Molecular Biology Commons^™

Knockout Of Highly Conserved Seminal Fluid Protein Ablates Male Fertility In Drosophila Melanogaster, Dominic Hockenbury

Theses - ALL

ABSTRACT In Drosophila, seminal fluid proteins (SFPs) are key components of the male ejaculate and are essential determiners of reproductive fitness. SFPs are required for inducing a range of post-mating physiological responses in females. To date nearly 300 SFPs have been identified, however the vast majority of these remain uncharacterized and their role in reproduction and/or postcopulatory sexual selection is not clear. SFPs are functionally diverse and contain proteins from a variety of biochemical processes, most notably proteases and protease inhibitors that are thought to be critically important in biochemical interactions with female proteins. Another class of proteins that is …

Unveiling The Nexus Of Cellular Quality Control: Exploring The Interplay Between Ribosome-Associated Protein Quality Control And Mitochondrial Quality Control Pathways, Foozhan Tahmasebinia

Biological Sciences Theses and Dissertations

In eukaryotic cells, the intricate interplay between cellular quality control mechanisms is crucial for maintaining homeostasis and safeguarding the integrity of vital processes, spanning from macromolecule synthesis to the renewal of entire cellular organelles.

Disruption of these networks can lead to severe diseases such as metabolic disorders, underscoring the interconnected nature and feedback control mechanisms inherent in biological systems, including cellular quality control systems. This interconnectedness extends to the intricate communication between organelles, enabling coordinated functioning and adaptation to changing cellular conditions, particularly in response to stressors.

While the exact mechanisms governing these communications within cellular quality control systems remain …

Cell Cycle Regulator Delays Pilus Production In Caulobacter Crescentus, Eli Johnson

Honors Theses

Caulobacter crescentus is a model bacterium for its unusual life cycle. This cycle features three distinct phases- the stalked stage, pre-divisional or actively dividing stage, and the swarmer stage, characterized by the production of a flagellum and multiple pili. Pili are necessary for cell attachment to surfaces and their reuptake into the cell can help drive the cell cycle forward. The gene that encodes the pilus subunit, pilA, is regulated by four binding sites for the cell cycle regulator CtrA. Previous research has determined that one site induces expression while two of the four sites inhibit expression. It is unknown …

Omani Camels From A Cultural And Genomics Perspective, Al Muatasim Al Zadjali

Electronic Theses and Dissertations

The Dromedarian camel, Camelus dromedarius, is native to the Arabian Peninsula, including the Sultanate of Oman. These camels are used for food, milk, as well as show and racing competitions. Despite their economic and cultural importance research on camels in Oman is limited. The goal of this study was to examine their genomic variation, relationship with camels in other parts of the Arabian Peninsula, and to determine if selective breeding has led to the establishment of distinct breeds in Oman. Information was compiled from multiple sources to produce a comprehensive review on the breeding, management, economic and cultural use, …

Impact Of Glycerophosphocholine Metabolism On Phenotypes In Saccharomyces Cerevisiae And Schizosaccharomyces Pombe, Victoria Hrach

Electronic Theses and Dissertations

Glycerophosphocholine (GPC) is an abundant metabolite in eukaryotes. In baker’s yeast, Saccharomyces cerevisiae, GPC can be produced via deacylation of the major membrane glycerophospholipid phosphatidylcholine (PC). My lab has identified a novel pathway to re-synthesize PC from GPC by acylating it at the sn-1 and sn-2 positions; this pathway has been termed the PC Deacylation-Reacylation Pathway (PC-DRP). We previously characterized the acyltransferase Gpc1 and its ability to synthesize one-tailed lyso-PC from GPC, as well as that noting that GPC1 is upregulated in inositol-free conditions and results in more saturated PC. Here, I add to this basic characterization by establishing …

Protein Oxidation In Aging And Alzheimer’S Disease Brain, Rukhsana Sultana, D. Allan Butterfield

Markey Cancer Center Faculty Publications

Proteins are essential molecules that play crucial roles in maintaining cellular homeostasis and carrying out biological functions such as catalyzing biochemical reactions, structural proteins, immune response, etc. However, proteins also are highly susceptible to damage by reactive oxygen species (ROS) and reactive nitrogen species (RNS). In this review, we summarize the role of protein oxidation in normal aging and Alzheimer’s disease (AD). The major emphasis of this review article is on the carbonylation and nitration of proteins in AD and mild cognitive impairment (MCI). The oxidatively modified proteins showed a strong correlation with the reported changes in brain structure, carbohydrate …

Predicting The Pathway Involvement Of Metabolites Based On Combined Metabolite And Pathway Features, Erik D. Huckvale, Hunter N. B. Moseley

Markey Cancer Center Faculty Publications

A major limitation of most metabolomics datasets is the sparsity of pathway annotations for detected metabolites. It is common for less than half of the identified metabolites in these datasets to have a known metabolic pathway involvement. Trying to address this limitation, machine learning models have been developed to predict the association of a metabolite with a “pathway category”, as defined by a metabolic knowledge base like KEGG. Past models were implemented as a single binary classifier specific to a single pathway category, requiring a set of binary classifiers for generating the predictions for multiple pathway categories. This past approach …

Mucin 5ac Modulates Cancer-Associated Fibroblast Heterogeneity Through Epigenetic Regulation, Rachel J. Kehrberg

Theses & Dissertations

Pancreatic cancer is characterized by a stroma component that comprises up to 90% of the tumor. Cancer-associated fibroblasts (CAFs) are a significant component of the stroma and contribute to cancer pathobiology through the secretion of extracellular matrix, growth factors, metabolites, and cytokines. CAFs are a highly heterogeneous population derived from various precursors, including adipose-derived and bone marrow- derived mesenchymal stem cells (AD-MSCs, BM-MSCs) and pancreatic stellate cells (PSCs). In this dissertation, we examine how mucin 5ac (Muc5ac) mediates the maturation of AD-MSCs, BM-MSCs, and PSCs into CAFs and the heterogeneity between CAFs derived from these various precursors. Muc5ac promotes the …

Cis-Regulatory Mechanisms Through Stages Of Erythroid Regenration, Yichao Zhou

Theses & Dissertations

Produced by steady state erythropoiesis, erythrocytes serve as vital regulators of metabolism and life by delivering oxygen to all the cells and tissues. Under acute anemia, steady state erythropoiesis is not sufficient to produce enough erythrocytes, leading to distinct mechanisms needed to regenerate large numbers of mature erythrocytes rapidly. Erythroid regeneration occurs in four stages: activation, expansion and differentiation, resolution, and post-resolution, according to the dynamics of erythrocyte numbers and progenitor activity. Erythroid regeneration throughout this timeline requires some critical extracellular cues, but the intrinsic molecular mechanisms needed to accelerate and decelerate the activity of erythroid progenitors in anemia and …

Identifying The Molecular Determinants Of Lung Metastatic Adaptation In Prostate Cancer, Grace M. Waldron

Theses & Dissertations

Prostate cancer (PC) stands as the primary diagnosed cancer in men in the US at approximately 299,010 cases in 2024 and ranks second globally, posing a significant public health challenge. Clinical presentations vary widely, from indolent to aggressive forms, necessitating stage-specific treatment regimens. Understanding its metastatic nature is critical due to the impact of cancer cell dissemination on disease morbidity, with bone and visceral organs serving as key sites of metastasis. Despite bone metastasis being the most common site for metastasis, visceral metastases at sites such as the liver and lungs correlate with poorer survival, emphasizing the role of microenvironmental …

Mucins: Drivers Of Cancer Cell And Microenvironment Crosstalk In Pancreatic Cancer, Xiaoqi Li

Theses & Dissertations

Mucins facilitate the pancreatic cancer (PC) initiation, progression, and metastasis. Among mucins, MUC4 has been reported to inhibit lymphokine-activated cell killing and induce the apoptosis of cytotoxic T-cells. Counterintuitively, MUC4 expression is upregulated by multiple T-cell-secreted cytokines, such as IFN-γ, IL-17, and stroma-secreted factors like retinoic acid. Previously, we have identified that nuclear receptor coactivator 3 (NCOA3) regulates the MUC1 and MUC4 expression by increasing chromatin accessibility and maintaining protein stability. However, the comprehensive crosstalk mediated by MUC4 in cancer cells and T-cells and how its upstream regulator, NCOA3, modifies the cancer cell-intrinsic behavior is still elusive. Here, we show …

Novel Spirocyclic Dimer (Spid3) Displays Potent Preclinical Effects In Hematological Malignancies, Alexandria Eiken

Theses & Dissertations

Chronic lymphocytic leukemia (CLL) is a heterogeneous disease characterized by the accumulation of mature CD5⁺ B-cells in the peripheral blood, bone marrow, and secondary lymphoid tissues (e.g., spleen and lymph nodes).Despite the efficacy of front-line therapies, CLL is still an incurable disease, highlighting the need for development of novel therapeutics and further study of resistance mechanisms. Within the lymph node CLL tumor microenvironment (TME), there is an upregulation of gene signatures associated with B-cell receptor (BCR) and downstream nuclear factor kappa B (NF-κB) signaling compared to CLL cells found within the blood or bone marrow niches. Additionally, BCR signaling …

Understanding The Non-Canonical Regulation Of Srebp In Aspergillus Fumigatus, Muhammad Abubakar Khan

Dartmouth College Ph.D Dissertations

Aspergillus fumigatus is an opportunistic fungal pathogen causing invasive pulmonary aspergillosis (IPA), with high mortality rates in immunocompromised individuals. Adaptation to the hypoxic microenvironment of IPA is crucial for fungal virulence. The transcription factor SrbA, a Sterol Regulatory Element-Binding Protein (SREBP) homolog, plays a key role in this hypoxic response and regulates genes involved in hypoxic growth, sterol biosynthesis, and azole resistance, making it an attractive therapeutic target.

However, SrbA activation in A. fumigatus lacks critical components of the canonical SREBP pathway, such as SCAP, Site-1 protease (S1P), and Site-2 protease (S2P). Instead, the rhomboid protease RbdB, signal peptide peptidase …

The Role Of Med13 In Proteaphagy, John Sauer, Brittany Friedson, Katrina Cooper

Rowan-Virtua Research Day

Regulation of proteasomes is important for adaptation to cellular stress. Previous studies have shown that following starvation stress, proteasomes are targeted for destruction by autophagy. However, how cells control proteasomes in response to nitrogen starvation remains unclear. This study delves into the intricate interplay between Med13, proteaphagy, and stress response regulation, aiming to elucidate their roles in cellular survival mechanisms. It focused on the highly conserved Cdk8 kinase module (CKM) of the Mediator complex a that plays a pivotal involvement in cellular signaling and gene regulation under stress conditions. During the investigation, we asked if the degradation of specific proteasome …

The Contribution Of Micrornas To Rybp Silencing In Glioblastoma Multiforme, Alex B. Lee

Graduate Theses

Glioblastoma multiforme (GBM) is a highly aggressive and invasive tumor of the central nervous system (CNS). Survival rates are abysmal, with only 7.2% of patients alive 5-years after diagnosis. Because of this, understanding epigenetic alterations that give GBM tumors their aggressive phenotypes is critical for the development of more targeted and effective therapies. These alterations frequently affect a group of proteins called the Polycomb group proteins, which play important oncogenic and tumor suppressive roles in cancer. One Polycomb protein, the RING1- and YY1-binding protein (RYBP), is downregulated in a majority of GBM patients, suggesting a strong tumor suppressive property. In …

Evaluation Of The Efficiency Of Muscle-Specific Promoters To Express Non-Endogenous Proteins In Skeletal Muscle, Gabrielle Bulliard, Made Harumi Padmaswari, Christopher E. Nelson

Biomedical Engineering Undergraduate Honors Theses

Gene therapies are emerging as powerful tools for treating genetic diseases and cancers, offering the potential for a permanent cure. Hemophilia B, affecting approximately 6,000 men in the U.S., results from a deficiency in coagulation factor IX protein (FIX), which is crucial for blood clotting. A substantial portion of patients, over 40%, suffer from severe hemophilia B, experiencing spontaneous, prolonged bleeding. Current prophylactic treatments involve frequent coagulation factor infusions, yet a curative approach would alleviate this burden. Gene editing technologies like CRISPR-Cas systems show promise for correcting genetic mutations, but the diverse nature of factor IX gene (F9) …

Investigating The Modulation Of Metastasis By Dax-1 In Adrenal Carcinoma Cells, Aarya Mishra

Undergraduate Honors Theses

The nuclear hormone receptor (NHR), DAX-1 (dosage-sensitive sex reversal, adrenal hypoplasia critical region, on chromosome X, gene 1), is important in adrenal and gonadal development as well as steroidogenesis. It is encoded by the NR0B1 gene and functions mainly as a transcriptional repressor. Classified as an orphan receptor within the NHR superfamily, DAX-1 has been shown to inhibit other NHRs including estrogen receptor, androgen receptor and steroidogenic factor 1. DAX-1 is found to be underexpressed in breast and prostate cancers and, specifically in prostate cancer, is believed to be a transcriptional repressor of genes that are involved in epithelial-mesenchymal transition …

Identifying Novel Therapeutics And Modifiers Of Myotonic Dystrophy Type 1, Jesus Alberto Frias

Legacy Theses & Dissertations (2009 - 2024)

The expansion of microsatellite repeats within the human genome has been identified as the cause of numerous hereditary diseases, including myotonic dystrophy (DM). DM is an autosomal dominant disease with a worldwide prevalence of ~1:8000 individuals. DM presents multisystemic symptoms such as myotonia, cardiac conduction defects, muscle wasting and weakness, insulin resistance, and cataracts. There are two genetically distinct, yet clinically similar types of DM: DM type 1 (DM1), caused by CTG repeat expansions in the 3’ UTR of the dystrophia myotonica protein kinase (DMPK) gene and DM type 2 (DM2), resulting from CCTG repeat expansions in the first intron …

A Phylogenetic Analysis Of The Population Dynamics Of A Captive Colony Of Diploptera Punctata., Nick Peterson

Theses/Capstones/Creative Projects

The unique milk production of Diploptera punctata makes this species a promising model species in entomology for studying the evolution of milk production and for insect endocrinology. Despite this, the genetic diversity of captive populations of the species is not well studied. To better evaluate the captive diversity and population dynamics of Diploptera punctata at UNO we extracted the DNA of 20 random individuals and amplified their DNA using 4 different primers before cleaning the amplified products and sequencing the genes of the samples for use in both individual and concatenated phylogenetic trees. Our results indicate the UNO colony of …

A Journey To The Center Of The Cell: The Characterization Of Novel Non-Canonical Mechanisms Of Notch Signaling, Tana Ranae Gazdik

Boise State University Theses and Dissertations

Cellular signaling pathways are the main method of communication between cells throughout the body. Of the many complex signaling pathways, the Notch signaling pathway is an ancient, highly conserved pathway critical to most animal life. This pathway is not only able to respond to juxtracrine signals from neighboring cells, but also acts as a microenvironment sensor, allowing cells to react to a variety of situations. Thus, understanding the mechanisms behind the regulation of Notch signaling is crucial to improving our basic understanding of Notch in cell biology and development. This dissertation introduces two previously undescribed non-canonical regulatory mechanisms of the …

Characterizing The Role Of Pa5189 Of Pseudomonas Aeruginosa In Deletion And Overexpression Mutants, Seh Na Mellick

Theses/Capstones/Creative Projects

In the context of rising multidrug resistance in biofilm-forming pathogens like Pseudomonas aeruginosa, this study investigates the role of the understudied transcription factor PA5189 in antibiotic resistance and biofilm formation. PA5189 deletion and overexpression mutants were created in a parent P. aeruginosa strain using pEX18Tc-based recombinant suicide vectors, with genotypic verification of putative triparental conjugants achieved through restriction digestion and PCR. The study revealed that PA5189 overexpression significantly increases resistance to commonly used broad spectrum antibiotics such as ciprofloxacin and imipenem. Additionally, differential expression of PA5189 was found to notably affect biofilm formation, with variations contingent on the nutrient …

Molecular Characterization Of Stress Response In Western Honey Bee (Apis Mellifera), Faizan Tahir

Master's Theses

Honey bees are incredibly important for the reproduction of flowering plants and the sustainability of agricultural ecosystems. However, they face various stressors such as pesticides, pathogens, habitat loss, and climate change. Extensive research has been conducted to understand how bees respond to these stressors. Scientists have discovered that honey bees exhibit complex physiological and behavioral responses to stress at individual and colony levels. Stress can have a significant impact on their immune function, foraging behavior, and reproductive success (Decourtye et al., 2010). Understanding bee responses to stress is crucial for several reasons. Firstly, honey bees are vital for the pollination …

Evaluating Novel Approaches For Improving Anadromous Fish Passage In Coastal Rivers, Aaron Bunch

All Dissertations

Few of the world's rivers remain free-flowing for over 1000 km, significantly impacting anadromous fish populations due to dam-induced habitat fragmentation. Three partial migration barriers (low-head dams) on North Carolina's Cape Fear River (USA)—lock and dam 1 (LD1), lock and dam 2 (LD2), and lock and dam 3 (LD3)—impact American shad Alosa sapidissima, Atlantic sturgeon Acipenser oxyrinchus oxyrinchus, and striped bass Morone saxatilis populations. Mitigation strategies to pass fish upstream have included conservation locking, nature-like fishway construction, and environmental flows (e-flows). This study introduced a novel e-flow (dam submergence flow), tested acoustic double-tagging techniques for tracking American …

Understanding Taf13 (Tata Box-Binding Protein-Associated Factor 13) Upregulation In Eukaryotic Cells, Selin Kaplanoglu

Honors Theses

TATA-binding protein (TBP) and TBP-associated factors (Tafs) comprise RNA Polymerase II (RNA Pol II) pre-initiation complex. This universal component carefully controls the transcriptional initiation process. One of the Tafs, Taf13, also plays an important role in the regulation of RNA Pol II transcription initiation which is evolutionarily conserved from yeast to humans. It is found that Taf13 is overexpressed in cancer cells, although the exact mechanism that is responsible for this overexpression is unclear. Our hypothesis suggests that targeted degradation by the 26S proteasome via ubiquitylation [Ubiquitin-Proteasome System (UPS)] may be the mechanism that regulates the stability of Taf13. To …

A Review Of Rheb Activation Of Mtorc1 And The Great Mystery Of One Missing Gef, Jack Gregory

Senior Honors Theses

The mTORC1 pathway is involved in the regulation of cell growth and translation. The pathway has a complex web of activators and inhibitors to activate mTORC1. mTORC1 is regulated via a small GTPase called Rheb, which interacts directly with mTORC1. This GTPase and its GTPase activating protein (GAP), TSC1/2, have been widely studied to understand how the variety of regulators of mTORC1 interact with these proteins. Despite this, the guanine nucleotide exchange factor (GEF) of Rheb has yet to be identified. This review broadly analyzes Rheb and mTORC1, their structures, regulations, and interactions, and explores the mystery of the missing …

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

Theses and Dissertations

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, …

Characterization Of The Androgen Receptor H1-H3 Loop As A Putative Fkbp Regulatory Surface, Isela Rodriguez

Open Access Theses & Dissertations

Prostate Cancer (PCa) is one of the most common life-threatening malignancies diagnosed among American men. Initiation and progression of PCa are dependent upon androgen receptor (AR) regulated genes. Functional receptor conformation is influenced by the cooperation of chaperone and cochaperone proteins including the 52 and 51 kDa FK506 binding proteins (FKBP52 and FKBP51). FKBP52 is known for being a positive regulator of AR, PR (progesterone receptor), and GR (glucocorticoid receptor) activity, whereas FKBP51 negatively regulates steroid hormone receptor activity. As a result, these two proteins have become highly promising therapeutic targets for the disruption of mechanisms important in several endocrine-related …

Plant Model Of Α-Synucleinopathy: Expression Of Α-Synuclein A53t Variant In Hairy Root Cultures Leads To Proteostatic Stress And Dysregulation Of Iron Metabolism, Jasmina Kurepa, Kristen A. Bruce, Greg A. Gerhardt, Jan A. Smalle

Neurology Faculty Publications

Synucleinopathies, typified by Parkinson’s disease (PD), entail the accumulation of α- synuclein (αSyn) aggregates in nerve cells. Various αSyn mutants, including the αSyn A53T variant linked to early-onset PD, increase the propensity for αSyn aggregate formation. In addition to disrupting protein homeostasis and inducing proteostatic stress, the aggregation of αSyn in PD is associated with an imbalance in iron metabolism, which increases the generation of reactive oxygen species and causes oxidative stress. This study explored the impact of αSyn A53T expression in transgenic hairy roots of four medicinal plants (Lobelia cardinalis, Artemisia annua, Salvia miltiorrhiza, and Polygonum multiflorum). In all …

Development And Application Of Environmental Dna (Edna) Techniques To Detect Rough-Footed And Yellow Mud Turtles: A Seasonal Field Study To Detect Turtle Edna, Sakib Tahmid Rishan

Theses and Dissertations

The application of environmental DNA (eDNA) has improved the ability of humans to detect the existence and geographical distribution of aquatic organisms. The present study highlights the development and application of eDNA techniques to detect rough-footed mud turtles and yellow mud turtles in different areas in Texas. Both mud turtle species were successfully detected in lakes/resacas using direct eDNA sampling techniques. Moreover, passive eDNA sampling techniques were conducted using different membrane filters to detect mud turtle species. The findings indicated that only the mixed cellulose esters (MCE) filter membranes effectively identified eDNA of yellow mud turtles in the fall, but …

Cellular Mechanisms Of Embryonic Eye Regrowth In Xenopus Laevis, Randolph L. Grell

UNLV Theses, Dissertations, Professional Papers, and Capstones

The African Clawed Frog, Xenopus laevis, has been an indispensable model organism for over 100 years in the study of embryogenesis and development. In recent years, this vertebrate model has emerged as a robust tool for deciphering the cellular and molecular mechanisms underlying various modes of tissue, limb, and organ regeneration. In the context of eye repair, Xenopus offers a unique model, where the adult frog eye has limited regenerative capacity compared to its pre-metamorphic embryonic and tadpole forms, which exhibit a robust capacity for regrowth. Understanding the intricate molecular mechanisms that underlie this developmental shift in regrowth ability …