV domain undergoes light-dependent structural changes leading to activation or repression of these catalytic and non-catalytic effectors. In silico analyses of high-throughput genomic sequencing data has led to the marked expansion …

The C. Neoformans Cell Wall: A Scaffold For Virulence, Christine Chrissian

Dissertations, Theses, and Capstone Projects

Cryptococcus neoformans is a globally distributed opportunistic fungal pathogen and the causative agent of life threatening cryptococcal meningoencephalitis in immunocompromised individuals, resulting in ~180,000 deaths each year worldwide. A primary virulence-associated trait of this organism is the production of melanin. Melanins are a class of diverse pigments produced via the oxidation and polymerization of aromatic ring compounds that have a characteristically complex, heterogenous, and amorphous structure. They are synthesized by representatives of all biological kingdoms and share a multitude of remarkable properties such as the ability to absorb ultraviolet (UV) light and protect against ionizing radiation. Melanin production in fungi …

Hur Ubiquitination By Brca1/Bard1 And Its Role In Controlling Gene Expression During Dna Damage Response, Gamage M. Aruggoda

Dissertations, Theses, and Capstone Projects

Despite our understanding of the biochemistry of the BRCA1/BARD1 E3 ligase, we know very little of the mechanism by which its cellular substrates, how they are chosen, how its E3 Ub ligase activity is regulated, which are the cofactors involved in this regulation, and how the substrates are modified during DDR. In this dissertation, I further evaluate BRCA1/BARD1-mediated E3 ligase activity and how CstF-50 and p97 regulate this reaction working as cofactors. My data show that BRCA1/BARD1 is an E3 ligase that ubiquitinates the RNA binding protein Human antigen R(HuR).

HuR is abundant in the nucleus and is transported to …

Through The Back Door: Proteins Escape Cells Without Conventional Permission, Michael J. Cohen

Dissertations, Theses, and Capstone Projects

Proteins secreted to the extracellular environment play a fundamental role as signals, in metabolism, and a variety of other processes. The process of secretion through the endoplasmic reticulum and Golgi to the plasma membrane is well documented, and all cargo in this pathway contains a signal peptide. However, a variety of proteins secreted from eukaryotes lack a signal peptide and are called unconventionally secreted proteins. Here we discuss known mechanisms of unconventional protein secretion, as well as model proteins which follow characterized pathways. Additionally, we summarize the roles various unconventionally secreted proteins play outside of cells and suggest criteria for …

Regulation Of The Tubulin Homolog Ftsz In Escherichia Coli, Monika S. Buczek

Dissertations, Theses, and Capstone Projects

Escherichia coli is a well-known pathogen, and importantly, a widely used model organism in all fields of biological sciences for cloning, protein purification, and as a model for Gram-negative bacterial species. And yet, researchers do not fully understand how this bacterium replicates and divides. Every year additional division proteins are discovered, which adds complexity to how we understand E. coli undergoes cell division. Due to their specific roles in cytokinesis, some of these proteins may be potential targets for development of antibacterials or bacteriostatics, which are much needed for fighting the current global antibacterial deficit. My thesis work focuses on …

Estrogen-Activated Mdm2 Disrupts Mammary Tissue Architecture Through A P53-Independent Pathway, Nandini Kundu, Angelika Brekman, Jun Yeob Kim, Gu Xiano, Chong Gao, Jill Bargonetti

Publications and Research

The Cancer Genome Atlas (TCGA) data indicate that high MDM2 expression correlates with all subtypes of breast cancer. Overexpression of MDM2 drives breast oncogenesis in the presence of wild-type or mutant p53 (mtp53). Importantly, estrogen-receptor positive (ER+) breast cancers overexpress MDM2 and estrogen mediates this expression. We previously demonstrated that this estrogen-MDM2 axis activates the proliferation of breast cancer cell lines T47D (mtp53 L194F) and MCF7 (wild-type p53) in a manner independent of increased degradation of wildtype p53 (ie, p53-independently). Herein we present data supporting the role of the estrogen-MDM2 axis in regulating cell proliferation and mammary tissue architecture of …

Human Anatomy And Physiology Preparatory Course (1st Edition), Carlos Liachovitzky

Open Educational Resources

The overall purpose of this preparatory course textbook is to help students familiarize with some terms and some basic concepts they will find later in the Human Anatomy and Physiology I course.

The organization and functioning of the human organism generally is discussed in terms of different levels of increasing complexity, from the smallest building blocks to the entire body. This Anatomy and Physiology preparatory course covers the foundations on the chemical level, and a basic introduction to cellular level, organ level, and organ system levels. There is also an introduction to homeostasis at the beginning.

Role Of The Polyadenylation Factor Cstf-50 In Regulating The Brca1/Bard1 E3 Ubiquitin (Ub) Ligase Activity, Danae Fonseca

Dissertations, Theses, and Capstone Projects

The cellular response to DNA damage is an intricate mechanism that involves the interplay among several pathways. The studies presented in this dissertation focus on the determination and characterization of the role of mRNA processing factor CstF-50 and escort protein p97 in the regulation of the BRCA1/BARD1 E3 ubiquitin (Ub) ligase activity during the DNA damage response (DDR).

As part of the studies presented in Chapter II, I determined that the polyadenylation factor CstF plays a direct role in DDR, specifically in transcription-coupled repair (TCR), and that it localizes with RNA polymerase II (RNAP II) and BARD1 to sites of …

Lipid Dependence In Ras-Driven Tumors, Darin Salloum

Dissertations, Theses, and Capstone Projects

Over past decade, metabolic alterations in cancer cells have received a substantial amount of interest. It had been established that cancer cells undergo a significant amount of metabolic alterations, and some of these alterations are similar to those in normal highly proliferative cells. However, it is becoming more apparent that many of the metabolic alterations are specific to particular oncogenic signaling pathways. Although altered metabolic machinery makes cancer cells more efficient at promoting growth when nutrients are supplied at the sufficient amounts, the dependency of cancer cells on particular metabolic reprogramming deems cancer cells susceptible to disruptions within metabolic network. …

Metabolic Checkpoints In Cancer Cell Cycle, Mahesh Saqcena

Dissertations, Theses, and Capstone Projects

Growth factors (GFs) as well as nutrient sufficiency regulate cell division in metazoans. The vast majority of mutations that contribute to cancer are in genes that regulate progression through the G1 phase of the cell cycle. A key regulatory site in G1 is the growth factor-dependent Restriction Point (R), where cells get permissive signals to divide. In the absence of GF instructions, cells enter the quiescent G0 state. Despite fundamental differences between GF signaling and nutrient sensing, they both have been confusingly referred to as R and therefore by definition considered to be a singular event in G1. Autonomy from …

Identification And Characterization Of Protein Phopshatases Regulating The Sma/Mab Pathway In C. Elegans, Sheng Xiong

Dissertations, Theses, and Capstone Projects

TGF-beta signaling is a conserved signaling pathway among eukaryotes, which controls various normal cellular responses from cell proliferation to cell death. The mutations in its components are found in developmental disorders and cancer. Therefore, this signaling pathway is extensively investigated so that new therapeutic targets could be discovered and novel drugs could be developed. Previous studies suggested the involvement of phosphatases in regulation of TGF-beta signaling, but these studies were performed in cell culture rather than intact organisms. C. elegans is a tractable organism in which to study signaling in vivo. In C. elegans, growth is controled by a conserved …